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The impact of antiretroviral therapy on morbidity and mortality of HIV infection in resource-limited settings

Emily P Hyle, MD
Scott Dryden-Peterson, MD
Section Editor
John A Bartlett, MD
Deputy Editor
Allyson Bloom, MD


The "3 by 5" initiative, launched by United Nations (UN) AIDS and World Health Organization (WHO) in 2003, was a global strategy to provide antiretroviral therapy (ART) to three million people living with HIV/AIDS in 50 developing countries by the end of 2005. Scale-up of services has been expansive, and UNAIDS now estimates that almost 17 million HIV-infected persons were receiving ART at the end of 2015 [1]. Additionally, reductions in new HIV cases, AIDS-related deaths, and overall mortality have been related to expanded access to ART [2]. Despite these achievements, too many patients eligible for ART by WHO criteria are not receiving it, inspiring the latest UNAIDS initiative, “90-90-90,” which aims to have 90 percent of people living with HIV/AIDS know their diagnosis, 90 percent of those diagnosed on ART, and 90 percent of those on ART be virologically suppressed by 2020 [3].

The impact of ART on HIV infection in resource-limited settings will be discussed here. The overall benefits of ART and information on the global epidemic are discussed elsewhere. (See "When to initiate antiretroviral therapy in HIV-infected patients" and "Global epidemiology of HIV infection".)


Of the estimated 37 million individuals with HIV infection worldwide in 2015, 26 million are in sub-Saharan Africa, where the overall prevalence is approximately 5 percent [1,4]. In some African countries, the prevalence exceeds 20 percent. More than half of the HIV-infected population in sub-Saharan Africa is women and children. The HIV prevalence in Southeast Asia is substantially lower (0.6 percent), representing approximately four million HIV-infected people living in this under-resourced region. In Latin America and the Caribbean, infection rates vary by region, with estimated prevalences ranging from 0.5 to 2 percent. Markedly high rates of infection exist within certain risk groups, such as men who have sex with men, prisoners, commercial sex workers, and injection drug users. The global epidemiology of HIV is discussed in detail elsewhere. (See "Global epidemiology of HIV infection", section on 'Worldwide statistics'.)


Initiation of antiretroviral therapy — In 2015, the World Health Organization (WHO) revised longstanding guidance to withhold treatment until development of immunodeficiency and instead recommended initiation of antiretroviral (ART) for all HIV-infected patients, regardless of CD4 cell count or clinical stage [5]. Those with advanced HIV disease (clinical stage 3 or 4 disease (table 1)) or a CD4 cell count of <200 cells/microL are a priority for ART initiation. In general, initiation of ART should be offered within seven days of an HIV diagnosis or, for those who are ready to start therapy, on the day of diagnosis [6]. For patients who have suspected or documented coinfection with tuberculosis or cryptococcal meningitis, ART initiation is deferred until those infections have been ruled out or treatment for those infections has been initiated. (See "Treatment of pulmonary tuberculosis in HIV-infected adults" and "Clinical management and monitoring during antifungal therapy of the HIV-infected patient with cryptococcal meningoencephalitis", section on 'Timing of antiretroviral therapy'.)

WHO guidelines also specify a single preferred first-line regimen of tenofovir, lamivudine (or emtricitabine), and efavirenz for all HIV-infected adults who initiate ART, including pregnant and breastfeeding women [5]. This regimen was chosen based on its virologic efficacy, safety, and its ability to be used in the setting of TB treatment, liver disease, and pregnancy, thus enabling HIV treatment to be streamlined across different populations.


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