10. HIV-AIDS pharmacotherapy pdf for pharmacy

10. Pharmacotherapy of HIV/AIDS
By:zenebe k

objectives
Upon completion of this session, the students will be able to:
1. Explain the routes of transmission for HIV and its natural disease
progression.
2. Identify typical and atypical signs and symptoms of acute and
chronic HIV infection.
3. Identify the desired therapeutic outcomes for patients with HIV
infection.
4. Recommend appropriate first-line pharmacotherapy interventions for
patients with HIV infection.
5. Recommend appropriate second-line pharmacotherapy interventions
for patients with HIV infection.
6. Describe the components of a monitoring plan to assess effectiveness
and adverse effects of pharmacotherapy for HIV infection.
7. Educate patients about the disease state, appropriate lifestyle
modifications, and drug therapy required for effective treatment.

INTRODUCTION
Acquired immunodeficiency syndrome (AIDS) is the most
severe manifestation of a clinical spectrum of illness
caused by infection with human immunodeficiency virus
(HIV).
HIV primarily affects the CD4 lymphocyte
When CD4 cells are destroyed, a person’s immunity is
impaired
As immune function decreases, opportunistic infections
increase
HIV progresses over time to death, if no treatment is
given

 AIDS is a chronic infectious disease caused by the
Human Immuno-deficiency Virus (HIV) types 1 and 2.
 It is essentially a disease of the immune system.
 It leaves the individual susceptible for various types
of infections and the development of malignancies.
 The most advanced stage of HIV infection is called
AIDS.
 AIDS is defined by the development of certain
cancers, infections, or other severe clinical
manifestations.
4

Epidemiology
 HIV/AIDS is a global pandemic, with cases reported
from virtually every country.
 According to WHO and UNAIDS, by the end of 2009:
 About 33.3 million individuals were living with HIV
 More than 95% of them reside in developing countries
 Global AIDS deaths totaled 1.8 million
 Estimated new cases of HIV infection were 2.6 million
 About 22.5 million [68%] of infected people live in
sub-Saharan Africa, even though sub-Saharan Africa is
home to just 10–11% of the world's population.

Epidemiology
 AIDS was first recognized in mid-1981in young,
previously healthy homosexual men in US.
 In Ethiopia:
 1984: The first evidence of HIV infection found.
 1986: The first two AIDS cases reported.
 1989: HIV/AIDS surveillance started:
The first sero-survey conducted in 1984-85 among
military recruits showed a prevalence of 0.07.
6

Background…..Summary of HIV Epidemic in
Ethiopia (2020)
7
622,326
383,781(62%)
238,545
44,138(7%)
578,188 (93%)
4,278 (37%)
7,437(63%)
8,920 (76%)
11,715
2,795 (24%) 1,967 (16%)
5,506 (43%)
7,179 (57%)
10,718 (84%)
12,685
PLHIV
New
Infection
AIDS
Related
Death

National Spectrum, 2021
8
5/26/2023
Source: Spectrum estimate, EPHI

Impact of HIV /AIDS in Ethiopia
I. Economical
o Loss of labor,skilled manpower,loss of worker
o expenses for funeral, tasker
II. Health Related
– Suffering from OI like TB, high bed occupancy
– Decrease life expectancy at Birth
– High health related costs
III. Social
– Elderly remaining without support
– Increased number of orphans
IV. Political –increase crime rate, forced migrations

Ethiopian National AIDS Policy 2021-2025
 The major objective: free AIDS Ethiopia
10

Transmission
Main modes of transmission are:
– Sexual – Heterosexual( anal,vaginal,oral)
- Homosexual
– Blood transfusion
– Needle prick; sharing of sharp materials; injection drug
use….parentral
– Mother to child [MTCT]…perinatal
– Mucosal exposure to infected blood and some body
fluids.

Table 1:Infectious and Non-Infectious Body Fluids
13

Etiology and Virology
 HIV has two major types and several subtypes/strains:
 HIV 1- Pandemic:
 HIV M (A,B,C,D,E,F,..J)- >95% Global burden
 HIV O
 HIV N
 HIV 2 – mainly in West Africa
 Subtype C viruses (of the M group) are the most
common, accounting for 50% of infections worldwide.
 In sub-Saharan Africa, the majority of infections are
caused by subtype C.
 Subtype B viruses are predominant in Americas,
western Europe, and Australia accounting for 12–13%
of global infections.

 HIV is an RNA virus whose hallmark is the reverse
transcription of its genomic RNA to DNA by the
enzyme reverse transcriptase.
 The greatest variability in strains of HIV occurs in the
viral envelope.
 HIV-2 has same genetic organization as HIV-1, but with
significant differences in the envelope glycoproteins.
 HIV-2 variant may be less pathogenic or have a longer
period of latency preceding disease.

16
HIV Virology: Structure of the Virus

Replication Cycle of HIV
– The CD4 molecule is found predominantly on T- helper
lymphocytes.
– It is also expressed on the surface of monocytes /
macrophages and dendritic/ Langerhans cells.
– The replication cycle of HIV begins with the high-affinity
binding of the gp120 protein to its receptor on the CD4
molecule.
– Once gp120 binds to CD4, the gp120 undergoes a
conformational change that facilitates binding to one of two
major co-receptors of HIV- 1 [CCR5 and CXCR4].
– The virus then firmly attaches to the host cell membrane in a
coiled-spring fashion via the newly exposed gp41 molecule.

– This facilitates fusion of the virion by penetrating the
plasma membrane of the target cell.
– Following fusion the preintegration complex is released into
the cytoplasm of the target cell.
– The complex enters the nucleus, the reverse transcription of
the genomic RNA into DNA occurs; and
– The protein coat opens to release the resulting double-
strand pro-viral HIV-DNA.
– With activation of the cell, Integrase catalyzes the
integration of viral DNA into the host cell chromosomes.

– Protease catalyzes cleavage and assembly of long HIV proteins,
enzymes, and genomic DNA to form a mature virion.
– Budding of the progeny virion occurs through the host cell
membrane, where the core acquires its external envelope.
– Finally a mature virus is released to the circulation to infect
another cell.
– The half-life of a circulating virion is 30–60 min and that of
productively infected cells is 1 day.
– About 1010–1011 virions are produced and cleared from the
circulation each day.
What is the importance of knowing the life cycle?

HIV Life Cycle: Sites for Therapeutic Intervention.

