Abstract

THPE041 - Poster Exhibition

Gender differences in virologic outcomes in a systematic review of randomized controlled clinical trials in HIV-1-infected patients on antiretroviral therapy

H. Kwakwa¹, L.L. Temme², D.E. Spencer³, C. Evans⁴, I.L. Walker², M.K. Rawlings<sup>2

1</sup>Philadelphia Department of Public Health, Philadelphia, United States, ²Gilead Sciences, Inc., Foster City, United States, ³Institute of Human Virology, University of Maryland School of Medicine, Baltimore, United States, ⁴AIDS ARMS Inc., Dallas, United States

Background: In 2009, women accounted for 24% of new HIV infections in the United States. Black and Hispanic women represent 81% of these new diagnoses in women, but account for < 25% of the female population in the United States. Globally, women account for nearly half of new infections. Despite the changing epidemiology of HIV among women, they are often underrepresented in clinical trials evaluating antiretroviral therapy (ART).
Methods: A systematic review was performed of randomized controlled trials (RCTs) and meta-analyses published from 1996- January 2012 that reported virologic suppression and/or virologic failure (VF) rates for both women and men. Thirteen studies were identified.
Results: In these­­ 13 clinical trials, 11,856 subjects (2,981 women; 8,875 men) were identified. Five of 10 trials reporting virologic suppression demonstrated lower suppression rates in women compared to men (difference, -16% to -4%). Two of 4 studies evaluating VF reported higher rates of VF in women compared to men (HR, 1.38-2.35).

Study	Follow-Up	Arms	Women (n)	Men (n)	% With <50 copies/mL (Women vs. Men)	Rate of VF (Women vs. Men)
ACTG 5142	112 weeks	2NRTIs + EFV vs. 2NRTIs + LPV/r vs. EFV + LPV/r	151	602	n/a	HR: 1.38 (1.01- 1.89)
ACTG 5202	96 weeks	FTC/TDF vs. 3TC/ABC with EFV or ATV + RTV	322	1535	n/a	HR for ATV + RTV with: 3TC/ABC: 1.72 (0.99-2.98); P=0.006 FTC/TDF: 2.35 (1.30-4.26); P=0.03
ACTG Meta-Analysis	48-120 weeks	Multiple regimens; NNRTI- and PI-based	473	2022	n/a	No difference in time to VF (HR 0.9 [0.8-1.1])
ARTEMIS	96 weeks	DRV + RTV vs. LPV/r with FTC/TDF	104	239	No difference DRV + RTV: 79% for both (LPV/r not reported)	n/a
CASTLE	96 weeks	LPV/r vs. ATV + RTV with FTC/TDF	277	606	ATV + RTV: 67% vs. 77% LPV/r: 63% vs. 71%	n/a
DART Substudy	48 weeks	AZT/3TC/TDF	198	102	OR: 2.47 (1.48-4.15); P=0.001	n/a
ECHO/ THRIVE	96 weeks	EFV vs. RPV with 2NRTIs	331	1037	No difference EFV: 78% vs. 77% RPV: 74% vs. 79%	EFV: 3% vs. 7% RPV: 13% vs. 11%
GRACE	48 weeks	DRV + RTV + OBR	287	142	51% vs. 58%	n/a
GSK Meta-Analysis	48 weeks	ABC vs. PI or AZT-containing regimens	415	1122	ABC: 68% vs. 71% Non-ABC: 60% vs. 68%	n/a

[Outcomes for Women vs. Men Across 13 Studies]

Study	Follow-Up	Arms	Women (n)	Men (n)	% With <50 copies/mL (Women vs. Men)	Rate of VF (Women vs. Men)
HEAT	96 weeks	FTC/TDF vs. 3TC/ABC with LPV/r	125	563	FTC/TDF: 52% vs. 59% 3TC/ABC: 46% vs. 62%	n/a
KLEAN	48 weeks	FPV + RTV vs. LPV/r	96	338	FPV + RTV: 64% vs. 75% LPV/r: 67% vs. 73%	n/a
REALMRK	48 weeks	RAL open-label	97	109	No difference 67.8% vs. 72.4%	n/a
STARTMRK	192 weeks	RAL vs. EFV with FTC/TDF	105	458	No difference RAL: 93% vs. 91% EFV: 86% vs. 85%	n/a

[Outcomes for Women vs. Men, Continued]


Conclusions: In 7 of 13 studies, women had a lower virologic suppression rate or higher risk of VF compared to men across various regimens. In some studies, this difference was attributed to a higher discontinuation rate in women. The implication of poorer clinical outcomes among women raises additional research questions regarding factors (e.g., contraception, access to care, stigma and adherence) which may contribute to gender-based differences in ART outcomes for earlier treatment and treatment as prevention. As women become an increasingly impacted by the HIV epidemic, a better understanding of these differences and associated factors will be critical to develop targeted interventions for women.
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