Social determinants impact health more than healthcare

Original Work, NO PLAGERIESM, Cite Reference, References,
100 words
https://www.kff.org/disparities-policy/issue-brief/beyond-
health-care-the-role-of-social-determinants-in-promoting-
health-and-health-equity/
Read article and just in your own words comment on your
thoughts regarding the article.
192177
by Elbert Washington
FILE
T IME SUBMIT T ED 28- DEC- 2017 12:25PM WORD
COUNT 11857
CHARACT ER COUNT 6537 3
DRAFT _19217 7 .DOCX (27 8.99K)

%5
SIMILARIT Y INDEX
EXCLUDE QUOT ES ON
EXCLUDE
BIBLIOGRAPHY
ON
192177
ORIGINALITY REPORT
192177
WRITECHECK REPORT
PAGE 1
PAGE 2
PAGE 3
PAGE 4

PAGE 6
PAGE 7
PAGE 8
PAGE 9
PAGE 10
PAGE 11
PAGE 12
PAGE 13
PAGE 14
PAGE 15
PAGE 16
PAGE 17
PAGE 18
PAGE 19
PAGE 20
PAGE 21
PAGE 22

PAGE 24
PAGE 25
PAGE 26
PAGE 27
PAGE 28
PAGE 29
PAGE 30
PAGE 31
PAGE 32
PAGE 33
PAGE 34
PAGE 35
PAGE 36
PAGE 37
PAGE 38
PAGE 39

PAGE 41
PAGE 42
PAGE 43
PAGE 44
PAGE 45
192177by Elbert Washington192177ORIGINALITY
REPORT192177WRITECHECK REPORT
How to conduct meta-analysis: A Basic Tutorial
Arindam Basu
University of Canterbury
May 12, 2017
Concepts of meta-analyses
Meta analysis refers to a process of integration of the results of
many studies to arrive at evidence syn-
thesis (Normand, 1999). Meta analysis is essentially systematic
review; however, in addition to narrative
summary that is conducted in systematic review, in meta
analysis, the analysts also numerically pool the
results of the studies and arrive at a summary estimate. In this
paper, we discuss the key steps of conducting
a meta analysis. We intend to discuss the steps of a simple meta

analysis with a demonstration of the key
steps from a published paper on meta analysis and systematic
review of the effectiveness of salt restricted
diet on blood pressure control. This paper is a basic
introduction to the process of meta-analysis. In subse-
quent papers in this series, we will discuss how you can conduct
meta analysis of diagnostic and screening
studies, and principles of network meta analyses, where you can
conduct a meta analysis with more than
one intervention or exposure variable.
Nine Steps to Meta Analyses
We recommend in general the following nine steps of meta
analysis. These nine steps are in general applicable
to all meta-analyses.
1. Frame a question (based on a theory)
2. Run a search (on Pubmed/Medline, Google Scholar, other
sources)
3. Read the abstract and title of the individual papers.
4. Abstract information from the selected set of final articles.
5. Determine the quality of the information in these articles.
This is done using a judgment of their
internal validity but also using the GRADE criteria
6. Determine the extent to which these articles are
heterogeneous
7. Estimate the summary effect size in the form of Odds Ratio
and using both fixed and random effects
models and construct a forest plot

8. Determine the extent to which these articles have publication
bias and run a funnel plot
9. Conduct subgroup analyses and meta regression to test if
there are subsets of research that capture
the summary effects
Step I: Frame a Question
For framing an answerable question in a meta analysis, use the
PICO framework (Schardt et al., 2007).
PICO is an acronym for ”Participant-Intervention-Comparator-
Outcomes”. “Participant” here refers to
1
PeerJ Preprints | https://doi.org/10.7287/peerj.preprints.2978v1 |
CC BY 4.0 Open Access | rec: 15 May 2017, publ: 15 May 2017
individuals or population of interest to us. For example, if we
are interested in the effectiveness of a drug
such as nedocromil on bronchoconstriction (narrowing of air
passages) among adult asthma patients, then
we shall include only adult asthmatics for our study, not
children or older adults (if such individuals are not
of our interest); on the other hand, if we are interested to study
the effectiveness of mindfulness meditation
for anxiety for adults, then again adult age group would be our
interest; we could further narrow down the
age band to our interest.
Intervention needs to be as broadly or as narrowly defined
keeping only the interventions of our interest.

Usually, meta-analyses are done in assimilating studies that are
RCTs or quasi-experimental studies where
pairs of interventions (intervention versus placebo or
interventions versus conventional treatment or inter-
ventions and no treatment) are compared (Normand, 1999). Note
that meta-analyses are not necessarily
restricted only to randomised controlled trials, these are now
increasingly applied to observational study de-
signs as well for example cohort and case control studies; in
these situations, we refer to the specific expsoure
variables of our interest (Stroup et al., 2000). Meta-analyses are
also conducted for diagnostic and screening
studies (Hasselblad and Hedges, 1995)
Let’s say we are interested to test the hypothesis that
consumption of plant-based diets is associated with
reduced risk of cardiovascular illnesses. You can see that for
ethical reasons, it is not possible to conduct
randomised controlled trials so that one group will be forced to
consume plant based diet and the other
group will be forced to consume non-plant based diet, but it is
possible to obtain that information about
heart diseases from two groups of people who have consumed
and not consumed certain levels of vegetarian
items in their diets. Such studies are observational
epidemiological studies and using observational studies
such as cohort and case control studies. In such situations, it is
useful to summarise findings of cohort and
case control studies. Intervention then is not appropriate;
however, we use the term ”Exposure”. Likewise,
the comparison group is important as well. The comparison
group can be ”no intervention”, or ”placebo”,
or ”usual treatment”.
The outcomes that we are interested can be narrowly or broadly
defined based on the objective of the meta

analysis. If the outcome is narrowly defined, then the meta
analysis is only restricted to that outcome, for
instance, if we are interested to study the effectiveness of
mindfulness meditation on anxiety then, anxiety is
our outcome; we are not interested to find out if mindfulness is
effective for depression. On the other hand,
if the objective of hte study is to test if mindfulness meditation
is useful for ”any health outcome”, then the
scope of the search is much wider. So, after you have set up
your theory and your question, now is the time
to rewrite the question and reframe it as a PICO formatted
question. Say we are interested to find out if
minduflness meditation is effective for anxiety, then we may
state the question in PICO as follows:
• P: Adults (age 18 years and above), both sexes, all ethnicity,
all nationality
• I: Mindfulness Meditation
• C: Placebo, Or No Intervention, or Anxiolytics Or Traditional
Approaches, or Drug Based Approaches,
or Other Cognitive Behavioural Therapy
• O: Anxiety Symptom Scores, or Generalised Anxiety
Then, on the basis of PICO, we reframe the question as follows:
”Among Adults, compared with all other
approaches, what is the effectiveness of Mindfulness Meditation
for the relief of Anxiety?”
Step II: Conduct a Search of the Literature Databases
After you have decided the PICO, you will conduct a search of
the literature databases. This will help
you to identify the appropriate search terms. These search terms

are arranged using Boolean Logic, fuzzy
logic, specific search related controlled vocabulary, symbols of
truncation or expansion, and placement of the
terms in different sections of a reported study (Tuttle et al.,
2009). In Boolean Logic, you use the connectors,
2
”AND”, ”OR”, and ”NOT” in various combinations to expand or
narrow down search results and findings.
For example,
• ”Adults” AND ”Mindfulness Meditation” will find only those
articles that have BOTH adults AND
mindfulness meditation as their subject topics. While,
• ”Adults” OR ”Mindfulness Meditation” will find all articles
that have EITHER ”Adults” OR ”Mind-
fulness Meditation” in their subject topics, so the number of
results returned will be larger.
• ”Adults” NOT ”Mindfulness Meditation” will find only those
articles that contain ”Adults” but will
exclude all articles that have ”Mindfulness Meditation” as their
topic area.
In addition to the use of Boolean logic, you can also use ”fuzzy
logic” to search for specific articles. When you
use fuzzy logic, you use search terms where you use words like
”Adults” NEAR ”Mindfulness” or ”Adults”
WITHIN 5 Words of ”Mindfulness” to search for articles that

are very specific. These can be combined in
many different ways.
Many databases, such as Pubmed/Medline, contain MeSH
(Medical Subject Headings) as controlled vo-
cabulary where hte curators of thse databses maintain or archive
difernet articles under specific search
terms (Robinson and Dickersin, 2002). When you search
Medline or Pubmed, you can use MeSH terms to
search for your studies. You can use or combine MeSH terms
along with other terms to search more widely
or more comprehensively.
Besides these, you will use specific symbols such as asterisk (*)
marks and dollar signs to indicate truncation
or find related terms to find out articles. For example, if you
use something like ”Meditat$” in a search
term, then you can find articles that use the terms ”meditating”,
or ”meditation”, or ”meditative” or
”Meditational”; you will find list of such symbols in the
documentation section of the database that you
intend to search (Robinson and Dickersin, 2002).
Finally, search terms can occur in many different sections and
parts of a study report. One way to search is
to search the title and abstract of most studies. Another way to
search place to search is within the entire
body of the article. Thus, combining these various strategies,
you can run a comprehensive search of the
publications or research that will contain data that you can use
for your meta-analysis.
Step III: Select the articles for meta analysis by reading Titles
and Abstracts
and full texts

First, read the titles and abstracts of all relevant searched
papers. But before you do so, set up a scheme
where you will decide that you will select and reject articles for
your meta analysis. For example, you can
set up a scheme where you can write:
• The article is irrelevant for the study question
• The article does not have the relevant population
• The article does not have the relevant intervention (or
exposure)
• The article does not have a relevant comparison group
• The article does not discuss the outcome that is of interest to
this research
• The article is published in a non-standard format and not
suitable for review
• The article is published in a foreign language and cannot be
translated
• The article is published outside of the date ranges
• The article is a duplicate of another article (same publication
published twice)
3

Use this scheme to go through each and every article you
retrieved initially on the basis of reading their titles
and abstracts. Usually only one clause is good enough to reject
a study and note it that study got rejected
on that criterion, and the first clause that rejects the study is
noted down as the main cause. So, even if a
study can be rejected on two clauses, the first one that rejects
the study is mentioned as the main clause
of rejection; you will need to put together a process diagram to
indicate which articles were rejected and
why. Such a process diagram is referred to as PRISMA
(Preferred Reporting Items of Systematic Reviews
and meta-analyses) chart (Moher et al., 2009). After you have
run through this step and have identified a
certain number of studies which must be included in the meta-
analysis, obtain their full texts. Then read
the full text once more and conduct this rejection exercise and
note the numbers. As may be expected, you
will reject fewer articles in this round. Then, read the full text
and hand search the reference lists of these
articles to widen your research. This step is critical. Often, in
this step, you will find out sources that you
must search, or identify authors whose work you must read to
get a full list of all works and researches that
have been conducted on this topic. Do not skip this step. In this
step, you will note that some authors
feature prominently, and some research groups surface; take a
note of them; you may have to write to a few
authors to identify if they have published more research. All
this is needed to run a thorough search of the
studies so that you will not miss any study that may be relevant
for this meta analysis.
Step IV: Abstract information from these articles
Once you know that you have a set of studies that you will work

with, you will need to work with, you
will now need to abstract data from them for your study. At the
minimum, you must obtain the following
information for each study included in you analysis:
1. The name of the first author
2. The year the article was published
3. The population on whom the study was conducted
4. The type of research (was it an RCT? Or if observational,
what type of study was it?)
5. What was the intervention exactly? (A brief description of
the intervention)
6. The comparison condition (what was it compared with?)
7. What was the outcome and how was it measured?
8. How many individuals were in the intervention (Ne)?
9. How many people were included in the control arm (Nc)?
10. If the outcomes were measured in a continuous scale, what
was the mean value of the outcome among
those in the intervention arm?
11. If the outcome was measured on a continuous scale, the
mean of the outcome among those in the
comparison condition
12. If the outcome was measured on a continuous scale, what
was the standard deviation of the measure
for the exposure or intervention?

