Inhibition of HIV-1 Disease Progression
Two important human lentiviruses have been described: (1) pandemic HIV type 1 (HIV-1), and (2) HIV type 2 (HIV-2), which is mainly confined to West Africa. Both viruses have similar transmission routes, cellular targets, and AIDS-defining HIV-related symptoms.
However, compared with HIV-1 infection, HIV-2 infection is characterized by lower transmission rates, a longer asymptomatic stage, a slower decline in CD4+ T-cell counts, and a lower mortality rate. Progressive immune dysfunction and AIDS develop in most persons who have untreated infection with HIV-1 only, as compared with only 20% to 30% of persons infected with HIV-2 only. However, several studies have reported that HIV-2 infection can alter HIV-1 infectivity and replication in vitro, suggesting that HIV-2 infection may inhibit the rate of HIV-1 disease progression.
This prospective study was conducted among subjects from the West African country of Guinea-Bissau who were enrolled from February 6, 1990, through December 31, 2007. All persons with regular employment in the Guinea-Bissau police force were eligible, and >98% enrolled. Blood samples were collected for serologic testing for HIV and measurement of T-cell counts, at enrollment and at follow-up visits every 12 to 18 months until September 1, 2009. Antiretroviral therapy was introduced in Guinea-Bissau in 2005 through a national treatment program. The police cohort was included in the program in early 2006.
A total of 223 participants were infected with HIV-1 after enrollment; 191 were infected with HIV-1 only (161 men and 30 women), and 32 were infected with both HIV-1 and HIV-2 (26 men and 6 women). Among the participants with dual infection, 12 had concomitant dual seroreactivity and 20 had HIV-2 seroreactivity before dual seroreactivity occurred.
The median time to AIDS was 104 months (95% confidence interval [CI], 75 to 133) in participants with both HIV-1 and HIV-2 infection and 68 months (95% CI, 60 to 76) in participants with HIV-1 infection only (P = 0.003 by the log-rank test). Stratification according to sex showed a slightly more pronounced difference in the time to AIDS between the groups (P=.001 by the log-rank test). The adjusted hazard ratio for progression to AIDS among HIV-1 infected participants versus participants with dual infection was 2.81 in a Cox proportional-hazards model controlling for age and sex (95 CI, 1.55-5.09; P<.001 by the Wald test).
The rate of decline in CD4+ T-cell percentage was similar with HIV-1 infection only and dual infection, with an average decline of 1.2% per year. CD4+ T-cell percentage was significantly higher in participants with dual infection (31.3%) compared with those with HIV-1 infection only (23.3%) (P<.001). There was a slower increase in CD8+ T-cell percentages among participants with dual infection (1.5% per year) than among those with HIV-1 infection only (3.0% per year, P=.03). A significant difference was also found between HIV-1 infection only and dual infection with HIV-2 seroreactivity recorded first (P=.002), but not between HIV-1 infection only and dual infection with simultaneous HIV-1 and HIV-2 seroreactivity recorded first.
The average increase in HIV-1 sequence diversity over time was similar in participants with HIV-1 infection only and those with dual infection, with an average of 1.75×10−3 substitutions per site per year. At similar time points after seroconversion, the diversity was significantly lower among participants with dual infection (5.67×10−3±1.61×10−3 substitutions per site) than among those with HIV-1 infection only (11.04×10−3±1.28×10−3 substitutions per site; P=.01 by the t-test).
