Dutch find no evidence of superinfection in patients experiencing virological failure

The natural evolution of HIV rather than superinfection with a drug-resistant strain of HIV is usually the explanation of antiretroviral treatment failure, according to a Dutch study published in the January 11^th edition of AIDS.

Transmitted drug resistance can severely limit the antiretroviral treatment choices for HIV-positive individuals. A significant proportion of new HIV infections (approximately 10% in the UK and 6% in the Netherlands) involve a strain of HIV that is resistant to one or more anti-HIV drugs. In addition, about 30 cases of superinfection with a second or drug-resistant strain of HIV have been reported worldwide.

Many gay men choose to have unprotected sex with other HIV-infected men (often called serosorting), and Dutch investigators therefore wished to see if superinfection was contributing to the virological failure of previously effective antiretroviral therapy.

The investigators examined the HIV pol sequences from 101 patients before anti-HIV therapy was started and after the virologic failure of their treatment.

Included in the study were 85 men and 16 women. Most of the men (68) were gay. Injecting drug use was the HIV risk activity for six individuals, 21 were infected through heterosexual sex, two from blood products, and the mode of HIV transmission was unknown for four patients.

Viral load fell to undetectable levels a median of four months after antiretroviral therapy was started, but then rebounded to detectable levels after a median of three months.

Half the patients were starting their first antiretroviral regimen, but eleven of these patients (23%) already had resistance to one or more anti-HIV drugs. The other 50% of patients were already treatment experienced, and 36 (72%) had drug-resistant virus.

Resistance tests performed after the emergence of virological failure showed that 81% of patients had drug-resistant virus.

Tests showed that eight individuals had virus that was significantly different after treatment failure compared to the start of anti-HIV therapy. But detailed analysis of HIV sequences from these patients showed that such differences were explained by the natural evolution of HIV. In none of the patients did the investigators find any evidence of superinfection or recombination of HIV.

This was despite the fact that significant levels of HIV risk behaviour were reported by individuals. Two injecting drug users reported sharing injecting equipment with other drug users, and one injecting drug user reported regular unprotected sex with another HIV-positive individual. In addition, four gay men reported unprotected anal sex in the period between starting antiretroviral therapy and the virological failure of their therapy.

“In conclusion”, write the investigators, “in this selected subgroup of patients who experienced virological failure while still on initially successful combination antiretroviral therapy, no evidence of superinfection with resistant HIV-1 was observed.”