HIV’s milder cousin may be less mild than previously thought

HIV-2’s virulence may have been underestimated and although progression to AIDS  and death in HIV-2 infection was slower than with HIV-1, it was the rule rather than the exception, new research from West Africa presented at last month's Conference on Retroviruses and Opportunistic Infections (CROI 2017) indicates.

HIV-2 crossed over into human beings 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 eight separate occasions. 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.

Its epidemiology 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.

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 of 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 within ten 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 one or two 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. Progression 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 was 2.84 times greater with HIV-1 and HIV-2, and to death 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 a 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 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.