Summary: Six steps in life cycle of HIV in the body
1. Attachment/Binding: HIV attaches to the CD4 cell.
2. Fusion: The virion penetrates the plasma membrane of the
CD4+ cells.
3. Reverse Transcription: The enzyme reverse transcriptase
makes DNA copy of the viral RNA.
4. Integration: New viral DNA is then integrated into CD4 cell
nucleus using the enzyme integrase.
5. Assembly: The newly formed viral components are
assembled together using the enzyme protease.
6. Budding and release: The new mature virus gets its envelop
proteins and is released in to the circulation through
budding to continue the cycle.

Pathogenesis (1)
 HIV binding
 The gp120 subunit is responsible for CD4 binding
• CD4 receptors (T-helper lymphocytes, monocytes,
macrophages, dendritic cells, and brain microglia)
• binding to chemokine co-receptors (CCR5 and
CXCR4)
 Viral fusion
 viral glycoprotein (gp41) assists with viral fusion to
the cell and internalization of the viral contents
22

Pathogenesis (2)
 Release of viral content
 the viral protein shell surrounding the nucleic acid
(capsid) is uncoated
 virus's RNA and specific enzymes (RNA-dependent
DNA polymerase (also known as reverse
transcriptase), integrase and plymerase)
23

Pathogenesis (3)
 Reverse transcription
 using the single-stranded viral RNA as a template, reverse
transcriptase synthesizes a complementary strand of DNA
 the single-stranded viral RNA is removed from the newly
formed DNA strand by ribonuclease H
 Integration
 The final double-stranded DNA product migrates into the
nucleus and is integrated into the host cell chromosome by
integrase enzyme
 HIV then uses the infected cell's machinery to translate,
transcribe, and produce immature viral proteins
24

Pathogenesis (4)
 Assembly and budding
 These proteins assemble beneath the bilayer of the host cell,
a nucleocapsid forms containing these proteins, and the virus
buds from the cell
 Maturation
 After budding, the virus matures when an HIV protease
enzyme cleaves large polypeptides into smaller functional
proteins
25

Natural History of HIV Infection
 The peak viremia during the acute retroviral syndrome is
followed by a steady-state viremia called the viral set
point;
 It has important prognostic implications for the
progression of HIV disease in the untreated patient.
– Patients with low set point at 6 months to 1 year following
infection progress to AIDS much more slowly.
 Most patients are relatively asymptomatic even with
progressive decline of CD4 cells.
 However, clinical latency does not mean disease latency
or microbiological latency.

Typical course of an untreated HIV-infected individual

Natural history of HIV (2)
a. Primary HIV infection
– this stage is called window period
– initial burst of viremia occurs
– after this burst of viremia, a transient depletion of CD4+ cells
occurs
– patients develop non-specific ‘flu-like’ symptoms
(acute HIV (retroviral) syndrome)
• fever, fatigue, pharyngitis, lymphadenopathy and
rash
• do not lead directly to the diagnosis of HIV
infection because the symptoms are nonspecific
29

a. Primary HIV infection
– the patient could be negative for HIV specific
antibodies despite the presence of infection
– The immune system reacts by producing antibodies against
HIV
• given the rapid production of new HIV particles
and the development of many new viral strain,
the antibody response is Inadequate.
Patients are most likely to transmit HIV during the
early stage of infection
30

b. Asymptomatic stage/clinical latent infection
Within 6 months, the host's immune response is
able to control the infection:
• to a point where the number of virus particles
produced per day equals the number of
particles destroyed per day
This steady-state is often referred to as the
patient's viral "set point.“
The higher a patient's viral set point, the greater the
risk for disease progression.
31

32
Year 1
Predictor for:
-Disease progression
-Risk of transmission
Low set point = slower
disease progression
High set point = faster
disease progression

c. AIDS
 Over time, HIV depletes the body of T cells,
which places the host at an increased risk for
opportunistic infections
N.B. The hallmark of HIV disease is depletion of
CD4 cell s and the associated development of OIs
and malignancies.
33

35
DIAGNOSIS of HIV infection and Disease staging
A. Clinical Diagnosis of HIV/AIDS:
 HIV/AIDS can manifest with a spectrum of illnesses and
diseases as a result of the:
1. Direct injury
– Nervous (encephalopathy and peripheral neuropathy)
– Kidney (HIVAN = HIV-associated nephropathy)
– Cardiac (HIV cardiomyopathy)
– Endocrine (hypogonadism in both sexes)
– GI tract (dysmotility and malabsorption)
2. Indirect injury
– Opportunistic infections and tumors as a consequence of
immunosuppresion
– Drug related
– Psychological
These manifestations, with lab. abnormalities, are used for
disease classification and staging.

Test
 ELISA
 Western blot
 HIV rapid
antibody test
Significance
 Screening test for HIV infection…antibody test
 Of ELISA tests 50% are positive within 22 days after
HIV transmission; 95% are positive within 6 weeks after
transmission.
 Sensitivity > 99.9%; to avoid false-positive results must
be confirmed with Western blot.
 Confirmatory test for HIV.
 Specificity when combined with ELISA > 99.99%.
 Indeterminate results with early HIV infection, HIV-2
infection, autoimmune disease, pregnancy, and
immunization.
 Screening test for HIV.
 Produces results in 10-20 minutes.
 Can be performed by personnel with limited training.
 Positive results must be confirmed ELISA and Western
blot.
B. Laboratory Findings:

Test
 Absolute CD4
lymphocyte count
and CD4
lymphocyte
percentage.
 HIV viral load tests
Significance
 Most widely used predictor of HIV progression.
 Percentage may be more reliable than the
absolute CD4 count.
 Risk of progression to an AIDS opportunistic
infection or malignancy is high with CD4 < 200
cells/mcL or CD4 % < 20 in the absence of
treatment.
 These tests measure the amount of actively
replicating HIV virus.
 Correlate with disease progression and
response to antiretroviral drugs.
 Best test available for diagnosis of acute HIV
infection (prior to seroconversion).

 Nonspecific laboratory findings with HIV infection
may include :
– anemia, leukopenia (particularly lymphopenia), and
thrombocytopenia in any combination
– elevation of ESR
– polyclonal hypergammaglobulinemia, and others

39
C. Disease staging:
WHY STAGING?...T staging vs clinical staging
– To assess disease severity, and to monitor disease
progression
– To decide on criteria to initiate ART
T-staging:
– Staging while on ART to asses progress or response.
– Up and down staging is possible .
– Guides when to change treatment.