13. If the outcome was measured on a continuous scale, what
was the standard deviation of the measure
for the comparison arm?
14. If the outcome was measured on a binary scale (more on this
later), the number of people with the
outcome in the intervention arm
15. If the outcome was measured on a binary scale, the number
of people with the outcome on the com-
parison arm
4
16. A quality score or a note on the quality or critical appraisal
of each study
This is just a suggestion; I do not recommend a fixed set of
variables and you will determine what variables
you need for each meta analysis. If you use a software such as
Revman, then that will guide you with the
process of abstraction of data from each article and you should
follow the steps there. Note that in this case,
we are only considering tabulation of these information per
article. Also note that in this case, we will work
with one intervention and one outcome in each table. You may
have more than one outcome in the paper; in
that case, you will need to set up different tables. Enter this
information on a spreadsheet, and export the
spreadsheet in the form of a csv file that you can input into R.

In this exercise we will use R for statistical
computing (R Core Team, 2013)
Step V: Determine the quality of information of these articles
For each study, you will need to critically appraise the
information contained within it and decide if the
study you are considering for your review meets the internal
validity criteria. At the minimum you will need
to identify the following:
• What is the theory and the hypotheses this research is about?
• Is the sample size adequate for the research question? is this
study underpowered?
• To what extent did the authors eliminate biases in the study?
Even if it is an RCT, was there blinding?
How confident are you that the authors conducted an
appropriate randomisation procedure? What is
the likelihood that the groups that were compared were very
different with respect to the prognosis?
- If this is an RCT, did the authors conduct an intention to treat
analysis?
• If this is an observational study, how did the authors eliminate
the risks of selection bias? How much
was the risks of information bias from the participants
eliminated?
• What confounding variables were controlled for? Are these
confounding variables sufficient? (This
will require that you will have to know something about the
biology of the relationship; if you are not
confident, ask someone)

A great way to ascertain the quality of each article (rather each
outcome within an article) is to use the
GRADE (Grading recommendations assessment, development
and evaluation) criteria and use the GRADE-
pro softwareto judge the quality of the outcome-intervention
pairing.
Step VI: Determine the extent to which the articles are
heterogeneous
Think about the distinction between a systematic review and a
meta analysis. A systematic review is one
where the analysts follow the same steps as above (frame a
question, conduct a search, identify the right
type of research, extract information from the articles). Then, in
a systematic review but not in a meta
analysis, all studies that are fit to be included in the review get
summarised and patterns of information
are tabulated and itemised. This means, that all study findings
for a set of outcomes and interventions
are identified, tabulated and discussed in systematic reviews.
On the other hand, in a meta analysis, there
is an implicit assumption that the studies have come from a
population that is fairly uniform across the
intervention and outcomes. This may indicate one of the two
issues: either that the body of the studies
that you have identified are exhaustive and the estimates that
you will obtain for the association between
the exposure or intervention and the outcome are based on the
subset of evidence that you have identified
and define or estimate the true association. This is the concept
of fixed effects meta analysis (Hunter and
Schmidt, 2000). Alternatively, you can conceptualise that the
studies that you have identified for this meta
analysis constitute a sample that is part of a larger population of
studies. That said, this subset of studies

from that larger population is interchangeable with any other
study in that wider population. Hence this
set of studies is just a random sample of all possible studies.
This is the notion of random effects meta
analysis (Hunter and Schmidt, 2000). So, are the studies very
similar or homogeneous in the scope of the
5
http://community.cochrane.org/tools/review-production-
tools/revman-5/revman-5-download
https://gradepro.org/
https://gradepro.org/
intervention or population, or outcomes? Therefore, it is
important that when we conduct a meta-analysis,
because if the studies are so different from each other that it is
impossible to pool the results together, then
we will have to abandon any notion of pooling the study
findings to arrive at a summary estimate. If the
findings are close enough then the studies are homogeneous and
we would conclude that it would be OK to
pool the study results together using what is referred to as fixed
effects meta analysis. If on the other hand,
we see that the studies are different by way of their results but
nevertheless there are other areas (selection
of the population, the intervention, and the outcomes) that are
sufficiently uniform, then we can combine
the results of the studies themselves but we may conclude that
the apparent lack of homogeneity would arise
as these studies are part of a larger wider population of all
possible studies and hence we would rather report

a random effects meta analysis.
We will discuss two ways to measure heterogeneity of the
studies. One way to test for heterogeneity is to
use a statistic referred to as Cochran’s Q statistic. The Q
statistic is a chi-square statistic. The assumption
here is that the studies are all from the same “population” and
therefore homogeneous and therefore a
fixed-effects meta-analysis would be an appropriate measure to
express the summary findings. Accordingly,
the software first estimates a fixed-effects summary estimate.
The fixed effects summary estimate is a sum
of the weighted effect size. The weight of each study is
determined by the variance of the effect estimate.
Then, the sum of squared difference between the summary
estimate and each individual estimate would have
a chi-squared distribution with K-1 degrees of freedom where K
= number of studies. If the chi-square value
would be low, this would indicate that the studies were indeed
homogeneous, otherwise, it would indicate
that the studies are heterogeneous. If the studies are found to be
statistically heterogeneous, the next step
for you would be to test whether there are real reasons for them
to be heterogeneous, i.e., the population,
the intervention, and the outcomes are very different from each
other. If this indeed would be the case,
then, you would summarise the study findings as you would
with a systematic review. On the other hand, if
you find that the studies are otherwise similar, but perhaps one
or more studies were to drag the summary
estimate to one direction rather than another, you would assume
while the studies are not homogeneous,
they may be based on a larger pool of studies. Hence you may
conduct a random effect meta analysis.
Another measure of heterogeneity or statistical heterogeneity

for meta analyses is mathPlaceholder0 es-
timate. I2 estimate is derived from another related estimate
referred to as H2, and H2 is given by:
H2 = Q/K − 1 where K is the number of studies. Then, if Q > K
- 1, then I2 is defined as (H2 − 1)/H2;
otherwise I2 is given a value of 0. For example, let’s say are
working with 10 studies, and the Q statistic is
36 (this will mean that the weighted sum of squared differences
between the estimated fixed effect size and
the individual effect size estimates in this case is 36); As Q > 9
for 10 studies (K = 10), therefore I2 will
be defined as 3/4 or 75%. A high I-squared statistic would mean
gross heterogeneity while a low I-squared
value would imply homogeneity of the studies (usually
conventionally set at 30%)
Step VII: Estimate summary effect estimate
First, we shall determine the summary effect estimate assuming
both fixed and random effects model
Second, we shall construct a Forest Plot to visually inspect how
the effect estimates of each individual study
are distributed around a null value but also around the overall
effect estimates.
Fixed and random effects models refer to the two assumptions:
fixed effects model assume that the popula-
tions on which these studies are based are uniform enough to
determine that these set of studies are sufficient
to draw conclusions about the relationship between the exposure
and the outcome; random effects model
assume that while we can relax the assumption that the
populations from where the studies arose were same
and therefore these sets of studies were sufficient to draw our
conclusions, the studies themselves form part

of an interchangeable body of evidence.
Forest Plot of the results
In addition to the display of the heterogeneity of the estimates
of the studies, the summary effect estimates
6
based on fixed effects and random effects meta-analyses, we
will also inspect a plot of all included studies
in the meta analysis; this is referred to as ”forest plot”. In the
”forest plot”, the effect estimate of each
study is presented in the form of a square box; the area of the
square box is proportional to the weight
assigned to this particular study; the weight in turn is assessed
on the basis of their variances - the higher
the variance the lower the area (so the area is inverse of the
variance of each study). Then, across each
study estimate runs a horizontal line - the length of this line is
same as the width of the 95% confidence
interval for the effect estimate for that particular study. The
studies themselves are organised along the
y-axis of the plot; the order in which the studies are arranged
can be varied or as presented in the data
set you created. On the x-axis of the forest plot the effect sizes
are presented. A neutral point is plotted
on the x-axis (this is either “1.0” when binary variables are
studied in the meta analysis so your effect for
each study is measured in terms of relative risk or odds ratio, or
0 when you used continuous measures for

your outcome variables, so your effect measure is in terms of
differences in the effect size between those with
intervention or exposure and those in the control arm). A
vertical broken line passes through the neutral
point to indicate the information on each side of the line. When
you are testing intervention, it will state
that one side of the neutral line “favours intervention”, and the
other side of the line “favours control”. In
addition to these two indicators (that is the x-axis and the effect
measures of each study in the form of
boxes), we also get to see two diamonds. These diamonds
represent the summary effect estimate in the form
of fixed and random effects meta analysis final or summary
estimates. The diamonds do not have a line that
corresponds to their 95% confidence interval, instead the width
of the diamond represent the 95% confidence
interval bands around them.
Step VIII: Assess Publication Bias
Now that you have identified:
• The heterogeneity of the studies
• The summary effect estimate and a forest plot
It’s time to test if there are biases that can impact the study
conclusions. This means you will test whether
your meta analysis has omitted studies that should have been
included (Dickersin, 1990). If a study is
based on a large sample size and has reported positive findings,
such a study has a higher likelihood of
getting published and be identified through searches than a
study that is small and has reported equivocal
or negative findings (Thornton and Lee, 2000). As this
phenomenon in the context of a meta-analysis or

systematic review will indicate that our results are based on a
selection of studies and a systematic exclusion
of studies that are nonetheless important, this leaves room for
bias. This bias is referred to as “publication
bias”. There may be several reasons for such a publication bias,
including:
• Preference of journal editors to select those studies that have
interesting study findings .
• Those who fund studies are more favorably likely to support
studies that are large and have positive
findings
• Investigators are less likely to publish smaller studies with
ambiguous or non-interesting findings
• Smaller studies are delayed in their publishing and are not
therefore captured
If we accept that smaller studies with equivocal findings (that is
findings that either does not support the
preferred intervention or does not reach a level of statistical
significance) tend to small in size and their
findings are different from the summary estimate, then we may
expect the following to be true:
1. Large influential studies will have their effect estimate close
to the summary estimate
2. Large influential studies will be few (one or two)
3. Smaller studies may have widely variable effect estimate
equally distributed around the summary
estimate

