Antiretroviral Treatment of HIV-2 Infection: Available Drugs, Resistance Pathways, and Promising New Compounds

Int J Mol Sci. 2023 Mar 21;24(6):5905. doi: 10.3390/ijms24065905.

Abstract

Currently, it is estimated that 1-2 million people worldwide are infected with HIV-2, accounting for 3-5% of the global burden of HIV. The course of HIV-2 infection is longer compared to HIV-1 infection, but without effective antiretroviral therapy (ART), a substantial proportion of infected patients will progress to AIDS and die. Antiretroviral drugs in clinical use were designed for HIV-1 and, unfortunately, some do not work as well, or do not work at all, for HIV-2. This is the case for non-nucleoside reverse transcriptase inhibitors (NNRTIs), the fusion inhibitor enfuvirtide (T-20), most protease inhibitors (PIs), the attachment inhibitor fostemsavir and most broadly neutralizing antibodies. Integrase inhibitors work well against HIV-2 and are included in first-line therapeutic regimens for HIV-2-infected patients. However, rapid emergence of drug resistance and cross-resistance within each drug class dramatically reduces second-line treatment options. New drugs are needed to treat infection with drug-resistant isolates. Here, we review the therapeutic armamentarium available to treat HIV-2-infected patients, as well as promising drugs in development. We also review HIV-2 drug resistance mutations and resistance pathways that develop in HIV-2-infected patients under treatment.

Keywords: HIV-2; HIV-2 treatment; antiretroviral drugs; resistance mutations; resistance pathways.

Publication types

  • Review

MeSH terms

  • Anti-HIV Agents* / pharmacology
  • Anti-HIV Agents* / therapeutic use
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Drug Resistance, Viral
  • HIV Infections* / drug therapy
  • HIV-2
  • Humans
  • Reverse Transcriptase Inhibitors / pharmacology

Substances

  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors