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Lopinavir/ritonavir: women versus men

Polly Clayden, HIV i-Base

Lopinavir/ritonavir (LPV/r) is used frequently in pregnancy and in second line regimens in resource limited settings.

An FDA meta-analysis showed that women made up only 21% of overall participants in phase 2-4 HIV studies from 2000-2006. LPV/r (Kaletra) was approved in 2005.

The originator manufacturer, Abbott, performed a meta-analysis from company data to provide some information on the efficacy, safety and tolerability of LPV/r in women compared to men.

Ashwaq Hermes presented findings from this analysis of seven randomised controlled trials that met the following inclusion criteria: prospective adult trials using the standard dose as part of a three drug regimen with available data to 48 weeks on viral load, CD4, adverse events and discontinuation rates.

The investigation included 2022 trial participants. Of these, 492 were women (286 treatment naïve and 206 experienced) and 1530 were men (1137 naïve and 393 experienced).

Treatment naïve women, treatment naïve men and treatment-experienced women were all younger, having mean ages of 39.2, 38.2 and 38.7 years respectively, than treatment-experienced men, who had a mean age of 41.6 years. White participants made up a greater proportion of both groups of men compared to women, 76.4 vs 48.3 and 58.5 vs 37.9, in the treatment naïve and experienced groups respectively. More treatment-experienced men had a CD4 count of <50 cells/mm3 at baseline, 12.6 vs 5.8. All comparisons p<0.05.

Intent-to-treat analysis revealed similar proportions of women and men with viral load <50 copies/mL at 48 weeks: 69 vs 74% in treatment naïve women and men, p=0.73, and 52 vs 57% in experienced women and men, p=0.3. Mean increases in CD4 count from baseline were also similar between sexes at 48 weeks: 209 vs 200 cells/mm3 in naïve women and men, p=0.42 and 138 vs 123 cells/mm3 in experienced, p=0.253.

Incidence of moderate to severe adverse events also did not differ greatly overall between sexes: 34.3 vs 34.9% in treatment naïve women and men, p=0.89, and 28.2 vs 25.4% in experienced women and men, p=0.495. Although there was a significant increase in the incidence vomiting, 6.6 vs 2.4%, and dyspepsia, 2.3 vs 0.7%, in naïve women compared to men, both p<0.05. Laboratory abnormalities were again similar overall, but with a greater incidence of raised triglycerides (>750 mg/dL) in 7.2 vs 1.4% in treatment-naïve and 7.6 vs 2.0% in treatment-experienced men vs women, respectively (both p<0.05).

When the investigators looked at overall rates of discontinuation of treatment for any reason, they found that these were greater in treatment-naïve women compared to men, 21.7 vs 15.4%, p=0.013. Lost to follow up made up a high proportion of this group, 8.7 vs 4.1%, of women compared to men, p=0.004.

Among experienced women and men, the overall rates of discontinuation were similar: 23.8 vs 21.9%, p=0.608.

Discontinuation due to adverse events was greater in treatment naïve women compared to men: 8.7 vs 5.2%, p=0.034. However, these rates were similar among the treatment experienced group: 7.8 vs 4.6% of women compared to men, p=0.136.

Dr Hermes noted that the older gel formulation was used in the treatment naïve trials whereas the tablet formulation was used in the trial of treatment-experienced patients.

The investigators concluded that this analysis revealed no substantial overall differences between women and men with regards to efficacy, safety and tolerability. They are continuing their evaluation of these data.

comment

Overall this meta-analysis of seven randomised controlled studies including 492 women and 1530 men did not find significant differences in virological or immunological response or overall incidence of adverse events.

Although there are always difficulties with interpretation with any post hoc analysis it seems a good idea for companies to look at their own data in this way.

Reference:

Hermes A et al. Efficacy, safety and tolerability of lopinavir/ritonavir in HIV-infected women: results of a meta-analysis of 7 prospective, randomised clinical trials through 48 weeks. 1st International Workshop on HIV and Women. 10–11 January 2011, Washington. Oral abstract O_17.

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