May 12, 2011
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The HPTN 052 study is a Phase III randomized clinical trial with the primary objective of evaluating whether antiretrovirals, which are medicines currently licensed to treat HIV infection, can prevent the sexual transmission of HIV among couples in which one partner is HIV-infected and the other is not (serodiscordant couples). Additionally, the study was designed to evaluate the optimal time to begin antiretroviral therapy in order to reduce illness and death among people infected with HIV/AIDS.
The study was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). Led by protocol chair Myron Cohen, M.D., director of the Institute for Global Health and Infectious Diseases at the University of North Carolina at Chapel Hill, the study was conducted by the HIV Prevention Trials Network (HPTN), which is largely funded by NIAID with additional funding from the National Institute on Drug Abuse and the National Institute of Mental Health, both part of the NIH. Additional support was provided by the NIAID-funded AIDS Clinical Trials Group.
The study began in April 2005. Enrollment ended in May 2010.
A total of 1,763 serodiscordant couples participated in the study. Each participant was at least 18 years of age (median age of 33). The vast majority of the couples (97 percent) were heterosexual. At the time of enrollment, the HIV-infected partners (890 men, 873 women) had CD4+ T-cell counts, a key measure of immune system health, between 350 and 550 cells per cubic millimeter (mm3) within 60 days of entering the study. The median CD4 count at study entry was 436 cells/mm3. The HIV-uninfected partners tested negative for the virus within 14 days of entering the study.
The study took place at 13 sites in Botswana, Brazil, India, Kenya, Malawi, South Africa, Thailand, the United States and Zimbabwe.
HPTN 052 participants were given a combination three- or four-drug regimen using the following 11 HIV drugs:
The study drugs were donated by Abbott Laboratories, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline and Merck & Co., Inc.
A data and safety monitoring board (DSMB) is an independent committee composed of clinical research experts, statisticians, ethicists, and community representatives that provides additional oversight of a clinical study. The DSMB regularly reviews data while a clinical trial is underway to ensure the safety of the participants and that any benefits shown in the study are quickly made available to all participants. A DSMB may recommend that a clinical trial, or part of a trial, be stopped or modified if there are safety concerns or if the trial objectives have been achieved or are unlikely to be achieved. A DSMB looks at analyses that are not available to the investigators. Restricting certain information to the DSMB while the trial is ongoing helps to maintain the integrity of the study.
The DSMB for the HPTN 052 study met at regular intervals throughout the course of the trial to review the study data. On April 28, 2011, the DSMB met for a scheduled interim review of the study’s safety and effectiveness data.
The DSMB found a total of 39 cases of HIV infection among the previously uninfected partners. Of those, 28 were linked through genetic testing to the HIV-infected partner as the source of
infection. Seven infections were not linked to the HIV-infected partner, and four infections are still undergoing analysis.
Of the 28 cases of linked HIV infection that occurred, 27 infections were among the 877 couples in which the HIV-infected partner delayed antiretroviral treatment. Only one case of HIV infection occurred among the 886 couples in which the HIV-infected partner began immediate antiretroviral treatment. Restated, this means that earlier initiation of antirerovirals led to a 96 percent reduction in HIV transmission to the HIV-uninfected partner. This result was statistically significant (P≤0.0001).
Based on this finding, the DSMB recommended that the study participants be notified of the results.
The study participants are being informed of the results. Antiretroviral therapy will be offered to all consenting HIV-infected participants in the deferred treatment arm. The study investigators will continue to follow the study participants for at least one year.
Individuals who became HIV-infected during the course of the study were referred to local services for appropriate medical care and treatment.
When the study began enrolling in April 2005, the protocol and the in-country guidelines of the participating site were consistent with the WHO treatment guidelines (November 2003) that recommended that anyone with advanced clinical HIV disease or those with CD4+ T-cell counts less than 200 cells/mm³ begin ART. However, the WHO guidelines were revised over time, recommending first that ART be considered between 200 and 350 cells/mm³ and initiated before 200 cells/mm³ (January 2006), and then to initiate antiretrovirals in all patients who have a CD4 cell count of less than 350 cells/mm³, irrespective of clinical symptoms (November 2009) In response to the first revision, most countries quickly adopted the new guidelines, and the study team changed the protocol such that the criteria for initiating antiretrovirals in the delayed treatment arm went from less than 200 cells/mm³ to between 200 and 250 cells/mm³ and raised the entry criteria for CD4 cell count from 300 to 500 cells/mm³ to 350 to 550 cells/mm³ to maintain the integrity of the study design. However, the second revision was not readily adopted by all of the countries participating in the study, primarily due to a lack of drug supply.
The study team, NIAID, and the DSMB carefully considered the same data that led to the second revision of the WHO guidelines. The DSMB concluded that no change in the study was necessary based on existing HPTN 052 data and taken into consideration the safety of the participants. Nevertheless, the study team and NIAID determined that all participants should be notified of the change in the WHO guidelines and any corresponding changes in country guidelines and reminded that they are free to leave the study at any time or to start antiretrovirals outside of the study, according to the local standard of care. This action was approved by all of the institutional review boards and ethics committees overseeing the study.
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Last Updated May 12, 2011
Last Reviewed May 11, 2011