SUMMARY: Treatment-naive and treatment-experienced women with HIV achieve antiretroviral therapy (ART) outcomes similar to those of men, according to a meta-analysis of more than 40 randomized clinical trials presented at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010) last month in Boston. Efficacy of all antiretroviral classes was similar for women and men, but women were less likely to prematurely stop study drugs due to treatment failure.

By Liz Highleyman

Since the early years of the HIV/AIDS epidemic, researchers and advocates have debated whether HIV positive women benefit as much as men from antiretroviral treatment. Some studies, especially those from the early ART era, suggested that women might not do as well, but this may be a reflection of socioeconomic status, less access to care, or other confounding factors.

Investigators with the U.S. Food and Drug Administration (FDA) conducted a medical literature search and performed a meta-analysis of efficacy outcomes among women in studies of antiretroviral drugs published between 2000 and 2008.

The researchers included registrational randomized clinical trials (RCTs) reporting 48-week efficacy outcomes with viral suppression defined as HIV RNA < 50 copies/mL. These trial findings were submitted to FDA for consideration of new drug approvals.

Eligible trials were stratified according to treatment-naive or treatment-experienced participants, and efficacy analyses were performed for all approved antiretroviral drug classes: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, fusion inhibitors, CCR5 antagonists, and integrase inhibitors.

Results

	The combined database included 43 RCTs with a total of 22,411 HIV positive participants, looking at 16 antiretroviral drugs.
	No clinically or statistically significant gender differences in 48-week efficacy outcomes were observed.
	Confidence intervals, a statistical measure of data validity, included zero, indicating that efficacy differences between men and women could have been due to chance alone:
	Treatment-naive patients: 95% CI -0.1 to 0.09; Treatment-experienced patients: 95% CI 0.095 to 0.16.
	Confidence intervals for gender differences also included zero for all antiretroviral drug classes:
	NRTIs: 95% CI -0.10 to 0.13; NNRTIs: 95% CI -0.29 to 0.35; Protease inhibitors: 95% CI -0.07 to 0.15; Fusion inhibitors: 95% CI -0.50 to 0.37; CCR5 antagonists: 95% CI -0.46 to 0.50; Integrase inhibitors: 95% CI -0.40, 0.58.
	There were also no gender differences observed for trial discontinuation due to adverse events, loss to follow-up, or death.
	However, about half as many women as men discontinued RCTs due to virological failure (4.25% vs 8.15%).

"FDA meta-analyses suggest no clinically or statistically significant gender differences in week 48 efficacy outcomes, regardless of treatment history, drug class, age, race, or geography," the investigators concluded. "These data could help providers and patients when constructing antiretroviral regimens."

Investigator affiliation: U.S. Food and Drug Administration, Silver Spring, MD.

10/8/10

Reference
G Soon, M Min, K Struble, and others. Meta-Analysis of Efficacy Outcomes for Treatment-Naive and Experienced HIV-Infected Women in Randomized Controlled Clinical Trials (RCTs) (2000-2008). 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010). Boston, September 12-15, 2010. Abstract H-1812.