Dataset Information

Analysis of genetic linkage of HIV from couples enrolled in the HIV Prevention Trials Network 052 trial.

ABSTRACT: BACKGROUND:The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early initiation of antiretroviral therapy (ART) reduces human immunodeficiency virus (HIV) transmission from HIV-infected adults (index participants) to their HIV-uninfected sexual partners. We analyzed HIV from 38 index-partner pairs and 80 unrelated index participants (controls) to assess the linkage of seroconversion events. METHODS:Linkage was assessed using phylogenetic analysis of HIV pol sequences and Bayesian analysis of genetic distances between pol sequences from index-partner pairs and controls. Selected samples were also analyzed using next-generation sequencing (env region). RESULTS:In 29 of the 38 (76.3%) cases analyzed, the index was the likely source of the partner's HIV infection (linked). In 7 cases (18.4%), the partner was most likely infected from a source other than the index participant (unlinked). In 2 cases (5.3%), linkage status could not be definitively established. CONCLUSIONS:Nearly one-fifth of the seroconversion events in HPTN 052 were unlinked. The association of early ART and reduced HIV transmission was stronger when the analysis included only linked events. This underscores the importance of assessing the genetic linkage of HIV seroconversion events in HIV prevention studies involving serodiscordant couples.

SUBMITTER: Eshleman SH

PROVIDER: S-EPMC3209811 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Analysis of genetic linkage of HIV from couples enrolled in the HIV Prevention Trials Network 052 trial.

Eshleman Susan H SH Hudelson Sarah E SE Redd Andrew D AD Wang Lei L Debes Rachel R Chen Ying Q YQ Martens Craig A CA Ricklefs Stacy M SM Selig Ethan J EJ Porcella Stephen F SF Munshaw Supriya S Ray Stuart C SC Piwowar-Manning Estelle E McCauley Marybeth M Hosseinipour Mina C MC Kumwenda Johnstone J Hakim James G JG Chariyalertsak Suwat S de Bruyn Guy G Grinsztejn Beatriz B Kumarasamy Nagalingeswaran N Makhema Joseph J Mayer Kenneth H KH Pilotto Jose J Santos Breno R BR Quinn Thomas C TC Cohen Myron S MS Hughes James P JP

The Journal of infectious diseases 20111011 12

<h4>Background</h4>The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early initiation of antiretroviral therapy (ART) reduces human immunodeficiency virus (HIV) transmission from HIV-infected adults (index participants) to their HIV-uninfected sexual partners. We analyzed HIV from 38 index-partner pairs and 80 unrelated index participants (controls) to assess the linkage of seroconversion events.<h4>Methods</h4>Linkage was assessed using phylogenetic analysis of HIV pol sequen ...[more]

PMID: 21990420

Similar Datasets

Project description:Obtaining the definitive data necessary to determine the safety and efficacy of using antiretroviral treatment (ART) to reduce the sexual transmission of HIV in heterosexual couples encountered an array of ethical challenges that threatened to compromise HIV Prevention Trials Network (HPTN) 052, the multinational clinical trial addressing this issue that has profound public health implications.To describe and analyze the major ethical challenges faced in HPTN 052.The ethical issues and modifications of HPTN 052 in response to these issues were cataloged by the principal investigator, the lead coordinator, and the ethicist working on the trial. The major ethical issues that were unique to the trial were then described and analyzed in light of the published literature as well as guidances and policies. The ethical challenges that must be addressed in many clinical trials, such as those related to obtaining informed consent and making provisions for ancillary care, are not described.When HPTN 052 was being designed, ethical questions emerged related to the relevance of the research question itself given data from observational research and a range of beliefs about the appropriate means of preventing and treating HIV infection and AIDS. Furthermore, ethical challenges were faced regarding site selection since there was a scientific need to conduct the research in settings where HIV incidence was high, but alternatives to study participation should be available. As in most HIV-prevention research, ethical questions surrounded the determination of the appropriate prevention package for all of those enrolled. During the course of the trial, guidance documents and policies emerged that were of direct relevance to the research questions, calling for a balancing of concerns for the research subjects and trial integrity. When the study results were made public, there was a need to ensure access to the treatment shown to be effective that in some cases differed from the guidelines used at the sites where the research was being conducted. In addition, questions were raised about whether there was an obligation to notify subjects about 'unlinked' transmissions of HIV, that is, infections acquired from someone other than the designated sexual partner enrolled in the study.The ethical issues described are limited to those discerned by the authors and not those of other stakeholders who may have identified additional issues or had a different perspective in analyzing them.Understanding the ethical challenges faced in HPTN 052 promises to inform the design and conduct of future complex, long-term clinical trials aimed at addressing critical scientific and public health questions, where data and practice patterns emerge over the course of the trial.

Dataset Information

Analysis of genetic linkage of HIV from couples enrolled in the HIV Prevention Trials Network 052 trial.

Publications

Analysis of genetic linkage of HIV from couples enrolled in the HIV Prevention Trials Network 052 trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets