Highly active antiretroviral therapy (HAART) has greatly reduced the illness and deaths of HIV-infected people worldwide. There are many options for first-line antiretroviral therapy (ART), but second-line therapy is necessary for people who fail the first-line treatment. This review attempted to assess the best ART regimen for HIV-infected people in low- and middle-income countries following treatment failure; however, the review found limited studies addressing this topic. One randomised trial and one abstract of an observational study evaluated whether or not to maintain lamivudine in second-line regimens; both suggested no difference in outcomes. There were no studies comparing boosted PI-containing second-line regimens in patients failing an NNRTI-based first-line regimen, nor any evaluating NRTI combinations after first-line with non-thymidine analog combinations. While such trials are difficult to conduct for a variety of reasons, randomised controlled trails comparing second-line therapies are needed, especially in resource-limited settings.
There is limited evidence to evaluate second-line therapies in patients with HIV who fail first-line treatment with a WHO-recommended regimen. One randomised trial in 136 patients and two observational studies (both of low quality) suggest no difference in virological suppression whether or not lamivudine is maintained in a second-line regimen. While outcomes of second-line regimens with boosted PIs are favourable in general, there are no studies comparing boosted PIs directly in populations starting second-line regimens. Current recommendations are based on available resources and patient- and public-health-level considerations.
Highly active antiretroviral therapy has reduced the morbidity and mortality of patients with HIV/AIDS. A common first-line ART regimen in low-resource settings includes a non-nucleoside reverse transcriptase inhibitor (NNRTI) and two nucleoside reverse transcriptase inhibitors (NRTIs). If treatment failure occurs, a change to second-line therapy is necessary.
This systematic review aimed to assess the optimum antiretroviral regimen for patients with HIV who fail first-line therapy (ART-naive) with a recommended World Health Organization (WHO) first-line regimen.
Electronic databases and conference proceedings were searched with relevant search terms without limits to language.
Randomised controlled trials of HIV-infected adolescent and adult patients administered second-line ART after virologic failure of a first-line regimen were included. Observational studies were included given the insufficient number of trials identified. The primary outcome measure included mortality. Secondary outcome measures included rate of adverse events, change in mean CD4 cell count, clinical resolution of symptoms, proportion of patients achieving undetectable viral load (VL) and acquisition of genotypic mutations.
Two authors assessed each reference for inclusion and exclusion criteria established a priori. Data were abstracted independently using a standardised abstraction form. Risk of bias was assessed for individual studies and the GRADE approach for assessing the quality of evidence across a body of evidence was also applied.
One randomised trial in 136 patients studied maintaining lamivudine in second-line regimens or not. There was no difference in virological outcomes in the group who maintained lamivudine and those who did not in their subsequent regimens. Two other small observational studies reported in abstract form also did not report a difference in the proportion of those with viral suppression after six months and time to HIV-1 RNA suppression among those on a lamivudine (3TC) or emtricitabine (FTC) regimen compared to those on a 3TC/FTC-sparing second-line regimen. There were no trials identified comparing boosted protease inhibitors (PIs) or nucleoside backbone combinations after first-line failure on non-thymidine analog combinations. Observational studies of populations starting ART in resource-limited settings suggest that short-term response on boosted PI-based regimens is encouraging.