Successful treatment of HIV eliminates sexual transmission
Authors: Myron S Cohen
Journal: The Lancet (2019)

In December, 2011, Science recognised the findings of the HPTN 052 study1Cohen MS Chen YQ McCauley M et al.Prevention of HIV-1 infection with early antiretroviral therapy.N Engl J Med. 2011; 365: 493-505Crossref PubMed Scopus (5412) Google Scholar as the scientific breakthrough of the year.2Cohen J Breakthrough of the year. HIV treatment as prevention.Science. 2011; 334: 1628Crossref PubMed Scopus (109) Google Scholar This study showed a 96% reduction in sexual transmission of HIV in serodifferent couples (one partner HIV positive, the other HIV negative) when the HIV-positive partner was successfully treated with antiretroviral therapy (ART).1Cohen MS Chen YQ McCauley M et al.Prevention of HIV-1 infection with early antiretroviral therapy.N Engl J Med. 2011; 365: 493-505Crossref PubMed Scopus (5412) Google Scholar However, the HPTN 052 study included only a small number of men who have sex with men (MSM), for whom HIV acquisition often includes anal exposure, an efficient route of HIV transmission.3Baggaley RF White RG Boily MC HIV transmission risk through anal intercourse: systematic review, meta-analysis and implications for HIV prevention.Int J Epidemiol. 2010; 39: 1048-1063Crossref PubMed Scopus (519) Google Scholar Furthermore, the couples in the HPTN 052 study were counselled to use condoms, so the observed benefits of ART also reflected the contribution of safer sexual behaviours. Accordingly, other investigators4Rodger AJ Cambiano V Bruun T et al.Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy.JAMA. 2016; 316: 171-181Crossref PubMed Scopus (860) Google Scholar, 5Rodger AJ Cambiano V Bruun T et al.Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER2): final results of a multicentre, prospective, observational study.Lancet. 2019; (published online May 2.)http://dx.doi.org/10.1016/S0140-6736(19)30418-0Summary Full Text Full Text PDF PubMed Scopus (441) Google Scholar have subsequently studied HIV transmission in couples who specifically chose not to use condoms. In 2016, the results of the PARTNER study were reported,4Rodger AJ Cambiano V Bruun T et al.Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy.JAMA. 2016; 316: 171-181Crossref PubMed Scopus (860) Google Scholar a study that had enrolled 1166 serodifferent couples at 75 sites in 14 European countries between 2010 and 2014; 340 gay couples were included. The study reported no HIV transmission from ART-treated gay men with viral suppression to their sexual partners, but the upper confidence limit of calculated risk from unprotected receptive anal intercourse with ejaculation was 2·70 per 100 couple-years of follow-up. The estimate for HIV transmission in gay couples was less precise than that obtained for heterosexual couples because of the lower number of couple-years of follow-up accrued; thus, the investigators launched the PARTNER2 study, the results of which are now reported by Alison Rodger and colleagues5Rodger AJ Cambiano V Bruun T et al.Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER2): final results of a multicentre, prospective, observational study.Lancet. 2019; (published online May 2.)http://dx.doi.org/10.1016/S0140-6736(19)30418-0Summary Full Text Full Text PDF PubMed Scopus (441) Google Scholar in The Lancet. From 2014 to 2017, the investigators continued recruitment of an additional 495 gay couples. In the PARTNER2 study, 782 couples provided evaluable results over 1593 couple-years of follow-up, including 76 088 self-reported episodes of condomless anal intercourse. The investigators observed no episodes of HIV transmission from the HIV-positive partners to their HIV-negative sexual partners. They concluded that the risk of HIV transmission from an HIV-infected man receiving ART with a plasma HIV-1 RNA (viral load) of less than 200 copies per mL over the preceding year was, remarkably, zero, with a narrow upper 95% CI limit of 0·23 per 100 couple-years of follow-up. These important results serve to inspire and challenge us. Timely identification of HIV-infected people and provision of effective treatment lead to near normal health and lifespan6Antiretroviral Therapy Cohort CollaborationSurvival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies.Lancet HIV. 2017; 4: e349-e356Summary Full Text Full Text PDF PubMed Scopus (611) Google Scholar and virtual elimination of the risk of HIV transmission.1Cohen MS Chen YQ McCauley M et al.Prevention of HIV-1 infection with early antiretroviral therapy.N Engl J Med. 2011; 365: 493-505Crossref PubMed Scopus (5412) Google Scholar, 4Rodger AJ Cambiano V Bruun T et al.Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy.JAMA. 2016; 316: 171-181Crossref PubMed Scopus (860) Google Scholar, 5Rodger AJ Cambiano V Bruun T et al.Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER2): final results of a multicentre, prospective, observational study.Lancet. 2019; (published online May 2.)http://dx.doi.org/10.1016/S0140-6736(19)30418-0Summary Full Text Full Text PDF PubMed Scopus (441) Google Scholar, 7Bavinton BR Pinto AN Phanuphak N et al.Viral suppression and HIV transmission in serodiscordant male couples: an international, prospective, observational, cohort study.Lancet HIV. 2018; 5: e438-e447Summary Full Text Full Text PDF PubMed Scopus (245) Google Scholar Yet maximising the benefits of ART has proven daunting, especially for MSM. It is not always easy for people to get tested for HIV or find access to care; in addition, fear, stigma, homophobia, and other adverse social forces continue to compromise HIV treatment. Furthermore, diagnosis of HIV infection is difficult in the early stages of infection when transmission is very efficient,8Pilcher CD Tien HC Eron Jr, JJ et al.Brief but efficient: acute HIV infection and the sexual transmission of HIV.J Infect Dis. 2004; 189: 1785-1792Crossref PubMed Scopus (538) Google Scholar and this limitation also compromises the treatment as prevention strategy.9Ratmann O van Sighem A Bezemer D et al.Sources of HIV infection among men having sex with men and implications for prevention.Sci Transl Med. 2016; 8: 320ra2Crossref PubMed Scopus (83) Google Scholar The US Government has recently announced a plan to end the HIV epidemic in the USA in the next 10 years.10Fauci AS Redfield RR Sigounas G Weahkee MD Giroir BP Ending the HIV epidemic: a plan for the United States.JAMA. 2019; (published online Feb 7.)DOI:10.1001/jama.2019.1343Crossref Scopus (669) Google Scholar The pillars of the strategic initiative include detection and treatment of HIV without delay, a goal clearly justified by the PARTNER2 results.5Rodger AJ Cambiano V Bruun T et al.Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER2): final results of a multicentre, prospective, observational study.Lancet. 2019; (published online May 2.)http://dx.doi.org/10.1016/S0140-6736(19)30418-0Summary Full Text Full Text PDF PubMed Scopus (441) Google Scholar The plan also includes detection and accelerated treatment of clusters of HIV-infected people with related HIV variants and social linkage; such clusters are often driven by the presence of undetected acute and early infections.8Pilcher CD Tien HC Eron Jr, JJ et al.Brief but efficient: acute HIV infection and the sexual transmission of HIV.J Infect Dis. 2004; 189: 1785-1792Crossref PubMed Scopus (538) Google Scholar, 9Ratmann O van Sighem A Bezemer D et al.Sources of HIV infection among men having sex with men and implications for prevention.Sci Transl Med. 2016; 8: 320ra2Crossref PubMed Scopus (83) Google Scholar Results of the PARTNER studies4Rodger AJ Cambiano V Bruun T et al.Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy.JAMA. 2016; 316: 171-181Crossref PubMed Scopus (860) Google Scholar, 5Rodger AJ Cambiano V Bruun T et al.Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER2): final results of a multicentre, prospective, observational study.Lancet. 2019; (published online May 2.)http://dx.doi.org/10.1016/S0140-6736(19)30418-0Summary Full Text Full Text PDF PubMed Scopus (441) Google Scholar along with those from other studies of MSM7Bavinton BR Pinto AN Phanuphak N et al.Viral suppression and HIV transmission in serodiscordant male couples: an international, prospective, observational, cohort study.Lancet HIV. 2018; 5: e438-e447Summary Full Text Full Text PDF PubMed Scopus (245) Google Scholar, 9Ratmann O van Sighem A Bezemer D et al.Sources of HIV infection among men having sex with men and implications for prevention.Sci Transl Med. 2016; 8: 320ra2Crossref PubMed Scopus (83) Google Scholar and heterosexual couples1Cohen MS Chen YQ McCauley M et al.Prevention of HIV-1 infection with early antiretroviral therapy.N Engl J Med. 2011; 365: 493-505Crossref PubMed Scopus (5412) Google Scholar also emphasise the impact of additional sexual relationships outside the couples. Incident sexually transmitted infections have frequently been detected in either partner in studies of serodifferent couples, indicating additional sexual contacts.1Cohen MS Chen YQ McCauley M et al.Prevention of HIV-1 infection with early antiretroviral therapy.N Engl J Med. 2011; 365: 493-505Crossref PubMed Scopus (5412) Google Scholar, 4Rodger AJ Cambiano V Bruun T et al.Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy.JAMA. 2016; 316: 171-181Crossref PubMed Scopus (860) Google Scholar, 5Rodger AJ Cambiano V Bruun T et al.Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER2): final results of a multicentre, prospective, observational study.Lancet. 2019; (published online May 2.)http://dx.doi.org/10.1016/S0140-6736(19)30418-0Summary Full Text Full Text PDF PubMed Scopus (441) Google Scholar, 7Bavinton BR Pinto AN Phanuphak N et al.Viral suppression and HIV transmission in serodiscordant male couples: an international, prospective, observational, cohort study.Lancet HIV. 2018; 5: e438-e447Summary Full Text Full Text PDF PubMed Scopus (245) Google Scholar In gay couples in the PARTNER studies, a total of 15 HIV infections acquired outside the primary partnership were observed.5Rodger AJ Cambiano V Bruun T et al.Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER2): final results of a multicentre, prospective, observational study.Lancet. 2019; (published online May 2.)http://dx.doi.org/10.1016/S0140-6736(19)30418-0Summary Full Text Full Text PDF PubMed Scopus (441) Google Scholar Use of pre-exposure prophylaxis (PrEP) with the combination of emtricitabine and tenofovir disoproxil fumarate by the HIV-negative partner was an exclusion criterion for eligible couple-years of follow-up in the PARTNER studies,4Rodger AJ Cambiano V Bruun T et al.Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy.JAMA. 2016; 316: 171-181Crossref PubMed Scopus (860) Google Scholar, 5Rodger AJ Cambiano V Bruun T et al.Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER2): final results of a multicentre, prospective, observational study.Lancet. 2019; (published online May 2.)http://dx.doi.org/10.1016/S0140-6736(19)30418-0Summary Full Text Full Text PDF PubMed Scopus (441) Google Scholar but this intervention has emerged as an important method for HIV prevention11Centers for Disease Control and PreventionPreexposure prophylaxis for the prevention of HIV infection in the United States–2017 update: a clinical practice guideline.https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2017.pdfDate: March 2018Date accessed: March 14, 2019Google Scholar and is one of the pillars of the US HIV elimination plan.10Fauci AS Redfield RR Sigounas G Weahkee MD Giroir BP Ending the HIV epidemic: a plan for the United States.JAMA. 2019; (published online Feb 7.)DOI:10.1001/jama.2019.1343Crossref Scopus (669) Google Scholar PrEP offers protection from HIV acquisition.10Fauci AS Redfield RR Sigounas G Weahkee MD Giroir BP Ending the HIV epidemic: a plan for the United States.JAMA. 2019; (published online Feb 7.)DOI:10.1001/jama.2019.1343Crossref Scopus (669) Google Scholar, 11Centers for Disease Control and PreventionPreexposure prophylaxis for the prevention of HIV infection in the United States–2017 update: a clinical practice guideline.https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2017.pdfDate: March 2018Date accessed: March 14, 2019Google Scholar Indeed, a recent survey reported PrEP to be more popular and trusted by MSM for HIV prevention than treatment as prevention,12Siegel K Meunier E Awareness and perceived effectiveness of HIV treatment as prevention among men who have sex with men in New York City.AIDS Behav. 2019; (published online Jan 29.)DOI:10.1007/s10461-019-02405-yCrossref Scopus (22) Google Scholar reflecting the complex considerations of the HIV-negative partner in a sexual relationship. It has taken considerable time and massive effort to prove that antiretroviral drugs can prevent HIV through treatment or as PrEP. During the course of these studies, antiretroviral drugs have become more effective, reliable, durable, easier to take, well tolerated, and much less expensive. The results of the PARTNER2 study provide yet one more catalyst for a universal test-and-treat strategy to provide the full benefits of antiretroviral drugs. This and other strategies10Fauci AS Redfield RR Sigounas G Weahkee MD Giroir BP Ending the HIV epidemic: a plan for the United States.JAMA. 2019; (published online Feb 7.)DOI:10.1001/jama.2019.1343Crossref Scopus (669) Google Scholar continue to push us toward the end of AIDS. I report advisory board travel fees from Merck and Gilead, outside the area of work commented on here. Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational studyOur results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV. Full-Text PDF Open Access