Compared with HIV-1, HIV-2 is considered to be more benign and without severe pathogenic consequences throughout the disease course for the majority of infected individuals. However, conclusive survival data from cohorts with long follow-up and estimated time of infection is lacking.
We followed 312 participants infected with HIV-1 or HIV-2 after enrollment in a cohort from Guinea-Bissau with 23 years of follow-up, according to the time from infection to AIDS or HIV-related mortality, and measures of T-cell dynamics. Weibull distributions were fitted to the survival data to assess the hypothesis of heterogeneous disease courses among HIV-2 infected individuals.
The median times to AIDS and mortality were 14.3 years (confidence interval [CI], 10.7-18.0) and 15.6 years (CI, 12.0-19.2) for HIV-2 infected participants, and 6.2 years (CI, 5.4-7.1) and 8.2 years (CI, 7.6-8.8) for HIV-1 infected individuals (p<0.001 for both comparisons, Log rank test). The Weibull analysis showed that HIV-2 infected individuals followed a uniform disease trajectory similar to HIV-1 infected individuals, but at a 53% lower acceleration rate. The proportion of HIV-2 infected individuals under risk at the end of follow-up was 17.5%, further supporting that the majority of HIV-2 infected individuals will progress to AIDS and HIV-related mortality if followed long enough. Linear mixed model analyses of T-cell dynamics showed both higher levels of CD4+ T-cell counts early after infection (p<0.001, Likelihood Ratio Test [LRT]) and slower decline rates among HIV-2 compared with HIV-1 infected individuals (p=0.028, LRT). Finally, CD4+ T-cell levels at clinical AIDS was higher in HIV-2 compared with HIV-1 infected individuals (18.2% vs. 8.2%, p<0.001, 2-tailed Mann-Whitney U Test).
Our results contradicts the common assumption that the majority of HIV-2 infected individuals remain long-term-non-progressors and suggest that, similar to HIV-1 infection, HIV-2 infection will result in disease development if followed long enough. This suggests that early treatment initiation would be beneficial also for HIV-2 infected individuals.