NEW YORK (Reuters Health) - HIV-2 is more pathogenic than previously believed, and without treatment, most infected individuals will progress to HIV-related disease and death - although more slowly than they would with HIV-1, an international study has found.
"Our findings suggest that early treatment initiation should be considered for all HIV-infected individuals, not only those infected by HIV-1," the authors recommend.
The authors say their study, online November 1 in The Lancet HIV, is the first to reliably estimate the time from HIV infection to AIDS or HIV-related death for HIV-2, with comparative estimates for both HIV-1-infected and HIV-negative individuals from the same population.
There seems to be a consensus in the scientific literature that "although HIV-2 infection can lead to HIV-related diseases, most HIV-2-infected individuals do not progress to immunodeficiency and AIDS during follow-up," corresponding author Dr. Joakim Esbjornsson, of Lund University, Malmo, Sweden, told Reuters Health by email.
Many studies also indicate that only 20-25% of HIV-2-infected individuals do progress to AIDS, he added. "This is in stark contrast to HIV-1, where in principle all infected individuals will develop AIDS," unless treated.
"This perception is also the most common when talking to clinicians," Dr. Esbjornsson continued. "This has led to a situation where a large proportion of HIV-2-infected patients are being monitored by CD4 and virus levels, instead of being offered immediate treatment, which is the WHO recommendation for HIV-1-infected patients."
The authors noted that research since the mid-1990s has shown that HIV-2 infection is "characterized by lower numbers of transmission, longer asymptomatic stages, slower declines in CD4 cell counts, and lower mortality."
"Without antiretroviral therapy (ART), most individuals develop AIDS and die within 3 to 13 years after HIV-1 infection," they continued, but comparable estimates in people with HIV-2 infection are not available.
The prospective, open cohort study began in 1990 and recruited male and female police officers in both urban and rural areas of Guinea-Bissau. Participants were added until September 2009, and HIV-positive individuals were followed until September 2013.
Blood samples were taken at study enrollment and yearly thereafter.
AIDS was defined according to World Health Organization staging as CD4 counts of 200 cells per microliter or less, or CD4 percentage of 14% or less; or AIDS-defining symptoms, per WHO 4 clinical criteria.
Over the 23-year study period, 872 participants tested HIV positive: 408 infected with HIV-1 and 464 with HIV-2.
Median survival was 8.2 years in HIV-1-infected individuals and 15.6 years in HIV-2-infected individuals (p<0.0001).
During follow-up, AIDS developed in 121 of 225 HIV-1 infected patients (54%) and in 37 of 87 HIV-2-infected participants (43%). Median time to AIDS was 6.2 years in HIV-1-infected individuals and 14.3 years in HIV-2-infected individuals (p<0.0001).
Among those with HIV-2, men had a significantly higher risk of AIDS than did women. Between HIV-1-infected men and women, the difference was not statistically significant.
When compared with a cohort of 2,984 HIV-uninfected individuals (median age at death, 73.7 years), both HIV-1- and HIV-2-infected participants died at significantly lower median ages (51.0 and 62.9 years, respectively, p<0.0001 for both).
Overall, the mortality rate with HIV-1 was estimated to be 1.83 times higher than with HIV-2. Their survival analysis, the authors concluded, "indicated that HIV-2-infected individuals follow a similar survival curve as HIV-1-infected individuals, albeit at a slower rate."
"(S)ome studies have suggested that HIV-2 infection is compatible with a normal lifespan in most infected individuals and that mortality estimates in HIV-2-infected populations may be heavily influenced by natural mortality," Dr. Esbjornsson commented. "In contrast, our study indicates a very marginal impact of natural mortality on mortality estimates among HIV-2 infected individuals."
"We believe that our study changes the perception of HIV-2 as a disease-causing agent, and we hope that our results will contribute to immediate treatment being offered also to HIV-2 infected patients," he concluded.
In an editorial, Drs. Christian Wejse and Bo L. Honge, of Aarhus University Hospital in Denmark, highlighted one of the researchers' findings: "Interestingly, they found that clinical AIDS seems to occur at higher CD4 cell counts for HIV-2-infected individuals than for HIV-1-infected individuals. This finding suggests that immunodeficiency is different for HIV-2 infection and warrants further research into characterizing specific HIV-type differences in immunophenotype and functionality."
"A large proportion of people infected with HIV-2 have undetectable HIV RNA concentrations, and these individuals have previously been thought of as possible non-progressors," the editorialists continued. The report is limited by the lack of HIV RNA measurements, they added, but they say its conclusion that survival curves for HIV-2-infected individuals are similar to those of HIV-1-infected individuals, but at a slower rate, is valid.
Dr. Geoffrey Gottlieb of the University of Washington, who has studied the treatment of HIV-infected individuals in West Africa, told Reuters Health by e-mail that this study, "is the longest and largest natural history study of HIV-2 infection to date" and that it adds "much more precise data on timing of initial HIV-2 infection and subsequent AIDS and death outcomes."
Although previous studies had shown that the rate of disease progression for HIV-2 is substantially slower than for HIV-1, he added, "This study is unique in that other HIV natural history studies in West Africa ended long ago, after the clear benefits of ART on reducing HIV morbidity and mortality were shown."
"The lack of widespread ART use in this population, which lagged behind ART use in other locales, and allowed for the continuation of this study until 2013, is concerning," Gottlieb said. "This study, along with recent clinical trials of ART for HIV-2 in France and West Africa, argues for early treatment with ART for HIV-2 infection, as is currently recommended for HIV-1."
The study was funded by various Swedish nonprofit or governmental entities. The authors declared no competing interests
SOURCE: http://bit.ly/2Uw1oMd
Lancet HIV 2018.
Reuters Health Information © 2018
Cite this: HIV-2 Is Deadlier Than Thought, Despite Slower Progression to AIDS - Medscape - Dec 10, 2018.
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