Publication: Early markers of HIV-1 disease progression in a prospective cohort of seroconverters in Bangkok, Thailand: Implications for vaccine trials
Issued Date
2004-07-01
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ISSN
15254135
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2-s2.0-3042813641
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Acquired Immune Deficiency Syndromes. Vol.36, No.3 (2004), 853-860
Suggested Citation
Kate Buchacz, Dale J. Hu, Suphak Vanichseni, Philip A. Mock, Thanyanan Chaowanachan, La Ong Srisuwanvilai, Roman Gvetadze, Frits Van Griensven, Jordan W. Tappero, Dwip Kitayaporn, Jaranit Kaewkungwal, Kachit Choopanya, Timothy D. Mastro Early markers of HIV-1 disease progression in a prospective cohort of seroconverters in Bangkok, Thailand: Implications for vaccine trials. Journal of Acquired Immune Deficiency Syndromes. Vol.36, No.3 (2004), 853-860. doi:10.1097/00126334-200407010-00013 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/21618
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Title
Early markers of HIV-1 disease progression in a prospective cohort of seroconverters in Bangkok, Thailand: Implications for vaccine trials
Abstract
Background: Some candidate HIV-1 vaccines may not prevent HIV-1 infection but may alter the course of disease. Surrogate endpoints based on early laboratory makers in HIV-1-infected persons who are antiretroviral therapy (ART)-naive will be useful for evaluating vaccine efficacy in slowing disease progression (VEp). We examined pretreatment HIV-1 viral loads and CD4 cell counts in recent HIV-1 seroconverters to inform selection of these endpoints. Methods: We studied 130 newly HIV-1-infected injection drug users identified from a prospective cohort of initially uninfected persons in Bangkok during 1995 through 1998. We analyzed trends in HIV-1 viral loads and CD4 cell counts as well as progression to the surrogate endpoint, defined as 2 consecutive CD4 cell counts of fewer than 350 cells/mm3, during 24 months after the first HIV-1 seropositive (FP) visit. Results: Median HIV-1 RNA copies/mL with interquartile ranges were 43,693 (14,320-94,767) at the FP visit, 46,924 (16,273-104,314) at 6 months, 28,446 (11,292-54,325) at 12 months, and 18,080 (8713-54,059) at 18 months. HIV-1 viral loads at the FP visit and at 18 months were positively correlated (r = 0.53, P < 0.0001). Of 130 participants, 12% reached the surrogate endpoint by 6 months, 16% by 12 months, and 27% by 18 months. In Cox regression analyses, HIV-1 viral loads of more than 50,000 copies/mL at the FP visit (hazard ratio [HR] = 2.3, 95% confidence interval [CI]: 1.1-4.8) and first CD4 cell count of 500 or fewer cells/mm 3 (HR = 7.6, 95% CI: 3.2-17.6) were independently associated with faster progression to the surrogate endpoint. Conclusions: Participants with high HIV-1 RNA levels and low CD4 cell counts close to the time of seroconversion were more likely to experience early immunologic progression. Approximately one quarter of seroconverters reached the surrogate immunologic endpoint within 18 months of their FP visit and before starting ART, suggesting the utility of this endpoint for analyses of VEp in some ongoing and planned HIV-1 vaccine efficacy trials.