40
WHO Staging System for HIV/AIDS/clinical staging
 Ethiopia uses the WHO Staging System.
 It is a tool used to guide management of HIV patients
in resource limited settings:
 Clinically based; CD4 count not required
 Simple, flexible and widely used
 It has 4 clinical stages based on the degree of
immunosuppresion and prognosis.
 Performed at each clinical visit
 At Diagnosis
 Entry to clinical care (pre-ART)
 Follow-up

41
WHO Staging of HIV/AIDS
 Primary HIV Infection /Acute retroviral syndrome
– Stage I - asymptomatic
– Stage II - mild disease
– Stage III - moderate disease
– Stage IV - advanced immunosuppresion

42
WHO Clinical Stage I
 Asymptomatic
or
 Persistent generalized lymphadenopathy (PGL):
 Bilaterally swollen lymph nodes in the cervical area, under
the arm, or groin.
 Usually not painful (“Rule of 1,2,3” >1cm,>2 sites, >3
months)
 Performance scale 1: able to carry on normal activity

Persistent Generalized Lymphadenopathy
(PGL)
43

44
WHO Clinical Stage II
 Moderate unexplained weight loss (<10% of presumed or
measured body weight)
 Recurrent upper respiratory tract infections
 Herpes zoster
 Angular cheilitis
 Recurrent oral ulcerations
 Papular pruritic eruptions
 Seborrheic dermatitis
 Fungal fingernail infections
And/or performance scale 2(normal activity with effort,but unable to do active work)

45
Pruritic Papular Eruption…
Courtesy of Charles Steinberg MD

46
Herpes Zoster
Courtesy of Tom Thacher, MD Courtesy of the Public Health Image Library/CDC

47
Courtesy of Dr. R. Ojoh
Seborrheic Dermatitis (Dandruff)

Clinical stage 2
50
Parotid enlargement Linear gingival erythema (LGE)

Clinical stage 2
51
Recurrent oral ulcerations Extensive molluscum
contagiosum
Fungal nail infections

52
WHO Stage III
 Conditions where a presumptive diagnosis can be made on
the basis of clinical signs or simple investigations:
– Severe wt loss (>10% of presumed or measured body wt)
– Unexplained chronic diarrhea for > one month
– Unexplained persistent fever (intermittent or constant for > one
month)
– Oral candidiasis
– Oral hairy leukoplakia
– Pulmonary tuberculosis (TB) diagnosed in last two years
– Severe presumed bacterial infections (e.g. pneumonia,
empyema, pyomyositis, bone or joint infection, meningitis,
bacteremia)
– Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis

53
 Conditions where confirmatory diagnostic testing is
necessary:
 Unexplained anemia (<8 g/dl), and or
 neutropenia (<500/mm3) and or
 thrombocytopenia (<50 000/ mm3) for more than one
month
Performance Scale 3 (bedridden <50% of the day for the past
month)

54
Oral Candidiasis
Courtesy of Samuel Anderson, MD Courtesy of Dr. R. Ojoh

55
Oral Hairy Leukoplakia
Courtesy of Dr. R. Ojoh

56
WHO Stage IV
 Conditions where a presumptive diagnosis can be made on the
basis of clinical signs or simple investigations:
– HIV wasting syndrome
– Pneumocystis pneumonia
– Recurrent severe or radiological bacterial pneumonia
– Chronic herpes simplex infection (orolabial, genital or anorectal
of more than one month’s duration)
– Oesophageal candidiasis
– Extrapulmonary TB
– Kaposi’s sarcoma
– Central nervous system (CNS) toxoplasmosis
– HIV encephalopathy, or
 Performance Scale 4 (bedridden >50% of the day for the
past month)

57
 Conditions where confirmatory diagnostic testing is
necessary:
– Disseminated non- tuberculous mycobacteria infection
– Progressive multifocal leukoencephalopathy (PML)
– Candida of trachea, bronchi or lungs
– Cryptosporidiosis
– Isosporiasis
– Visceral herpes simplex infection
– Extrapulmonary cryptococcosis including meningitis

58
 Conditions where confirmatory diagnostic testing is
necessary:
– Cytomegalovirus (CMV) infection (retinitis or of an organ other
than liver, spleen or lymph nodes)
– Any disseminated mycosis (e.g. histoplasmosis, coccidiomycosis,
penicilliosis)
– Recurrent non-typhoidal salmonella septicemia
– Lymphoma (cerebral or B cell non-Hodgkin)
– Invasive cervical carcinoma
– Visceral leishmaniasis

59
HIV Wasting Syndrome
Wt loss >10% body wt
plus
Unexplained chronic
diarrhea (>1 mo) or
Unexplained fever (>1
mo) plus chronic weakness

60
Kaposi’s Sarcoma (KS)
 Usually, multiple dark
raised lesions
 Lesions themselves
are not itchy and
are rarely painful
Courtesy of Tom Thacher, MD

Severe Chronic Herpes Simplex Ulcers
62

Management
1. Prevention:
A. Primary Prevention:
– Vaccine development is on trial;
– Effective prevention of transmission through universal precautions of IP
is vital.
– PMTCT
B. Secondary Prevention:
– HAART and prophylactic regimens can prevent opportunistic infections and improve
survival.
– Prophylaxis for common OIs should be given to patients per the national guideline.
– Secondary prophylaxis includes PEP.
2. HAART:
– HAART is one component of the comprehensive care and treatment of PLWHA.
– Experimental treatment regimens for HIV infection are constantly changing.
– People are still doing well over 20 years with good adherence to HAART.

Highly active Antiretroviral therapy (HAART)
– Anti-Retroviral Therapy (ART) is the lifelong treatment
of HIV infected individuals with antiretroviral drugs.
– It is the use of at least three anti-retroviral drugs with
different class for the treatment of HIV infection to
achieve effective viral suppression.
65

Goals of ART
– Clinical goal: Prolong and improve quality of life
– Virologic goal: Reduce viral load
– HIV RNA < 50 copies/mL or “undetectable” within 4-6 months
of ART initiation is good achievement.
– Immunologic goal: Immune reconstitution
– Therapeutic goals: Maintain future treatment options,
minimizes toxicity and maximizes benefit.
– Preventive goals: Reduce HIV transmission:
– PMTCT
– PEP

Classes of Antiretrovirals
1. Reverse transcriptase (RT) inhibitors
– Nucleoside RT inhibitors (NRTI)…AZT/3TC
– Non-nucleoside RT inhibitors (NNRTI)…EFV,NPV
– Nucleotide RT inhibitors (NtNRI)…TDF
2. Protease inhibitors (PI)…LPV/r, ATV/r
3. Fusion inhibitor/Entry inhibitors
4. Integrase inhibitors….DTG,RTG
5. CCR5 Inhibitor

