Journal ArticleDOI
HIV Viral Load and Transmissibility of HIV Infection: Undetectable Equals Untransmittable.
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The underlying science-based evidence supporting the Undetectable = Untransmittable (U = U) concept is examined and the behavioral, social, and legal implications associated with the acceptance are examined.Abstract:
In 2016, the Prevention Access Campaign, a health equity initiative with the goal of ending the HIV/AIDS pandemic as well as HIV-related stigma, launched the Undetectable = Untransmittable (U = U) initiative.1 U = U signifies that individuals with HIV who receive antiretroviral therapy (ART) and have achieved and maintained an undetectable viral load cannot sexually transmit the virus to others. This concept, based on strong scientific evidence, has broad implications for treatment of HIV infection from a scientific and public health standpoint, for the self-esteem of individuals by reducing the stigma associated with HIV,2 and for certain legal aspects of HIV criminalization.3 In this Viewpoint, we examine the underlying science-based evidence supporting this important concept and the behavioral, social, and legal implications associated with the acceptance of the U = U concept. A major breakthrough in HIV/AIDS therapeutics came in 1996 with the advent of 3-drug combinations of antiretrovirals, including the newly developed protease inhibitors. These therapeutic regimens resulted in substantial decreases in viral load in a high percentage of patients, usually below the level of detection in plasma and sustained for extended periods.2 Although not appreciated at the time, the accomplishment of a sustained, undetectable viral load was likely the definitive point when the U = U concept became a reality. Proof of that concept would await further clinical trials and cohort studies. Based on a review of scientific data, a statement from Switzerland in 2008 indicated that individuals with HIV who did not have any other sexually transmitted infection, and achieved and maintained an undetectable viral load for at least 6 months, did not transmit HIV sexually.4 This was the first declaration of the U = U concept, but it was not universally embraced because it lacked the rigor of randomized clinical trials. In 2011, the HIV Prevention Trials Network (HPTN) study 052 compared the effect of early with delayed initiation of ART in the partner with HIV among 1763 HIVdiscordant couples, of whom 98% were heterosexual. The finding of a 96.4% reduction in HIV transmission in the early-ART group, vs those in the delayed group, provided the first evidence of treatment as prevention in a randomized clinical trial.5 At that point, the study could not address the durability of the finding or provide a precise correlation of the lack of transmissibility with an undetectable viral load. Importantly, after 5 additional years of follow-up, the durable, protective effect of early ART to maintain viral suppression and prevent HIV transmission was validated. There were no linked transmissions when viral load was durably suppressed by ART.6 Subsequent studies confirmed and extended these findings. The PARTNER 1 study determined the risk of HIV transmission via condomless sexual intercourse in 1166 HIV-discordant couples in which the partner with HIV was receiving ART and had achieved and maintained viral suppression (HIV-1 RNA viral load <200 copies/mL). After approximately 58 000 condomless sexual acts, there were no linked HIV transmissions.3 Since a minority of the HIV-discordant couples in PARTNER 1 were men who have sex with men (MSM), there was insufficient statistical power to determine the effect of an undetectable viral load on the transmission risk for receptive anal sex. In this regard, the Opposites Attract study evaluated transmissions involving 343 HIV-discordant MSM couples in Australia, Brazil, and Thailand. After 16 800 acts of condomless anal intercourse there were no linked HIV transmissions during 588.4 couple-years of follow-up during which time the partner with HIV had an undetectable viral load (<200 copies/mL).3 Building on these studies, the PARTNER 2 study conclusively demonstrated that there were no cases of HIV transmission between HIV-discordant MSM partners despite approximately 77 000 condomless sexual acts if the partner with HIV had achieved viral suppression and the uninfected partner was not receiving preexposure prophylaxis or postexposure prophylaxis.7 The validity of the U = U concept depends on achieving and maintaining an undetectable viral load in an individual with HIV. Because of the promise of U = U, achieving and maintaining an undetectable viral load becomes an aspirational goal and offers hope for persons with HIV. The principles involved in achieving and maintaining an undetectable viral load are related to (1) taking ART as prescribed and the importance of adherence; (2) time to viral suppression; (3) viral load testing recommendations; and (4) the risk of stopping ART (Box). Taking ART as prescribed is essential for achieving and maintaining an undetectable viral load. The Centers for Disease Control and Prevention (CDC) reported that of the individuals with HIV in the United States in HIV clinical care in 2015, approximately 20% had not achieved viral suppression (<200 HIV-1 RNA copies/mL) at their last test. CDC also noted that 40% of the individuals in HIV clinical care that same year did not maintain viral suppression for more than 12 months.8 Lack of adherence with ART is associated with many factors, including the lack of accessibility of quality health care. The stability of health care provided by programs such as the Ryan White HIV/AIDS Program shows that high rates of viral suppression are possible in the context of quality care delivery. VIEWPOINTread more
Citations
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Ending the HIV Epidemic: A Plan for the United States.
