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

Seventy per cent of people with HIV-2 progress to AIDS within 20 years
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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.

Glossary

virulence

The power of bacteria or viruses to cause a disease. Different strains of the same micro-organism can vary in virulence.

 

morbidity

Illness.

pol

The HIV gene that encodes a group of enzymes needed for viral replication (called protease, integrase and reverse transcriptase).

gag

One of the three proteins encoded within the retroviral genome.

env

One of the three proteins encoded within the retroviral genome.

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.

References

Esbjörnsson J et al. High rate of disease progression in untreated HIV-2 infection. Conference on Retroviruses and Opportunistic Infections (CROI 2017), Seattle, abstract 37, 2017.  

View the abstract on the conference website.

View a webcast of this presentation on the conference website.