RVI drugs
 NNRTIs: Efavirenz (EFV), delavirdine (DLV), nevirapine (NVP)
and etravirine (ETR).
 N R T I : Zidovudine (AZT/ZDV), Didanosine(ddi),
Lamivudine(3TC), Stavudine(d4t), Zalcitabine (ddc),
Abacavir(ABC), Tenofofir (TDF)…NtRTI
 protease inhibitors (PIs) : amprenavir (APV) and its prodrug
fosamprenavir (FPV), atazanavir (ATV), darunavir (DRV),
indinavir (IDV), lopinavir (LPV), nelfinavir (NFV), ritonavir (RTV),
saquinavir (SQV), and tipranavir (TPV).
 Entry inhibitors: fusion inhibitors (Enfuvirtide (ENF)) and CCR5
antagonists (Maraviroc )
 Integrase inhibitors: Dolutegravir, Raltegravir
68

General Rules of Therapy
 Combination of at least 3 drugs:
 2 NRTIs
 1 NNRTI or 1-2 PIs; OR integrase inhibitor
 Rarely Triple NRTIs
Therapy with only one or two agents allows HIV to
overcome therapy through resistance mutations.
Regular follow up is mandatory with clinical and
laboratory evaluation.
CD4 counts every 3-6 months
Viral load tests every 3-6 months and 1 month
following a change in therapy. 69

Why a Combination of 3 or more ARV drugs use?
 To have sustained viral suppression (low level of
virus in the body)…HIV makes new copies of itself
very rapidly
 Antiretroviral drugs from different drug groups attack
the virus in different ways.
 To overcome or delay emergence of resistance.
70

Preparing patients for ART
– The benefits of ART, advantage of Rapid initiation
including same day over delayed initiation,
– Possible adverse effects of ARVs & OI medications,
– Information regarding lifelong treatment,
– The required follow-up and monitoring visits,
– Detailed examination and treatment of OIs,
– Proper adherence counseling and support,
– Counseling on effective FP planning choices,
– Counseling on disclosure and screening of family
members,
– Education on safer sex
71

Eligibility Criteria to start HAART
1. HIV positive test result with written documentation,
2. Verification of HIV infection with re-testing at ART
initiation point,
3. Ensure TB or/and cryptococcal meningitis have been
rulled out.
4. Ensure that all adherence barriers are addressed,
5. Readiness of the patient for ARV therapy
72

When to Start ART?
 PLHIV should be started on ART right away after confirmation
of HIV diagnosis except when they have TB and/or cryptococcal
meningitis…rapid ART initiation
 Rapid ART initiation is defined as initiation of ART same day or
within seven days of HIV diagnosis .
 ART should be offered on the same day for people who are
ready to start
==provided that all adherence barrier is addressed==
73

when to start ART in adults, adolescents, pregnant
and breast feeding women and children(summary)
 Start ART rapidly, preferably same day,(i.e. on the
date of confirmed HIV diagnosis) who are ready and
willing regardless of their WHO clinical stages and
CD4 counts, except for those delaying ART initiation
is recommended (TB meningitis and cryptococcal
meningitis).
74

When to start ART in children
 Start ART as early as possible regardless of their WHO
clinical stages and CD4 counts, except when there is TB
meningitis.
 If a patient has TB meningitis ,delay ART for at least 4
weeks and initiate within 8weeks after treatment of TB
meningitis is initiated and delayed by 4-6 weeks for
cryptococcal meningitis.
 For HIV infected infants diagnosed with the first DNA PCR
result, initiate ART and take DBS specimen for confirmatory
DNA PCR. Continue ART if the second DNA PCR confirms
positive results; whereas if the second DNA PCR turns
negative, without holding the ART, make the 3rd DNA PCR
test.
76

What ART regimen to start with (First-line
ART)?
 The preferred first-line regimen for adults and
adolescents (>10 years of age or >30 kg body
weight) including pregnant and breast-feeding women
is TDF+ 3TC+DTG as a once-daily dose.
First-line ART for children:
 The preferred first-line regimen for children > 4weeks
and ≥3kg but less than 10 years/<20 kg is
ABC+3TC+DTG(DTG 10mg dispersible tablet).
.
77

Updated summary of first-line ART regimens
for adults, adolescents, and children
Population Preferred first-line Alternative first
line
Special circumstances a
Adolescents (10 to
19 years OR weight
≥30 kg), adults,
pregnant,breastfee
ding TB/ HIV- co
infection
DF+ 3TC+DTGb (FDC) TDF + 3TC + EFV
AZT + 3TC + DTG
AZT + 3TC + EFV
AZT+ 3TC + ATV/r
TDF+ 3TC+ ATV/r
ABCc+3TC+DTG
Children > 4weeks
and ≥3kg but less
than 10 years
ABC + 3TC + DTGb* ABC+ 3TC+LPV/r
AZT+3TC+DTG
ABC+3TC+EFV d
AZT+3TC+EFV
AZT+3TC+LPV/ra
81

WHO definitions of clinical, immunological and virological
failure for the decision to switch ART regimens
82

second-line ART for adults and adolescents
 Second-line ART for adults should consist of two NRTIs + a ritonavir-
boosted PI….use PI instead of NNRI or Integrase inhibitor
 The following sequence of second-line NRTI options is recommended:
 After failure on a TDF + 3TC (or FTC)–based first-line regimen, use AZT
+ 3TC as the NRTI backbone in second-line regimens.
 After failure on an AZT + 3TC–based first-line regimen, use TDF + 3TC
(or FTC) as the NRTI backbone in second-line regimens.
 Use of NRTI backbones as a fixed-dose combination is recommended
as the preferred approach
 Heat-stable fixed-dose combinations of ATV/r and LPV/r are the
preferred boosted PI options for second-line ART

Summary of preferred second-line ART regimens for adults
and adolescents
85

Summary of preferred second-line ART regimens for children
86

PMTCT
Risk factors for MTCT:
 Maternal (high viral load, advanced HIV disease, mixed
feeding)
 Obstetric (Vaginal delivery, prolonged rupture of
membranes >4 hours, placental infection)
 Infant (prematurity <37 weeks, low birth weight, oral
candidiasis)
Initiate ART and maintain after delivery and cessation of
breastfeeding (TDF+ 3TC or FTC + EFV)

Infant prophylaxis:
 NVP for 6 months for breast feeding or 4-6 month for
replacement feeding
 Alternative for replacement feeding: AZT for 4-6 month
BID
 when a breastfeeding mother initiates ART very late in
pregnancy during labour or postpartum, increasing the
duration of infant NVP prophylaxis to 12 weeks can be
considered.

