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

TitleAnalysis of genetic linkage of HIV from couples enrolled in the HIV Prevention Trials Network 052 trial.
Publication TypeJournal Article
Year of Publication2011
AuthorsEshleman SH, Hudelson SE, Redd AD, Wang L, Debes R, Chen YQ, Martens CA, Ricklefs SM, Selig EJ, Porcella SF, Munshaw S, Ray SC, Piwowar-Manning E, McCauley M, Hosseinipour MC, Kumwenda J, Hakim JG, Chariyalertsak S, de Bruyn G, Grinsztejn B, Kumarasamy N, Makhema J, Mayer KH, Pilotto J, Santos BR, Quinn TC, Cohen MS, Hughes JP
JournalJ Infect Dis
Volume204
Issue12
Pagination1918-26
Date Published2011 Dec 15
ISSN1537-6613
KeywordsAdult, Bayes Theorem, Female, Genetic Linkage, HIV Seropositivity, HIV-1, Humans, Male, Phylogeny, pol Gene Products, Human Immunodeficiency Virus, Sequence Analysis, DNA, Sexual Partners
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.

DOI10.1093/infdis/jir651
Alternate JournalJ. Infect. Dis.
PubMed ID21990420
PubMed Central IDPMC3209811
Grant ListP30 AI050410 / AI / NIAID NIH HHS / United States
R01 AI029168 / AI / NIAID NIH HHS / United States
R01 DA024565 / DA / NIDA NIH HHS / United States
R01DA024565 / DA / NIDA NIH HHS / United States
U01AI068613 / AI / NIAID NIH HHS / United States
U01AI068617 / AI / NIAID NIH HHS / United States
U01AI068619 / AI / NIAID NIH HHS / United States
UM1AI068613 / AI / NIAID NIH HHS / United States
/ / Intramural NIH HHS / United States