HIV-2 Dual Infection Helps Slow HIV-1 Progression
July 20, 2012 — When there is dual infection with HIV-2, HIV-1 is inhibited and shows slower progression compared with infection with HIV-1 alone, according to study of West African patients that spanned approximately 20 years.
Joakim Esbjörnsson, PhD, from the Department of Experimental Medical Science, Section of Molecular Virology, Lund University, Sweden, and colleagues report the study results in the July 19 New England Journal of Medicine.
HIV-2, which is largely confined to West Africa, is considered a less aggressive form of the virus and is associated with lower transmission rates, a longer asymptomatic stage, slower declines in CD4+ T-cell counts, and a lower mortality rate compared with HIV-1.
The prevalence of dual infection with HIV-1 and HIV-2 in West Africa has been reported as 0 to 3.2%, the authors write. Some previous studies have suggested that HIV-2 could inhibit the rate of HIV-1 progression; however, the studies have had various limitations, including low numbers of participants and short follow-up times.
In the new study, the researchers evaluated data on 223 participants who were members of the Guinea-Bissau police force and who were infected with HIV-1 after enrollment in the study. The participants had either HIV-1 infection alone or HIV-1 and HIV-2.
Among participants with dual infection, the median time to development of AIDS was 104 months (95% confidence interval [CI], 75 - 133 months), compared with 68 months (95% CI, 60 - 76 months; P = .003) in the participants with HIV-1 only.
Participants with dual infection also showed slower disease progression, as indicated by higher CD4+ T-cell levels and slower increases in CD8+ T-cell levels.
Infection with HIV-2 before infection with HIV-1 was associated with the longest time to AIDS and the highest levels of CD4+ T-cell counts.
"Our observation of significantly higher CD4+ T-cell percentages in participants with dual infection than in those with HIV-1 infection only, in combination with similar rates of decline in CD4+ T-cell percentages, indicates that determinants of differences in disease outcome may be related to events in early infection," the authors write. "The slower increase in CD8+ T-cell percentages over time in participants with dual infection than among participants infected with HIV-1 only suggests that alteration in cellular immune activation may contribute to the disease outcome."
The researchers also found significantly lower HIV-1 genetic diversity in participants with dual infections compared with the HIV-1 infection alone at similar points after infection.
"Our observation that HIV-1 diversity was significantly lower in participants infected with both HIV-1 and HIV-2 than in those infected with HIV-1 only at similar time points after HIV-1 infection, while the rates of increase in diversity were similar, supports the hypothesis that slower disease progression may be related to inhibitory effects early in HIV-1 infection," they write. "Such inhibitory effects would result in a lower initial diversity and a longer asymptomatic stage before the diversity threshold is reached."
The findings could be important in the development of HIV-1 vaccines and medications, the authors note.
"Further investigation of the interplay between HIV-1 and HIV-2 and of any systemic immunologic effects of a contemporaneous HIV-2 infection on HIV-1 pathogenesis could reveal new and critical mechanisms important for the development of future HIV-1 interventions," they conclude.
The research was supported by grants from the Swedish International Development Cooperation Agency–Swedish Agency for Research Cooperation With Developing Countries, the Swedish Research Council, the Crafoord Foundation, the Royal Physiographic Society, the Lars Hierta Memorial Foundation, the Konsul Thure Carlsson Fund for Medical Research, the Tegger Foundation, the Medical Faculty of Lund University, and the regional agreement on medical training and clinical research between Region Skâne and the Medical Faculty of Lund University. The authors have disclosed no relevant financial relationships.