Infant prophylaxis
Infant age Daily dose Of NVP Daily dosing of AZT
Birth to 6 week
• Birth weight 2 kg−2.499 kg
• Birth weight ≥2.5 kg
10 mg once daily for 6 wks
15 mg once daily for 6 wks
10 mg twice daily for 4-6 wks
15 mg twice daily for 4-6 wks
> 6 weeks to 6 months 20 mg once daily
AZT is only
recommended in
settings with
replacement
feeding
> 6 months to 9 months 30 mg once daily
9 months until
breastfeeding ends
40 mg once daily
Infants weighing <2kg the suggested starting dose is 2 mg/kg twice daily.
If toxicity from infant NVP requires discontinuing the drug or if infant NVP is not available,
infant 3TC can be substituted

PEP
Indications for PEP
 Occupational exposure (healthcare workers, police)
o Exposure to other people’s blood
 Non occupational
o Discordant couples following barrier protection breakage,
o Rape
o Female sex worker
PEP regimens
 AZT/3TC: 1 bid for 28 days
 TDF/3TC: 1 qd for 28 days
 Add Kaletra: 2 bid for 28 days in case of high risk
 Given at earliest possible opportunity, within 72 hours of exposure
 Currently 3 drug PEP (preferred regimen: TDF +3TC+DTG)

PrEP
 Oral PrEP is the daily use of ARV drugs by HIV-
uninfected people to block the acquisition of HIV
 Serodiscordant couples- daily TDF or TDF + FTC for
the uninfected partner.
 If same sex- TDF + FTC daily ( male to male)
 Men and transgender women who have sex with men- TDF
+ FTC

Management of common co-infections of HIV
1. Co-trimoxazole preventive therapy (CPT)
 recommendations cover initiation of CPT among
adults, adolescents, pregnant women and children.
 for prevention of Pneumocystis pneumonia,
toxoplasmosis, bacterial infections & diarrhea
caused by Isospora belli or Cyclospora species, as
well as benefits for malaria prophylaxis.

‘Dapsone as an alternative for CPT toxicity’
93

TB preventive therapy
 TPT is a cost-effective intervention that reduces TB
incidence and mortality among high risk groups. The
efficacy of currently available preventive
treatments ranges from 60% to 90%.
 To interrupt disease transmission with eventual goal
of ending TB
 To avert the suffering and catastrophic economic
costs associated with developing active TB and its
associated complications
 To reduce massive expenditure imposed on health
system due to TB disease and its complications

New WHO guidelines recommendations (2020)
1. Daily INH for 6 months (6H)
2. Daily INH for 9 months (9H)
3. Rifapentine + isoniazid weekly for 3 months (3HP)*
4. Rifapentine + isoniazide daily for 1 month (1HP)**
5. Rifampicin plus isoniazid daily for 3 months for children and adolescents
<15y (3HR)*
6. Rifampicin daily for 4 months (4R)**
TB preventive treatment recommended for
- Adults and children living with HIV
- HIV-negative adult and child contacts
- Other HIV negative at-risk groups
TB preventive Treatment options
WHO Consolidated guidelines on Tuberculosis- Module 1: Prevention Tuberculosis preventive treatment, 2020
Current national guideline recommends: 3HP, 3RH, 6H

What is 3HP?
 One of short-course TPT regimen recommended by WHO for
treatment of latent TB infection
 Combination of two drugs: isoniazid (H) and rifapentine (P)
 Full course of treatment: 12 doses administered once weekly
for three months duration

Benefits of 3HP
 3HP was found to be non-inferior to (as effective as) isoniazid monotherapy
in preventing TB disease
 3HP has shorter duration of treatment
 3HP improves patient adherence and associated with high treatment
completion rates
 3HP is less toxic to the liver than IPT regimen
 Rifapentine can be safely co-administered with anti-retroviral drugs such
as Efavirenz, DTG and Raltegravir.

Baseline assessment for TPT/3HP
1. Rule out active TB
2. Assess Personal history and potential contraindications
3. Elicit medication history and Assess drug – drug
interactions
4. Consider baseline liver testing for at-risk individuals if
indicated
5. Initiate appropriate TPT and B6 ( for those at risk
of peripheral neuropathy)

Selection of TPT regimen for PLHIV
Age group and ART regimen
Selection of TPT regimen
Preferred regimen Alternative regimen
1. Adults, adolescents, children and infants of all ages
taking a PI-based ART regimen
Daily isoniazid preventive treatment
(IPT) for 6 months
2. Children and adolescents aged <15 years taking a
DTG-based ART regimen
Daily isoniazid preventive treatment
(IPT) for 6 months
3. Children and adolescents aged 2-14 years taking a
EFV-based ART regimen
Weekly isoniazid Plus rifapentine for 3
months (3HP)
- Daily rifampicin Plus isoniazid
for 3 months (3RH)
- Daily isoniazid preventive
treatment (IPT) for 6 months
4. Adolescents and adults living with HIV (≥ 15 years
of age) taking non-PI based ART regimen
Weekly isoniazid Plus rifapentine for 3
months (3HP)
- Daily isoniazid preventive
treatment (IPT) for 6 months

Weekly dosage of INH & Rifapentine (3HP) for adults and adolescents
above 14 years of age
Medicine Formulation
Weight bands for patients aged >14 years
Comments
30–35 kg 36–45 kg 46–55 kg 56–70 kg >70 kg
Isoniazid 300 mg 3 3 3 3 3
Rifapentine 150 mg 6 6 6 6 6
Isoniazid + Rifapentine
FDC
300 mg / 300 mg 3 3 3 3 3
FDC being
developed

Weekly dosage of INH & Rifapentine for children and adolescents (3HP) between 2-14
years of age
Dosing of rifapentine and isoniazid (3HP) for treatment of latent TB infection
Medicine Formulation
Weight bands for patients aged 2-14 years
Comments
10–15 kg 16–23 kg 24–30 kg 31–34 kg >34 kg
Isoniazid 100 mg 3 5 6 7 7
adult 300 mg tab. can
reduce pill burden
Rifapentine 150 mg 2 3 4 5 5
Isoniazid +
Rifapentine FDC
150 mg /150 mg 2 3 4 5 5 FDC being developed

When to start ART in adults, adolescents
and children with TB
– start ART in all TB patients living with HIV as soon as
possible within 8 weeks following initiation of anti-
TB treatment regardless of their CD4 count.
– TB patients with profound immune suppression (e.g.,
CD4 < 50 cells/ml) should receive ART within the first
2 week of initiation of TB treatment.
– Start CPT for TB/HIV co-infected patients.
– For patients taking DTG while they are on TB
treatment, the dose of DTG need to be 50mg BID.
104

