HAART: What's Best in Treatment-Naive HIV Patients?

With the many agents available for highly active antiretroviral therapy (HAART), selecting the best regimen in HAART-naïve patients is not an easy task.

HAART is a multipronged attack that combats HIV morbidity, progression, and mortality using multiple combinations of drugs, many of which have significant side effects. The cornerstone of successful HAART is patient adherence, which may be difficult to achieve in patients experiencing adverse events that accompany these drugs.

Recently, a team of multinational researchers compared standard recommendations from established guidelines’ newer antiretroviral drug classes, and found better tolerability and efficacy in the latter. They conducted a systematic review and meta-analysis of randomized clinical trials, comparing recommended antiretroviral regimens in treatment-naïve adults and adolescents with HIV. The significant primary outcomes were viral suppression and discontinuation due to adverse events.

Integrase strand transfer inhibitors (INSTIs) dolutegravir and raltegravir resulted in better viral suppression at 48 weeks compared with the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz.

Compared with standard-dose efavirenz, low-dose efavirenz and the INSTIs were less likely to be discontinued due to adverse events.

Current WHO guidelines on the use of antiretroviral drugs for the treatment and prevention of HIV infection recommend a first-line antiretroviral regimen that includes an NNRTI and 2 NRTIs. Efavirenz in combination with tenofovir and lamivudine (or emtricitabine) is recommended as the preferred regimen to initiate HAART. Results from the authors’ analysis indicate that dolutegravir and low-dose efavirenz had better tolerability and efficacy than the recommended standard-dose efavirenz.

The study’s authors acknowledge that efavirenz plus 2 NRTIs remains safe and efficacious, but indicate that the reported benefits of dolutegravir and low-dose efavirenz signal the potential for a change in future guidelines.

The WHO-recommended regimen is available as a fixed-dose combination with once daily dosing. Dolutegravir is also available as a fixed-dose combination with emtricitabine and abacavir. However, HLA-B*5701 screening for abacavir hypersensitivity reactions complicates the use of this formulation, especially in low- and middle-income countries.

This study appears in the November 2016 issue of The Lancet HIV.