7
4. The smaller a study, more variable will be the distribution of
their results. So, if we consider small
studies, they will be widely distributed around the neutral line
or a line representing summary estimate
when plotted in a graph.
These can be tested by plotting the effect estimates of the
studies on x axis and either the sample size of
the studies or the effect measure variability (variance or
standard deviation or a similar measure) on the y
axis of a plot. If there would not be serious publication biases,
the plot would resemble a funnel with one or
two dots representing studies with large sample size or low
variance and effect estimate close to or identical
to the summary estimate. The base of the funnel will be
populated by small sized studies (or studies with
large variances) with effect estimates scattered evenly around
the summary estimate (Duval and Tweedie,
2000). If on the other hand, there is publication bias, then we
would expect that one of the quadrants of
the “funnel” in the lower side will be absent or blank. This is a
visual assessment and most meta analysis
packages and software allow for this plot.
Step IX: Run subgroup analyses and meta regression
After you have examined the heterogeneity of the studies,
estimated the summary effect size, plotted the
forest plot, and tested for publication bias by testing and

plotting the funnel plot, you can comment about
the association between the exposure or the intervention and the
outcome. But that would still mean that
there are certain aspect of the study that need to be examined or
some characteristics of the participants
that need to be examined separately or in separate analyses. For
example, you could examine what would be
the relationship between the intervention and the outcome if
only studies of longer duration or studies with
predominantly sicker participants were included? Or you could
run regress the effect estimate on average
age of the participants the studies to test if the summary
estimate would vary with age. Such analyses are
referred to as subgroup analyses or meta-regression and part of
any meta analysis.
In summary, a meta-analysis is a method of analysis where data
from diverse studies are synthesised to arrive
at a summary estimate. The steps of meta analysis are similar to
that of a systematic review and include
framing of a question, searching of literature, abstraction of
data from individual studies, and framing of
summary estimates and examination of publication bias. It is
very important to conduct subgroup analyses
and meta regression to test how the summary effects would
change with different types of studies or different
chracteristics of participants in the study. We now move to a
real life example of a meta-analysis to illustrate
a few of these points.
Meta Analysis: Reanalysis of DASH diet on hypertension
The dietary approaches to stop hypertension (DASH) is a diet
and lifestyle based intervention to prevent
hypertension and related illnesses (Sacks et al., 2001). In this
meta analysis, we are interested to find out if

longer term salt restriction is beneficial for people with normal
blood pressure as well. We are going to rerun
a meta analysis from the following paper by FJ He and GA
Macgregor (He and MacGregor, 2002). We are
only going to look at the subset of studies dealing with
normotensives n the paper. Here is a simplified step
(not the nine step we outlined earlier but seven steps):
• Step I: PICO question and framing of search terms
• Step II: Listing of the studies on which they based their meta
analysis
• Step III: Abstraction of data from the studies and developing
the data set
• Step IV: Examination whether the studies are heterogeneous
(Cochran’s Q and Iˆ2)
• Step V: Summary Estimates and Forest Plot
• Step VI: Examination of Publication Bias
• Step VII: Subgroup analysis and meta regression
8
PICO
“Whether for normotensive individuals (that is, those with
normal levels of blood pressure), moderate
restriction of salt in the diet as opposed to no salt restriction
leads to reduction in blood pressure over long
time?” Following this, here is the screen shot of the search they
conducted:
Figure 1: Figure 1. The Search Terms they included in the

paper. labelPlaceholder1
Identification of studies
The search terms and the search processes are shown in the
following diagram The search algorithm and the
criteria of selection of the studies are here The PRISMA
diagram of how the studies were selected is here
We will work on the basis of the 28 studies the authors
identified (we can identify additional studies if we
want or if we take this as a starting point but for this exercise
this serves as a good illustrative example)
9
Figure 2: Figure 2. The PRISMA chart to select the studies for
this review. labelPlaceholder1
Abstraction of data and setting up our own table
labelPlaceholder1
We reconstruct the spreadsheet table and we will reanalyse. We
have saved the data for normotensive
individuals in the file hypertension.csv. Using R, we first read
the data and save the data to a dataframe,
thus:
htn meta <- read.csv(“hypertension.csv”, header = T)
Examination of Heterogeneity

If we review the data set and summarise without weighing the
studies in any way, we get to see that the
average drop in the diastolic blood pressure with normotensive
individuals with prolonged ingestion of low
salt diet was about 1 point and for systolic blood pressure was
about 3 points. So, let’s run a formal meta
analysis to see if the weighted averages are any different
10
library(meta)
## Loading ‘meta’ package (version 4.8-1).
htn meta m <- metagen(d sbp, sbp se, data = htn meta)
print(summary(htn meta m))
## Number of studies combined: k = 11
## ## 95%-CI z p-value
## Fixed effect model -2.0196 [-2.5483; -1.4908] -7.49 <
0.0001
## Random effects model -2.2689 [-3.4881; -1.0496] -3.65
0.0003 ##
## Quantifying heterogeneity: ## tauˆ2 = 2.3111; H = 1.90
[1.40; 2.57]; Iˆ2 =
72.2% [48.9%; 84.9%]
## ## Test of heterogeneity: ## Q d.f. p-value ## 35.99 10 <
0.0001
So, several things to note here:
• The first point is that, the studies are heterogeneous,

• Q is high 35.99 with K = 11 and therefore K-1 = 10
• Q is also highly significant statistically
• The Iˆ2 is at 72.2% which is very high
• The fixed effects summary estimate is that, there is a 2 point
drop in systolic blood pressure.
Examination of summary measures and Forest Plot
Let’s take a look at the forest plot
print(forest(htn meta m))
Figure 3: Figure 3. Forest Plot for the systolic blood pressure
11
The forest plot suggests that there are a few small studies with
strong effect size but majority of the studies
are within the 2 point drop mark.
Let’s check the summary estimates for diastolic blood pressure,
diastolic <- metagen(d dbp, dbp se, data = htn meta)
print(summary(diastolic)) ## Number of studies combined:
k = 11 ## ## 95%-CI z p-value
0.0001
## Random effects model -0.8199 [-1.7468; 0.1070] -1.73

0.0830
## ## Quantifying heterogeneity: ## tauˆ2 = 1.3987;
H = 1.86 [1.37; 2.53];
Iˆ2 = 71.2% [46.9%; 84.4%] ## ## Test of heterogeneity:
## Q d.f. p-value ## 34.78 10 0.0001
Figure 4: Figure 4. Forest Plot to study distribution of the effect
estimates of the diastolic blood pressure
for the DASH study
Examination of Publication bias
At this point, let us review evidence of publication bias in this
meta analysis. To test this, we construct
a funnel plot. We issue funnel() function in R and we can now
examine the funnel plot. Note that the x
axis of this plot provides the effect size of each study and the y-
axis of this plot provides the standard error.
As standard error is essentially a function of the sample size,
you can see that the smallest standard error
(that is studies with the largest sample size) is placed on the top
of the y-axis and the largest standard error
(that is, studies that indicate smaller through smallest sample)
are placed on the bottom of the y axis. An
examination of this plot reveals that the lower right quadrant of
the funnel is ’empty’ indicating that the
data of this meta analysis is mostly derived from large studies
(that is studies with relatively low standard
error) and those with large effect estimate in the direction of
estimate that favours the interventions (the
12

left side of the funnel base).
Figure 5: Figure 5. Funnel Plot, where we see that there is a
relative absence of studies in the right lower
quadrant
Subgroup analysis and meta regression
We are not done yet. We have only reviewed some aspect of the
analyses of this analysis. We still need to
run if there were important differences between the studies as in
our original tests for heterogeneity we found
that the studies were heterogeneous; also, we had different
types of studies included, some studies had longer
duration of the treatment, and other studies had shorter duration
of treatment. We also had some studies
that were based on crossover trials, and some studies were
based on parallel arms trials, so it is possible that
these studies would yield different summary estimates? In order
to examine this possibility, we run what is
referred to as subgroup analysis or meta regression. If you can
divide the set of studies into different groups
based on some criteria on a categorical variable (for which you
have collected data of course and included
them in the original data set that you used for analyses), then
you can conduct a subgroup analyses. Often,
you will be left with a variable (say age, or a specific
concentration of a biomarker), then you can conduct
what is referred to as meta regression, where you can regress
the summary estimates on the various factors
that can influence or explain the relationships. Remember that
you will need at least 10 studies to run
subgroup analyses. In this analysis presented below, we ran the
subgroup analyses based on whether the

studies were crossover trials or whether they were parallel arm
trials. You can see that the parallel arm trials
were more homogeneous and has smaller effect size. The
crossover trials were more heterogeneous and larger
effect size. Even then, there were no statistically significant
difference between the studies (that is whether
they were crossover or parallel arm trials) in terms of their
overall effect size.
13
subgroup analysis <- update.meta(diastolic, byvar = design)
#print(summary(subgroup analysis))
subgroup syst <- update.meta(htn meta m, byvar = design)
print(summary(subgroup syst))
## Number of studies combined: k = 11 ## ## 95%-CI z p-value
0.0001
## Random effects model -2.2689 [-3.4881; -1.0496] -3.65
0.0003
## ## Quantifying heterogeneity: ## tauˆ2 = 2.3111; H = 1.90
[1.40; 2.57]; Iˆ2
= 72.2% [48.9%; 84.9%]
## ## Test of heterogeneity: ## Q d.f. p-value ## 35.99 10 <
0.0001
## ## Results for subgroups (fixed effect model): ## k 95%-CI
Q tauˆ2 Iˆ2
## design = P 4 -1.4190 [-2.1504; -0.6876] 0.44 0 0.0%
## design = X 7 -2.6773 [-3.4427; -1.9119] 30.12 4.788 80.1%
## ## Test for subgroup differences (fixed effect model):
## Q d.f. p-value ## Between groups 5.43 1 0.0198

