Infection with both of the major subtypes of HIV at the same time slows the progression of disease, researchers reported.
In a long-running cohort study, people co-infected with both HIV-1 and HIV-2 took three years longer to develop AIDS than those infected only with HIV-1, according to Joakim Esbjörnsson, PhD, of Lund University in Lund, Sweden, and colleagues.
And the slower rate of progression was most marked in those who were infected with HIV-2 before HIV-1, Esbjörnsson and colleagues reported in the July 19 issue of the New England Journal of Medicine.
The researchers also found that the slower rate of disease progression in those with a dual infection was reflected in higher numbers of CD4-positive T cells and lower levels of viral diversity at similar time points after infection.
The findings suggest that HIV-2 inhibits HIV-disease progression and may hold clues to the development of vaccines or new therapeutics, Esbjo"rnsson and colleagues argued.
Both strains of HIV are lentiviruses, but HIV-1 – the pandemic strain – is derived from simian viruses in chimpanzees and gorillas. The less pathogenic HIV-2 strain arises from viruses found in sooty mangabeys.
While both subtypes can cause disease, progressive immune dysfunction and AIDS develop in most people with HIV-1 in the absence of treatment. In contrast, the researchers noted, that will happen in only 20% to 30% of those infected with HIV-2 only.
In West Africa – where both subtypes circulate - the prevalence of co-infection is estimated to be as high as 3.2%, Esbjo"rnsson and colleagues noted, and there is some laboratory evidence that HIV-2 inhibits HIV-1.
To investigate the issue, they turned to a prospective study of members of the police force in the small West African country of Guinea-Bissau, who were eligible to join the study from Feb. 6, 1990 through Dec. 31, 2007.
Participants had blood samples collected and tested at study entry and every 12 to 18 months afterward, until Sept. 1, 2009. The country introduced antiretroviral therapy in 2005 through a national treatment program, which included the police cohort starting in early 2006.
Participants who got treatment had their data censored when they started therapy.
All told, Esbjo"rnsson and colleagues reported, 223 participants were infected with HIV-1 during about 20 years of follow-up - 191 were infected with HIV-1 alone and 32 with both subtypes.
Among those with both subtypes, 20 were infected with HIV-2 before HIV-1, while the other 12 seroconverted to both at about the same time.
The researchers found that the median time to AIDS – defined by CD4 count, clinical signs, or death with AIDS symptoms – was 104 months, or 8.7 years, in participants with dual infection compared with 68 months, or 5.7 years in those with HIV-1 only. The 3-year difference was significant at P=0.003.
They also found that the 20 who got HIV-2 first had an even longer median time to AIDS – 129 months, or 10.75 years, which was also significantly greater, at P=0.007, than the time for those with HIV-1 infection only.
The longer time to AIDS was paralleled by slower changes in the immune system, the researchers noted.
Specifically, the percentage of CD4 cells at seroconversion was significantly higher (at P<0.001) in those with dual infection – 31.3% versus 23.3%. And the rate of increase of CD8-positive T cells was significantly slower (at P=0.03) - 1.5% versus 3.0% per year.
And, they reported, the viral diversity of HIV-1 – which has been correlated in other studies with time to AIDS - was markedly greater in those with just HIV-1 infection.
The study had support 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, 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 Ska*ne and the Medical Faculty of Lund University.
Esbjörnsson did not report any potential conflicts.
Primary source: New England Journal of Medicine
Source reference: Esbjo"rnsson J, et al “Inhibition of HIV-1 disease progression by contemporaneous HIV-2 Infection” N Engl J Med 2012; 367:224-232.