Heavily treatment-experienced patients with HIV: are new mechanisms of action enough?

Abstract

Antiretroviral (ARV) drug resistance poses a threat to ending the HIV epidemic. As the rates of integrase resistance continue to increase globally, the availability of options for HIV treatment becomes limited. Heavily treatment-experienced (HTE) people with HIV (PWH) are limited to two or fewer available fully active ARV classes and are more likely to have an AIDS-defining event. Appropriate identification and management of HTE PWH is crucial to improving patient outcomes and reducing the future spread of drug-resistant HIV. As treatment options become more limited owing to drug resistance, the availability of more potent drugs with a marked increase in virologic suppression is needed in the current ART era. The purpose of this narrative review is to review the identification of HTE PWH, novel mechanisms of resistance, and management of HTE PWH in resource-rich and resource-limited settings using novel ARVs and combination ART.

Keywords: AIDS; HIV; HIV drug resistance; HIV salvage therapy; antiretroviral therapy; heavily treatment-experienced people with HIV.

Figure 1.

Treatment algorithm for management of heavily treatment-experienced people with HIV^, *>1000 copies/mL in resource-limited settings. ^†Assessment of antiretroviral therapy (ART) adherence, drug–drug interactions, drug–food interactions, drug tolerability, HIV RNA level and CD4 cell count trends over time, ART history, co-existing medical conditions, previous ART, and all drug-resistance test results should be considered. ^‡Non-adherence, pill burden, drug–drug interactions, drug–food interactions, drug adverse effects, affordability, and/or stigma-related concerns. ^§In resource-limited settings, consider a regimen containing dolutegravir, boosted darunavir, and an optimized nucleoside reverse-transcriptase inhibitor backbone. ^¶Simplification, modernization, drug–drug interactions, drug–food interactions, drug adverse effects, affordability, pregnancy, and/or stigma-related concerns.