all the data presented in this presentation is authentic from WHO website and Pharmacology book goodman gillman's Basic of therapeutics

1. ANTI-HIV STANDARD REGIMENS
AND NEWER DRUGS
SHIVANSHU BAJAJ
M.PHARMACY (PHARMACOLOGY)
2nd SEMESTER
SPER, JAMIA HAMDARD
DELHI

2. Contents
1) Introduction
2) Types and strain of HIV
3) Virus structure
4) How the virus cause disease
5) Stages of HIV infection
6) Diagnosis
7) Anti-HIV regimen
8) WHO-ART regimens on different population
9) Newer drugs
10)References

3. INTRODUCTION
Human immunodeficiency viruses are lentiviruses, a family of
retroviruses evolved to establish chronic persistent infection with
gradual onset of clinical symptoms.
 Replication is constant following infection, and although some
infected cells may harbor nonreplicating virus for years.
 Humans and nonhuman primates are the only natural hosts for
these viruses.

4. Types and Strains of HIV
 There are two main types of human immunodeficiency virus HIV-1 and HIV-2. Both
can lead to AIDS. However, they're very different from each other.
 HIV-1 is the most common type.
 HIV-2 occurs in a much smaller number of people, mostly in West Africa.
 In the U.S., it makes up only 0.01% of all HIV cases, and those are primarily people
from West Africa.
 It's harder to transmit HIV-2 from person to person, and it takes longer for the infection
to turn into AIDS.
 HIV constantly makes copies of itself. Some strains multiply faster and can be passed
from person to person more easily than others.

5. Groups of HIV-1
Group M (Major)
strains: A, B, C, D,
F, G, H, J, and K
Groups N
small group of
people in
Cameroon
Groups O
group has almost
as many variations
as the M
Groups P
newest group of
HIV-1
The B strain is the most common in the U.S. Worldwide, the most common
HIV strain is C

6. Virus Structure
• HIV is a typical retrovirus with a small RNA genome of 9300 base pairs.
Two copies of the genome are contained in a nucleocapsid core
surrounded by a lipid bilayer, or envelope that is derived from the host
cell plasma membrane .
• The viral genome encodes three major
1) gag
2) pol
3) env
 gag encodes a polyprotein that is processed to release the major structural
proteins of the virus;

7.  pol overlaps gag and encodes
three important enzyme activities (an RNA-dependent DNA polymerase
or reverse transcriptase with RNAase activity, protease, and the viral
integrase
 env encodes the large transmembrane envelope protein responsible for
cell binding and entry.
 Several small genes encode regulatory proteins that enhance virion
production or combat host defenses. These include tat, rev, nef, and
vpr.

9. Virus Life Cycle
 Understanding the HIV life cycle is crucial to understanding the rational therapy of
HIV infection.
 HIV tropism is controlled by the envelope protein gp160 (env). The major target for
env binding is the CD4 receptor present on lymphocytes and macrophages,
although cell entry also requires binding to a coreceptor, generally the chemokine
receptors CCR5 or CXCR4.
 CCR5 is present on macrophage lineage cells.
 A shift from CCR5 to CXCR4 utilization is associated with advancing disease, and
the increased affinity of HIV-1 for CXCR4 allows infection of T-lymphocyte lines.

10. How the Virus Causes Disease

12. What Are the Stages of HIV Infection?
Without treatment, HIV advances in stages, overwhelming the immune
system and getting worse over time.
The three stages of HIV infection are:
(1) acute HIV infection
(2) clinical latency
(3) AIDS (acquired immunodeficiency syndrome).

13. Acute HIV Infection Stage
Within 2 to 4 weeks after infection, many, but not all, people
develop flu-like symptoms, often described as “the worst flu
ever.” Symptoms can include fever, swollen glands, sore
throat, rash, muscle and joint aches and pains, and headache.
This is called “acute retroviral syndrome” (ARS) or “primary
HIV infection,” and it’s the body’s natural response to the HIV
infection

14. Clinical Latency Stage
After the acute stage of HIV infection, the disease moves into
a stage called the “clinical latency” stage. “Latency” means a
period where a virus is living or developing in a person
without producing symptoms. During the clinical latency
stage, people who are infected with HIV experience no
symptoms, or only mild ones. (This stage is sometimes called
“asymptomatic HIV infection” or “chronic HIV infection.”)