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Webster Mavhu,Nicola Willis,Juliet Mufuka,Sarah Bernays,Maureen Tshuma,Collin Mangenah,Hendramoorthy Maheswaran,Walter Mangezi,Tsitsi Apollo,Ricardo Araya,Helen A. Weiss,Frances M. Cowan +11 more
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References
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Journal ArticleDOI
Prevention of HIV-1 Infection with Early Antiretroviral Therapy
Myron S. Cohen,Ying Q. Chen,Marybeth McCauley,Theresa Gamble,Mina C. Hosseinipour,Nagalingeswaran Kumarasamy,James Hakim,Johnstone Kumwenda,Beatriz Grinsztejn,José Henrique Pilotto,Sheela Godbole,Sanjay Mehendale,Suwat Chariyalertsak,Breno Santos,Kenneth H. Mayer,Irving F. Hoffman,Susan H. Eshleman,Estelle Piwowar-Manning,Lei Wang,Joseph Makhema,Lisa A. Mills,Guy de Bruyn,Ian Sanne,Joseph J. Eron,Joel E. Gallant,Diane V. Havlir,Susan Swindells,Heather J. Ribaudo,Vanessa Elharrar,David N. Burns,Taha E. Taha,Karin Nielsen-Saines,David D. Celentano,Myron Essex,Thomas R. Fleming +34 more
TL;DR: In this article, Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples.
Journal ArticleDOI
Prevention of HIV-1 infection with early antiretroviral therapy
TL;DR: The exciting evidence generated by this paper – that antiretroviral treatment of HIV-1 infection definitively reduces the risk of onward transmission of the virus by 96% – was rightly dubbed Science magazine's ‘Breakthrough of the Year’ in 2011.
Journal ArticleDOI
Antiretroviral Therapy for the Prevention of HIV-1 Transmission
Myron S. Cohen,Ying Q. Chen,Marybeth McCauley,Theresa Gamble,Mina C. Hosseinipour,Nagalingeswaran Kumarasamy,James Hakim,Johnstone Kumwenda,Beatriz Grinsztejn,José Henrique Pilotto,Sheela Godbole,Suwat Chariyalertsak,Breno Santos,Kenneth H. Mayer,Irving F. Hoffman,Susan H. Eshleman,Estelle Piwowar-Manning,Leslie Cottle,Xinyi C. Zhang,Joseph Makhema,Lisa A. Mills,Ravindre Panchia,Sharlaa Faesen,Joseph J. Eron,Joel E. Gallant,Diane V. Havlir,Susan Swindells,Vanessa Elharrar,David N. Burns,Taha E. Taha,Karin Nielsen-Saines,David D. Celentano,Max Essex,Sarah E. Hudelson,Andrew D. Redd,Thomas R. Fleming +35 more
TL;DR: The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners, and was associated with a 93% lower risk of linked partner infection than was delayed ART.
Personnes seropositives ne souffrant daucune autre mst et suivant un traitement antiretroviral efficace ne transmettent pas le hiv par voie sexuelle
P Vernazza,B Hirshel +1 more
TL;DR: In this paper, the Commission federale pour les problemes lies au sida (CFS) arrive a conclusion suivante: Une personne seropositive ne souffrant d'aucune autre MST and suivant un traitement antiretroviral (TAR) avec une viremie entierement supprimee (condition designee par ''TAR efficace» ci-apres) ne transmet pas le VIH par voie sexuelle, c’esta-dire qu�
Journal ArticleDOI
Risk of sexual transmission of human immunodeficiency virus with antiretroviral therapy, suppressed viral load and condom use: a systematic review
Jennifer LeMessurier,Gregory Traversy,Olivia Varsaneux,Makenzie Weekes,Marc T. Avey,Oscar Niragira,Robert Gervais,Gordon H. Guyatt,Rachel Rodin +8 more
TL;DR: There is a negligible risk of sexual transmission of HIV when an HIV-positive sex partner adheres to antiretroviral therapy and maintains a suppressed viral load of less than 200 copies/mL measured every 4 to 6 months.
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