Antiretroviral Therapy for the Prevention of HIV-1 Transmission
18 Jul 2016-The New England Journal of Medicine (Massachusetts Medical Society)-Vol. 375, Iss: 9, pp 830-839
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.
Abstract: BackgroundAn interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. MethodsWe randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked H...
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TL;DR: The results suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero, which supports the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV.
552 citations
23 Jul 2021
TL;DR: These guidelines for the treatment of persons who have or are at risk for sexually transmitted infections (STIs) were updated by CDC after consultation with professionals knowledgeable in the field of STIs who met in Atlanta, Georgia, June 11-14, 2019.
Abstract: These guidelines for the treatment of persons who have or are at risk for sexually transmitted infections (STIs) were updated by CDC after consultation with professionals knowledgeable in the field of STIs who met in Atlanta, Georgia, June 11-14, 2019. The information in this report updates the 2015 guidelines. These guidelines discuss 1) updated recommendations for treatment of Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis; 2) addition of metronidazole to the recommended treatment regimen for pelvic inflammatory disease; 3) alternative treatment options for bacterial vaginosis; 4) management of Mycoplasma genitalium; 5) human papillomavirus vaccine recommendations and counseling messages; 6) expanded risk factors for syphilis testing among pregnant women; 7) one-time testing for hepatitis C infection; 8) evaluation of men who have sex with men after sexual assault; and 9) two-step testing for serologic diagnosis of genital herpes simplex virus. Physicians and other health care providers can use these guidelines to assist in prevention and treatment of STIs.
544 citations
TL;DR: 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. VIEWPOINT
434 citations
TL;DR: Transmission rates in couples reporting condomless anal intercourse are calculated, when HIV-positive partners were virally suppressed, and daily pre-exposure prophylaxis (PrEP) was not used by HIV-negative partners.
292 citations
TL;DR: In this paper, the authors address the significant mental health and substance use problems among people living with HIV (PLWH) and people vulnerable to acquiring HIV (PVC) and highlight the need to prioritize mental health treatment with appropriate resources to address the current mental health screening and treatment gaps.
Abstract: Tremendous biomedical advancements in HIV prevention and treatment have led to aspirational efforts to end the HIV epidemic. However, this goal will not be achieved without addressing the significant mental health and substance use problems among people living with HIV (PLWH) and people vulnerable to acquiring HIV. These problems exacerbate the many social and economic barriers to accessing adequate and sustained healthcare, and are among the most challenging barriers to achieving the end of the HIV epidemic. Rates of mental health problems are higher among both people vulnerable to acquiring HIV and PLWH, compared with the general population. Mental health impairments increase risk for HIV acquisition and for negative health outcomes among PLWH at each step in the HIV care continuum. We have the necessary screening tools and efficacious treatments to treat mental health problems among people living with and at risk for HIV. However, we need to prioritize mental health treatment with appropriate resources to address the current mental health screening and treatment gaps. Integration of mental health screening and care into all HIV testing and treatment settings would not only strengthen HIV prevention and care outcomes, but it would additionally improve global access to mental healthcare.
289 citations
Cites methods from "Antiretroviral Therapy for the Prev..."
...Findings from the HPTN 052 trial and PARTNER studies have definitively demonstrated that HIV treatment is prevention [3,4]....
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References
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University of North Carolina at Chapel Hill1, Fred Hutchinson Cancer Research Center2, FHI 3603, University of Zimbabwe4, Johns Hopkins University5, Oswaldo Cruz Foundation6, Chiang Mai University7, Fenway Health8, Harvard University9, Kenya Medical Research Institute10, University of the Witwatersrand11, University of California, San Francisco12, University of Nebraska Medical Center13, National Institutes of Health14, University of California, Los Angeles15, University of Washington16
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.
Abstract: Background Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. Methods In nine countries, we...
5,871 citations
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.
Abstract: MS Cohen, YQ Chen, M McCauley N Engl J Med 2011 365:493–505.
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 2011.1 ,2
It has long been known that the probability of sexual transmission of HIV is strongly correlated with concentrations of HIV in blood and genital fluids.3 ,4 Effective antiretroviral therapy (ART) produces prolonged and sustained suppression of HIV replication in these compartments, reducing the amount of free virus.5 ,6 Thus, there has long been a …
4,259 citations
TL;DR: The viral load is the chief predictor of the risk of heterosexual transmission of HIV-1, and transmission is rare among persons with levels of less than 1500 copies of HIV -1 RNA per milliliter.
