Association between HIV genotype, viral load and disease progression in a cohort of Thai men who have sex with men with estimated dates of HIV infection

<div><p>Background</p><p>Differences between HIV genotypes may affect HIV disease progression. We examined infecting HIV genotypes and their association with disease progression in a cohort of men who have sex with men with incident HIV infection in Bangkok, Thailand.</p><p>Methods</p><p>We characterized the viral genotype of 189 new HIV infections among MSM identified between 2006–2014 using hybridization and sequencing. Plasma viral load (PVL) was determined by PCR, and CD4+ T-cell counts were measured by flow cytometry. We used Generalized Estimating Equations to examine factors associated with changes in CD4+ T-cell counts. Factors associated with immunologic failure were analyzed using Cox proportional hazard models.</p><p>Results</p><p>Among 189 MSM, 84% were infected with CRF01_AE, 11% with recombinant B/CRF01_AE and 5% with subtype B. CD4+ T-cell decline rates were 68, 65, and 46 cells/μL/year for CRF01_AE, recombinants, and subtype B, respectively, and were not significantly different between HIV subtypes. CD4+ T-cell decline rate was significantly associated with baseline PVL and CD4+ T-cell counts (p <0.001). Progression to immunologic failure was associated with baseline CD4+ T-cell ≤ 500 cells/μL (AHR 1.97; 95% CI 1.14–3.40, p = 0.015) and PVL > 50,000 copies/ml (AHR 2.03; 1.14–3.63, p = 0.017). There was no difference in time to immunologic failure between HIV subtypes.</p><p>Conclusion</p><p>Among HIV-infected Thai MSM, low baseline CD4+ T-cell and high PVL are associated with rapid progression. In this cohort, no significant difference in CD4+ T-cell decline rate or time to immunologic failure was seen between CRF01_AE and other infecting HIV subtypes.</p></div

Hazard ratios (HRs) for clinical progression from estimate date of infection (EDI) to immunologic failure.

<p>Hazard ratios (HRs) for clinical progression from estimate date of infection (EDI) to immunologic failure.</p

Baseline characteristics of MSM infected with HIV-1 subtype B, CRF01_AE and recombinant B/CRF01_AE, Bangkok Men Who Have Sex with Men Cohort Study, Bangkok, Thailand, 2006–2014.

<p>Baseline characteristics of MSM infected with HIV-1 subtype B, CRF01_AE and recombinant B/CRF01_AE, Bangkok Men Who Have Sex with Men Cohort Study, Bangkok, Thailand, 2006–2014.</p

Kaplan-Meier survival curves.

<p>(A) Time to immunologic failure by infecting HIV subtype; (B) Time to immunologic failure by age at HIV conversion; (C) Time to immunologic failure by baseline CD4+ cell counts; (D) Time to immunologic failure by baseline viral load.</p

First-line drug susceptibility test results, Lesotho, 2008–2009 (N = 984).

<p>^†Missing results—new patients with missing isoniazid result = 13</p><p>^§Missing results—previously treated patients with missing isoniazid result = 3</p><p>First-line drug susceptibility test results, Lesotho, 2008–2009 (N = 984).</p

Map of Lesotho.

<p>Image source: <a href="https://www.cia.gov/library/publications/the-world-factbook/index.html" target="_blank">https://www.cia.gov/library/publications/the-world-factbook/index.html</a>.</p

Lesotho Drug Resistance Survey (DRS) Sampling Flow Diagram.

<p>Lesotho Drug Resistance Survey (DRS) Sampling Flow Diagram.</p

Previously unreported <i>AK2</i> missense variants detected in clinical trial participants located in Bangkok, Thailand, Cape Town, South Africa, and New York City, USA.

<p>Previously unreported <i>AK2</i> missense variants detected in clinical trial participants located in Bangkok, Thailand, Cape Town, South Africa, and New York City, USA.</p

Previously unreported <i>CKM</i> missense variants detected in clinical trial participants located in Bangkok, Thailand, Cape Town, South Africa, and New York City, USA.

<p>Previously unreported <i>CKM</i> missense variants detected in clinical trial participants located in Bangkok, Thailand, Cape Town, South Africa, and New York City, USA.</p

HPTN 067 participant enrollment location and gender information.

<p>HPTN 067 participant enrollment location and gender information.</p