Catherine Godfrey1, Michael D Hughes2, Justin Ritz2, Lara Coelho3, Robert Gross4, Robert Salata5, Rosie Mngqibisa6, Carole L Wallis7, Makanga E Mumbi8, Mitch Matoga9, Selvamuthu Poongulali10, Marije Van Schalkwyk11, Evelyn Hogg12, Courtney V Fletcher13, Beatriz Grinsztejn3, Ann C Collier14. 1. Division of AIDS NIAID, NIH, Bethesda, MD. 2. Harvard T.H. Chan School of Public Health, Boston, MA. 3. Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, Brazil. 4. University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 5. Case Western Reserve University School of Medicine, Cleveland, OH. 6. Durban International CRS, Enhancing Care Foundation, Durban, South Africa. 7. Lancet Laboratories and BARC SA, Johannesburg, South Africa. 8. KEMRI Centre for Global Health Research, Kisumu, Kenya. 9. UNC Project, Lilongwe, Malawi. 10. CART Clinical Research Site, Voluntary Health Services, Chennai, India. 11. FAM-CRU CRS, Stellenbosch University, Cape Town, South Africa. 12. Social & Scientific Systems, Silver Spring, MD. 13. University of Nebraska Medical Center, Omaha, NE; and. 14. University of Washington School of Medicine, Seattle, WA.
Abstract
BACKGROUND: Sex differences in studies of antiretroviral (ART) drug exposure and treatment outcomes support the hypothesis that some ART combinations may not be well tolerated in women. We evaluated disparities in outcomes between men and women participating in ACTG A5288, an interventional strategy trial for individuals failing a protease inhibitor-based second-line ART regimen in low- and middle-income countries. METHODS: Participants were assigned to one of 4 cohorts (A-D) based on resistance profiles and ART history. Cohort A had no lopinavir/ritonavir (LPV/r) resistance and stayed on their second-line regimen, and cohorts B, C, and D had increasing resistance and accessed novel ART regimens. In this secondary analysis, we evaluated sex differences in the primary endpoint, HIV-1 RNA ≤200 copies/mL at week 48; confirmed virologic failure ≥1000 copies/mL (VF); and clinical outcomes and adverse events (intent-to-treat). RESULTS: Women made up 258/545 (47%) of the study population. More women than men were assigned to cohort A. Median follow-up was 72 weeks. Fewer women than men had HIV-1 RNA ≤200 copies/mL at week 48: 39% vs. 49% in cohort A and 83% vs. 89% in cohorts B, C, and D combined. More women experienced VF, grade ≥3 signs and symptoms, but similar grade ≥3 diagnoses or laboratory abnormalities. CONCLUSIONS: More women than men entered the study with a resistance profile suggesting that their second-line regimen could have been effective in maintaining virologic suppression. The more frequent occurrence of grade ≥3 signs and symptoms in women suggests that tolerability issues were under recognized in women on protease inhibitor-based therapy.
BACKGROUND: Sex differences in studies of antiretroviral (ART) drug exposure and treatment outcomes support the hypothesis that some ART combinations may not be well tolerated in women. We evaluated disparities in outcomes between men and women participating in ACTG A5288, an interventional strategy trial for individuals failing a protease inhibitor-based second-line ART regimen in low- and middle-income countries. METHODS: Participants were assigned to one of 4 cohorts (A-D) based on resistance profiles and ART history. Cohort A had no lopinavir/ritonavir (LPV/r) resistance and stayed on their second-line regimen, and cohorts B, C, and D had increasing resistance and accessed novel ART regimens. In this secondary analysis, we evaluated sex differences in the primary endpoint, HIV-1 RNA ≤200 copies/mL at week 48; confirmed virologic failure ≥1000 copies/mL (VF); and clinical outcomes and adverse events (intent-to-treat). RESULTS: Women made up 258/545 (47%) of the study population. More women than men were assigned to cohort A. Median follow-up was 72 weeks. Fewer women than men had HIV-1 RNA ≤200 copies/mL at week 48: 39% vs. 49% in cohort A and 83% vs. 89% in cohorts B, C, and D combined. More women experienced VF, grade ≥3 signs and symptoms, but similar grade ≥3 diagnoses or laboratory abnormalities. CONCLUSIONS: More women than men entered the study with a resistance profile suggesting that their second-line regimen could have been effective in maintaining virologic suppression. The more frequent occurrence of grade ≥3 signs and symptoms in women suggests that tolerability issues were under recognized in women on protease inhibitor-based therapy.
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Authors: Tanakorn Apornpong; Beatriz Grinsztejn; Michael Hughes; Justin Ritz; Stephen J Kerr; Courtney V Fletcher; Kiat Ruxrungtham; Catherine Godfrey; Robert Gross; Evelyn Hogg; Carole L Wallis; Sharlaa Badal-Faesen; Mina C Hosseinipour; Rosie Mngqbisa; Breno R Santos; Sarita Shah; Laura J Hovind; Sajeeda Mawlana; Marije Van Schalkwyk; Nuntisa Chotirosniramit; Cecilia Kanyama; Nagalingeswaran Kumarasamy; Robert Salata; Ann C Collier; Monica Gandhi Journal: AIDS Date: 2021-07-15 Impact factor: 4.632