Summary
If we were to summarise the findings of this meta analysis, we
see that for normotensive individuals, the
studies that were included in the analyses were heterogeneous,
that their effects were small and most studies
pointed to a small amount of reduction in systolic and diastolic
blood pressure that might not be clinically
very relevant, and that, this meta analysis has missed studies
that are small and that had effect estimates in
different directions, leaving room for publication bias. Based on
this meta analysis, you will need to conduct
more studies on the relationship between salt restriction (longer
term) among normotensive individuals to
test their effectiveness as a treatment. So, even though you may
have well conducted studies that would
suggest that salt restriction works, available evidence over
many studies would not justify such a conclusion.
References
Kay Dickersin. The existence of publication bias and risk
factors for its occurrence. Jama, 263(10):1385–1389,
1990.
Sue Duval and Richard Tweedie. Trim and fill: a simple funnel-
plot–based method of testing and adjusting
for publication bias in meta-analysis. Biometrics, 56(2):455–
463, 2000.
Vic Hasselblad and Larry V Hedges. Meta-analysis of screening
and diagnostic tests. Psychological bulletin,
117(1):167, 1995.
Feng J He and Graham A MacGregor. Effect of modest salt

reduction on blood pressure: a meta-analysis
of randomized trials. Implications for public health. Journal of
human hypertension, 16(11):761, 2002.
John E Hunter and Frank L Schmidt. Fixed effects vs. random
effects meta-analysis models: implications for
cumulative research knowledge. International Journal of
Selection and Assessment, 8(4):275–292, 2000.
David Moher, Alessandro Liberati, Jennifer Tetzlaff, Douglas G
Altman, Prisma Group, et al. Preferred
reporting items for systematic reviews and meta-analyses: the
PRISMA statement. PLoS med, 6(7):
e1000097, 2009.
Sharon-Lise T Normand. Tutorial in biostatistics meta-analysis:
formulating, evaluating, combining, and
reporting. Statistics in medicine, 18(3):321–359, 1999.
R Core Team. R: A Language and Environment for Statistical
Computing. R Foundation for Statistical
Computing, Vienna, Austria, 2013. URL http://www.R-
project.org/.
14
http://www.R-project.org/
Karen A Robinson and Kay Dickersin. Development of a highly
sensitive search strategy for the retrieval of
reports of controlled trials using PubMed. International journal
of epidemiology, 31(1):150–153, 2002.

Frank M Sacks, Laura P Svetkey, William M Vollmer, Lawrence
J Appel, George A Bray, David Harsha,
Eva Obarzanek, Paul R Conlin, Edgar R Miller, Denise G
Simons-Morton, et al. Effects on blood pressure
of reduced dietary sodium and the Dietary Approaches to Stop
Hypertension (DASH) diet. New England
journal of medicine, 344(1):3–10, 2001.
Connie Schardt, Martha B Adams, Thomas Owens, Sheri Keitz,
and Paul Fontelo. Utilization of the PICO
framework to improve searching PubMed for clinical questions.
BMC medical informatics and decision
making, 7(1):16, 2007.
Donna F Stroup, Jesse A Berlin, Sally C Morton, Ingram Olkin,
G David Williamson, Drummond Rennie,
David Moher, Betsy J Becker, Theresa Ann Sipe, Stephen B
Thacker, et al. Meta-analysis of observational
studies in epidemiology: a proposal for reporting. Jama,
283(15):2008–2012, 2000.
Alison Thornton and Peter Lee. Publication bias in meta-
analysis: its causes and consequences. Journal of
clinical epidemiology, 53(2):207–216, 2000.
Brandi D Tuttle, Megan von Isenburg, Connie Schardt, and
Anne Powers. PubMed instruction for medical
students: searching for a better way. Medical reference services
quarterly, 28(3):199–210, 2009.
15

TITLE
Effectiveness of Pre-exposure prophylaxis (PrEP) in reducing
the transmissions of HIV virus in heterosexual Sero-discordant
sexual encounters. A systematic literature review.
BACKGROUND
Human Immunodeficiency Virus (HIV) infection, is a
bloodborne sexually transmitted disease which has evolved as a
worldwide pandemic with huge healthcare and economic
implications, especially in developing countries. The
aforementioned, evolved from the Simian immunodeficiency
virus. Globally, more than 36 million people are living with
HIV infection. This is due to a rise in the number of newly
diagnosed cases in recent times in addition to the effective
preventive methods which have led to a reduction in Acquired
Immunodeficiency Syndrome (AIDs) related deaths.
Nevertheless, the prevalence of HIV remains at an all-time high
in Sub-Saharan Africa where it is believed not to have yet
peaked in some countries. The impact of HIV infection affecting
individuals, their families, health workers, economy and the
healthcare sector. A number of key interventions such as clean
needles and condoms are widely available but till date have
been unsuccessful in eliminating the transmission of HIV.
The use of pharmacological interventions in the form of
antiretroviral drugs such as Pre-exposure prophylaxis (PrEP) is
a means of preventing HIV transmission to sero-negative
individuals. PrEP, is a means by which individuals at significant
risk of HIV but without the infection can inhibit its
transmission by taking a daily pill. PrEP (comprising tenofovir
and emtricitabine), marketed as Truvada is a once daily dosing
preparation. It’s mode of action is preventing the establishment
of the HIV virus after exposure by either sex or via injection by

drug users. PrEP has been proven to decrease the likelihood of
HIV infection up to 92% in individuals who are at significant
risk. However, its efficacy is dependent on the consistent oral
intake of the medication. Taking daily PrEP has been shown to
reduce HIV transmission by up to 90% and the risk of infection
to less than 75% amidst heterosexual couples in which one
companion had HIV infection, and the other partner uninfected.
According to research, sexual transmission of HIV can be
prevented using PrEP in a sero-discordant couple trying to
conceive provided there is adherence. Adherence is critically
important for the effectiveness of oral PrEP (tenofovir
disoproxil fumarate (TDF) and emtricitabine).
JUSTIFICATION FOR THE REVIEW.
Making PrEP available to high-risk populations is accepted as
best practice. The World Health Organization (WHO) advocates
that PrEP containing (TDF) should be offered as part of HIV
prevention programmes to people at ‘substantial risk of HIV
infection’. WHO defines ‘substantial risk’ as ‘HIV incidence
around 3 per 100-person years or higher in the absence of PrEP.
Researches have been published looking at various intervention
to reduce the transmission of HIV amongst sero-discordant
heterosexual partners. However, while a lot of research has
begun to emerge on the effectiveness of PrEP in men sleeping
with men(MSM) and men sleeping with men and women
(MSMW), the evidence generated to date is limited. Further,
more rigorous research is required on the effectiveness of PrEP
in sero-discordant heterosexual sexual encounters. The purpose
of this study is to explore how PrEP reduces the transmission of
HIV infection in sero-discordant heterosexual sexual
encounters. There has only been one systematic review done for
PrEP in HIV sero-discordant heterosexual sexual encounters and

this was carried out in 2011 by the WHO. It was broad in remit
and it looked at different interventions and outcome measures.
However, new studies and new prep formulations have emerged
since 2011 and this project would in cooperate the new data.
Furthermore, the systematic review conducted by WHO failed to
adhere fully to the Cochrane level of formulating systematic
review which form the basis for my review.
OBJECTIVES
1, To determine the effectiveness of PrEP in reducing the
transmissions of HIV virus in heterosexual sero-discordant
sexual encounters.
2, To measure gender differences in the uptake of Prep.
3, To measure safety
RESEARCH QUESTION
To explore the use of PrEP in preventing HIV transmission in
serodiscordant sexual encounters by critically interrogating
the existing body of research evidence.
SEARCH STRATEGY FOR IDENTIFICATION OF STUDIES
There would be comprehensive data search through the library
of various electronic databases such as research gate, Medline,
PubMed, Academia.edu and Wiley Library. The reference list of
relevant papers, reports and journals would be hand searched.
The published research evidence on PrEP was carefully perused
to recognize specific terms to aid the formulation of a robust
and highly precise and sensitive search string.
Furthermore, the references in these reviews support the

evidence that PrEP is effective in reducing HIV transmission in
heterosexual couples. The terms “Sero- Discordant” and “HIV
Transmission” and “ Pre-exposure Prophylaxis led to the
following extracts.
· Cohen et al. (2013), states that the effectiveness of PrEP is
dependent on the individual being at high-risk for HIV infection
and the provider of healthcare's awareness of PrEP.
· Galea et al. (2011) assert that there are obstacles to uptake and
adherence to PrEP like likely sexual risk disinhibition, stigma,
and prejudice associated with PrEP use, and mistrust of health
care specialists.
· Golub et al. (2010), assert that the benefit of PrEP relies on
behavioural and social factors that may define its appropriate
use and formation of support groups address this concern
adequately.
· Marcus et al. (2014) assert that compliance is critical for
maximising the effectiveness of PrEP in preventing HIV
infection, and the use of a multi-modal intervention to support
PrEP adherence is an
· identified effective intervention.
SEARCH STRATEGY ON PUBMED
PUB MED Database
Search Strategy
Number of Hits
From Jan 1980-10.07.2017
("sero-discordant"[All Fields] OR serodiscordant[All Fields]
OR discordant[All Fields] OR ("family characteristics"[MeSH
Terms] OR ("family"[All Fields] AND "characteristics"[All
Fields]) OR "family characteristics"[All Fields] OR

"couple"[All Fields])) AND ("pre-exposure prophylaxis"[All
Fields] OR PrEP[All Fields] OR ("emtricitabine"[MeSH Terms]
OR "emtricitabine"[All Fields]) OR ("tenofovir"[MeSH Terms]
OR "tenofovir"[All Fields]) OR ("emtricitabine, tenofovir
disoproxil fumarate drug combination"[MeSH Terms] OR
("emtricitabine"[All Fields] AND "tenofovir"[All Fields] AND
"disoproxil"[All Fields] AND "fumarate"[All Fields] AND
"drug"[All Fields] AND "combination"[All Fields]) OR
"tenofovir disoproxil fumarate drug combination
emtricitabine"[All Fields] OR "truvada"[All Fields]) OR
("emtricitabine"[MeSH Terms] OR "emtricitabine"[All Fields]
OR "ftc"[All Fields]) OR TDF[All Fields]) AND (("hiv"[MeSH
Terms] OR "hiv"[All Fields]) OR ("acquired immunodeficiency
syndrome"[MeSH Terms] OR ("acquired"[All Fields] AND
"immunodeficiency"[All Fields] AND "syndrome"[All Fields])
OR "acquired immunodeficiency syndrome"[All Fields] OR
"aids"[All Fields]))
4286
CRITERIA FOR CONSIDERING STUDIES FOR THIS
REVIEW
Population – Heterosexual individuals with HIV infection or at
very high risk of HIV transmission or Infection.
Intervention – Pre-exposure prophylaxis
Comparator – Placebo or no intervention at all
Outcome – HIV infection adverse reaction
METHOD
The qualitative, randomized controlled trial (RCT) study design
is the most robust and highly esteemed experimental design
used in health research. The advantage of this gold standard

study design is that it allows for comparison to be made of the
measured outcome between the group receiving PrEP as an
intervention and the control as it relates to the transmission of
HIV infection. This exercise mainly entails working with
modest samples and generalising, using the reasoning of
induction and the use of more advanced statistical tests, to much
larger
populations, It also allows for the control of extraneous
variables, may eliminate bias, strengthens internal validity and
allow for meta-analysis.
Quality assessment
Methodological quality assessment is the hallmark of a well
formulated systematic literature review. Quality assessment is a
quality assurance mechanism which safeguards the integrity of
published studies and makes it difficult for studies of poor
methodological quality to be published. A thorough quality
assessment looks at the internal and external validity of
individual primary studies and informs whether these studies
have adhered to the cogent reporting standards as advocated by
consort, Prisma, Scottish Intercollegiate guideline network and
a whole host of other published reporting standards available.
Quality assessment in RCT’s within biomedical research has
received a lot of empirical attention. Tools available are
multifaceted, ranging from individual markers, checklists and
scales such as the Jadad scale and Schulz approach, CASP
checklist, van Tulder scale and Cochrane collaboration risk of
bias tool (CCRBT). Consequently, quality assessment for this
investigation would look at important design and analysis of
RCT's.
Such as methods of randomisation, blinding, allocation
concealment, study confounding, results, methods of analysis,
reporting, study participation, sampling techniques and the
handling of losses to follow up [attrition]. Quality assessment is
going to be undertaken by two blinded reviewers, and kappa

statistic calculated to show predictive, construct and concurrent
validity and inter-rater reliability. Using the formula the intra
class correlation coefficient will be calculated to verify the
inter-rater agreement between myself and the second reviewer.
In this systematic review, the author is going to utilise the
CASP checklist because it has simple application, usability, and
better psychometric properties and is relatively easy to convert
the textual data into quantitative data for analysis. Please see
appendix for the quality assessment form.
Data Abstraction
To ensure uniformity and consistency, two individual
researchers will obtain data from primary studies to eliminate
possible bias, lost or incomplete research data requested from
the original authors of the studies. These will aim to retrieve
research information, study design, quality, setting,
characteristics, confounders, the population, strength of
association, results and the method of measuring outcomes.
Data would be extraction using a slightly modified form
adopted from the Cochrane collaboration to suit the current
systematic literature review. To ensure reliability and validity,
the data abstraction form would be piloted on a subset of the
research papers.
.
DATA ANALYSIS
Data would be analysed statistically. The Review Manager
software will be employed for statistical analysis. Study

outcomes presented on a forest plot and further analysis such as
subgroup analysis and meta-regression would be undertaken on
covariates chosen to assess the presence of confounding.
Subgroup analysis explored on geographical location of the
study, gender, method of HIV acquisition, PrEP adherence as
depicted by ABG, quality ratings, PrEP dosing regimen, PrEP
modality used, duration of follow up, age (<25 or ≥25 years),
etc. The CCRBT will be used to appraise the adequacy of
randomisation, allocation concealment, blinding, selective
reporting and publication bias. The key quantitative outcome
measures such as the odd ratio, relative risk ratio (RRR) and
numbers needed to treat (NNT) would be abstracted from
primary studies and between study comparisons would be made
on the key outcome measures to ascertain consistencies or
inconsistencies on the strengths of association of the outcome
measures. Cochran’s Q and the I² statistic will be calculated
to determine the magnitude of heterogeneity. If heterogeneity is
widespread, the random effects meta-analysis will be deployed.
However, if heterogeneity between studies is less than 45%, the
fixed effect model will be invoked.
Inclusion and ExclusionCriteria
Inclusion
· All RCT studies reporting and evaluating use of oral PrEP as
intervention to reduce HIV transmission in high risk
heterosexual individuals in comparison with placebo or usual
treatment/
· Peer Review Journal publications evaluating oral PrEP
interventions specific to HIV/AIDs
· Studies with participants who are male and female over the
age of 18yrs
· Studies with heterosexual men and women whose partners
have undiagnosed or untreated HIV infection.
· Published and unpublished RCTs with heterosexual men and

women.
Exclusion
· Data on men sleeping with men.
· Data on men sleeping with men and women.
· Data on use of topical PreP.
· All non RCT study designs.
Time Line
Academic Calendar Week number
Activity
9
Research proposal submission approval
10-13
Literature search, screening titles and abstract review
14
Quality assessment
15-18
Data extraction, literature review and initial draft
19-20
Initial draft submission and Feedback from supervisor
21-23
Data analysis, synthesis and second draft
24-25
Second draft submission and Feedback from supervisor
26-28
Discussions

29-30
Conclusions and Recommendation
31
Feedback on conclusion and write up from supervisor
32
Proof reading the final version
33
Printing and Binding
34
Dissertation Thesis Submission
Resources
The data collection and analysis required for the research would
be sourced from the University of Essex Library. Additional
materials would be sourced from the North Middlesex
University Library to which I have free access as one of the
local General Practitioners working in the National Health
Services(NHS). Payment would be made for access to articles
that are not freely available online and subscriptions made
where necessary. Additionally, an EndNote manager software
would be purchased to ensure accurate and complete references
of all data sources.

Key Literature Sources
Aidsmap, n.d. How Effective is PrEP. Available at:
http://www.aidsmap.com/How-effective-is-PrEP/page/2983351/.
Accessed 10 July 2017.
Centre for Disease Control and Prevention, 2016. Pre-Exposure
Prophylaxis (PrEP). Available at:
https://www.cdc.gov/hiv/risk/prep/index.html. Accessed 13 July
2017
Cochrane Collaboration risk of bias tool Available at:
http://methods.cochrane.org/bias/assessing-risk-bias-included-
studies. Accessed 12 August 2017.
Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour
MC, Kumarasamy N, et al. Prevention of HIV-1 infection with
early antiretroviral therapy. N Engl J Med. 2011;365(6):493–
505. doi:10.1056/NEJMoa1105243.
Curtis, E, & Drennan, J 2013, Quantitative Health Research:
Issues And Methods, McGraw-Hill Education, Maidenhead.
E, King and T Lupiwa, 2008. A Systematic literature review of
HIV and AIDS research in Papua New Guinea. Available at:
https://pharmacy.utah.edu/ICBG/pdf/WebResources/HIVandNati
onalAidsCouncilpublications/Systematic_PNG_Literature_Revie
w_of_HIV_and_AIDS.pdf. Accessed 11 July 2017
Galea JT, Kinsler JJ, Salazar X, et al. Acceptability of pre-
exposure prophylaxis as an HIV prevention strategy: barriers
and facilitators to pre-exposure prophylaxis uptake among at-
risk Peruvian populations. Int J STD AIDS. 2011;22(5):256–262
Giovanni Andrea Cornia and Fabio Zagonari. N.d. The
HIV/AIDS Impact on the Rural and Urban Economy. Available
at: https://www.unicef-irc.org/research/ESP/aids/chapter10.pdf.
Accessed 11 July 2017
Golub SA, Kowalczyk W, Weinberger CL, Parsons JT. Pre-
exposure prophylaxis and predicted condom use among high-
risk men who have sex with men. J Acquir Immune Defic Syndr.
2010;54(5):548–555.
Higgins JPT, Green S (editors). Cochrane Handbook for

Systematic Reviews of Interventions Version 5.1.0 [updated
March 2011]. The Cochrane Collaboration, 2011. Available
from http://handbook.cochrane.org.
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ,
Gavaghan DJ, et al. Assessing the quality of reports of
randomized clinical trials: is blinding necessary? Control Clin
Trials1996;17:1-12.
Pre-exposure prophylaxis (PrEP) for HIV sero-discordant
couples: a systematic review, 2012. Available at:
https://www.ncbi.nlm.nih.gov/books/NBK132001/. Accessed 9
July 2017.
Pre-exposure prophylaxis of HIV in adults at high risk: Truvada
(emtricitabine/tenofovir disoproxil). Available at:
https://www.nice.org.uk/advice/esnm78/chapter/Key-points-
from-the-evidence. Accessed 7 August 2017
Reginald M. H, 2015. Pre-exposure Prophylaxis (PrEP)
Education Improvement Project. Available at:
http://repository.usfca.edu/cgi/viewcontent.cgi?article=1123&co
ntext=capstone, Accessed 13 July 2017
R, Jonga, 2015.Prognostic Utility of Pre -Treatment Weight
Loss on Head and Neck Cancer Patients Undergoing
chemotherapy: Systematic review of Published Studies.
Marcus JL, Glidden DV, Mayer KH, et al. No evidence of
sexual risk compensation in the iPrEx trial of daily oral HIV
pre-exposure prophylaxis. PLoS One. 2013;8(12):e81997.
NICE, 2016. Pre-exposure prophylaxis of HIV in adults at high
risk: Truvada (emtricitabine/tenofovir disoproxil) Available at:
https://www.nice.org.uk/advice/esnm78/chapter/Key-points-
from-the-evidence. Accessed 14 August 2017.
Schulz K,F, 2001. Assessing allocation concealment and
blinding in randomized controlled trials: why bother? Evid
Based Nurs2001;4:4-6.
Sleasman J,W & Goodenow M,M, 2003. HIV-1 Infection.

