All people with HIV-2 should receive HIV treatment – without it, most will progress to AIDS and death

Most people with HIV-2 infection will progress to AIDS and death unless they receive antiretroviral therapy (ART), according to the results of a study conducted in Guinea-Bissau and published in The Lancet HIV.

HIV-2 infection has been considered more benign than HIV-1 infection, and it had been thought that many people would have a normal lifespan, even without ART. But after analysing over 20 years of follow-up data from people with HIV-1 and HIV-2, investigators found that both types of HIV infection had a high probability of developing and dying from AIDS without ART. While HIV-2 was associated with a slower disease course, AIDS occurred at higher CD4 cell levels than in people with HIV-1 infection.

“We showed that most individuals infected with HIV-2 will progress to HIV-related disease and death without treatment. This observation is based on longitudinal data from HIV-1-infected and HIV-2-infected individuals with an estimated HIV infection date," comment the authors. "The incubation time from infection to development of AIDS can last for several years.” 

Their findings suggest that early treatment initiation should be considered for all people with HIV, not only those with HIV-1 infection.

Globally, the vast majority of infections are of HIV-1, but HIV-2 is a different virus that is prevalent in West Africa and was first identified in 1986. HIV-2 has long been considered to be more benign than HIV-1, with a lower risk of AIDS and death. However, a literature search by Joakim Esbjörnsson and colleagues found that this belief is based on an extremely thin evidence base. They therefore determined to compare time to AIDS and death, and also changes in CD4 cell percentage and count, between individuals with HIV-1 and HIV-2 infection.

Data were obtained from a prospective cohort of police offices in Guinea-Bissau. Participants were assessed at enrolment and then annually. The date of incident HIV infection was considered to be the median date between the last HIV-negative test and the HIV-positive test. Recruitment stated in 1990 and ended in 2009, with follow-up for HIV-positive individuals continuing until 2013. 

Overall, 872 individuals tested HIV-positive at baseline or during follow-up. Only 48 of these people started ART during follow-up and once they did so, they were excluded from further analysis.

The main analysis compared outcomes between people diagnosed with HIV-1 (n = 225) and HIV-2 (n = 87) during follow-up. Most of these people were men (around 83%) and the median age was between 36 and 38 years.

Median survival was 8.2 years for people with HIV-1 compared to 15.6 years for people with HIV-2. After controlling for age and sex, HIV-1 was associated with a more than three-fold increase in mortality risk compared to HIV-2 (HR = 3.50; 95% CI, 2.22-5.52, p < 0.0001).

AIDS developed in 54% of people with HIV-1 and 43% of people with HIV-2. The median time to AIDS was significantly faster for individuals with HIV-1 than for those with HIV-2 (6.2 years vs. 14.3; p < 0.001). After controlling for age and sex, people with HIV-1 had an almost three-fold increase in risk of AIDS  (HR = 2.84; 95% CI, 1.91-4.22; p < 0.001).

Results for people who were infected with HIV-1 or HIV-2 before enrolment (and therefore did not have an estimated date of infection) were similar.

A graph plotting outcome showed that HIV-1 and HIV-2 follow a comparable disease course, with both groups progressing to AIDS and death, though the rate of progression was slower in people with HIV-2.

Two or more CD4 cell percentage values were available for 85 HIV-1-infected individuals and 48 HIV-2-infected individuals. The mean rate of decline was 0.9% and 0.4% per year, respectively, a significant difference (p = 0.028). The mean CD4 percentage at time of HIV infection for people with HIV-1, HIV-2 and HIV-negative controls was 22.3%, 28% and 38%, respectively.

CD8 percentage increased significantly faster in people with HIV-1 than in those with HIV-2, indicating greater systemic immune activation among HIV-1-infected individuals.

Absolute CD4 cell counts declined by a mean of 22.5 cells per year among people with HIV-1 and by 12.8 cells per year among people with HIV-2 (p = 0.060). Mean CD4 cell count at time of infection also differed between people with HIV-1 and HIV-2 (448 vs. 571 cells/mm³, respectively; p = 0.012).

Interestingly, AIDS occurred at higher CD4 cell counts in people with HIV-2 than people with HIV-1. The median CD4 cell percentage at AIDS diagnosis was 8.2% for people with HIV-1 compared to 18.2% for individuals with HIV-2 (p < 0.001). Analysis of CD4 cell count at the time of AIDS showed similar results.

“Our results support the recent WHO [World Health Organization] ART guideline for early treatment for all HIV-infected individuals, not only those infected by HIV-1,” conclude the authors. “Clinical trial data are urgently needed to establish the evidence base for optimal usage of ART in HIV-2 infection.”