Scaling up the distribution of HIV medication over the last decade has vastly increased the number of people receiving treatment around the world. An estimated 8 million infected people received the antiretroviral drugs in 2011, compared to just 400,000 in 2003. But with this massive roll-out comes an inevitable and potentially dangerous consequence: The AIDS virus can more easily develop resistance to these life-saving drugs.
The first study to assess the global trend in HIV drug resistance in low- and middle-income countries concluded that it has been rising in parts of sub-Saharan Africa since the antiretrovirals became widely available.
Researchers examined data from dozens of studies on HIV drug resistance that included more than 26,000 patients in 42 countries. They focused their attention on people with HIV who were older than 15 and had never received treatment. If these people already had some resistance to the drugs, it would be a sure sign that more dangerous versions of the virus were spreading from person to person.
The research team reported the highest increases in drug resistance in East Africa, where it has climbed 29% every year since widespread roll-out of medication. In southern Africa, drug resistance increased at an annual rate of 14%.
Among the the HIV-positive people surveyed, 7.4% in East Africa had drug resistance, as did 3% in southern Africa. The results were published Sunday by the medical journal Lancet.
A major problem was growing resistance to a class of drugs called non-nucleoside reverse transcriptase inhibitors, which are the most common first-line antiretroviral drugs used to treat HIV in Africa. This class of drugs is also used to prevent virus transmission from mother to child.
The researchers did not observe significant changes in drug resistance in Latin America or the Caribbean. In Asia, the results varied too greatly among countries to assess an overall trend for the region.
The study authors said the rates of increase were expected, but they warned that the situation requires careful monitoring to make sure the problem doesn’t escalate.
“The good news is that it’s still modest, contained, and not alarming,” said Dr. Silvia Bertagnolio of the World Health Organization, who presented a related study this week at the International AIDS Conference in Washington. “But we have to be vigilant” to make sure the rates don’t keep going up, she added.
HIV becomes drug-resistant through random mutations that occur when the virus copies its genetic material. Antiretroviral medications prevent HIV from replicating, but if a person doesn’t take these pills daily, drug resistance can arise.
Taking pills every day for life is a challenging order, and many people may lapse without proper support or access to clinics. Patchy supplies of drugs in developing countries can also interrupt treatment. And the new push to start treatment earlier to help prevent the transmission of HIV increases the odds that someone will develop drug resistance over his or her lifetime.
HIV may develop resistance to one type of medication but not others. Catching resistance early and switching a patient’s medication attacks HIV from a different angle. This type of surveillance is essential to keep drug resistance from running rampant, Bertagnolio said.
However, drug resistance monitoring is not available in many poorer parts of the word. And once people develop resistance to the standard first-line drugs, they must switch to more potent second-line medications that are in short supply in many developing countries. Continued spread of drug resistance could jeopardize efforts to curtail the AIDS epidemic in the developing world.
Bertagnolio said the WHO report reveals that many clinics lose contact with up to one-third of the people who start antiretroviral treatment. Following up with all patients is a key to ensuring they take their medication without fail.
In light of these results, “the greatest challenge is to reduce the frequency of treatment failure and cases of drug resistance,” Dr. Douglas Richman, director of the Center for AIDS Research at UC San Diego, wrote in a commentary also published in Lancet. “Weak drug supply chains and drug stock-outs jeopardize the treatment of even highly adherent patients.”
Richman pointed out that health officials in the United States in Europe also faced the risk of increasing HIV drug resistance as treatment became more widespread, but doctors and patients have filled in the gaps to keep resistance from rising.
In a related study presented at the AIDS conference, researchers from South Africa found that about 20% of patients treated in 17 rural clinics there were failing their first-line drug treatment. Members of the team analyzed samples of HIV collected from 240 of the patients and found that 87% had some kind of mutation for drug resistance.
At least 1.8 million people in South Africa currently receive treatment, said Justen Manasa, a doctoral student in virology at the University of KwaZulu-Natal who presented the study results on Tuesday. “The rapid scale-up of antiretroviral therapy in South Africa has put enormous strain on health systems,” he said.
Manasa said these rates of drug resistance are not unique to South Africa - Botswana and Zimbabwe show similar trends.