Available online at:
https://www.ncbi.nlm.nih.gov/pubmed/12592304. Accessed 11
July 2017
WHO, 2012. Guidance on oral pre-exposure prophylaxis (PrEP)
for sero-discordant couples, men and transgender women who
have sex with men at high risk of HIV. Available at :
http://www.who.int/hiv/pub/guidance_prep/en/. Accessed
12/8/17
van Tulder M, Furlan A, Bombardier C, Bouter L. Updated
method guidelines for systematic reviews in the Cochrane
Collaboration Back Review Group. Spine (Phila Pa 1976)
2003;28:1290–1299.
PrEP efficacy on sero-discodant 6
EFFICACY OF PrEP IN HIV PREVENTION AMONG THE
HETEROSEXUAL SERO-DISCORDANT SENSUAL
PARTNERS
by [Name]
Course
Professor’s Name
University

City
Date
Abstract
HIV/ AIDS is continuously becoming the world significant
health threat has so far claimed more than 36M lives, and the
higher percentage being recorded in the year 2016. WHO
carried out an analysis and realized that more than 1.8 m people
were infected in 2016 and the number keeps increasing yearly.
The primary infection being, the groups who are at increased
risk of HIV irrespective of epidemic type or local context. They
include men who have sex with men, people who inject drugs,
people in prisons and other closed settings, sex workers and
their clients, and transgender people.
Health care practitioners earlier before 2014, introduced
the need to use preventive measures including the use of
condoms and the abstinence methods which were by then the
available methods. Later on, new techniques were introduced by
the Center for Disease Control (CDC).The introduction of prep
decreased the reported number of new HIV infection every year
by approximately 19 %. Although its efficacy is found to be
high, who have researched and found that, the individual should
be strictly committed to taking it daily. A lot of research has
been done on the PrEPs efficacy, but its effectiveness on
serodiscordant couples is not yet proven. Therefore, practical
research on this ought to be carried out. A standard Cochrane
method will be used to acquire data. This will be done in a
population targeting 18 and above by age with no restriction to
the language spoken. RCT will be used, and statistical analysis
was done using STATA. In addition to this primary study,
information will be searched online from research institutions
together with database information; this will entail the
extraction from the database from the year 2011 onwards.
Efficacy of PREP in HIV Prevention among The Heterosexual
Sero-Discordant Sensual PartnersChapter One:

IntroductionBackground Information
Human Immunodeficiency Virus (HIV) infection, refers to
the blood-borne disease that is transferred sexually and has
grown to be a global pandemic which has a significant effect on
the economy and health sector, and mainly, among the
developed nations. The disease progressed from the Simian
immunodeficiency virus. Worldwide, over 36 million people
have been established to live with this infection. The high
figure resulted from the conduction of research by WHO (2015)
among other organizations (WHO, 2015). These organizations
have come out with a higher infection rate statistics in the
African region, which recorded more than 25 million patients by
2016. As per Zarwell, 2016 case, HIV infection dramatically
impacts the infected individuals, their families, healthcare
sector and the economy (Zarwell, 2016). Despite advanced
treatment for HIV, it has remained to be the most significant
burden on the health system, economy, community and the
individuals. Karnoski, 2017 argued that the application of PrEP
in uninfected people (HIV negative), but who are at risk of
contracting it, is becoming the major tool in HIV prevention
(Karnoski, 2017). Various significant interventions like clean
needles and the use of condoms have been widely used, but
these have since remained unsuccessful in the reduction of the
HIV infection.
Since a lot of research on prevention measures used in
reducing HIV infection has been conducted, still no accurate
method can be used as a sole preventive tool. Due to this
finding, research on a novel tool or combination of existing
tools for efficacy ought to be carried out more so, for
serodiscordant couples. According to Sagaon et al., et al. 2016,
the use of Antiretroviral therapy has shown a decrease in the
mortality and morbidity rate in persons infected with HIV
however, there is a massive demand of knowledge about the
potentiality of PrEP in reducing the infection among the
heterosexual serodiscordant sexual encounters, since much of
knowledge on PrEP performance on, men who have sex with

men (MSM), young heterosexual adults (male and female) and
drug users by injection method has been given out (Sagaon et
al., et al. 2016).
The use of (PrEP) is a pharmacological methodology of
averting the Human Immunodeficiency Virus spread. According
to Snowden et al. 2016, PrEP is an experimental approach to the
prevention of HIV consisting of taking antiretroviral drugs
before any possible HIV exposure to minimize the infection risk
(Snowden et al. 2016). These drugs are then continued during
the periods of exposure to the threat. The PrEP can either be in
the form of vaginal or rectal gel application or orally taken
pills. The PrEP medicine, consisting of tenofovir and
emtricitabine, often promoted as Truvada, is a singular every
day medicating incidence. It works through prevention of
establishment of the virus following contact by either injection
by the intravenous drug abusers or through sexual intercourse as
per Snowden et al., 2016). The use of pills PrEP has been
confirmed to minimize the infection chances of HIV by as much
as 92% among high-risk individuals. The efficacy is however
dependent on the adherence to the medication. Zarwell, 2016
found out that, the consistent use of the PrEP decreases the
transmission rate of the infection by 90% and the contamination
risks less than 75% among heterosexual couples wherein, one
partner had the HIV infection, while the other was uninfected
(Zarwell, 2016).
Choopanya et al. 2013, discovered that the major
advantage of the use of oral PrEP is that it complements other
effective HIV prevention methods (Choopanya et al. 2013). For
instance, it may give another option to help in the protection of
people unable to negotiate the use of condoms with their
partners, among the intravenous drug users and serodiscordant
relationships. There are however some safety concerns
associated with the use of PrEP medications. Drug resistance
may limit one’s future options for treatment. Thus it is essential
to ensure that a person is HIV negative before initiation of oral
PrEP. A person may also become drug resistant if they become

HIV positive during the time they are taking the oral PrEPs. It
is thus crucial that regular HIV testing is carried out even
among people taking these pills. The introduction of the Pre-
exposure prophylactic (PrEP) into the market by CDC among
the several existing means, aimed at reducing new HIV
infections has been attributed to the constant decrease. PrEP is
found to be more efficient if it’s combined with other tools, for
example, the use of condoms than applying it alone. The means
of introduction into the body is also of more importance when it
comes to efficiency test.
According to Shattock et al., 2011, findings high
population of people who are using prep, are at very high risk of
contracting HIV, introducing behavioral and biomedical
interventions like condoms, HIV test and prep as well on these
group has been found to reduce the infection rate anonymously
(Shattock et al., 2011). For the serodiscordant couples, the
highest risk period for infection comes when the HIV infected
partner haven’t taken or has delayed the medication, hence the
virus has not been suppressed. During such moments prep can
be introduced as an integral element to a prevention strategy
combined. Problem Statement
PrEP has been studied for some years on its effectiveness
on HIV infection. This measure has been known to be effective
in individuals. For instance, gay persons and drug addicts by
injection method. WHO is recommending the usage of the drug
for people are vulnerable to contracting HIV. Much of studies
on its effectiveness in MSM has widely been researched,
however, minimum research on its efficacy on heterosexual
serodiscordant sexual encounters has been done. It was done in
the year 2011, and incorporated several tools for prevention but
was not explicitly detailed on PrEP effect on serodiscordant
couples. Since then, new data and information about it have
been emerging, hence the need to conduct a recent study
comparing and combining the acquired data from health
research centers and the primary data obtained.Justification
The acceptable best practice involved in making PrEP

accessible to the populations deemed to be at high risk.
According to WHO, PrEP which has (TDF) should be provided
by health sector professionals as part of the preventive tool to
individuals who are exposed to the considerable risk of
infection with HIV/AIDs. The WHO defines the sizeable risk as
HIV prevalence of approximately three persons for every 100
individuals or higher without the existence of PrEP. Research
studies have been carried out to investigate the several
intervention measures that can be used to reduce the transfer of
HIV amidst the partners who are serodiscordant (BBC, 2017).
However, despite the extensive scope of evidence concerning
the effectiveness of PrEP medication, the generated proof is
limited since currently, the trend of homosexuality in the
society is on the rise. More comprehensive research is therefore
recommended on the efficacy of this type of treatment to come
up with well-conclusive results on this topic. Only one study
was conducted in regards to this study topic in 2011 by the
WHO.
The study involved a broad scrutiny of the various
available intervention approaches as well as the outcome of the
proposed measures. However, more studies have emerged since
the first examination of this issue which resulted in the
establishment of modern formulations of the PrEP drugs that
this study looks into. The WHO systematic review nevertheless
failed to stick to the Cochrane stage of formulating the
systematic analysis which forms the foundation of this study
exploration.
Research Questions
· Is the usage of PrEP efficient in reduction of HIV transmission
amongst couples of dissimilar gender?
· Does the gender difference affect the outcome of the prep
application?
· Are the approaches presently employed for PrEP utilization
safe to humans?General Objectives
· To determine the efficacy of PrEP in prevention of the
transmissions of HIV among the heterosexual serodiscordant

sexual couples.Specific Objectives
· Selecting serodiscordant couples of above 18 years randomly
for PrEP efficacy analysis
· To analyze the effect of PrEP on gender difference.
· To measure the safety of the PrEP on individualsLiterature
Review
HIV Prevalence
In today’s world, approximately 35 million individuals
living with HIV. HIV prevention is on the rise by use of the
following methods; condom barriers for both male and female,
male circumcision, at the hospital vigilant use of sharp objects
such as needles, to avoid viral transmission, correct use of
disinfection processes, at the aggressive delivery use of
hindrance of mother to kid infections. Mahapatra, 2016),
claimed that the new HIV infections incidence has been on the
rise since 2008, a predictable 2.9 million persons were once
more infected. There is an alarming need to grant safe methods
that have been proven to be useful to achieve prevention of HIV
and AIDS. Among the newly infected persons are the
serodiscordant partners who are either married or at the young
stage. The partners (one infected with HIV and another one
not), are said to be at the highest risk of being infected.
However, due to researchers understanding the biology of the
disease and the introduction of the preventive measures, the
infection risk among the couples has been reduced to deficient
levels. According to Okwundu, et. al. 2016, prevention of HIV
in serodiscordant couples maybe easier than in other types of
relationships, for instance, casual relationships and
seroconcordant couples, this is due to awareness and strict
adherence on the prescription (Okwundu, et. al. 2016).
PrEP is a treatment modality that uses medicine to prevent
infections of HIV in people who are already exposed to the
virus. It uses antiretroviral medication to stop the HIV infection
acquisition by healthy individuals. There is evidence from
research by use of laboratory animals and also in the clinical
studies among human, where the use of antiretroviral therapy by

