Gender differences in the treatment of HIV infection.

In recent years, following the successful development of highly active antiretroviral therapy (HAART), several studies have evaluated potential differences between men and women in the course of HIV infection, response to treatment, and drug pharmacokinetics. A slightly lower HIV viral load in untreated women has been reported, particularly at higher CD4+ levels, but this difference does not translate into gender-specific recommendations concerning initiation of therapy. Data on drug response suggest similar response of treatment and similar outcomes in men and women, but female subjects appear to be more susceptible to adverse events related to antiretroviral treatment. Social and behavioural factors may determine gender differences in therapeutic adherence and treatment discontinuation. The available evidence on pharmacokinetics of antiretroviral drugs suggests higher exposure in women compared to men. The factors and mechanisms more likely to be clinically relevant in determining this difference are represented by body weight and composition, renal clearance, and P-glycoprotein activity. Many antiretroviral drugs influence P450 activity, and interactions are common. The results of the studies exploring gender differences in pharmacokinetics of anti-HIV drugs are often not consistent, but several mechanisms may be involved in determining a final difference, and it might be difficult to adjust for all potential confounders. Specific considerations are needed in the selection of anti-HIV regimens in pregnancy, which must ensure protection from both HIV transmission and adverse neonatal outcomes. In order to optimize treatment in all infected people with HIV, there is the need to conduct further research on gender differences in HIV therapeutics. To obtain this goal, specific studies should be designed and females' participation in both cohort studies and clinical trials should be promoted.