15. AIDS
This is the stage of HIV infection that occurs when the immune
system is badly damaged and become vulnerable to opportunistic
infections. When the number of your CD4 cells falls below 200 cells
per cubic millimeter of blood (200 cells/mm3), it is considered to
have progressed to AIDS. (In someone with a healthy immune
system, CD4 counts are between 500 and 1,600 cells/mm3.) It is also
considered to have progressed to AIDS if you develop one or more
opportunistic illnesses, regardless of your CD4 count.

16. What tests are used to diagnose HIV?
1. Antibody/antigen tests -Antibody/antigen tests are the most commonly used tests.
They can show positive results typically within 18–45 days after someone initially
contacts HIV
2. Antibody tests
These tests check the blood solely for antibodies. Between 23 and 90 days after
transmission, most people will develop detectable HIV antibodies, which can be found in
the blood or saliva
OraQuick HIV Test. An oral swab provides results in as little as 20 minutes.
Home Access HIV-1 Test System. After the person pricks their finger, send a blood sample to a
licensed laboratory.

17. HIV is transmitted through bodily fluids that
include:
1) blood
2) semen
3) vaginal and rectal fluids
4) breast milk

18. Anti – HIV regimen
Available agents and formulations constitute several
thousand possible regimens. Knowing the essential
features of the pathophysiology of this disease and
how chemotherapeutic agents affect the virus and the
host is critical in developing a rational approach to
therapy.

20. Drug therapy for HIV
For therapy various classes of drug used either individually or in
combination
1) Nucleoside and nucleotide reverse transcriptase inhibitors
2) Non-Nucleoside reverse transcriptase inhibitor
3) HIV protease inhibitor
4) Entry inhibitor
5) Integrase inhibitor

21. 1)Nucleoside and nucleotide reverse transcriptase
inhibitors (NRTI)
NRTIs prevent infection of susceptible cells but
do not eradicate the virus from cells that already
harbor integrated proviral DNA.
Nearly all patients starting antiretroviral
treatment do so with at least one agent from this
class.

24. Nonnucleoside Reverse Transcriptase
Inhibitors
The NNRTIs include a variety of chemical substrates that bind to a hydrophobic
pocket in the p66 subunit of the HIV-1 reverse transcriptase, in a
site distant from the active site. These compounds induce a
conformational change in the 3-dimensional structure of the enzyme that
greatly reduces its activity, and thus they act as noncompetitive inhibitors.
Because the binding site for NNRTIs is virus-strain specific, the
approved agents are active against HIV-1 but not HIV-2 or other retroviruses
and should not be used to treat HIV-2 infection

26. Drugs Therapeutic use Clinical pharmacology

27. HIV Protease Inhibitors
The HIV PIs are peptide-like chemicals that competitively inhibit the
action of the virus aspartyl protease . This protease is a
homodimer consisting of two 99-amino-acid monomers; each monomer
contributes an aspartic acid residue that is essential for catalysis. The
preferred cleavage site for this enzyme is the N-terminal side of proline
residues, especially between phenylalanine and proline.

29. Drugs Therapeutic use Clinical pharmacology

31. Entry Inhibitors
The two drugs available in this class, enfuvirtide and maraviroc, have different
mechanisms of action. Enfuvirtide inhibits fusion of the viral and cell membranes
mediated by gp41 and CD4 interactions.
Maraviroc is a chemokine receptor antagonist and binds to the host cell CCR5
receptor to block binding of viral gp120

33. Integrase Inhibitors
Chromosomal integration is a defining characteristic of retrovirus life cycles and
allows viral DNA to remain in the host cell nucleus for a prolonged period of
inactivity or latency. Because human DNA is not known to undergo
excision/reintegration, this process is an excellent target for selective antiviral
intervention. The HIV integrase inhibitors prevent formation of covalent bonds
between host and viral DNA—a process known as strand transfer. In clinical trials,
HIV integrase inhibitors produce a more rapid decline in plasma
viral RNA over the first 3–4 months of therapy than other antiretroviral
agents and are generally better tolerated than comparator agents.

