Comparative gender analysis of the efficacy and safety of atazanavir/ritonavir and lopinavir/ritonavir at 96 weeks in the CASTLE study

Kathleen E Squires, Margaret Johnson, Rong Yang, Jonathan Uy, Louise Sheppard, Judith Absalon, Donnie McGrath, Kathleen E Squires, Margaret Johnson, Rong Yang, Jonathan Uy, Louise Sheppard, Judith Absalon, Donnie McGrath

Abstract

Objectives: To examine whether the overall results of the CASTLE study pertain to both genders, we analysed the efficacy and safety of atazanavir/ritonavir and lopinavir/ritonavir in 277 female and 606 male patients in the open-label, multinational trial over 96 weeks. The trial is registered with ClinicalTrials.gov, number NCT00272779.

Methods: Treatment-naive patients aged ≥ 18 years with HIV-1 RNA ≥ 5000 copies/mL were randomized to receive either atazanavir/ritonavir 300/100 mg once daily or lopinavir/ritonavir 400/100 mg twice daily, with fixed-dose tenofovir/emtricitabine 300/200 mg once daily.

Results: At week 96, confirmed virological response rates (HIV RNA <50 copies/mL; intent-to-treat analysis) were higher in women and men receiving atazanavir/ritonavir than those receiving lopinavir/ritonavir and lower in women than men in both treatment arms (67% of women and 77% of men on atazanavir/ritonavir and 63% of women and 71% of men on lopinavir/ritonavir). These differences were not observed in the on-treatment analysis. Mean change in CD4 cell count from baseline to week 96 was 265 cells/mm(3) for women and 269 cells/mm(3) for men on atazanavir/ritonavir and 298 cells/mm(3) for women and 286 cells/mm(3) for men on lopinavir/ritonavir. Discontinuation rates were higher in women than men in each treatment arm (22% of women and 15% of men on atazanavir/ritonavir and 29% of women and 18% of men on lopinavir/ritonavir). In women and men, grade 2-4 nausea and diarrhoea were more frequent in the lopinavir/ritonavir group; jaundice and hyperbilirubinaemia occurred more frequently in the atazanavir/ritonavir group.

Conclusions: Once-daily atazanavir/ritonavir is an effective and well-tolerated therapeutic option for women and men with HIV-1 infection. The sex-based differences in response may be due to higher discontinuation rates in women.

Figures

Figure 1.
Figure 1.
Trial profile for female and male patients in the CASTLE study. aInsufficient viral load response determined by investigators. bTwo cases of rash, one case of tuberculosis (TB), one case of thrombocytopenia, one gastrointestinal problem and one gastrointestinal problem plus dizziness, jaundice, hepatomegaly and hyperbilirubinaemia. cTwo cases of jaundice, two gastrointestinal problems, one case of abdominal pain, one case of Mycobacterium infection and one case of Fanconi syndrome. dTwo cases of TB, one case of hypersensitivity, one case of hypertrophic cardiomyopathy, one case of rash and one case of proteinuria. eSeven cases of diarrhoea, one case of furnicle, one case of major depression, one case of rash, one case of rhabdomycosis, one case of lipoma, two cases of hyperlipidaemia, one case of lipodystrophy and one case of Kaposi's sarcoma. fProtocol-defined for discontinuation. gOne pregnancy and one poor/non-compliance. hOne lost to follow-up and one poor/non-compliance.
Figure 2.
Figure 2.
CVR (HIV RNA

Figure 3.

Mean percentage change in fasting…

Figure 3.

Mean percentage change in fasting lipid concentrations in female and male patients from…

Figure 3.
Mean percentage change in fasting lipid concentrations in female and male patients from baseline through week 96 (as-treated). ATV, atazanavir; LPV, lopinavir; RTV, ritonavir.
Figure 3.
Figure 3.
Mean percentage change in fasting lipid concentrations in female and male patients from baseline through week 96 (as-treated). ATV, atazanavir; LPV, lopinavir; RTV, ritonavir.

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Source: PubMed

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