pregnant women has been shown to prevent the babies from
getting infected with HIV. As of now, there are HIV negative
babies who have been born to HIV positive mothers. One of the
key drawbacks to consider is the safety of the drugs being used
as antiretroviral therapy in such patients. For PrEP to be
effective the side effect profile of the drug must be one that can
be tolerated by patients. Drugs such as tenofovir and
emtricitabine have been shown to be safe following clinical
trials as indicated by Mahapatra, 2016.
The initial trial to generate the study outcomes was the
iPrex experiment. The experiment involved a multi-phase-3
clinical research which examined if the daily combination of the
emtricitabine and tenofovir were possible to efficiently and
safely prohibit the transfer of HIV infection among the gay men
as well as the bisexual women. Approximately about 46%
reduction by using the improved target-treatment analysis in the
transmission of HIV was recorded. However, the observance of
this regime was found to be lower than the anticipated in the
various countries. The trial was done in 2010 in the human
being to produce sounding statistical facts about PrEP. The test
was done on gays, and they were given oral pill as well as
placebo, and it was noted that the oral introduction reduced the
HIV infection by 44% this is according to Kim et al. 2010
findings. Recent research by Straub et al. 2017, shows that Men
who are reported to consuming the pills in about 90 percent or
even additional days recorded a 75% efficacy of the PrEP use.
Resistance was conversely found among 3 participants who
showed an existing severe infection of HIV which was
undetectable at the baseline and randomized to active medicine.
A marked tendency in the line of risk drug minimization,
especially the escalated condom utilization and the decreased
amount of couples was reported in all sites (Snowden, et. al.
2017). The second research as shown by FHI, (2011) which was
used to generate the grades was the experimental study
regarding the daily tenofovir and emtricitabine among the high-
risk women of African origin. However, the study was

dismissed due to the insufficiency of the infections quantity in
the placebo arms with the PrEP usage.
The 3rd trial was conducted by U.S CDC and by The
Botswana ministry of health this was done on daily oral
emtricitabine, and tenofovir consumption in both men and
women by CDC, (2011) .the results of this research study gave
out an indication that the infection reduced by up to 63%.
Another research which is the fourth one was done in Kenya and
Uganda. This was a daily orally taken regime of emtricitabine
and tenofovir in HIV-1 serodiscordant partners. Mujugira et al.,
(2011) found that those who took tenofovir only had fewer HIV
infection by 62%, those who received emtricitabine with
tenofovir had reduced the disease by 73% than those who had a
placebo.
The above systemic study has raised concern on, should
TDF or TDF plus FTC be taken daily by the serodiscordant
couples in preventing HIV infection?
Since several studies have been done, trials have shown
that for the PrEP to work efficiently, the dose should be taken
correctly and as prescribed, if a person misses taking the dosage
accurately, as per the dosage pattern, he/she is likely to increase
the risk of infection. According to BBC, 2017, THE DRUG HAS
BEEN KNOWN TO REDUCE HIV infection to nearly zero.
Nevertheless, PrEP cannot prevent one against infection by
STDs and STIs BBC, 2017).
Earlier before 2015 PrEP was being used only by specific
consumers just who are infected by HIV, not until WHO
recommended the use of the drug by people at risk of
contracting it. This had benefited the worldwide population and
has reduced the risk of infection to anyone unlike previously
when it was only targeting, sex workers, versus men sex, and
drug users by injection mean as by the UNAIDS, 2016).The
united nations general assembly is targeting to provide 3M
people at risk of HIV contraction with PrEP by or before the
end of 2020. However, this initiation has recorded about
100,000 people who are the beneficiaries by October 2016. The

majority of the recipients are in the USA. The activities of Prep
are continuously increasing worldwide with minimum
beneficiaries outside the USA. The drugs tenofovir and
emtricitabine in the form of the single drug Truvada is the very
recent drug known to be a preventive measure against HIV.
Kim et al. 2010 found that, in the early years, there was
the use of traditional interventions, which was proved to be
inefficient, this is what led to more research on other means of
prevention (Kim et al. 2010). Recently the use of prep orally as
well as topically is promising success in prevention measures.
Evidence Base
Numerous RCT studies have proven the efficiency of PrEP
when a combination of FTC/TDC uses or when only the
utilization of TDF to prevent it is used. The approach has been
indicated to reduce the rates of the disease spread among the
sexually active women and men in the study conducted in
Botswana which a country has known for its HIV infection
burden. Similar results were found among the heterosexual
partners living in the East African region, as well as the IDUs
of Thailand (Shattock, et. al. 2011). The Cochrane investigation
of these researchers revealed that the comparative danger of
obtaining HIV involved 0.48 (94% interval of confidence, 0.27-
0.84) for persons consuming FTC or TDC and o.34 (94%
interval of confidence, 0.23-0.56) for the ones only taking TDF
as per Mahapatra, 2016, findings. The result of these studies,
however, did not indicate any statistically substantial
dissimilarity in the difference of HIV prevalence among the
groups of persons consuming the FTC/TDF as compared to the
individuals using TDF alone (Mahapatra, 2016). Previous
results from the successive open-label reviews propose that
PrEP is efficient and the adherence to its use is great in
practical life and the investigational backgrounds.
The advantages of PrEP in feminine patients who do not
utilize the antiretroviral medicines are however minimally clear.
Young et al. 2017 said that the various randomized control tests
in several locations around Africa further failed to indicate the

substantial statistical minimization in HIV frequency between
the women who use PrEP on a daily basis (Young et al. 2017).
Other two studies examined the utilization of the post and pre-
coital tenofovir vaginal gel where only one research led to the
discovery of the significant impact of HIV infection incidence.
When PrEP is taken orally in a combination of TDF and
FTC (Truvada), it shows a high reduction of viral infection.
Additionally, it has been noted that prep might be less forgiving
in male than females and that STDs are modulating the efficacy
of the prep. Pharmacometrics model is being generated to
assess the relationship between prep efficiency and gender.The
Finest Candidate for Pre-exposure Prophylaxis
Pre-exposure prophylaxis is known to be effective for the
avoidance of HIV. In 2012, US FDA (Food and Drug
Administration) approved that, Daily uptake
oftenofovirDisoproxilFumarate and emtricitabine (FTC/TDF)
for the HIV prevention amongst adults. In 2014, the US, CDCs
(Centers for Disease Control and Prevention) recommended the
use of TDF as the better-approved method of HIV prevention.
Mahapatra, 2016 argued that Pre-exposure prophylaxis can
prevent up to nearly 100% infection (Mahapatra, 2016). It
includes homosexuals and women and men who are
heterosexually active. For gays, pointers to Pre-exposure
prophylaxis comprise of participating in anal sex without the
use of a condom, possessing multiple sex partners, recent
Sexually Transmitted Infection that is bacterial and having a
sexual partner infected with HIV. Indications for heterosexual
women and men include participating in condomless sex with
partners who are highly susceptible to HIV infection and having
an infected sexual partner. People who inject drugs portray risks
such as having injecting partners who are HIV-infected,
injecting medications while undergoing drug treatment and
sharing injection equipment. Concerning the 1.2 million
Americans having signed for Pre-exposure prophylaxis, only
about 100,000 have received a prescription. To identify Pre-
exposure prophylaxis culprits in healthcare settings, a sexual

history is taken followed by a non-condemnatory and open-
minded interrogation about drug and sexual behaviors.
Nevertheless, this account is not always acquired. Additionally,
many beneficiaries of Pre-exposure prophylaxis are not aware of
the risks they expose themselves. To increase knowledge of
providers to address sexual health of patients better, National
Network of Sexually Transmitted Diseases Prevention Training
Centers has unveiled courses to equip the providers. The
providers, as well as their clients, can now use online tools to
assess individuals’ risks. Zarwell, 2016 found that A better
platform is the Sex Pro which lets individuals answer questions
about their behavior then converts the answers in the form of a
score that makes them know how they are protecting themselves
against infection by HIV-infection (Zarwell, 2016).
However, these tools and guidelines are not sufficient
enough to identify the beneficiaries of Pre-exposure
prophylaxis. It is, therefore, crucial to take HIV observance and
native epidemiology into consideration in drug and sexual by
use of networks. For example, black homosexuals are more
stuck by STIs and HIV despite having similar or inferior risks at
individual-levels. Acceptance of Pre-exposure prophylaxis in
black gays is lower than in the whites as investigated by
Zarwell, 2016). The case also applies to women primarily due to
incomplete awareness of Pre-exposure prophylaxis among them
and their providers. Providers should, therefore, consider
demographic factors to address health differences. Additionally,
due to feeling uncomfortable in disclosing HIV risk behaviors
by some patients, the prescription should be granted to only
those who request for it.The Standard Evaluation
Providers should evaluate patients’ interest and knowledge
in Pre-exposure prophylaxis (PrEP) through the inclusion of a
description of how PrEP works especially the likelihood of
passing syndrome identified through gastrointestinal indicators
that appear after weeks and bone toxicity and renal risks. The
patients’ last exposure to HIV should be determined and
assessment of signs of HIV infection done. Health practitioners

ought to record a counteractive HIV antibody test before
starting the PrEP which can be combined with HIV test. Higgs
& Green, 2011 argued that, due to the lower sensitivity of oral
examinations, rapid verbal tests should not be used to test for
HIV infection (Higgs & Green, 2011). Other providers acquire
an HIV RNA test especially for patients with current exposures.
For high suspicion of acute HIV, PrEP should be postponed till
HIV RNA results are ascertained since introducing PrEP
through acute HIV can result in the growth of mutations which
offer antiretroviral resistance. Renal function should be
determined, and tests conducted for infection with hepatitis B
and C types. PrEP should not be given to patients with a
creatinine permission of 60 ml per minute. Re-energized HBV
infection can lead to hepatic damage. As such, patients’
hepatitis B status should be noted to ensure that liver function
is monitored correctly. It should be noted that hepatitis B is not
a concise indication of the usage of PrEP. Providers ought to
assess for risk factors for renal ailments. They should further
screen patients for chlamydia, gonorrhea, and syphilis and at
extra-genital parts since a bulk of extragenital infections are
asymptomatic (Straub, et. al. 2017). Johnsen, et al. 2017)
argued that women being introduced to prep should be tested for
pregnancy and counseling should be offered to patients
regarding adherence and optimization of PrEP. Immunizations
for vaccine-preventable Sexually Transmitted Infections should
also be provided (Johnsen, et al. 2017). The main aim of the
prep is to achieve protection against an increase in the
concentration of HIV in the infected cell. This can be achieved
through the fight by the immunity in combination with other
prevention measures. Prep efficacy is shown to be excellent in
miming the multinational iPrEx study (Semprini, et. al. 2013).
Semprini et al. 2013 indicated that in cases where an HIV
positive lady is opting to conceive from an HIV positive man,
prep has also been proved effective in preventing infection
(Semprini, et. al. 201). This has been achieved through ART
treatment of HIV partner then orally dosage of TDF/FTC by the