When to start ART in HIV/HBV co-infected
adults
 Start ART in all HIV/HBV co-infected patients
regardless of their CD4 count.
 The preferred regime for first line ART
(TDF+3TC+EFV) is already the treatment for HBV.
105

ARV drug toxicities
AZT(Zidoudine)
 Anemia, neutropaenia,myopathy, lipodystrophy
 Lactic acidosis or severe hepatomegaly with
steatosis
Mgt:
 substitute AZT with TDF or ABC if used in 1st -
line ART

TDF
– Tubular renal dysfunction, Fanconi syndrome
(malabsorption proximal tubule due to defect)
– Decreases in bone mineral density
– Lactic acidosis or severe hepatomegaly with steatosis
Mgt :
 substitute TDF with AZT or ABC if being used in 1st -
line ART
 substitute TDF with ABC,if being used in 2nd -line ART

ABC
– Hypersensitivity reaction
– Electrocardiographic abnormalities (PR interval
prolongation)
Mgt :
 substitute ABC with TDF or AZT if is being used in first-
line ART
 substitute ABC with TDF if ABC is being used in second-
line ART

EFV
– Persistent CNS toxicity (such as abnormal dreams, depression
or mental confusion)
– Convulsions
– Hepatotoxicity
– Hypersensitivity reaction, Stevens-Johnson syndrome
– Male gynaecomastia
Mgt :
 Substitute with NVP
 If the person cannot tolerate either NNRTI, use boosted
PIs

NVP
 Hepatotoxicity
 Severe skin rash and hypersensitivity reaction (Stevens-
Johnson syndrome)
Mgt:
 substitute with EFV
 If the person cannot tolerate either NNRTI, use boosted PIs

LPV/r
– ECG abnormality (PR and QT interval prolongation)
– Hepatotoxicity
– Pancreatitis
– Risk of prematurity, lipoatrophy or metabolic
syndrome(insulin resistance,DM), dyslipidaemia or severe
diarrhoea
Mgt:
 If LPV/r is used in 1st -line ART for children, use an age-
appropriate NNRTI
 (NVP for <3 years age and EFV for children 3 years and
older). ATV can be used for children older than 6 years
 If LPV/r is used in 2nd -line ART for adults, use ATV/r or DRV/r.
 If boosted PIs are contraindicated and the person has failed on
treatment with NNRTI in first-line ART, consider integrase inhibitors.

DTG
 Hepatotoxicity
 Hypersensitivity reactions
 Insomnia
 Body weight gain or obesity
Mgt
 substitute EFV, boosted PI or
 consider morning dose
112

Clinical Grading of ARV toxicity
Grade 1 (Mild reaction): do not require changes in therapy
Grade 2 (Moderate reaction): consider continuation of ART as long
as feasible. If the patient does not improve in symptomatic therapy,
consider single-drug substitution.
Grade 3 (Severe reaction): Substitute offending drug without stopping
ART. Closely monitor using laboratory and clinical parameters.
Grade 4 (Severe life-threatening reaction): Immediately discontinue all
ARV drugs, manage the medical event and reintroduce ARV drugs
using a modified regimen (i.e. with an ARV substitution for the
offending drug) when the patient is stabilized.
 Life-threatening toxicity includes severe hepatitis, pancreatitis, lactic
acidosis or Steven-Johnson syndrome.
113

Reading assignment
 DRUG-DRUG INTERACTION AMONG ARVs
 GRADE OF TOXICITY AND THEIR MANAGEMENT

Opportunistic infection and their
Management
115

Definition of OIs
 Infections that develop as a result of damage to the
immune system.
 OIs take advantage of the opportunity provided by a
weakened immune system.
 Predominant causes of morbidity and mortality among
HIV-infected pts.
 The level of immunity determines the occurrence and
type of OIs.
116

Pneumocystis jiroveci (formerly carinii)
Pneumonia (PCP)
– The cause of pneumocystosis is a fungal agent.
– PCP has been and continues to be the most common
life-threatening OI in pts with AIDS.
– P. jiroveci was formerly named P. carinii
– The name change was made to distinguish the organism
that infects humans (P. jiroveci) from the strain that
infects rodents (P. carinii).
– Frequently PCP occurs when the CD4 count drops below
200 cells/µL
118

 Typical clinical presentations
 insidious onset of low grade fever(79-100%)
 dry cough (95%)
 dyspnea exacerbated by exertion (95%)
 P/E often reveals
 fever
 tachypnea
 tachycardia
 scattered rales in the lungs but examination of the lungs
can appear normal in some pts.
 Extra pulmonary manifestations: hepatosplenomegaly,
skin lesions, and pleural effusions
119

– Cotrimoxazole 3- 4 SS tablets three or four times daily
for 21 days.
– Close monitoring is necessary during the initial five days
of treatment and if pt grows sicker, administration of
oxygen is useful.
– Toxicity of cotrimoxazole, like skin rash, bone marrow
suppression, hepatitis and renal failure can be
troublesome in some pts with advanced HIV disease and
requires close monitoring.
120
Treatment:

 Alternative regimens for mild to moderate PCP:
1. Clindamycin 600 mg qid plus primaquine 15mg
bid or
2. Clindamycin 600 mg qid plus dapsone 100 mg QD
 Secondary prophylaxis after completion of the course of
treatment with cotrimoxazole should be started
 Pt has to be prepared for ART as s/he is automatically
eligible for ART regardless of the CD4 count.
121

Adjuvant corticosteroid therapy for PCP
– Indicated for severely ill pts with marked respiratory
distress and extensive CXR findings (paO2 <70 mm Hg)
– Reduces mortality by 50%
– Start within 72 hrs of presentation
– Regimen
 Prednisone 40 mg po bid x 5 days
o 40 mg po qd x 5 days
o 20 mg qd x 11 days
 No benefit for mild episodes
 Use cautiously if diagnosis is not confirmed, and watch for
other OIs
122

PCP Prophylaxis Indications
 Primary prophylaxis (to prevent disease)
 CD4 < 350/mm3
 WHO Stage II, III, IV
 HIV-associated oral candidiasis
 Unexplained fever
 Secondary prophylaxis (after pneumonia, to prevent
recurrence)
 Prior episode of PCP
123

PCP prophylaxis agents
 Standard regimen
 Cotrimoxazole (TMP/SMX) 160/800 mg tab QD
 Alternate regimens
 Dapsone 100mg QD
 May safely discontinue if immune system restored from
ART
 Must have CD4 > 200 for 3 months
124

