Dual Infection Contributes to Rapid Disease Progression in Men Who Have Sex With Men in China

Abstract

Background: Considerable numbers of HIV-1-infected men who have sex with men (MSM) show a relatively rapid disease progression in China; however, the cause remains elusive. HIV-1 dual infection was reported to occur commonly among the MSM population, and its contribution to clinical prognosis remains controversial. We investigated the occurrence and impact on disease progression of dual infection in a prospective MSM cohort in China.

Methods: Sixty-four HIV-1 early-infected participants were longitudinally followed up for 2 years. Deep sequencing was used as dual-infection screening. CD4 T-cell counts and HIV-1 viral load were compared between coinfection and single-infection participants and pre- versus post-superinfection.

Results: Eight coinfected participants and 10 superinfected participants were identified, including 9 participants with intersubtype and 9 with intrasubtype dual infections. The prevalence of coinfection was 13.1%, with a superinfection incidence of 15.6%. Coinfection participants showed lower CD4 T-cell counts at 120 days after infection (P = 0.042) and a higher viral set point tendency (P = 0.053) as compared with single-infection participants. Kaplan-Meier analysis showed that the time for the viral load to increase to above 4 log10 copies per milliliter was shorter in coinfection participants than in single-infection participants (P < 0.001). After superinfection, the median CD4 T-cell count decreased from 635 to 481 cells/μL (P = 0.027).

Conclusions: The occurrence of dual infection among Chinese MSM is relatively high, and HIV-1 dual infection might contribute to rapid disease progression seen in the MSM population.

FIGURE 1.

Intersubtype dual-infection participant P1. Neighbor-joining tree analyses of consensus sequences (>200 bp identical reads) from P1 in 2009 (A) and 2011 (B) are shown. Red branch labels represent consensus sequences from initial strains (sequence labels include sample number, year of sampling, sequence number, and the number containing the raw sequence), blue branch labels represent consensus sequences of superinfecting strains, and black branch labels represent reference sequences. Reference sequences were from the Los Alamos database. Bootstrap values >80% are indicated (1000 replicates).

FIGURE 2.

Intrasubtype dual-infection participant P19. Neighbor-joining tree analyses of consensus sequences (>200 bp identical reads) from P19 in 2011 (A) and 2013 (B) are shown. Red branch labels represent consensus sequences from initial strains of individual P19, blue branch labels represent consensus sequences of superinfecting strains, and black branch labels represent reference sequences. Reference sequences were from the Los Alamos database. Bootstrap values >80% are indicated (1000 replicates).

FIGURE 3.

Impacts of coinfection on CD4⁺ T-cell count, VL, and disease progression. CD4⁺ T-cell count (A) and VL (B) were compared between coinfection and single-infection participants. Kaplan–Meier curves of the time for CD4⁺ T-cell counts to decline below 350 cells/μL or VL to increase above 4 log₁₀ copies per milliliter in coinfection and single-infection participants; P values were calculated using a log rank test (C and D).

FIGURE 4.

Impacts of superinfection on CD4⁺ T-cell count and VL. CD4⁺ T-cell counts (A) and VL (B) were compared pre- versus post-superinfection in 10 superinfected participants. As a control group, changes in CD4⁺ T-cell count and VL of 12 single-infection participants were determined at corresponding time points (C and D).