Recombinant forms of HIV that mix viral subtypes, and which may have greater potential to evade some of the vaccines now in development, are emerging at an alarming rate in west and east Africa, according to researchers speaking at AIDS Vaccine ’06 this week in Amsterdam.
Recombinant viruses emerge when an individual is exposed to two HIV infections within a short period of time, and genetic material from the two viral starins recombines within one cell to generate a new quasi-species that becomes dominant in the body.
Recombinants are emerging most frequently in high-risk sexual or drug using networks in high HIV prevalence regions, said Francine McCutchan of the US Military HIV Research Program. Multiple exposures to infectious partners within a short space of time generate dual infections and recombination events.
Recombinants are most evident between different subtypes of HIV, and tend to appear in regions where different HIV subtypes are ciurculating within the population.
Francine McCutchan points to East Africa as a region in which recombinants are emerging frequently due to the co-existence of subtypes A, C and D within the population.
“In East Africa the recombinants are much more mixed, much less geographically specific than in Asia, emphasising the regional nature of the epidemic. In Asia high risk networks of drug users are contained within national boundaries, where they communicate locally with lower risk sexual networks.”
“Targeting prevention to the highest risk and most mobile populations may limit the complexity of the strains that we have to deal with. The effective size of the social network [through which HIV can spread] in East Africa is very large, and this has implications also for the dissemination of drug-resistant virus in the [region].”
The Los Alamos group has been able to analyse patterns of HIV dissemination at a population level by looking at breakpoints in the HIV genome – points at which HIV’s genetic sequence splices together genetic patterns associated with different viral subtypes. Some of the these breakpoints seem remarkably persistent over many viral generations, suggesting a cost in fitness if the virus swaps genetic material in other ways.
This hugely labour-intensive work showed that almost two-thirds of Asian recombinant strains had a shared ancestry, yet there was little traffic between Thailand and China in terms of recombinant viruses or viral sequences.
If recombinants are not being seen in gay men in Europe and North America, this is because gay men continued to be predominantly infected with one clade – subtype B – but in Brazil recombinant forms are being seen in men who have sex with men.
The long-term prognosis for people infected with recombinants is not known to be different, although some examples of rapid disease progression after dual infection and emergence of recombinant virus have been seen in South Africa.
Bette Korber of Los Alamos National Laboratory in the United States said that the only way to cope with recombinant viruses in vaccine design was to hope that a vaccine which targeted the most conserved sequences of HIV-1 – those common to all viruses with group M ancestry, which covers virtually all circulating forms of HIV-1 – would be effective.
“If all the major group M clades are covered by T-cell-based vaccine, it is likely that their recombinants will be too,” she said.
However she also emphasised that more work needs to be done to track the recombinants and gain better information about the forms in circulation, especially in China where information is particularly sketchy.