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RNA and CD4 Response to Lopinavir
Similar in Women and Men in 7-Trial Analysis
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1st International Workshop on HIV and Women, January 10-11, 2011, Washington, DC
Mark Mascolini
Responses to lopinavir/ritonavir through 48 weeks in seven randomized trials were similar for women and men when investigators considered viral suppression, CD4-cell gains, and rates of most side effects [1]. Discontinuation rates were higher for women than for men in the six trials that enrolled antiretroviral-naive people but not in the single study that enrolled antiretroviral-experienced patients.
Although women made up small minorities of patient populations in early antiretroviral trials, the FDA calculated that women accounted for one in five enrollees in phase 2 to 4 HIV studies from 2000 to 2006. To compare responses to lopinavir/ritonavir in women and men, Abbott investigators performed a meta-analysis involving six trials in antiretroviral-naive people and one in antiretroviral-experienced people [1]. Most guidelines, the researchers noted, list lopinavir/ritonavir as a preferred protease inhibitor in pregnancy and as an option for women of childbearing age.
Meta-analysis participants had to receive a standard dose of lopinavir/ritonavir and have 48-week results on virologic response below 50 copies, change in CD4 count from baseline, treatment-related adverse events and lab abnormalities, and trial discontinuation. Trials that had such data in antiretroviral-naive people were M97-720, M98-863, M99-056, M02-418, M05-730, and M10-336. The one trial that enrolled antiretroviral-experienced people was M06-802. The meta-analysis considered 2022 people, including 286 naive women, 1137 naive men, 206 experienced women, and 393 experienced men. Thus women comprised 20% of naive trial members and 34% of experienced trial enrollees.
For the four groups—naive women, naive men, experienced women, and experienced men--age averaged 39.2, 38.2, 38.7, and 41.6. Proportions of whites/blacks were 48.3%/44/8%, 76.4%/18%, 37.9%/47.1%, and 58.5%/28.2%. There were significantly more white men than white women in both the naive and experienced groups. CD4 counts for the four groups averaged 218, 255 (P < 0.05 for naive women versus naive men), 259, and 251. Proportions who entered the trials with more than 100,000 HIV RNA copies were 39.9%, 49%, 15%, and 15.5%.
Through 48 weeks of follow-up, a significantly higher proportion of naive women than naive men dropped out of the trial for any reason (21.7% versus 15.4%, P = 0.013), though dropout rates for women and men were similar in the one trial that enrolled treatment-experienced people (23.8% versus 21.9%). In the naive trials, a significantly higher loss to follow-up rate among women than men (7.3% versus 3.3%, P < 0.05) accounted for the higher overall dropout rate in women. Other specific causes of discontinuation did not differ between women and men: adverse events or HIV events, withdrawn consent, nonadherence, virologic failure, or death.
A noncompleter-equals-failure analysis and an on-treatment analysis revealed no gender-based difference in proportions who had a viral load below 50 copies at week 48. In the noncompleter analysis of trials that enrolled antiretroviral-naive people, sub-50-copy rates were 69% for women and 74% for men at week 48; in the trial that enrolled antiretroviral-experienced people, respective rates were 52% and 57%. CD4 gains through 48 weeks did not differ between naive women and men (+209 and +200) or experienced women and men (+138 and +123).
The only side effect differences between women and men occurred in the naive trials: vomiting affected 6.6% of women and 2.4% of men, and dyspepsia (upset stomach) affected 2.3% of women versus 0.7% of men (P < 0.05 for both comparisons). In contrast, triglyceride elevations above 750 mg/dL proved less common among women than men in the naive trials (1.4% versus 7.2%) and the experienced trial (2.0% versus 7.6%) (P < 0.05 for both comparisons).
The Abbott team noted that the less tolerable Kaletra gel capsule was used in all trials of antiretroviral-naive people, while the more tolerable tablet was used in the single trial enrolling treatment-experienced patients. The researchers will continue to scrutinize these data to assess lopinavir response similarities and difference in women and men.
Reference
1. Hermes A, Fredrick L, Pasley M, Trinh R, Norton M, Martinez M. Efficacy, safety and tolerability of lopinavir/ritonavir in HIV-infected women: meta-analysis of 7 randomized clinical trials through 48 weeks. 1st International Workshop on HIV and Women. January 10-11, 2011. Washington, DC. Abstract O_17.
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