IMPORTANCE: New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults.
OBJECTIVE: To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis.
EVIDENCE REVIEW: A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence.
FINDINGS: Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and monitoring during treatment is recommended to assess response, adverse effects, and adherence. Approaches are recommended to improve linkage to and retention in care are provided. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. When indicated, postexposure prophylaxis should be started as soon as possible after exposure.
CONCLUSIONS AND RELEVANCE: Antiretroviral agents remain the cornerstone of HIV treatment and prevention. All HIV-infected individuals with detectable plasma virus should receive treatment with recommended initial regimens consisting of an InSTI plus 2 NRTIs. Preexposure prophylaxis should be considered as part of an HIV prevention strategy for at-risk individuals. When used effectively, currently available ARVs can sustain HIV suppression and can prevent new HIV infection. With these treatment regimens, survival rates among HIV-infected adults who are retained in care can approach those of uninfected adults.
Significant progress is being made in the global scale-up of prevention of mother-to-child transmission of HIV (PMTCT), including in high burden and resource-limited settings. For the first time, the elimination of mother-to-child transmission of HIV (MTCT) is now considered a realistic public health goal and an important part of the campaign to achieve the millennium development goals. In the light of the global effort, it is critically important to provide the best evidence-based interventions to reduce the risk of transmission from an HIV-infected mother to her newborn child, while at the same time promoting the health of both the mother and the child. Since WHO issued revised guidelines in 2006, important new evidence has emerged on the use of antiretroviral (ARV) prophylaxis to prevent MTCT, including during breastfeeding, on the optimal time to initiate antiretroviral therapy (ART) in individuals who need treatment, and on safe feeding practices for HIV-exposed infants. This evidence forms the basis for the new recommendations contained in these 2010 revised guidelines and summarized in preliminary form in the 2009 Rapid Advice: Use of antiretroviral drugs for treating pregnant women and preventing HIV infection in infants. The Rapid Advice gives a list of the key recommendations whereas the full guidelines document presents in detail the scientific evidence and rationale supporting these recommendations. The detailed guidelines document provides the necessary information for countries to adapt the WHO recommendations to their local settings. The 2010 guidelines are developed to provide international standards, primarily for low- and middle-income settings, in support of the global scale-up of more effective interventions aimed at preventing MTCT in resource-limited settings. Once implemented, these recommendations could reduce the risk of MTCT to less than 5% (or even lower) in breastfeeding populations from a background risk of 35%, and to less than 2% in non-breastfeeding populations from a background risk of 25%, and will ensure increased maternal and child survival. The 2010 revision of the WHO guidelines on PMTCT complies with the recently updated WHO guidelines development process, which requires systematic review of new evidence for key questions and recommendations, as well as a consideration of programme feasibility and the cost implications of potential new recommendations. WHO has simultaneously revised guidelines for adult ART as well as HIV and infant feeding. All three sets of guidelines were updated in a harmonized fashion.
New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults.
OBJECTIVE:
To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis.
EVIDENCE REVIEW:
A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence.
FINDINGS:
Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and monitoring during treatment is recommended to assess response, adverse effects, and adherence. Approaches are recommended to improve linkage to and retention in care are provided. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. When indicated, postexposure prophylaxis should be started as soon as possible after exposure.
CONCLUSIONS AND RELEVANCE:
Antiretroviral agents remain the cornerstone of HIV treatment and prevention. All HIV-infected individuals with detectable plasma virus should receive treatment with recommended initial regimens consisting of an InSTI plus 2 NRTIs. Preexposure prophylaxis should be considered as part of an HIV prevention strategy for at-risk individuals. When used effectively, currently available ARVs can sustain HIV suppression and can prevent new HIV infection. With these treatment regimens, survival rates among HIV-infected adults who are retained in care can approach those of uninfected adults.
