A study of antiretroviral treatment specifically for women with HIV showed that a single-tablet regimen containing the integrase inhibitor elvitegravir suppressed the virus better than a regimen containing ritonavir-boosted atazanavir, according to a poster presented at the Eighth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015) last month in Vancouver, Canada. This study is important in part because it demonstrates that including more women in clinical trials is feasible.
Most research to date suggests that women and men respond about equally well to modern antiretroviral therapy (ART), but women with HIV have been underrepresented in most clinical trials, so subtle or uncommon sex-related influences on treatment effectiveness or tolerability may be difficult to discern.
Kathleen Squires of Thomas Jefferson University in Philadelphia and fellow investigators conducted the WAVES (Women AntiretroViral Efficacy and Safety) study to compare the safety and efficacy of two commonly used and widely recommended antiretroviral regimens in women living with HIV. It is one of the few non-pregnancy-related multinational phase 3 clinical trials of antiretroviral treatment to enrol all women.
WAVES included 575 women living with HIV who had not previously taken HIV treatment. The women were living in North America, Europe, Russia, Africa and Asia; most were from Russia (33%), Uganda (28%) and the US (20%). Nearly half were black, about 43% were white, about 5% were Asian and the mean age was 35 years. Demographics and other baseline characteristics were balanced across treatment arms and reflect the global nature of the study, according to the researchers.
Participants in this double-blind study were randomly assigned to receive one of the following regimens:
- A once-daily single-tablet regimen containing elvitegravir, cobicistat as a booster, and tenofovir/emtricitabine (Stribild).
- Once-daily ritonavir-boosted atazanavir (Reyataz) plus tenofovir/emtricitabine (the drugs in Truvada).
Most women (78%) had asymptomatic HIV infection and the median baseline CD4 cell count was approximately 350 cells/mm3. A majority had relatively low pre-treatment viral load (<100,000 copies/ml). They had normal kidney function (estimated GFR >70 ml/min), which is important because tenofovir can cause kidney toxicity in susceptible individuals. Women who become pregnant had the option to continue on their assigned treatment, as none of the drugs have been shown to be harmful for pregnant women or a developing foetus.
The primary study endpoint was the proportion of women achieving undetectable viral load, or HIV RNA below 50 copies/ml, at week 48 of treatment. Safety was assessed throughout the study.
At 48 weeks, 87% of women taking Stribild and 81% of those taking boosted atazanavir had undetectable viral load, showing that Stribild was statistically superior. Among women with high baseline viral load, response rates were 90% and 78%, respectively. Mean CD4 cell increases were similar in the two arms (221 vs 212 cells/mm3, respectively).
Virological failure rates were comparable in the Stribild and atazanavir arms (9% vs 12%, respectively). Treatment-emergent drug resistance was detected in three women (1%) who experienced virological failure on atazanavir, but none in the Stribild arm.
Both regimens were generally safe and well-tolerated, with most side-effects being mild. Overall, 29 women (10%) discontinued treatment early in the Stribild arm and 45 (16%) did so in the atazanavir arm; of these, five women taking Stribild and 19 taking atazanavir dropped out due to adverse events.
Mean decreases in kidney function, as measured by eGFR, were small and similar in the Stribild and atazanavir arms. Bone mineral density changes at the hip and spine were also comparable in the study arms. Total cholesterol increased more in the Stribild arm, but the total-to-HDL ratio did not differ significantly.
"[Elvitegravir/cobicistat/tenofovir/emtricitabine] was superior to [atazanavir/ritonavir/tenofovir/emtricitabine] at 48 week, and demonstrated its safety and efficacy for the treatment HIV-1 infection in women," the researchers concluded. "Recruitment, enrolment and retention of women in large multinational trials is feasible."
Squires K et al. Elvitegravir (EVG) / cobicistat (COBI) / emtricitabine (FTC)/ tenofovir disoproxil fumarate (TDF) is superior to ritonavir (RTV) boosted atazanavir (ATV) plus FTC/TDF in treatment naïve women with HIV-1 infection (WAVES Study). 8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015), Vancouver, abstract MOLBPE08, 2015.
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