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

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

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

Phylogenetic tree of hexon sequences and reference strains.

<p>Neighbor-joining phylogenetic tree of partial length HAdV hexon gene sequences obtained from 64 clinical samples (blue) and reference strains (red).</p

Adenoviral shedding by study day.

<p>Pattern of HAdV shedding from the lower gastrointestinal tract by study day. Y axis: Log₁₀ HAdV titers from rectal swab material. X-axis: study day. Outlined bars: no typing attempted. Black bars: sequence-based HAdV typing performed. Gray bars: serotyping unsuccessful.</p

Cohort demographics and clinical data.

<p>Demographic, clinical and virologic data obtained from 20 MSM providing rectal swabs over 18 weeks. “Positive swabs” indicate swabs in which adenovirus was detected by real-time PCR. Baseline HIV viral load provided as log₁₀ copies/ml plasma on day 1.</p

Baseline serum neutralizing antibody titers by subject.

<p>Serum neutralizing antibody titers to HAdV-35, −5, −26 and −48 in each subject at beginning of study.</p

Kaplan-Meier estimates of time (28 day months) from date HIV was detected using nucleic acid amplification until the mid-point date between the last non-reactive and first reactive oral fluid HIV test.

<p>(A) By study drug group: tenofovir or placebo. (B) Controlling for study drug group, by HIV subtype: CRF01_AE or other subtypes.</p

HIV test results of participants in the Bangkok Tenofovir Study, 2005–2012.

<p>OraQuick, OraQuick Rapid HIV-1/2 Antibody Test; EIA, enzyme immune assay; NAAT, nucleic-acid amplification test. ^aTwo participants with reactive OraQuick tests during follow-up were later found to have been HIV-infected before enrollment. ^bPlasma collected at 3-monthly visits from participants with a non-reactive OraQuick test result was tested for HIV using EIA.</p