Co-trimoxazole toxicity
 Skin rash, bone marrow toxicity and hepatotoxicity
 Desensitization can be performed
125

Co-trimoxazole toxicity grading scale for adults and
adolescents
126

 Desensitization can be attempted two weeks after a non-severe
(grade 3 or less).
 Desensitization should not be attempted in individuals with a history
of grade 4 reaction to previous co-trimoxazole or other sulfa drugs.
 It is recommended to commence an antihistamine one day prior to
starting the regimen and to continue daily until completing the dose
escalation.
 On the first day of the regimen, the step 1 dose is given and
subsequently increased one step each day.
 If a severe reaction occurs, the desensitization regimen is terminated.
 If a minor reaction occurs, repeat the same step for an additional
day.
 If the reaction subsides, advance to the next step; if the reaction
worsens, the desensitization regimen is terminated.
127

Protocol for co-trimoxazole desensitization
among adults and adolescents
128

OI…Cryptococcal Meningitis
 Cryptococcal Meningitis
most common form of fungal meningitis
major cause of morbidity and mortality in immunosuppressed
pts
Treatment
• Management of raised ICP
• Antimicrobials:
• Amphotericin B 0.5 to 1 mg/kg/day X 2 weeks and if
improving combined with flucytosine,100 mg/kg/day, is more
effective
• Fluconazole
• 400 mg QD x 6 weeks
• 200 mg QD until CD 4 > 200 for at least 6 months.
129

OI…Cryptococcal Meningitis
 Treatment….three phases
Induction
Amphotericin B 0.7-1 mg/kg/day plus 5-flucytosine
100mg/kg/day x 2 weeks then
Consolidation
Fluconazole 400 mg/day x 6-10 weeks then
Suppression (maintaince)
• Fluconazole 200 mg/day until CD4 >200 for minimum of
6months?
• AIDS-associated cryptococcal meningitis need life long
maintenance or suppression therapy with fluconazole
130

Treatment of cryptococcal disease for adults and
adolescents living with HIV.
131
Options Induction (14 days) Consolidation
(56 days)
Maintenance(1
year)
Option A (High dose) Fluconazole 600
mg BID (In children 12mg/kg
BID) ± flucytosine 25 mg/kg
PO QID
Fluconazole 800
mg/day (children
12mg/kg/day)
Fluconazole 200
mg daily (children
6mg/kg/day) for
at least 1 year
Option B  Amphotericin 0.7-
1mg/kg/day + fluconazole
800 mg/day OR
 Fluconazole
400-800
mg/day or
 Itraconazole
200 mg PO
BID
 Amphotericin B, 0.7 to 1mg/kg
PLUS Flucytosine, 100mg/kg

OI….Toxoplasmosis
Cerebral Toxoplasmosis:
 the most common focal brain infection in HIV-infected patients
and caused by bacteria toxoplasmosis gondi
 Treatment:First-line therapy is pyrimethamine plus
sulfadiazine, given concomitantly with leucovorin/folica acid to
prevent severe hematologic adverse effects secondary to
pyrimethamine
 Alternatives: Clindamycin if sulfa drug is contr-indicated or
Sulfamethoxazole-trimethoprim in patients unable to take oral
therapy…in Ethiopia cotrimoxazole 480mg, oral, 4 tablets 12
hourly for 28 days, followed by 2 tablets 12 hourly for 3
months in adults.
 Adjunctive corticosteroids and anticonvulsant therapy should
be considered to reduce sequelae from the inflammatory
process and control active seizures, respectively 132

OI…other virus
HSV encephalitis: Acyclovir 10mg/kg IV Q8h
Herpes simplex: Acyclovir 400mg TID for 5 to 10
days
Herpes zoster: Acyclovir 800mg 5X per day for
seven days….Monitor renal function
Diarrhea ?????...read on GIT infections ppt
133

11.Pharmacotherapy of TB
and Leprosy
By:zenebe k

Pharmacotherapy of TB
 TB is a chronic infectious disease caused in most cases by
Mycobacterium tuberclae and some times by M. bovis
Classification:
 Pulmonary TB..primary affect lung paranchama(ghon complex)
 Extrapulmonary TB:..out of lung organs
TB of lymph- nodes (TB- lymphadenitis)
Bone TB
Intestinal TB
TB meningitis
Milary TB/Dissiminated TB….through blood
136
1

Pharmacotherapy of TB…
 Mycobacterial infections are the most difficult of all
bacterial infections to treat because;
1 They are resistant to many drugs
2. The mycobacterial cell wall is impermeable to many
drugs
3. A substantial proportion of mycobacterial organisms
are intracellular, residing with in macrophages and
inaccessible to drugs
137
1

Pharmacotherapy of TB…
Reasons for drug combination
 To delay / reduce resistance
 To shorten duration of therapy
 Rapid reduction of bacterial load  fast recovery &
reduce communicability.
138
1

Diagnosis and laboratory test
Requires clinical suspicion and microbiologic
identification of the bacilli.
1. Microbiologic tests to identify the bacilli
a. sputum direct microscopy: Ziehl Nielsen (acid fast bacilli) (AFB)
staining ….not easily decolored by stain…’acid fast bacilli’…AFB
 Three sputum specimens (SPOT-EARLY MORNING-SPOT) need to
be collected and examined in two consecutive days
b. Gene Xpert MTB/RIF
– A fully automated DNA/molecular diagnostic test to detect TB and
Rifampicin resistance simultaneously.

Cont…
c. Sputum culture and drug susceptibility
– Culture is the gold standard
– It takes weeks to get the results.
– If sputum AFB and/or Gene Xpert are negative and
there is a strong suspicion,
d. Line Probe Assay (LPA)
– A test to identify the presence of specific mutations
on the genes of TB bacilli which are responsible for
Isoniazid and Rifampicin resistance.
– It is a rapid and accurate test to identify MDR-TB.

