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. There is usually a single “first-line” regimen (mainly dolutegravir-based with efavirenz as an alternative) and a “second-line” regimen (with the protease inhibitors lopinavir/ritonavir or atazanavir/ritonavir, as backbones). 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 have been suppressed on their current PI-based regimen. Consistent with guidelines, these women were therefore kept on their protease inhibitor-based 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” or that interfered with their daily living, although laboratory values were not significantly more abnormal in women than men. The group of participants that reported severe symptoms was unlikely to achieve virological suppression.

Based on findings from other ACTG and non-ACTG studies that women have higher protease inhibitor plasma concentrations then men at the same dose, the authors hypothesize that increased drug levels lead to decreased tolerability of the PI regimens. The decrease in tolerability will result in lapses in adherence and ultimate virological failure. 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 improve and mitigate symptoms of ART in women may lead to improved virological success. Moreover, counseling of women should include a systematic assessment of adherence barriers, including tolerability concerns.

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.