Meta-Analysis of Gender Differences in Efficacy Outcomes for HIV-Positive Subjects in Randomized Controlled Clinical Trials of Antiretroviral Therapy (2000–2008)

Abstract

Women are often underrepresented in randomized clinical trials (RCT) of HIV-1 drugs. As a result, determining whether women have different virologic outcomes compared to men is not always possible because the gender-related analyses usually lack statistical power. To address this important public health concern, the Food and Drug Administration's (FDA) Division of Antiviral Products (DAVP) created a database including 20,328 HIV-positive subjects from 40 RCTs in 18 New Drug Applications (NDAs) submitted to the FDA between 2000 and 2008. These RCTs were conducted for at least 48 weeks in duration and were used to support approval of new molecular entity, new formulation, or major label change. To delineate potential gender differences in antiretroviral treatment (ART), we evaluated the percentage of subjects with HIV RNA less than 50 copies per milliliter at 48 weeks. Analyses of the database represent the most systematic review of gender-related ART efficacy data to date. Overall, the meta-analyses did not demonstrate statistically or clinically significant gender differences in virologic outcome at week 48. However, the corresponding subgroup analyses appear to show several statistically significant gender differences favoring males.

Participation of Women and Sex Analyses in Late-Phase Clinical Trials of New Molecular Entity Drugs and Biologics Approved by the FDA in 2007–2009

“…Of note, between 2007 and 2009, three new HIV drugs were approved by the FDA, with an average of 12% women participating in the LPCTs of these drugs. The data indicated that participation of women in HIV drug trials is low (12%) and has decreased compared with the 20% that was reported for randomized controlled clinical trials of antiretroviral therapy products approved by the FDA from 2000 to 2008 by Soon et al,19 and the participation rate is lower than the disease prevalence; in 2008, the CDC reported that women make up 25% of HIV patients living in the United States. 20 Although gout is a disease that predominately affects men, disease prevalence in women has increased in the last few decades, and a 2004 study reported that about 30% of the patients are women.…”

Insights on GRACE (Gender, Race, And Clinical Experience) from the Patient's Perspective: GRACE Participant Survey

“…2,3 Between 2000 and 2008, only 15% of treatment-experienced patients enrolled in the 18 randomized controlled trials of HIV drugs submitted for approval to the Food and Drug Administration (FDA) were women. 3 Women of color have been particularly under-represented, despite the fact that they comprise a large portion of new infections.…”

“…2,3 Between 2000 and 2008, only 15% of treatment-experienced patients enrolled in the 18 randomized controlled trials of HIV drugs submitted for approval to the Food and Drug Administration (FDA) were women. 3 Women of color have been particularly under-represented, despite the fact that they comprise a large portion of new infections. 4,5 In addition to HIV-related stigma, women of color may face both sex-based and race-based discrimination, culminating in increased rates of mental health issues.…”

Implementation challenges for long-acting antivirals as treatment

“…During the phase III trials and in postmarketing surveillance and studies, the pharmacokinetics and treatment responses of long-acting ART must be studied in adequate numbers of women for sex-stratified results to be presented [56–58]. Studies in children and in pregnant and breastfeeding women will be important to extend the benefits of these agents to these key populations.…”