Other tests
 Body fluid analysis and identification of pathogen
 Fine needle aspiration(FNA) : enlarged lymph nodes
 Tissue biopsy and histopathology…pleural, skin,
endometrium,
 Imaging:….confirmatory test
– Chest X-ray.
– Abdominal U/S,brain/spinal MRI: the suspected extra
pulmonary
141

Risk factors
• Risk factors for infection
– Close contacts of pulmonary TB patient
– living in crowded conditions
– Social problems (homelessness, drug abuse etc.)
• Risk Factors for Disease
– HIV-infection (100x)
– Underlying immune suppression (e.g., renal failure, cancer,
and immunosuppressive drug)
– Children younger than 2 years of age and adults older
than 65 years of age.
– Recent infection (the first 2 years) 143

Transmission of TB
– TB is usually spread human to human
– Through the air by droplet nuclei particles that are 1 to
5 m in diameter containing MTB complex organisms.
– TB enters the air when patients with active pulmonary
TB: cough, speak, sneeze, or sing
– Since TB is a disease of respiratory Transmission of MTB
transmission, optimal conditions for transmission
include:
 Overcrowding, Poor personal hygiene and Poor public
hygiene

Management of TB
 They given based on weight
 They may present as fixed dose or loose
form

Drugs used in the treatment of TB
Isoniazide (INH)
-Most active drug against M.TB
– Bactericidal
– Can enter phagocytic cells so it is active against both
intracellular and extracellular organisms.
– It inhibits the synthesis of mycolic acid which is essential
component of mycobacterial cell wall.
– Metabolism (acetylation) is genetically determind and
there are fast and slow acetylators.
Adverse effects
 Peripheral neuropathy, INH promotes excretion of
vitamin B6 (Pyridoxine ),liver toxicity
151
1

Drugs ..
Rifampicin
- Strongly binds to bacterial DNA dependent RNA
polymerase thereby inhibits RNA syntheis.
– it is active against both intracellular and extracellular
organisms
- Causes harmless orange color to urine, sweat and
tears.
Adverse effects: rashes, nephritis, hepatitis
- It is an enzyme inducer  interaction with
anticoagulants, anticonvulsants, contraceptives,
ketoconazole and chloramphenicol. 152
1

Drugs ..
3. Ethambutol
 Inhibits synthesis of mycobacterial cell wall
 Adverse effects: loss of visual acuity, red green color
blindness.
 Contraindication- in children below 6 years of age.
 But the loose form of ethambutol which is 100mg
can be used.
153
1

Drugs ..
4. Pyrazinamide
 Bactericidal
 Inhibits mycolic acid biosynthesis
 Adverse effects: hepatotoxicity, nausea, vomiting,
hyperuricemia, (acute gouty arthritis)
154
1

Combination chemotherapy
Phases of therapy…duration of therapy short 6 month
 Intensive Phase …for two months with 4 drugs
- (Initial phase): Includes the time between initiations of
therapy to the end of the second month.
- Three or more drugs are used in this phase and is
essential for rapid destruction of the mycobacterium
and reduce communicability
- Destroy extracellular organisms
156

Combination chemotherapy
Continuation phase…for 4 month or greater
 This phase starts from end of intensive phase to the
time completion of therapy is declared.
 This phase is intended to confirm radical cure of the
patient.
 Destroy both intra-cellular and extracellular organisms
157
1

For extrapulmonary TB…additional duration
Extended continuation phase….may go upto- 9-12 month
– The following extrapulmonary forms of Tb require prolonged
continuation phase
– CNS (TB meningitis or Tuberculoma)
– Bone or joint TB (Vertebral(TB spondylitis), joint and
osteomyelitis), which require prolongation of the continuation
phase for Regimen (a total of 12 months : 2months intensive
phase and 10 months continuation phase)
– 2RHZE/10RH
158

Adjuvant corticosteroid therapy…extra TB
 Adjuvant corticosteroid therapy , dexamethasone or
prednisolone tapered over 6-8weeks should be used
for patients with the following two extrapulmonary
forms
– TB meningitis
– TB pericarditis
– TB lymph adenitis
Corticosteroid for TB meningitis
 Dexamethasone 12 mg/day OR Prednisolone 60mg/day
for 3 weeks and then decreased gradually during the
subsequent 3 weeks.
159

Treatment category and regimen
Category I
 Includes those new patients who have smear-positive
Pulmonary TB and those who are seriously ill with
smear-negative Pulmonary and Extra-pulmonary TB
cases.
2 (RHZE) / 6 (EH) or 2 (RHZE) / 4RH
160
1

Treatment category…
Category II- Retreatment regimen
This category is applied to a group of TB patients: Who
relapsed after being treated and declared free from the
disease,
OR
In those patients who are previously treated for more than one
month and found to be smear positive up on return,
OR
Who still remains smear positive while under treatment, at month
five and beyond…upto six month…otherwise…go to MDR TB
2 SE (RHZ) / 1E (RHZ) / 5 E3 (RH)3.( three times per week)…old
 Currently streptomycin is not recommended…so continue
2RHZE/4RH
161
1

Category III
 This refers to patients who have smear negative
Pulmonary TB, Extra-pulmonary TB , TB in Children.
2(RHZE/)/6(EH)
162
1

Category IV
Category IV
Treatment of chronic cases
 Chronic cases can be described as those cases that
continue to be smear-positive after completion of a
fully supervised (initial phase and continuation phase)
treatment with the treatment regimen.
 These are cases who are multi drug resistant
 Use second line drugs
163
1

"Second-line" drugs
This category of agents includes
 moxifloxacin or
 gatifloxacin,
 ethionamide,
 Aminosalicylicacid,
 cycloserine,
 amikacin, kanamycin, capreomycin, and linezolid
164
1

Second line – anti-TB drugs
• For a variety of reasons, many TB patients do not
complete their full treatment regimen.
• The TB bacillus then becomes resistant due to this
incomplete, erratic, or inadequate treatment.
• 2nd lines are less active, more toxic or more active
against atypical strains of mycobacteria
• Multidrug resistant tuberculosis (MDR TB)???
–When a strain is resistant to at least isoniazid
and rifampicin
• Did you know?
• About 50% of TB cases are resistant to at least one drug and about
20% are MDR. (WHO, 2008)

166
1
Pharmacotherapy of leprosy

Pharmacotherapy of leprosy
 Leprosy is a chronic infectious disease of man which
predominantly affects peripheral nerves and the skin,
although other tissues, such as the eye, mucosa of the
upper respiratory tract, muscles, bone and testis can
also be involved.
 is caused by Mycobacterium leprae.
 Infection with M. leprae is considered to occur through
the nasal mucosa from droplet infection.
 Two types based on skin lesions involved
167
1

Treatment
1. Multibacillary leprosy:
 More than 5 skin lesion or patches
 Use the following three drugs as follows for a period of
one year
– Rifampicin, 600 mg p.o. once-monthly, supervised.
plus
– Dapsone, 100 mg daily, self-administered.
plus
– Clofazimine, 300 mg once-monthly, supervised and 50mg
daily, self-administered.
168
1

2. Paucybacillary leprosy (adult dosage)
 Defined as five or fewer skin lesions without
detectable bacilli on skin smears
 Require six months of treatment
 Rifampin 600mg once monthly, supervised +
 Dapsone 100mg daily, self administered
169
1

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