2. How to carry out post-test counselling
Test result negative
Discuss transmission and
need for behaviour
modification
Advise second test 3 months
after last exposure
Test result positive
• Explain meaning of result
• Organise medical follow-up
• Stress importance of disclosure
• Explain value of antiretroviral therapy
• Provide written information and useful
Internet resources
• Discuss confidentiality issues
• Organise emotional and practical
support
• Facilitate notification of sexual partners
3. Viral transmission
Acute retroviral
syndrome: 2-3 weeks
Seroconversion: 2-20
weeks
Asymptomatic chronic
HIV infection: 8 yrs
Symptomatic HIV
infection/AIDS 1.3 yr
Stages of
Untreated HIV
Infection
4. Type of HIV Progression
Proportion
among PLHIV
CD4 cells drop Characteristic features
Typical progression 50-70% 35-50 CD4
cells/year
Develop end-stage disease within 8-10
years after seroconversion
Rapid progression 10% 50 CD4
cells/month
Develop symptoms of AIDS or end-stage
HIV disease within 2-3 years after
infection & also in children
Slow progression 5-15% Very slow Remain free of symptoms of AIDS for
more than 10-15 years
Long term Non-
progression
5-10% Stable CD4 Living with HIV for >15 years and have
stable CD4+ counts of ≥ 500 cells/mm³
blood. No HIV related diseases and no
previous ART
5. ANTIRETROVIRAL THERAPY
The cornerstone of medical management of HIV infection is combination antiretroviral
therapy, or cART. Suppression of HIV replication is an important component in
prolonging life as well as in improving the quality of life of pts with HIV infection.
Antiretroviral drugs fall into five main categories: those that inhibit the viral reverse
transcriptase enzyme, those that inhibit the viral protease enzyme, those that inhibit
viral entry, and those that inhibit the viral integrase enzyme.
6. The Goals of Antiretroviral Therapy
(ART)
To achieve maximal
and most durable
suppression of viral
replication
Improve the
quantity and
quality of life
Improve the CD4
count to over 200
cells/mm3
To prevent
emergence of drug
resistant mutants
7. Goals Principle
Clinical To prolong life & improve quality of life
Virological Greatest possible sustained reduction in viral load
Immunological Immune reconstitution is both: 1.Quantitative (CD4 within normal
range) 2.Qualitative (pathogen specific immune response)
Therapeutic Rational sequencing of drugs to achieve previous 3 goals while:
1.Maintaining future therapeutic options
2.Minimising drug toxicities & side effects 3.Maximising treatment
adherence
Epidemiological Reduce HIV transmission
8. MANAGEMENT OF HIV FALLS UNDER THREE MAJOR CATEGORIES
1. TREATMENT/MANAGEMENT OF HIV-AIDS
2. POST EXPOSURE PROPHYLAXIS(P.E.P)
3. TREATMENT OF ADJOINING CONDITIONS
- Infections-Bacterial, fungal, Viral infections
-NEOPLASIAS -misc.( recurrent aphthous ulcers, xerostomia,
salivary Gland enlargement)
9. MANAGEMENT OF HIV-AIDS
• The management of HIV/AIDS normally includes the use of multiple
antiretroviral drugs in an attempt to control HIV infection.
• •There are several classes of antiretroviral agents that act on different
stages of the HIV life-cycle. The use of multiple drugs that act on
different viral targets is known as highly active antiretroviral therapy
(HAART).
HAART decreases the patient's total burden of HIV, maintains
function of the immune system, and prevents opportunistic
infections that often lead to death.
• •Treatment has been so successful that in many parts of the world,
HIV has become a chronic condition in which progression to AIDS is
increasingly rare.
11. Generic Name Dose Adverse effects
Tenofovir (TDF) 300 mg once daily Renal toxicity, bone
demineralization
Lamivudine (3TC) 150 mg twice daily or 300 mg once
daily
Minimal toxicity, rash (though very
rare)
Abacavir (ABC) 300 mg twice daily or 600 mg once
daily
Hypersensitivity reaction in 3 to 5%
(can be fatal), fever,
rash, fatigue, nausea, vomiting,
anorexia, RS- (sore throat, cough,
shortness of breath)
Nevirapine 200 mg once daily for 14 days,
followed by 200 mg twice daily
Hepatitis (usually within 12 weeks);
Stevens Johnson syndrome (SJS)
and Toxic Epidermal Necrolysis
(TEN).
