Darunavir/ritonavir-based antiretroviral therapy is equally effective in treatment-experienced women and men, US investigators report in the Annals of Internal Medicine.
However, within four weeks of the study starting, women were more likely to withdraw from the trial than men. The investigators believe that this shows that more needs to be done to retain women in clinical trials.
There was no real difference in overall side-effects between women and men, but women were more likely to report nausea.
“Darunavir-ritonavir antiretroviral combinations have similar efficacy outcomes and incidence of adverse-events in treatment-experienced men and women”, comment the investigators.
Women represent a growing proportion of the population affected by HIV. However, they are often under-represented in clinical trials, especially those involving treatment-experienced patients.
If women comprise less than 25% of a study population then the ability of a clinical trial to detect sex-based differences in outcomes is compromised.
Women were under-represented in studies exploring the safety and efficacy of ritonavir-boosted darunavir (Prezista) in treatment-experienced patients. To gain a clearer understanding of the effects of the drug on women, investigators designed the open-label GRACE (Gender, Race, and Clinical Experience) study.
According to the study protocol, 70% of participants were to be women. In addition, the percentage of white men enrolled in the study was carefully monitored, and was limited to less than 25% of the planned study population.
Patients were required to have a viral load of above 1000 copies/ml and experience of treatment with all the three main classes of antiretroviral drugs.
The study medication consisted of 600/100mg darunavir/ritonavir twice daily, plus optimised background therapy. The trial lasted 48 weeks and was conducted between 2006 and 2008.
A total of 429 individuals were recruited to the study. Just over two-thirds (67%) were women and 84% were black or Hispanic.
Women were more likely than men to be black (67% vs. 51%, p = 0.011), but were less likely to have developed an AIDS-defining condition (36% vs. 47%, p = 0.021).
A third of women stopped treatment early compared to 23% of men (difference, p = 0.042). It became apparent as early as week four of the study that more women were withdrawing, and this difference persisted through to week 48.
Women were more likely than men to be lost to follow-up (8% vs. 6%), or to withdraw because of side-effects (8% vs. 4%). However, neither of these differences was statistically significant.
Treatment adherence of 95% or greater was reported by 64% of women and 69% of men.
In the intent-to-treat analysis, 51% of women compared to 59% of men achieved and maintained a viral load below 50 copies/ml.
When the analysis was restricted to patients who remained on treatment, equal proportions of women and men were found to have had a good virologic outcome to therapy (73% vs. 73%).
Statistical analysis that controlled for baseline viral load and CD4 cell count showed that in the intent-to-treat population, women were approximately 10% less likely than men to suppress their viral load to undetectable levels. However, this was difference was not statistically significant (p = 0.067).
A non-significant difference in treatment response was also seen in the on-treatment analysis.
The investigators believe that these differences had nothing to do with the virologic efficacy of the therapy. Rather they attribute them to the “high number of women who withdrew for reasons other than virologic failure.”
Significantly better (p = 0.033) CD4 cell count increases were observed in women than men.
Rates of confirmed virologic failure were comparable in women and men (29% vs. 28%). The investigators looked at the outcomes of such patients with a viral load above 1000 copies/ml and found that women were slightly less likely than men to develop resistance.
A total of 16% of women and 23% of men experienced serious side-effects. Two women and two men died, but none of these deaths were associated with the study medication.
Comparable proportions of women and men (27% vs. 34%) experienced a grade 3 or 4 side-effect, as well as any side-effect that considered by the investigators to be possibly related to darunavir/ritonavir (47% vs. 43%).
The only side-effects that was significantly more likely to occur in women than men was nausea and vomiting (5% vs. 3%). This did not have any clinical impliations.
“Virologic response rate did not significantly differ between women and men,” comment the investigators. They add, “overall, darunavir-ritonavir therapy seemed to be well tolerated in our study”.
They conclude that the study shows that it is possible to recruit large numbers of women to a clinical trial. However, “the high discontinuation rate in women, which was driven by reasons other than failure, highlights the need for additional efforts to retain diverse populations in studies.
Currier J et al. Sex-based outcomes of darunavir-ritonavir therapy: a single-group trial. Ann Intern Med, 153: 349-57, 2010.