TREATMENT OF HIV

PRINCIPLES OF TREATMENT

NUCLEOSIDE/NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS Zidovudine Lamivudine Emtricitabine Abacavir Tenofovir (Nucleotide reverse transcriptase inhibitors)

NON NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS Nevirapine Efavirenz Rilpivirine Etravirine

PROTEASE INHIBITORS Ritonavir Darunavir Atazanavir

ENTRY INHIBITORS Enfuvirtide Maraviroc

INTEGRASE INHIBITORS Raltegravir Dolutegravir Elvitegravir

CLASSES OF DRUGS (NACO)

WHEN TO START TREATMENT ? When the CD4 Count is <350/cumm !! (As recommended by the US Dept of Health and Health Services) Trials are underway to know the role of ART in CD4 counts >=350/cumm

WHAT NACO SAYS

SPECIAL MENTION REGARDING NEVIRAPINE BASED REGIMENS

WHY SUCH A FUNNY REGIMEN FOR NEVIRAPINE? The lead-in period for NVP dosing at 200 mg once daily for the first two weeks produces adequate NVP levels. Due to enzyme auto-induction, NVP levels decline over two weeks and an increase in the dosage to 200 bid is required to maintain adequate levels. Starting with the full NVP dosage without a lead-in period results in a very high serum concentration of the drug and increases the risk of hepatotoxicity and rash. If NVP is restarted after more than 14 days of treatment interruption (due to whatever reason, e.g. elevated liver enzymes), the lead-in dosing is again necessary. PIs are not recommended in first-line regimen because their use in an initial treatment regimen essentially rules out second-line regimen options

ROLE OF EFAVIRENZ? In PLHIV receiving concurrent Rifampicin-containing anti-TB regimen (ATT) for the duration of the anti-TB treatment. • In cases with clinical or laboratory evidence of hepatic dysfunction, e.g. due to hepatitis B/C co-infection or other causes. • In patients with significant NVP side-effects/toxicity and in whom NVP re-challenge cannot be done. EFV is contraindicated in pregnant HIV-infected women during the first trimester of pregnancy because of concerns of teratogenicity

PROPHYLAXIS WITH COTRIMOXAZOLE

WHEN TO STOP COTRIMOXAZOLE PROPHYLAXIS?

DRUG TOXICITIES

PROPHYLAXIS AGAINST OPPORTUNISTIC INFECTIONS ( OI )

MUTATIONS IN CASE OF RESISTANCE TO ART

ALTERNATIVES IN CASE OF FAILURE OF FIRST LINE ART

HIV + HBV

HIV + HCV

2015 WHO ART RECOMMENDATIONS

START Study The study examined the rates of AIDS and serious AIDS-defining illness or death among people who were randomized to receive immediate ART versus deferring ART until their CD4 count dropped below 350 cells/mm3 Showed a 57% reduction in negative outcomes among those treated early . The study also showed that immediate ART reduced both AIDS-related and non- AIDS-related events, but the benefit was greater for AIDS-related events. Tuberculosis (TB), Kaposi sarcoma and lymphoma — the most common AIDS-related events — all occurred less frequently in the immediate ART group. Cancer rates (combining AIDS and non-AIDS malignancies) were lower in the immediate ART group, but cardiovascular disease rates were similar between groups. These effects were consistent in countries of different income levels and across geographical regions

HPTN 052 Study The HIV Prevention Trials Network (HPTN) 052 study showed that starting ART early reduced the overall risk of HIV sexual transmission to uninfected partners by 93% . 1763 participating couples were randomly assigned to one of two treatment groups. In the first group, the participants living with HIV began ART immediately. In the second group, the participants living with HIV delayed treatment until their CD4 counts fell below 250 cells/mm3 or they were diagnosed with an AIDS-related illness .

COMPARING BENEFITS AND HARM The benefits of earlier ART initiation include fewer events of severe HIV morbidity and disease progression, improved uptake and initial linkage to care, better immune recovery and decreased HIV transmission. However, not all observational studies have consistently demonstrated the beneficial effect of initiating ART at CD4 cell count at or above 500 cells/mm3 on mortality, the incidence of inflammation-related non-AIDS events and ongoing viral replication compared with initiation at CD4 at or below 500 cells/mm3. Follow-up will be needed to evaluate the potential harm and benefits of ART over a lifetime. It is increasingly recognized that, in settings with a high burden of HIV and TB infections, increasing ART coverage is associated with decreasing TB case notifications, and this is likely to improve when ART is started earlier

THE QUESTION OF COST The same modeling exercise indicates that expanding ART eligibility criteria to above 500 cells/ mm3 or regardless of CD4 cell count and linking to HIV care could result in 6–14% fewer people dying from HIV-related causes during the next decade . In this exercise, the vast majority of the impact is caused by programmatic simplification leading to more people initiating ART in a timely manner and therefore avoiding adverse outcomes during the per-ART period rather direct therapeutic benefits. The increased cost of earlier ART would be partly offset by subsequent reduced costs (such as decreased hospitalization and increased productivity) and preventing people from acquiring HIV infection. The modeling results suggest that such a change is likely to be cost-effective in many settings if people initiating ART adhere to treatment and retention in care is maintained. Costs will increase significantly but far less than if the additional outreach interventions required to maintain individuals in pre-ART care are also included .

THANK YOU !!