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Disease progression by infecting HIV-1 subtype in a seroconverter cohort in sub-Saharan Africa.

Amornkul PN, Karita E, Kamali A, Rida WN, Sanders EJ, Lakhi S, Price MA, Kilembe W, Cormier E, Anzala O, Latka MH, Bekker LG, Allen SA, Gilmour J, Fast PE, IAVI Africa HIV Prevention Partnersh - AIDS (2013)

Bottom Line: Adults and youth with documented HIV-1 infection in the past 12 months were recruited from seroincidence cohorts in East and Southern Africa and followed at 3-6 month intervals.From 2006 to 2011, 615 participants were enrolled at nine research centers in Kenya, Rwanda, South Africa, Uganda, and Zambia; 579 (94.1%) had viral subtyping completed.Predominant subtypes were C (256, 44.2%), A (209, 36.1%), and D (84, 14.5%).

View Article: PubMed Central - PubMed

Affiliation: aInternational AIDS Vaccine Initiative, New York, New York, USA bProject San Francisco, Kigali, Rwanda cMedical Research Council/Uganda Virus Research Unit, Research Unit on AIDS, Entebbe, Uganda dBiostatistics Consultant, Arlington, Virginia, USA eCentre for Geographic Medicine-Coast/Kenya Medical Research Institute, Kilifi, Kenya fUniversity of Oxford, Oxford, UK gZambia-Emory HIV Research Project, Lusaka, Zambia hKenya AIDS Vaccine Initiative, University of Nairobi, Nairobi, Kenya iAurum Institute, Rustenburg jDesmond Tutu HIV Centre, University of Cape Town, Cape Town, Republic of South Africa kEmory University, Atlanta, Georgia, USA lIAVI Human Immunology Laboratory, Imperial College, London, UK.

ABSTRACT

Objective: To describe immunologic, virologic, and clinical HIV disease progression by HIV-1 subtype among Africans with well documented estimated dates of HIV infection (EDIs).

Design: Prospective cohort.

Methods: Adults and youth with documented HIV-1 infection in the past 12 months were recruited from seroincidence cohorts in East and Southern Africa and followed at 3-6 month intervals. Blood for lymphocyte subset and viral load determination was collected at each visit. Pol was sequenced from the first positive specimen to ascertain subtype. Preantiretroviral therapy disease progression was measured by three time-to-event endpoints: CD4 cell count 350 cells/μl or less, viral load measurement at least 1 × 10 copies/ml, and clinical AIDS.

Results: From 2006 to 2011, 615 participants were enrolled at nine research centers in Kenya, Rwanda, South Africa, Uganda, and Zambia; 579 (94.1%) had viral subtyping completed. Predominant subtypes were C (256, 44.2%), A (209, 36.1%), and D (84, 14.5%). After adjustment for age, sex, and human leukocyte antigen alleles in Cox regression analyses, subtype C-infected participants progressed faster than subtype A to all three endpoints [CD4 hazard ratio 1.60, 95% (confidence interval) CI 1.16, 2.20; viral load hazard ratio 1.59, 95% CI 1.12, 2.25; and AIDS hazard ratio 1.60, 95% CI 1.11, 2.31). Subtype D-infected participants reached high viral load more rapidly (hazard ratio 1.61, 95% CI 1.01, 2.57) and progressed nearly twice as fast to AIDS compared to subtype A (hazard ratio 1.93, 95% CI 1.21, 3.09).

Conclusion: Subtype-specific differences in HIV disease progression suggest that the local subtype distribution be considered when planning HIV programs and designing and defining clinical endpoints for HIV prevention trials.

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Related in: MedlinePlus

Kaplan–Meier survival curves. (a) Time to CD4+ cell count ≤ 350 cells/μl, (b) time to viral load (VL) ≥105 copies/ml, and (c) time to AIDS by HIV-infecting subtype among participants with human leukocyte antigen (HLA) data (n = 491).
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Figure 1: Kaplan–Meier survival curves. (a) Time to CD4+ cell count ≤ 350 cells/μl, (b) time to viral load (VL) ≥105 copies/ml, and (c) time to AIDS by HIV-infecting subtype among participants with human leukocyte antigen (HLA) data (n = 491).

Mentions: Figure 1 shows the Kaplan–Meier curves for the proportion of participants reaching each disease progression endpoint by infecting HIV-1 subtype and the P-value from the corresponding log-rank test. The significant P-values for time to CD4+ cell count 350 cells/μl or less and time to viral load at least 1 × 105 copies/ml reflect the different rates of progression between subtype A-infected and C-infected participants. However, both subtype C-infected and D-infected participants progressed faster to AIDS than those with subtype A.


Disease progression by infecting HIV-1 subtype in a seroconverter cohort in sub-Saharan Africa.

Amornkul PN, Karita E, Kamali A, Rida WN, Sanders EJ, Lakhi S, Price MA, Kilembe W, Cormier E, Anzala O, Latka MH, Bekker LG, Allen SA, Gilmour J, Fast PE, IAVI Africa HIV Prevention Partnersh - AIDS (2013)

Kaplan–Meier survival curves. (a) Time to CD4+ cell count ≤ 350 cells/μl, (b) time to viral load (VL) ≥105 copies/ml, and (c) time to AIDS by HIV-infecting subtype among participants with human leukocyte antigen (HLA) data (n = 491).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3815107&req=5

Figure 1: Kaplan–Meier survival curves. (a) Time to CD4+ cell count ≤ 350 cells/μl, (b) time to viral load (VL) ≥105 copies/ml, and (c) time to AIDS by HIV-infecting subtype among participants with human leukocyte antigen (HLA) data (n = 491).
Mentions: Figure 1 shows the Kaplan–Meier curves for the proportion of participants reaching each disease progression endpoint by infecting HIV-1 subtype and the P-value from the corresponding log-rank test. The significant P-values for time to CD4+ cell count 350 cells/μl or less and time to viral load at least 1 × 105 copies/ml reflect the different rates of progression between subtype A-infected and C-infected participants. However, both subtype C-infected and D-infected participants progressed faster to AIDS than those with subtype A.

Bottom Line: Adults and youth with documented HIV-1 infection in the past 12 months were recruited from seroincidence cohorts in East and Southern Africa and followed at 3-6 month intervals.From 2006 to 2011, 615 participants were enrolled at nine research centers in Kenya, Rwanda, South Africa, Uganda, and Zambia; 579 (94.1%) had viral subtyping completed.Predominant subtypes were C (256, 44.2%), A (209, 36.1%), and D (84, 14.5%).

View Article: PubMed Central - PubMed

Affiliation: aInternational AIDS Vaccine Initiative, New York, New York, USA bProject San Francisco, Kigali, Rwanda cMedical Research Council/Uganda Virus Research Unit, Research Unit on AIDS, Entebbe, Uganda dBiostatistics Consultant, Arlington, Virginia, USA eCentre for Geographic Medicine-Coast/Kenya Medical Research Institute, Kilifi, Kenya fUniversity of Oxford, Oxford, UK gZambia-Emory HIV Research Project, Lusaka, Zambia hKenya AIDS Vaccine Initiative, University of Nairobi, Nairobi, Kenya iAurum Institute, Rustenburg jDesmond Tutu HIV Centre, University of Cape Town, Cape Town, Republic of South Africa kEmory University, Atlanta, Georgia, USA lIAVI Human Immunology Laboratory, Imperial College, London, UK.

ABSTRACT

Objective: To describe immunologic, virologic, and clinical HIV disease progression by HIV-1 subtype among Africans with well documented estimated dates of HIV infection (EDIs).

Design: Prospective cohort.

Methods: Adults and youth with documented HIV-1 infection in the past 12 months were recruited from seroincidence cohorts in East and Southern Africa and followed at 3-6 month intervals. Blood for lymphocyte subset and viral load determination was collected at each visit. Pol was sequenced from the first positive specimen to ascertain subtype. Preantiretroviral therapy disease progression was measured by three time-to-event endpoints: CD4 cell count 350 cells/μl or less, viral load measurement at least 1 × 10 copies/ml, and clinical AIDS.

Results: From 2006 to 2011, 615 participants were enrolled at nine research centers in Kenya, Rwanda, South Africa, Uganda, and Zambia; 579 (94.1%) had viral subtyping completed. Predominant subtypes were C (256, 44.2%), A (209, 36.1%), and D (84, 14.5%). After adjustment for age, sex, and human leukocyte antigen alleles in Cox regression analyses, subtype C-infected participants progressed faster than subtype A to all three endpoints [CD4 hazard ratio 1.60, 95% (confidence interval) CI 1.16, 2.20; viral load hazard ratio 1.59, 95% CI 1.12, 2.25; and AIDS hazard ratio 1.60, 95% CI 1.11, 2.31). Subtype D-infected participants reached high viral load more rapidly (hazard ratio 1.61, 95% CI 1.01, 2.57) and progressed nearly twice as fast to AIDS compared to subtype A (hazard ratio 1.93, 95% CI 1.21, 3.09).

Conclusion: Subtype-specific differences in HIV disease progression suggest that the local subtype distribution be considered when planning HIV programs and designing and defining clinical endpoints for HIV prevention trials.

Show MeSH
Related in: MedlinePlus