Abstract: Background and Methods We examined the influence of viral load in relation to other risk factors for the heterosexual transmission of human immunodeficiency virus type 1 (HIV-1). In a community-based study of 15,127 persons in a rural district of Uganda, we identified 415 couples in which one partner was HIV-1–positive and one was initially HIV-1–negative and followed them prospectively for up to 30 months. The incidence of HIV-1 infection per 100 person-years among the initially seronegative partners was examined in relation to behavioral and biologic variables. Results The male partner was HIV-1–positive in 228 couples, and the female partner was HIV-1–positive in 187 couples. Ninety of the 415 initially HIV-1–negative partners seroconverted (incidence, 11.8 per 100 person-years). The rate of male-to-female transmission was not significantly different from the rate of female-to-male transmission (12.0 per 100 person-years vs. 11.6 per 100 person-years). The incidence of seroconversion was highest among ...
2,897 citations
TL;DR: The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+, but the risks of unscheduled hospital admissions were similar in the two groups.
Abstract: BACKGROUND Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. METHODS We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non–AIDS-related event, or death from any cause. RESULTS A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 personyears), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non–AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P = 0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. CONCLUSIONS The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.)
2,215 citations
University College London1, University of Copenhagen2, University of St. Gallen3, University of Hamburg4, Hospital Clínico San Carlos5, University of Liverpool6, Universidad Miguel Hernández de Elche7, University of Victoria8, University of Zurich9, Karolinska University Hospital10, University of Bern11, Medical University of Vienna12, University Hospital of Basel13, Praxis14, Helsinki University Central Hospital15, Warwickshire Hospital16
TL;DR: Evaluating the rate of within-couple HIV transmission among serodifferent heterosexual and MSM couples during periods of sex without condoms and when the HIV-positive partner had HIV-1 RNA load less than 200 copies/mL found no phylogenetically linked transmissions.
Abstract: Importance A key factor in assessing the effectiveness and cost-effectiveness of antiretroviral therapy (ART) as a prevention strategy is the absolute risk of HIV transmission through condomless sex with suppressed HIV-1 RNA viral load for both anal and vaginal sex. Objective To evaluate the rate of within-couple HIV transmission (heterosexual and men who have sex with men [MSM]) during periods of sex without condoms and when the HIV-positive partner had HIV-1 RNA load less than 200 copies/mL. Design, Setting, and Participants The prospective, observational PARTNER (Partners of People on ART—A New Evaluation of the Risks) study was conducted at 75 clinical sites in 14 European countries and enrolled 1166 HIV serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex (September 2010 to May 2014). Eligibility criteria for inclusion of couple-years of follow-up were condomless sex and HIV-1 RNA load less than 200 copies/mL. Anonymized phylogenetic analysis compared couples’ HIV-1 polymerase and envelope sequences if an HIV-negative partner became infected to determine phylogenetically linked transmissions. Exposures Condomless sexual activity with an HIV-positive partner taking virally suppressive ART. Main Outcomes and Measures Risk of within-couple HIV transmission to the HIV-negative partner Results Among 1166 enrolled couples, 888 (mean age, 42 years [IQR, 35-48]; 548 heterosexual [61.7%] and 340 MSM [38.3%]) provided 1238 eligible couple-years of follow-up (median follow-up, 1.3 years [IQR, 0.8-2.0]). At baseline, couples reported condomless sex for a median of 2 years (IQR, 0.5-6.3). Condomless sex with other partners was reported by 108 HIV-negative MSM (33%) and 21 heterosexuals (4%). During follow-up, couples reported condomless sex a median of 37 times per year (IQR, 15-71), with MSM couples reporting approximately 22 000 condomless sex acts and heterosexuals approximately 36 000. Although 11 HIV-negative partners became HIV-positive (10 MSM; 1 heterosexual; 8 reported condomless sex with other partners), no phylogenetically linked transmissions occurred over eligible couple-years of follow-up, giving a rate of within-couple HIV transmission of zero, with an upper 95% confidence limit of 0.30/100 couple-years of follow-up. The upper 95% confidence limit for condomless anal sex was 0.71 per 100 couple-years of follow-up. Conclusions and Relevance Among serodifferent heterosexual and MSM couples in which the HIV-positive partner was using suppressive ART and who reported condomless sex, during median follow-up of 1.3 years per couple, there were no documented cases of within-couple HIV transmission (upper 95% confidence limit, 0.30/100 couple-years of follow-up). Additional longer-term follow-up is necessary to provide more precise estimates of risk.
1,039 citations