Consensus: Controlling HIV With TasP and PrEP
Consensus: Controlling HIV With TasP and PrEP
The development of effective antiretroviral therapy (ART) and the expansion of access to this life-saving and enhancing medical interventions across the world have been critical successes in HIV treatment. Since 1996, ART has added 14 million years of life in low- and middle-income countries alone; more than 9 million of those are in sub-Saharan Africa.
In contrast, despite the diligent work advanced by many, prevention efforts have experienced slower progress. Although HIV incidence has declined globally, it remains at unacceptably high levels in many developed and developing world countries. Biobehavioral prevention (biomedical interventions that require ongoing self-administration to be effective)—both treatment as prevention (TasP; the provision to and use of ART by HIV-infected individuals to reduce morbidity and mortality as well as the risk of onward HIV transmission through durable viral suppression) and preexposure prophylaxis (PrEP; the use of oral ART or topical microbicides by HIV-uninfected individuals before and after potential sexual exposure to HIV to reduce the risk of acquisition of the virus)—now offers new options for preventing HIV infection and the potential to end the HIV pandemic. Over the past year, TasP and PrEP have reached important milestones.
HTPN 052, a study of 1763 serodiscordant (also referred to as serodifferent) couples in which the HIV-infected partner had a CD4 count of 350 to 550 cells/mm, was stopped early when the independent data and safety monitoring board saw a 96% reduction of transmission from the HIV-infected partner to the uninfected partner in couples who initiated ART when they entered the study. On the basis of this result, Science selected TasP as the scientific breakthrough of the year for 2011. In April 2012, the World Health Organization published guidance on testing and counseling of HIV serodiscordant couples which includes the use of ART to reduce the risk of transmission. Earlier epidemiological studies suggested that expanded ART coverage played a role in decreasing HIV infection rates in San Francisco, British Columbia, and Denmark, as well as mathematical models support the theory that expanding access to TasP to the community level will decrease the HIV incidence. Although expanding access to treatment has clearly had significant impact, ongoing and planned research will further examine the impact of earlier initiation of ART on HIV incidence as part of a combination prevention strategy, taking into account the diversity of the HIV epidemic in different parts of the world. Despite the promising findings from HPTN 052 and other studies, initiation of ART upon diagnosis with HIV irrespective of CD4 count for those who want to initiate treatment will require resources and political will.
The iPrEx study in men who have sex with men (MSM) provided with daily oral emitricitabine-tenofovir (FTC-TDF) reported a 44% reduction (95% confidence interval [CI]: 15%-63%) in new HIV infections; the result in participants with detectable drug levels in plasma was a 92% reduction (95% CI: 40%-99%). After these results were released, the US Centers for Disease Control and Prevention issued interim guidance on FTC-TDF use for PrEP in high-risk MSM. The partners PrEP study of serodiscordant couples showed a 75% reduction (95% CI: 55%-87%) in new HIV infections with daily oral FTC-TDF and 67% (95% CI: 44%-81%) with TDF, again with better results (90% for FTC-TDF and 86% for TDF) in patients with detectable drug levels. On July 16, 2012, the US Food and Drug Administration (FDA) approved FTC-TDF for PrEP for HIV-uninfected MSM, HIV-uninfected partners in serodiscordant couples, and other individuals at risk of acquiring HIV through sexual activity. Two other PrEP studies had equivocal results, perhaps due to difficulties with adherence. Research continues with studies of alternatives to daily dosing (eg, twice weekly and sex-dependent regimens); studies of different antiretroviral (ARV) agents (including nonnucleoside reverse transcriptase inhibitors such as dapivirine, entry inhibitors such as maraviroc, and integrase inhibitors); and studies of non-oral PrEP technologies such as vaginal and rectal microbicides, intravaginal rings, and injectable agents.
Background
The development of effective antiretroviral therapy (ART) and the expansion of access to this life-saving and enhancing medical interventions across the world have been critical successes in HIV treatment. Since 1996, ART has added 14 million years of life in low- and middle-income countries alone; more than 9 million of those are in sub-Saharan Africa.
In contrast, despite the diligent work advanced by many, prevention efforts have experienced slower progress. Although HIV incidence has declined globally, it remains at unacceptably high levels in many developed and developing world countries. Biobehavioral prevention (biomedical interventions that require ongoing self-administration to be effective)—both treatment as prevention (TasP; the provision to and use of ART by HIV-infected individuals to reduce morbidity and mortality as well as the risk of onward HIV transmission through durable viral suppression) and preexposure prophylaxis (PrEP; the use of oral ART or topical microbicides by HIV-uninfected individuals before and after potential sexual exposure to HIV to reduce the risk of acquisition of the virus)—now offers new options for preventing HIV infection and the potential to end the HIV pandemic. Over the past year, TasP and PrEP have reached important milestones.
Treatment as Prevention
HTPN 052, a study of 1763 serodiscordant (also referred to as serodifferent) couples in which the HIV-infected partner had a CD4 count of 350 to 550 cells/mm, was stopped early when the independent data and safety monitoring board saw a 96% reduction of transmission from the HIV-infected partner to the uninfected partner in couples who initiated ART when they entered the study. On the basis of this result, Science selected TasP as the scientific breakthrough of the year for 2011. In April 2012, the World Health Organization published guidance on testing and counseling of HIV serodiscordant couples which includes the use of ART to reduce the risk of transmission. Earlier epidemiological studies suggested that expanded ART coverage played a role in decreasing HIV infection rates in San Francisco, British Columbia, and Denmark, as well as mathematical models support the theory that expanding access to TasP to the community level will decrease the HIV incidence. Although expanding access to treatment has clearly had significant impact, ongoing and planned research will further examine the impact of earlier initiation of ART on HIV incidence as part of a combination prevention strategy, taking into account the diversity of the HIV epidemic in different parts of the world. Despite the promising findings from HPTN 052 and other studies, initiation of ART upon diagnosis with HIV irrespective of CD4 count for those who want to initiate treatment will require resources and political will.
Preexposure Prophylaxis
The iPrEx study in men who have sex with men (MSM) provided with daily oral emitricitabine-tenofovir (FTC-TDF) reported a 44% reduction (95% confidence interval [CI]: 15%-63%) in new HIV infections; the result in participants with detectable drug levels in plasma was a 92% reduction (95% CI: 40%-99%). After these results were released, the US Centers for Disease Control and Prevention issued interim guidance on FTC-TDF use for PrEP in high-risk MSM. The partners PrEP study of serodiscordant couples showed a 75% reduction (95% CI: 55%-87%) in new HIV infections with daily oral FTC-TDF and 67% (95% CI: 44%-81%) with TDF, again with better results (90% for FTC-TDF and 86% for TDF) in patients with detectable drug levels. On July 16, 2012, the US Food and Drug Administration (FDA) approved FTC-TDF for PrEP for HIV-uninfected MSM, HIV-uninfected partners in serodiscordant couples, and other individuals at risk of acquiring HIV through sexual activity. Two other PrEP studies had equivocal results, perhaps due to difficulties with adherence. Research continues with studies of alternatives to daily dosing (eg, twice weekly and sex-dependent regimens); studies of different antiretroviral (ARV) agents (including nonnucleoside reverse transcriptase inhibitors such as dapivirine, entry inhibitors such as maraviroc, and integrase inhibitors); and studies of non-oral PrEP technologies such as vaginal and rectal microbicides, intravaginal rings, and injectable agents.