Antiretroviral therapy and drug resistance in human immunodeficiency virus type 2 infection

Antiviral Res. 2014 Feb;102:70-86. doi: 10.1016/j.antiviral.2013.12.001. Epub 2013 Dec 15.

Abstract

One to two million people worldwide are infected with the human immunodeficiency virus type 2 (HIV-2), with highest prevalences in West African countries, but also present in Western Europe, Asia and North America. Compared to HIV-1, HIV-2 infection undergoes a longer asymptomatic phase and progresses to AIDS more slowly. In addition, HIV-2 shows lower transmission rates, probably due to its lower viremia in infected individuals. There is limited experience in the treatment of HIV-2 infection and several antiretroviral drugs used to fight HIV-1 are not effective against HIV-2. Effective drugs against HIV-2 include nucleoside analogue reverse transcriptase (RT) inhibitors (e.g. zidovudine, tenofovir, lamivudine, emtricitabine, abacavir, stavudine and didanosine), protease inhibitors (saquinavir, lopinavir and darunavir), and integrase inhibitors (raltegravir, elvitegravir and dolutegravir). Maraviroc, a CCR5 antagonist blocking coreceptor binding during HIV entry, is active in vitro against CCR5-tropic HIV-2 but more studies are needed to validate its use in therapeutic treatments against HIV-2 infection. HIV-2 strains are naturally resistant to a few antiretroviral drugs developed to suppress HIV-1 propagation such as nonnucleoside RT inhibitors, several protease inhibitors and the fusion inhibitor enfuvirtide. Resistance selection in HIV-2 appears to be faster than in HIV-1. In this scenario, the development of novel drugs specific for HIV-2 is an important priority. In this review, we discuss current anti-HIV-2 therapies and mutational pathways leading to drug resistance.

Keywords: Drug resistance; Entry inhibitors; HIV-2; Integrase; Protease; Reverse transcriptase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Africa, Western
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods*
  • Asia
  • Drug Resistance, Viral*
  • Europe
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV-2 / drug effects
  • HIV-2 / isolation & purification*
  • Humans
  • North America

Substances

  • Anti-HIV Agents