35. Drugs Therapeutic use Clinical pharmacology

36. Drugs HIV-1 HIV-2 Interaction
Zidovudine + + Probenecid
fluconazole
atovaquone
valproic acid
Stavudine + + ethambutol,
isoniazid, phenytoin,
and vincristine
Lamivudine + +
Abacavir + ethanol
Tenofovir + + didanosine
Didanosine + + ciprofloxacin and
indinavir

37. Drugs HIV-1 HIV-2 Interaction
Nevirapine + Glucocorticoids
Methadone
Efavirenz + phenobarbitalphenytoin
carbamazepine
methadone
Phenobarbital
Rilpivirine + rifampin carbamazepine,
phenobarbitalphenytoin
Etravirine + Tipranavir
Ritonavir
fosamprenavir
Atazanavir
Delavirdine + Delavirdine increases the
plasma concentrations of
most HIV PIs

38. Drugs HIV-1 HIV-2 Interaction
Saquinavir + + rifampin, phenytoin
carbamazepine
Ritonavir + + midazolam, triazolam,
fentanyl, and ergot
Derivatives
disulfiram metronidazole
Fosamprenavir + + ritonavir
Lopinavir + + disulfiram metronidazole
amprenavir
nevirapine efavirenz
Maraviroc + +
Enfuvirtide + coadministered drugs.

39. Drugs HIV-1 HIV-2 Interaction
Raltegravir + + Rifampin antacids
sucralfate
Elvitegravir + + cobicistat elvitegravir
Rifamycins
oral divalent cations
Dolutegravir + + double concentrationof
metformin

40. WHO-ART regimens in
different set of population

41. Abbrevation
Lamivudine (3TC)– both HIV
Tenofovir (TDF)– NRTI used for pre exposure prophylaxis
Efavirenz (EFV)–
Zidovudine(AZT) – prevent mother to child
Nevirapine(NVP) – hiv 1
Stavudine (d4t)– reduce amount of virus in body
Lopinavir (LPV/r)- prental HIV

42. First-line ART for adults
Consolidated ARV guidelines, June 2013
New recommendations
First-line ART should consist of two nucleoside reverse-transcriptase inhibitors
(NRTIs) plus a non-nucleoside reverse-transcriptase inhibitor (NNRTI)
• Tenofovir + lamivudine + Efavirenz as a fixed-dose combination is
recommended as the preferred option to initiate ART (strong
recommendation, moderate-quality evidence).
• If Tenofovir + lamivudine + Efavirenz is contraindicated or not available,
one of the following options is recommended:
• Zidovudine + lamivudine + Efavirenz
• Zidovudine + lamivudine + Nevirapine
• Tenofovir + lamivudine + Nevirapine (strong recommendation,
moderate-quality evidence).

43. First-line ART for pregnant and breastfeeding women and ARV
drugs for their infants
Consolidated ARV guidelines, June 2013
New recommendations
A once-daily fixed-dose combination of TDF + 3TC (or FTC) +
EFV is recommended as first-line ART in pregnant and
breastfeeding women, including pregnant women in the first
trimester of pregnancy and women of childbearing age.
If infants are receiving replacement feeding, they should be
given four to six weeks of infant prophylaxis with daily NVP (or
twice-daily AZT).

44. First-line ART for children younger than three years of age
Consolidated ARV guidelines, June 2013
New recommendations
A LPV/r-based regimen should be used as first-line ART for all
children infected with HIV younger than three years (36 months)
of age, regardless of NNRTI exposure. If LPV/r is not feasible,
treatment should be initiated with a NVP-based regimen (strong
recommendation, moderate-quality evidence).
Where viral load monitoring is available, consideration can be
given to substituting LPV/r with an NNRTI after virological
suppression is sustained(conditional recommendation, low-
quality evidence).

