HIV is striking back against the antiretroviral drugs that keep it largely in check in rich countries, thanks both to its exposure to the major drugs and to individuals who don’t realise they’re infected and so spread resistant strains to new partners.

Drug-resistant strains of HIV have already been documented in San Francisco and elsewhere in the US, and Europe. Now a model of their transmission, based on studies of gay San Francisco men, forecasts a rapid upsurge in the next five years.

What’s more, as access to antiretroviral therapy is expected to expand in poorer countries, they could experience a rise in resistance too, predicts Sally Blower of the University of California, Los Angeles, lead author on the analysis.

Cocktail of resistance

Currently, people with HIV tend to be given a cocktail of drugs, making it less likely that resistance will emerge. That’s because even if a strain evolves resistance to one of the drugs, it will still succumb to the others.


However, the virus can evolve resistance nonetheless. Currently, about 15 per cent of new infections in San Francisco are from resistant strains, some of them resistant to all three major classes of drug used to combat the virus.

To see how this might increase in future, Blower’s team created a model of HIV transmission that predicts how and when resistant strains will emerge. When they fed it data from San Francisco, it correctly predicted how drug-resistant HIV has already evolved and spread among gay men there over the past 20 years.

Self-sustaining epidemics

When the team used the model to look into the future, it predicted a rapid upsurge in the spread of resistant strains. The model suggested that 60 per cent of the resistant strains currently circulating in San Francisco could cause “self-sustaining epidemics”, says Blower, in which each infected individual spreads the resistant strain to more than one new recipient.

The most serious surge in resistance it predicted was against non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as nevirapine, introduced in the mid-1990s. Like the earliest anti-HIV drugs such as zidovudine (AZT), introduced 10 years earlier, these block enzymes vital for viral multiplication.

“We predict a wave of NNRTI-resistant strains will emerge over the next five years in San Francisco, due to transmission from untreated individuals,” says Blower.

Rapid diagnosis

By 2013, the proportion of new infections resistant to NNRTIs may have increased by 30 per cent in the city compared with now, says Blower. The more individuals infected with resistant strains, the faster they will spread.

Resistant strains can be kept in check provided infected individuals are diagnosed rapidly, before they pass on the virus, and treated with drugs to which the virus remains vulnerable, says Blower.

But resistance may be more difficult to contain in poorer countries. And according to Blower, a strategy recently unveiled by the World Health Organization to “test and treat” as many people as possible in such countries may hasten the emergence of drug-resistant strains, by exposing more people to the drugs.

“The best approach for resource-constrained countries would be to carefully roll out first-line regimens, making sure second-line regimens are available whenever there’s resistance to the first-line regime,” says Blower.

However, Carl Dieffenbach, director of the division of AIDS at the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland – which this week launched a similar pilot “test and treat” program in Washington DC – says that development of resistance is not an insoluble problem. “The emergence of HIV drug resistance is not a dead end,” he says. “We can identify patients who are failing treatment and switch them to other, effective regimens.”

“The advantage of having the model developed by Blower is that it can predict where problems may occur, and this allows us not to move forward blindly, but to proceed while taking the model’s predictions into account,” he adds.

Journal reference: Science, DOI: 10.1126/science.1180556