Viral linkage in HIV-1 seroconverters and their partners in an HIV-1 prevention clinical trial.
Viral linkage in HIV-1 seroconverters and their partners in an HIV-1 prevention clinical trial.
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DOI：
10.1371/journal.pone.0016986
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发表时间：
2011-03-02
期刊：
影响因子：
3.7
通讯作者：
Partners in Prevention HSV/HIV Transmission Study Team
中科院分区：
文献类型：
--
作者：
Campbell MS;Mullins JI;Hughes JP;Celum C;Wong KG;Raugi DN;Sorensen S;Stoddard JN;Zhao H;Deng W;Kahle E;Panteleeff D;Baeten JM;McCutchan FE;Albert J;Leitner T;Wald A;Corey L;Lingappa JR;Partners in Prevention HSV/HIV Transmission Study Team
Characterization of viruses in HIV-1 transmission pairs will help identify biological determinants of infectiousness and evaluate candidate interventions to reduce transmission. Although HIV-1 sequencing is frequently used to substantiate linkage between newly HIV-1 infected individuals and their sexual partners in epidemiologic and forensic studies, viral sequencing is seldom applied in HIV-1 prevention trials. The Partners in Prevention HSV/HIV Transmission Study (ClinicalTrials.gov #NCT00194519) was a prospective randomized placebo-controlled trial that enrolled serodiscordant heterosexual couples to determine the efficacy of genital herpes suppression in reducing HIV-1 transmission; as part of the study analysis, HIV-1 sequences were examined for genetic linkage between seroconverters and their enrolled partners. We obtained partial consensus HIV-1 env and gag sequences from blood plasma for 151 transmission pairs and performed deep sequencing of env in some cases. We analyzed sequences with phylogenetic techniques and developed a Bayesian algorithm to evaluate the probability of linkage. For linkage, we required monophyletic clustering between enrolled partners' sequences and a Bayesian posterior probability of ≥50%. Adjudicators classified each seroconversion, finding 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) indeterminate transmissions, with linkage determined by consensus env sequencing in 91 (84%). Male seroconverters had a higher frequency of unlinked transmissions than female seroconverters. The likelihood of transmission from the enrolled partner was related to time on study, with increasing numbers of unlinked transmissions occurring after longer observation periods. Finally, baseline viral load was found to be significantly higher among linked transmitters. In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner, illustrating the relevance of these methods in the design of future HIV-1 prevention trials in serodiscordant couples. A hierarchy of sequencing techniques, analysis methods, and expert adjudication contributed to the linkage determination process.
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雌性生殖道内HIV-1的隔室化是由于单型和低多样性变体而不是不同的病毒群体引起的。
影响因子：
3.7
作者：
Bull M;Learn G;Genowati I;McKernan J;Hitti J;Lockhart D;Tapia K;Holte S;Dragavon J;Coombs R;Mullins J;Frenkel L
通讯作者：
Frenkel L
DOI：
10.1073/pnas.0802203105
发表时间：
2008-05-27
影响因子：
11.1
作者：
Keele, Brandon F.;Giorgi, Elena E.;Shaw, George M.
通讯作者：
Shaw, George M.
影响因子：
5.8
作者：
Deng, Wenjie;Nickle, David C.;Mullins, James I.
通讯作者：
Mullins, James I.
影响因子：
3.7
作者：
Lingappa, Jairam R.;Kahle, Erin;Celum, Connie
通讯作者：
Celum, Connie
影响因子：
5.4
作者：
Bull, Marta E.;Learn, Gerald H.;Frenkel, Lisa M.
通讯作者：
Frenkel, Lisa M.