AIDS SOCIETY OF INDIA

Initial Regimen for ART-naïve HIV-1 Infected Patients in India

• Regimen selection should be individualized, taking into consideration a number of factors including: co-morbidity or conditions such as tuberculosis, liver disease, depression or mental illness, cardiovascular disease, adherence potential; cost of treatment and affordability, dosing convenience including pill burden, dosing frequency, storage requirement, and food and fluid considerations; potential adverse events; gender; and pregnancy potential.
• An NNRTI based regimen is recommended as first line therapy for most ART-naïve HIV infected patients. Recommended regimen for initial therapy in treatment naïve patients are depicted in Table 2.
• NNRTI- based regimens are potent and have shown comparable efficacy to unboosted PI based regimens and are superior to 3 NRTI based regimens.29-31 NNRTI-based regimens have the advantage of lower pill burden and are cheaper compared.

Recommended NNRTI-Based Reimens for India(1-NNRTI + 2-NRTIs)

*Stavudine is considered as an alternative ARV because it is associated with a high incidence of adverse events including peripheral neuropathy, pancereatitis, hyperlactatemia and lipodystrophy and dyslipidemia that may not be reversible on treatment discontinuation.26-28 to most of the PI-based regimens. Use of NNRTI-based regimens as initial therapy can preserve the PIs for later use, reduce or delay patient exposure to some of the adverse events more commonly associated with PIs.

• The major disadvantage of currently available NNRTIs is their low genetic barrier for development of resistance. These agents only require a single mutation to confer resistance (mutations at codons 103, 181, 106, see section on treatment failure), and cross-resistance often develops across the entire class. 32 As a result, patients who fail this initial regimen may lose the utility of other NNRTIs and/or may transmit NNRTI-resistant virus to others.
• The major short-term adverse event associated with efavirenz is CNS disturbances. Usually these are self-limiting and wane off within two to four weeks and do not warrant discontinuation ofefavirenz.33 Patient should be forewarned about these before initiating treatment. Efavirenz should be avoided during pregnancy (especially during the first trimester) or in women who are planning to conceive or women who are not using effective and consistent contraception, as it is associated with neural tube defects in the baby.
• Nevirapine may be used as an alternative to efavirenz for the initial NNRTI-based regimen in adult females with pre-treatmentCD4+ T cell counts <250 cells/mm3 or adult males with pre-treatment CD4+ T cell counts <400 cells/mm3. 34 Symptomatic, sometimes serious or life-threatening hepatic events were observed with higher frequency in women with pre-treatment CD4+ T cell counts >250/mm3 and men with pre-treatment CD4+ T cell counts>400/mm3.35 Nevirapine should be used with caution in patients already having background liver disease like hepatitis B and C co-infected patients. When starting nevirapine, a 14-day lead-in period at a dose of 200mg once daily should be prescribed before increasing to the maintenance dose of 200mg twice daily.
• Efavirenz is the only NNRTI, which can be concomitantly used with rifampicin. An efavirenz-based regimen is recommended in HIV infected patients receiving rifampicin based antituberculous therapy (see section on drug- drug interactions and HIV and TB).
• A large randomized controlled trial has shown similar efficacy between nevirapine and efavirenz based first line regimens, although there were differences in safety profile.36 Hence the choice between using NVP and EFV is based on toxicity concerns.37