Ritonavir 100 mg twice daily diarrhoea, nausea, vomiting,
abdominal pain
12. Nucleoside/Nucleotide Analogues
These agents act by causing premature DNA-chain termination during the reverse
transcription of viral RNA to proviral DNA and should be used in combination with
other antiretroviral agents. The most common usage is together with another
nucleoside/nucleotide analogue and a nonnucleoside reverse transcriptase inhibitor
or protease inhibitors
13. Nonnucleoside Reverse Transcriptase Inhibitors
These agents interfere with the function of HIV-1 reverse transcriptase by binding
to regions outside the active site and causing conformational changes in the
enzyme that render it inactive. Five members of this class, nevirapine, delavirdine,
efavirenz, etravirine, and rilpivirine are currently available for clinical use. These
drugs are licensed for use in combination with other antiretrovirals.
14. Protease Inhibitors
These drugs are potent and selective inhibitors of the HIV-1 protease enzyme and
are active in the nanomolar range. As with other classes of antiretroviral drugs, the
protease inhibitors should be used only in combination with other antiretroviral
drugs.
15. HIV Entry Inhibitors
These agents act by interfering with the binding of HIV to its receptor or co-
receptor or by interfering with the process of fusion. A variety of small molecules
that bind to HIV-1 co-receptors are currently in clinical trials. The first drugs in
this class to be licensed are the fusion inhibitor enfuvirtide and the entry inhibitor
maraviroc.
16. HIV Integrase Inhibitors
These drugs interfere with the integration of proviral DNA into the host cell genome.
The first agent in this class, raltegravir, was approved in 2007 for use in treatment-
experienced pts. Three other integrase inhibitors, dolutegravir, elvitegravir, and
bictegravir are also licensed.
17. Principles of Therapy of HIV Infection
1. Ongoing HIV replication leads to immune system damage, progression to AIDS,
and systemic immune activation.
2. Plasma HIV RNA levels indicate the magnitude of HIV replication and the rate of
CD4+ T cell destruction. CD4+ T cell counts indicate the current level of competence
of the immune system.
3. Maximal suppression of viral replication is a goal of therapy; the greater the
suppression, the less likely the appearance of drug-resistant quasispecies.
4. The most effective therapeutic strategies involve the simultaneous initiation of
combinations of effective anti-HIV drugs with which the pt has not been previously
treated and that are not cross-resistant with antiretroviral agents that the pt has
already received.
5. The antiretroviral drugs used in combination regimens should be used according to
optimum schedules and dosages.
6. Women should receive optimal antiretroviral therapy regardless of pregnancy
status.
7. The same principles apply to children and adults. The treatment of HIV-infected
children involves unique pharmacologic, virologic, and immunologic considerations.
8. Compliance is an important part of ensuring maximal effect from a given regimen.
The simpler the regimen, the easier it is for the pt to be compliant.
18. Selecting antiretroviral regimens
• The standard combination antiretroviral regimens are two NRTIs together
with an NNRTI, protease inhibitor (PI) or integrase inhibitor.
• Dual NRTI combinations are usually emtricitabine or lamivudine (they have
the same mechanism of action and so are never combined), together with
one of abacavir, tenofovir or zidovudine.
• It is possible to construct effective regimens without NRTIs if there is
intolerance or resistance to the NRTIs.
• Currently used PIs should always be administered with ritonavir.
19. Initial Combination Regimens Recommended for Most Treatment-Naïve
Pts Regardless of HIV RNA Level or CD4 Count
Dolutegravir + tenofovir* + emtricitabine**
Raltegravir + tenofovir* + emtricitabine**
Bictegravir + tenofovir* + emtricitabine**
Elvitegravir + cobicistat + tenofovir* + emtricitabine**
Dolutegravir + abacavir + lamivudine** (only for those
HLA-B*5701 negative)
20. Indications for Changing Antiretroviral Therapy in Pts with HIV Infection
1. Less than a 1-log drop in plasma HIV RNA by 4 weeks following the initiation of
therapy
2. A reproducible significant increase (defined as threefold or greater) from the
nadir of plasma HIV RNA level not attributable to intercurrent infection, vaccination,
or test methodology
3. Persistently declining CD4+ T cell numbers
4, Clinical deterioration
5. Side effects
21. HIV AND HEALTH CARE WORKER
There is a small but definite risk to health care workers of acquiring HIV infection via
needle stick exposures, large mucosal surface exposures, or exposure of open
wounds to HIV-infected secretions or blood products.
The risk of HIV transmission after a skin puncture by an object contaminated with
blood from a person with documented HIV infection is ∼0.3%, compared with a 20–
30% risk for hepatitis B infection from a similar incident.
U.S. Public Health Service guidelines for postexposure prophylaxis recommend a
combination of two nucleoside analogue reverse transcriptase inhibitors plus a third
drug given for 4 weeks for high-risk or otherwise complicated exposures. Regardless
of which regimen is used, treatment should be initiated as soon as possible after
exposure and take into count any available resistance data on the infecting virus.
Prevention of exposure is the best strategy and includes following universal
precautions and proper handling of needles and other potentially contaminated
objects.
