title: Antiretroviral therapy and drug resistance in human immunodeficiency virus type 2 infection.
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.
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (Consejo Superior de Investigaciones Científicas & Universidad Autónoma de Madrid), c/Nicolás Cabrera, 1, Campus de Cantoblanco, 28049 Madrid, Spain. Electronic address: lmenendez@cbm.csic.es.
authors.forename: Luis
authors.initials: L
authors.lastname: Menéndez-Arias
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (Consejo Superior de Investigaciones Científicas & Universidad Autónoma de Madrid), c/Nicolás Cabrera, 1, Campus de Cantoblanco, 28049 Madrid, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Alvarez
mesh_terms: D000354:Africa, Western; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D001208:Asia; D024882:Drug Resistance, Viral; D005060:Europe; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015498:HIV-2 / Q000187:drug effects / Q000302:isolation & purification*; D006801:Humans; D009656:North America
chemical_list: D019380:Anti-HIV Agents
keywords: Drug resistance; Entry inhibitors; HIV-2; Integrase; Protease; Reverse transcriptase