Brief Report: Sex Differences in Outcomes for Individuals Presenting for Third-Line Antiretroviral Therapy

JAIDS, June 2020

In resource-limited settings, there are fewer regimens available to people living with HIV compared to individuals in resource-rich countries. Moreover, the options for people experiencing virological failure on protease inhibitor regimens are very limited. This paper describes the differences in the experiences of men and women who were referred for third-line therapy in ACTG sites in low- and middle-income countries.

More women entered study A5288 with a resistance pattern suggesting that they could still be suppressed on their current PI-based regimen and were therefore kept on that regimen, with changes in the NRTI backbone as needed. At the end of the study, fewer women than men achieved virological suppression. Women with virological failure more commonly had no new resistance mutations, suggesting incomplete adherence. Women were more likely to have symptoms that they graded as “severe,” and this group was less likely to achieve virological suppression.

Based on findings from other ACTG and non-ACTG studies that women have higher protease inhibitor plasma concentrations than men at the same dose, the authors hypothesize that increased drug levels lead to decreased tolerability of the PI regimens. Although ART regimens are given at a single dose for men and women, the clinical trials that led to the approval of most antiretrovirals often did not have adequate representation of women. Interventions designed to address or mitigate symptoms of ART in women may lead to improved virological success.

The main findings of A5288 were published earlier this year in Lancet HIV.

Godfrey, C., Hughes, M. D., Ritz, J., Coelho, L., Gross, R., Salata, R., Mngqibisa, R., Wallis, C. L., Mumbi, M. E., Matoga, M., Poongulali, S., Van Schalkwyk, M., Hogg, E., Fletcher, C. V., Grinsztejn, B., & Collier, A. C. (2020). Brief Report: Sex Differences in Outcomes for Individuals Presenting for Third-Line Antiretroviral TherapyJournal of Acquired Immune Deficiency Syndromes (1999)84(2), 203–207. https://doi.org/10.1097/QAI.0000000000002324