46. First-line ART for children three years and older (including adolescents)
Consolidated ARV guidelines, June 2013
New recommendations
For children infected with HIV three years and older (including adolescents), EFV is the
preferred NNRTI for first-line treatment and NVP is the alternative(strong
recommendation, low-quality evidence).
For children infected with HIV three years to less than 10 years old (or adolescents less
than 35 kg), the NRTI backbone for an ART regimen should be one of the following, in
preferential order:
ABC + 3TC
AZT or TDF + 3TC (or FTC)

47. For adolescents infected with HIV (10 to 19 years old) weighing 35 kg or more, the
NRTI backbone for an ART regimen should align with that of adults and be one of the
following, in preferential order:
TDF + 3TC (or FTC)
AZT + 3TC
ABC + 3TC

49. T B co-treatment in children with HIV
Consolidated ARV guidelines, June 2013
TB is one of the most common opportunistic infections affecting
children with HIV. Selecting regimens that are compatible with
TB therapy is therefore essential. Interactions between
rifampicin and LPV/r or NVP mean that co-treatment in children
under three years is challenging, but a recent large randomized
controlled trial of ART in children has generated preliminary
evidence on the efficacy of triple nucleoside therapy which,
despite limited data in the context of TB co-treatment, offers a
suitable option for children who require TB treatment while
already receiving ART

51. Drug drug interaction pertaining to two drug antiretroviral combination
Agent Drugs that increase serum levels Drugs that decrease serum level
Atazanavir Ritonavir Didanosine, efavirenz,
elvitegravir/cobicistat, etravirine,
fosamprenavir, nevirapine, stavudine,
tenofovir, tipranavir
Darunavir Indinavir Efavirenz, lopinavir/ritonavir, saquinavir
Delavirdine Didanosine, fosamprenavir
Didanosine Tenofovir Atazanavir, ritonavir
Indinavir Darunavir, delavirdine, nelfinavir, ritonavir Didanosine, efavirenz, etravirine, nevirapine
Maraviroc Atazanavir, darunavir, lopinavir/ritonavir,
nevirapine,
saquinavir, ritonavir
Efavirenz, etravirine, tipranavir
Ritonavir Darunavir Didanosine, efavirenz, fosamprenavir,
nelfinavir, nevirapine,
tipranavir

52. Global Data on HIV

53. Data and statistics
The WHO country profiles provide an overview of latest
available data on the HIV epidemic in low- and middle-income
countries as of 2018. Besides demographic and
epidemiological HIV data, these profiles also include
information on country's HIV policies and plans; antiretroviral
therapy coverage and pricing; elimination of mother-to-child
transmission of HIV and syphilis; paediatric HIV; key
populations; and 90-90-90 progress towards 2020 targets.

56. Number of new HIV infections Data by country

57. Number of deaths due to HIV/AIDS
Estimates by country

59. Antiretroviral therapy coverage
Data and estimates by country

60. Prevention of mother-to-child transmission
Estimates by country

67. Recent advances
1) November 2018 – drug known as gammora found to be 99% effective
against HIV
2) Sep 2018 - broadly neurtralizing antibodies or bNAbs (pronounced bee-
nabbs), were found to be both safe and more effective than any previously
tested antibody therapy
3BNC117 and 10-1074 attack HIV from two different angles, the
researchers suspected that administering the two drugs together might evade
resistance--an approach first tested in animals
3) July 2017 - Johnson & Johnson announces encouraging first-in-human
clinical data for investigational HIV preventive vaccine

68. Reference
1) Bertram Katzung , Basics and clinical pharmacology ,14th ed, Mc Graw Hill
Education,page-863
2) Goodman and Gillman , The Pharmacological Basis of Therapeutics , 13th ed, Mc
Graw Hill Education,page-1139
3) https://www.who.int/hiv/data/en/
4) https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-
aids
5) https://www.webmd.com/hiv-aids/types-strains-hiv#1