woman for a month before conception, then the introduction of
the processed sperms from the partner. Alternatively, a limited
unprotected sex at a fertility period of the woman can be
applied.
CHAPTER THREE: METHODOLOGYStudy Design
The main reliable sources of information for this
dissertation were secondary data. Research conducted by global
medical research center formed the basis of this study. The
project was determining the uptake, use, and effectiveness of
pre-exposure prophylaxis for HIV negative individuals. Related
to this study were several other types of research for instance,
those investigating antiretroviral prophylaxis for HIV
prevention amongst heterosexual women and men. In another
research conducted by AIDS-London, the study was based on
determining safety and effectiveness of pre-exposure
prophylaxis of HIV across different populations. A study
conducted by Emory University department of medicine,
division of infectious diseases on the other hand also formed
part of this research while an abstract from the national institute
of health did provide vital information for this research tool.
The research encompassed the HIV prevention. Furthermore, the
research carried out by a team from the center for YRG on
AIDS Research and training profoundly contributed to the
compilation of this report. The research was assessing the risk
dynamics for the transmission of HIV between discordant
heterosexual individuals based in south India. In addition to the
findings a research conducted by from the Center for Global
Health, Massachusetts Department of Medicine were evaluating
the current conception for PrEP adherence among different
populations.
The different methods deployed in investigating the above
research works are as described below.
1. Research based on effectiveness, uptake, and use of PrEP for
HIV negative individuals and who dwelled with HIV positive
persons.Study Population
The project was based in East Africa in two countries;

Kenya and Uganda and was completed in 3 years. HIV care
centers were deployed in Thika and Kisumu in Kenya and
kabwohe and Kampala in Uganda to deliver the intervention.
These clinics were involved in the engagement of HIV
prevention research before.Delivery
The delivery model was such that PrEP was incorporated
into HIV treatment services whereby PrEP was prioritized for
partners who were HIV negative and were in a serodiscordant
relationship before during the initial half a year period after the
partner living with HIV incorporated antiretroviral therapy
(ART). MEMS bottles (medication event monitoring system)
were used to measure adherence to PrEP. In addition to this
plasma samples from randomly selected participants were
subjected to quantification of tenofovir. Concrete interventions
were deployed so that implementation strategies employed in
the clinics would ensure delivery approach would be efficient.
HIV serodiscordant couples were selected from events
such community outreach or referrals from VCT centers
(voluntary counseling and testing centers). Other referrals
included ART and antenatal clinics. The couples were of more
than 17 years of age. Besides this, they were sexually active and
were supposed to continue as partners for at least 12 months.
When the couples were being enrolled, the couples who were
HIV-negative had not at any moment utilized PrEP. Their
medical results indicated a normal function of the renal organ;
pregnancy test was negative with absence of the hepatitis B
virus infection. The HIV positive spouses did not use ART at
the time of enrollment. Spouses were omitted from the study if
the HIV condition was acute and needed the immediate use of
ART. Study Procedure
Couples were to have study visitations together for 24
months whereby a series of couples-based HIV prevention
strategies such as the management and supervision of the STIs
(Sexually Transmitted Infection) as well as the use of condoms
were delivered.
Participants were required to undergo monthly visits,

which included indulgence of 30 medication study days and the
gathering of the previous month’s unutilized mediation,
assessment of any side effects experienced, individual’s
adherence counseling and HIV-1 testing.
Pregnancy would be tested in women on a monthly basis,
and if there were a case of pregnancy, study medication would
be withheld from the women and they, would be referred to
receive antenatal care. This ensured the safety of the unborn
child. They would be allowed to continue with the study
medication after the pregnancy period was over.
The way in which PrEP was delivered is as follows; PrEP
was provided to all the HIV-negative members in the form of
co-framed tenofovir/emtricitabine disoproxil
(TDC/FTC).Streamlined messages were used to ensure
adherence to PREP focusing on individual’s challenges to day-
to-day usage and ways in which these problems would be
overcome.
It was ensured that ART was available in the clinics at the
start of the study for all participants who were HIV positive. A
CD4 count was conducted and found to be less than 350 cell/uL.
ART was delivered to members through community hospitals.
Before the study, each HIV, positive person was assessed for a
count of CD4 and also during follow up which took place at an
interval of 6 months. The individuals who were subject to the
study and were using PrEP were advised to terminate PrEP use
after their partner living with HIV had used ART for not less
than six months.
This strategy of using PrEP for a limited time by the HIV-
negative partner till the partner living with HIV had used ART
for at least six months was included in the counseling
discussions. In some situations, the counselor would advise the
HIV negative partner to continue with PrEP such as when ART
was not adherent or HIV status was unknown within the partners
or couples were having intentions of pregnancy.As indicated
earlier MEMS caps (medication event monitoring system) were
the primary measure of adherence. They recorded all openings

of PrEP pill bottles where self-reporting pharmacy pill counts
were collected from participants during their visitations. The
level of adherence which would be sufficient to protect against
HIV transmission was measured in two ways which were a
dosage 4 and six pills a week. If couples were reported to have
had less than 100% condom use before six months use of ART,
then the risk of acquiring HIV was high. If there was 100% use
of condoms, then the risk was low otherwise if there was no
sexual activity the risk was very low.
HIV negative partners were tested for HIV at each follow-
up visit to ascertain any incidence of HIV. Immunoassay
enzyme (EIA) and HIV RNA quantification enzyme were used
to confirm the results of the tests conducted. If seroconversion
were confirmed the Seroconverters that were approved, samples
would then beer quantified for HIV RNA. If samples were
positive for HIV RNA, it was presumed that the samples had
been infected before the start of the project and if the samples
were negative for HIV RNA it was concluded that they
comprised of incident infections. HIV resistance was detected
using archived plasma samples . Also, to determine the
incidence of seroconversion samples from the HIV positive
partner would be sequenced together with the HIV negative
partner and a phylogenetic analysis done to assess if the
infection came from the partner under study.
2. Research on anti-retroviral prophylaxis for HIV-1 prevention
among couples who are in serodiscordant relationship
heterosexual men and women.Study Procedure
The research was undertaken in Kenya and Uganda and it
comprised of heterosexual couples where one participant was
HIV positive. The partners that were HIV seronegative were
randomly assigned to tenofovir (TDF), a combination of
emtricitabine/tenofovir (FTC/TDF) and placebo. A follow up
then took place monthly for 36 months. This follows up
constituted HIV testing, adherence counseling and assessment
of any side effects experienced. A CD4 cell count was also
conducted on HIV positive partners after every six months.

3. The following study conducted by AIDS (LONDON) the
study design was through systematic review and meta-analysis.
The study was based on secondary data, and the outcome
of this methodology included resistance for ART drugs, HIV
infections, and concerns on reproduction well as behavioral
characteristics (use of condoms and how many sexual partners a
person has).
4. From the study conducted by Emory University and the
University of California on HIV pre-exposure prophylaxis for
women, clinical trials were conducted to investigate the
delivery of HIV acquisition in women. The trials conducted
showed the efficacy of PrEP in the reduction of HIV.
5. Below is a description of how the research that was assessing
risk factors for HIV transmission among heterosexual
discordant couples was conducted.
The study population comprised a cohort of serodiscordant
couples who sought medical attention at Education and Aids
YRG center (YRG CARE). Through clinical visitations, patients
were engaged in interviews about sexual risks and protective
behaviors as well. Partners that were not infected with HIV
would then be assessed for HIV status at every visit, and this
would take place every three to six months. Partners who were
living with HIV-positive would complete a survey that was
assessing adherence to ART for three months usage of condoms
with their primary partners in the previous months and also the
rate of alcohol consumption. Through the clinic visitations
partners were counseled together concerning STIs and strategies
that would reduce risk. At enrollment, all patients that were
infected with HIV blood samples were taken and tested for HIV.
The critical features that were captured in the research include
population and clinical traits, CD4 cell count and also plasma
HIV-1 RNA loads. In addition to these sexual behaviors was
also assessed. These features were evaluated at enrollment and
longitudinally during follow up for a period of more than 12
months.
6. The research that was based on current features for PrEP

adherence described methods to aid PrEP adherence and the
current ways in which adherence to PrEP is perceived. This
review was based on different demonstration projects and
clinical trials that had been already conducted earlier. Projects
such as iPrEx, IPERGAY and VOICE were some the researchers
that were used.Results
For the research based on effectiveness of PrEP for HIV
negative persons with partners living with HIV descriptive
statistics was used to summarize the traits of the couples and
trends of PrEP use. The total number of couples that were
deployed for this study were n=1010. More than a quarter of the
couples showed characteristics that indicated high risk for HIV
transmission, that is, 41%(n=414)of the couples living with HIV
concentration of HIV RNA was>50000copies/ml and
65%(n=657) reported to having not used condoms during sex in
the previous months.
More than half of the couples (66.7% n=674) the HIV- negative
partner was male and 67% (n=452) of these males had not been
circumcised. About 94% of the enrolled couples were married
(n=954). The median for the time the couples lived together was
2.3 years. Very few couple knew their HIV discordant status
given the median time know in years was 0.1.About 97.1% of
the participants who were negative used PrEP including the
95%(n=960) that at enrollment were introduced into the project.
Median time for PrEP usage was 12 months with an interquartile
range of 6-18. Of the participants 81 % (818) that were HIV-
negative used PrEP until their HIV positive was entirely
dependent on ART. This included the 535(51.3%) who used
PrEP for 6 months after their partner has initiated ART use. Due
to fertility desires in some partners, about 15.5% (n=114) of
PrEP users used PrEP for more than 6 months. Other reasons
that accounted to usage of PrEP for at least 6 months was
pregnancy (41%). Partners who were HIV negative and were not
using PrEP were 28and 89 % (n=25) had partners living with
HIV and were using ART. Those that were not protected by
PrEP were 0.3 % (n=3). Since the partners were HIV negative.

Social determinants impact health more than healthcare

Social determinants impact health more than healthcare

Recommended

Recommended

More Related Content

Similar to Social determinants impact health more than healthcare

Similar to Social determinants impact health more than healthcare (20)

More from gerardkortney

More from gerardkortney (20)

Recently uploaded

Recently uploaded (20)

Social determinants impact health more than healthcare