22. POST EXPOSURE PROPHYLAXIS (THE EMERGENCY PILL)
• • If an individual believes they have been exposed to the virus within
the last 72 hours (three days), anti-HIV medication, called PEP (post-
exposure prophylaxis) may stop infection.
The treatment should be taken as soon as possible after contact
with the virus.
• • PEP is a very demanding treatment lasting four weeks. It is also
associated with unpleasant side effects (diarrhea, malaise, nausea,
weakness and fatigue).
• • After a positive HIV diagnosis, regular blood tests are necessary to
monitor the progress of the virus before starting treatment.
The therapy is designed to reduce the level of HIV in the blood.
23. •CLINICAL MONITORING
• Monthly clinical evaluation
Body weight, overall well-being, any new symptoms / signs, for symptom
screening for TB at every visit
Monthly Treatment Adherence-Evaluation--pill count, self-reported
adherence
Adherence to ART must be assessed at each visit and adherence must be
reinforced through counselling at each visit
Adverse reactions of ART / OI drugs
Drug-drug interactions, look for all concomitant drug use (prescribed and
over the counter)
IRIS (Immune Reconstitution Inflammatory Syndrome)
24. Adverse effects
• Each class and individual antiretroviral carries unique risks of adverse
side effects.
NRTIs
The NRTIs can interfere with mitochondrial DNA synthesis and lead to
high levels of lactate and lactic acidosis, liver steatosis, peripheral
neuropathy, myopathy and lipoatrophy.
Current first line NRTIs such as lamivudine/emtrictabine, tenofovir, and
abacavir are less likely to cause mitochondrial dysfunction.
NNRTIs
NNRTIs are generally safe and well tolerated. The main reason for
discontinuation of drugs is neuro-psychiatric effects including suicidal
ideation. Nevirapine can cause severe hepatotoxicity, especially in
women with high CD4 counts.
25. Protease inhibitors
Protease inhibitors (PIs) are often given with ritonavir, a strong inhibitor
of cytochrome P450 enzymes, leading to numerous drug-drug
interactions. They are also associated with lipodystrophy, elevated
triglycerides and elevated risk of heart attack.
Integrase inhibitors
Integrase inhibitors (INSTIs) are among the best tolerated of the
antiretrovirals with excellent short and medium term outcomes. Given
their relatively new development there is less long term safety data.
They are associated with an increase in creatinine kinase levels and
rarely myopathy.
26. PREVENTION
Education, counseling, and behavior modification along with the consistent and
correct use of condoms in risk situations remain the cornerstones of HIV
prevention efforts.
Avoidance of shared needle use by IDUs is critical. If possible, breast-feeding
should be avoided by HIV-positive women, as the virus can be transmitted to
infants via this route. In societies where withholding of breast-feeding is not
feasible, treatment of the mother, if possible, greatly decreases the chances of
transmission.
Adult male circumcision in the prevention of acquisition of heterosexually
transmitted HIV infection in men. In addition, pre-exposure prophylaxis (PrEP) with
Truvada, a single pill formulation containing emtricitabine and tenofovir that has
been approved for PrEP in men who have sex with men and in heterosexual men
and women engaging in risk behaviors, has proven to be an effective means of
prevention of HIV acquisition.
Finally, treatment of the HIV-infected partner in heterosexual discordant couples
has proved highly effective in preventing transmission of HIV to the uninfected
partner.
27. Prophylaxis against Secondary Infections
Primary prophylaxis is clearly indicated for P. jiroveci pneumonia (especially
when CD4+ T cell counts fall to <200 cells/µL)
For M. avium complex infections in pts with CD4+ T cell counts <50 cells/µL,
and for M. tuberculosis infections in pts with a positive PPD or anergy if at
high risk of TB.
Vaccination with influenza and pneumococcal polysaccharide vaccines is
generally recommended for all pts and may need to be repeated in those with
CD4+ T cell counts <200/µL when their counts increase to >200/µL.
Secondary prophylaxis, when available, is indicated for virtually every
infection experienced by HIV-infected pts until they have significant
immunologic recovery.
28. UNAIDS 90,90,90 STRATEGY IN HIV
UNAIDS “90-90-90” strategy calls for 90% of HIV-infected individuals to be
diagnosed by 2020, 90% of whom will be on anti-retroviral therapy (ART) and
90% of whom will achieve sustained virologic suppression. Reaching these
targets by 2020 will reduce the HIV epidemic to a low-level endemic disease by
2030.
29. VACCINE
A clinical trial conducted in Thailand demonstrated moderate (31%
effective) protection against acquisition of HIV infection. However,
this modest degree of efficacy does not justify deployment of the
vaccine; active investigation continues in the pursuit of a safe and
effective vaccine against HIV, including focusing on the induction
of broadly neutralizing antibodies to HIV.