- Category: HIV Disease Progression
- Published on Wednesday, 08 March 2017 00:00
- Written by Gus Cairns
The virulence of HIV-2 virulence may have been underestimated, and although progression to AIDS and death in people with HIV-2 infection was slower than with HIV-1, it was the rule rather than the exception -- 70% progressed to AIDS within 20 years -- according to new research from West Africa presented at last month's Conference on Retroviruses and Opportunistic Infections.
HIV-2 crossed over into humans from the sooty mangabey monkey, rather than from chimpanzees and gorillas like HIV-1. Its entry into humans probably precedes that of HIV-1 and its variety of strains -- some only recorded in a single case -- suggests that it may have crossed into humans on as many as 8 separate occasions.
The epidemiology of HIV-2 reflects its animal origin; sooty mangabeys are a west African species and HIV-2 is most common in Guinea-Bissau, Cape Verde, Gambia, Sierra Leone, and also in Mali, Senegal, Ivory Coast, and Nigeria.
For a virus that acts so similarly to HIV-1, it is remarkably genetically different; the pol and gag genes of HIV-2 are only 60% similar to the same genes in HIV-1, and the env gene, which constructs the viral shell, is only 30%-40% similar.
Because HIV-2 is less virulent than HIV-1, and therefore less frequently transmitted, it has tended to be out-competed by HIV-1. Surveillance of HIV in pregnant women in Guinea-Bissau has shown that while HIV-1 prevalence was virtually zero till the early 1990s, it had increased to 6% by 2008. In contrast, HIV-2 prevalence was 8% between 1987 and 1992 but decreased to 1% by 2008.
The issue today is not so much HIV-2 transmission as its treatment. While World Health Organization guidelines have changed their title from "Guidelines for HIV-1 treatment" to "Guidelines for HIV treatment," HIV-2 is not specifically mentioned in those guidelines.
Presenter Joakim Esbjörnsson from the University of Oxford said that in previous literature some authors had suggested that only 15%-25% of people with HIV-2 progress to AIDS at all, and only a minority do so within 10 years. These estimates were cited in a previous 2012 article on HIV-2 on aidsmap.com.
HIV-2 is less easy to transmit, and typically viral loads in blood are 1 or 2 orders of magnitude lower than with HIV-1, at about 2500 copies/mL. However, the amount of proviral DNA integrated into cells is the same as with HIV-1.
Esbjörnsson suggested that the estimates of progression to AIDS and death had been underestimated. His study looked at progression to AIDS and death among the Guinea-Bissau police cohort. Initiated in 1990, this includes 4820 members with HIV-1 and HIV-2, all police officers, 13% of them women. The median follow-up time was 5.9 years. Antiretroviral therapy has been available since 2006.
In this cohort, the mean time for progression to AIDS was 6.2 years with HIV-1 and 14.3 years with HIV-2. Time to death was 8.2 years with HIV-1 and 15.6 years with HIV-2. The likelihood of progression to AIDS within a given time frame was 2.84 times greater with HIV-1 compared to HIV-2, and time to death was 3.5 times greater.
Nonetheless, 20 years after the initiation of the cohort, while 90% of people with HIV-1 had progressed to AIDS, so had 70% of people with HIV-2, showing that previous studies had considerably underestimated the mortality and morbidity due to HIV-2. HIV-2 was nearly 90% lethal within 25 years of infection.
The average CD4 decline in cells/mm3 was 22.5 per year in people with HIV-1 and 12.8 in people with HIV-2. One interesting finding from the cohort, however, was that progression to AIDS happened at a higher CD4 count with HIV-2 than with HIV-1: average CD4 count at AIDS diagnosis was 237 cells/mm3 in people with HIV-2 and 137 cells/mm3 in people with HIV-1.
J Esbjörnsson, F Månsson, A Kvist,et al. High rate of disease progression in untreated HIV-2 infection. Conference on Retroviruses and Opportunistic Infections. Seattle, February 13-16, 2017. Abstract 37.