Antiretroviral regimens for patients with HIV who fail first-line antiretroviral therapy.

BACKGROUND: 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. OBJECTIVES: 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. SEARCH STRATEGY: Electronic databases and conference proceedings were searched with relevant search terms without limits to language. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

Prevention of diarrhoea in children with HIV infection or exposure to maternal HIV infection.

BACKGROUND: Diarrhoea is a major cause of morbidity and mortality among infants and children worldwide, especially in low- and middle-income countries. Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is a condition that similarly disproportionately affects low- and middle-income countries; of the nearly 2.1 million children under age 15 years living with HIV/AIDS, the large majority reside in sub-Saharan Africa. Infants and children with HIV infection have more frequent and more severe diarrhoea than children without HIV. Interventions including vitamin A, zinc and cotrimoxazole may contribute substantially to preventing diarrhoea in children with HIV infection or exposure to HIV. OBJECTIVES: We perform a systematic review of randomised controlled trials and nonrandomised studies that examine the effectiveness of vitamin A, zinc and cotrimoxazole on mortality and morbidity from diarrhoea in HIV-infected and -exposed infants and children. SEARCH STRATEGY: Electronic databases including Pubmed, Central and EMBASE were searched without limits to language from 1980 to April 2010. Conference database searches were performed, experts were contacted and bibliographies were handsearched. SELECTION CRITERIA: Randomised controlled trials (RCTs) and nonrandomised studies (NRSs) that examined the effectiveness of the three interventions were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed citations for eligibility and double-extracted included studies. Assessment of bias of individual studies was performed independently by both reviewers. Only two summary estimates were performed due to heterogeneity in study design and interventions. MAIN RESULTS: Four RCTs were identified for vitamin A. One RCT was identified for zinc. One RCT and two NRSs were identified for cotrimoxazole. Vitamin A reduced mortality overall in children with HIV infection (four studies). A pooled estimate of three studies for reduction in mortality from vitamin A compared to placebo had a relative risk (DerSimonian and Laird method, random effects) of 0.50 (95% confidence interval (CI): 0.31 to 0.79) in 267 patients. Diarrheoa-specific mortality did not reach statistical significance and diarrhoeal morbidity outcomes were variable in three trials. Zinc supplementation reduced the number of physician visits for watery diarrhoea in one trial. Cotrimoxazole reduced mortality and hospitalisations compared to placebo in one RCT, although diarrhoea-specific morbidities were not significant. AUTHORS' CONCLUSIONS: Vitamin A shows benefits in reduction of mortality in HIV-infected children. The effect of vitamin A on children with HIV exposure is not clear and needs further review. Zinc and combination vitamin A, zinc and micronutrient supplementation did not show an effect compared to vitamin A alone in children with HIV infection. Cotrimoxazole reduced mortality and some morbidity in children with HIV infection. Further research may clarify the effects of these interventions on morbidity from diarrhoea and in the population of children with HIV exposure.