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The success of HIV treatment is increasing the risk of drug-resistance

December 07, 2016

Global health agencies are succeeding in getting more people with HIV on antiretroviral therapy, a combination of drugs that suppress the virus to undetectable levels in the blood and reduce the risk of transmission to another person. But scientists are beginning to detect a disturbing new trend: The rise of drug-resistant HIV strains, especially in countries such as Kenya, Zambia, Uganda, Nigeria, Tanzania and South Africa.

Like tuberculosis and other diseases, drug resistant HIV strains emerge in part because a person doesn’t take the proper dose of drugs at the right time every day. In poor regions like Sub-Saharan Africa, this is more likely to happen, not because of a lack of will on the part of the patient, but because there are so few health clinics, or political and economic instability could make it exceedingly difficult to access life-saving treatment on time.

A World Health Organization report from July examined data from more than 12,000 clinics in 59 countries and found that on average, about 20 percent of people with HIV simply drop out of patient records one year after beginning ART treatment. About 73 percent of patients don’t maintain their treatment and 36 percent of clinics experienced drug stock-outs — when a pharmacy simply runs out of drugs.

All of these factors increase the risk of drug-resistance. And in fact, the report also found that HIV drug-resistance was rising. In 2010, the estimated prevalence of drug resistance was a moderate 7 percent in developing countries. That number is now at or above 10 percent for those starting ART for the first time, and up to 40 percent for those restarting ART. If health officials don’t find a way to put a stop to these multi-drug resistant strains, experts fear that they will spread much like drug-resistant tuberculosis has.

“Treatment of HIV is not a solved problem.” said Johns Hopkins University School of Medicine molecular sciences professor Dr. Charles Flexner, who is also professor of medicine in the Divisions of Clinical Pharmacology and Infectious Diseases. “There are still issues we need to wrestle with, and if we’re not very careful, we could wind up creating a situation where treatment of HIV, especially in resource-limited settings, is even more difficult than it is today.”

The scope of the drug resistance proble

Already, scientists estimate that drug-resistant HIV-1 strains could cause up to 425,000 deaths and 300,000 new infections in the next five years. And the Centers for Disease Control and Prevention predicts that as the world achieves the United Nations’ 90-90-90 goal by 2020 (90 percent of people with HIV diagnosed, 90 percent of diagnosed people on ART and 90 percent of people on ART with suppressed viral levels), over 3 million people, or one-third of all of those living with HIV that has not been suppressed, will likely have drug-resistant strains of the virus.

A recent meta-analysis illustrates the emerging problem well. Scientists examined 712 people in Sub-Saharan Africa for whom first-line ART treatments had failed, and found that 115 of them (16 percent) had mutations in their HIV strain that were linked to resistance against thymidine analogues, an older generation of ART.

These 115 people were also more likely to be resistant to newer generations of ART. Ninety-three of them, for instance, were also resistant to tenofovir, which is central to the newer ART regimens in most HIV treatment plans and a worrying sign that modern first-line treatment won’t be able to help treat these people.

What’s the WHO is doing about it

The WHO is developing a five-year Global Action Plan for drug-resistant HIV, focusing primarily on poor- and middle-income populations from 2017 through 2021. The organization published a draft of the plan online in July and invited public comment, but the plan has yet to be formally approved or launched.

It also released a report on the issue that warns that simply giving people WHO-recommended ART drugs, without proper medical care and follow-up, is not enough to treat HIV or contain the pandemic. In fact, it could be exacerbating drug-resistance.

The risk of drug resistance will increase as global efforts to spread ART and preventive HIV treatments around the world are more successful, the WHO concludes.

“While concerns about resistance should not stop the provision of antiretroviral therapy (ART) to all in need, the long-term implications of earlier initiation on adherence and drug resistance need to be closely monitored and responded to,” the organization said in a statement about the global action plan.

The same standard of medical care globally is key

The threat of creating drug-resistant strains of HIV was, in fact, one of the objections to widespread ART distribution in general, among both developing and developed nations. Thankfully, the world’s scientists and the U.S. government concluded that treating people with HIV as soon as they are diagnosed should take precedence above all other concerns.

This global consensus on ART, embodied most dramatically in former President George W. Bush’s 2004 President’s Emergency Plan for AIDS Relief, has saved millions of lives and prevented millions of HIV cases from taking root. In 2015 alone, for instance, the PEPFAR provided ART to 9.5 million people around the world, including pregnant women who were then able to prevent passing the virus on to their newborns.

But just because more people in developing countries are receiving ART, that doesn’t mean they’re enjoying the same level of care someone in the U.S. might experience if they contracted HIV, explained HIV resistance expert Dr. Jonathan Li, an assistant professor at Harvard Medical School and Brigham and Women’s Hospital. Americans with HIV, for instance, are tested frequently for both signs of drug resistance and viral mutations, so that doctors can further customize their ART regimen over time if a certain drug begins losing its effectiveness.

These kinds of tests are exactly what people in developing countries need to prevent the development of drug-resistant HIV strains, argues Ravindra Gupta, lead investigator of the meta-analysis that measured rising drug resistance in Sub-Saharan Africa.

As it stands, most of the people who receive ART are treated in developing countries that don’t have the resources to provide tailored care. These HIV patients are also more likely to receive cheaper, more toxic drugs that are more prone to breed resistance, as opposed to the developed world’s less toxic drugs that are more forgiving if you occasionally skip a dose or two, Li said. Add the lack of medical tests to inconsistent ART access, and you’ve got a recipe for drug resistance.

“Patients are left on failing regimens for longer periods of time, meaning that their virus has more chance to develop resistance to the drugs that they’re on,” Li explained.

It’s clear that as countries continue to work together to expand ART access to all who need it, basic standards of medical care and follow-up also need to become a standard part of the package. If they don’t, the world could face a problem even more dire than the current HIV/AIDS pandemic: A virus that doesn’t respond to first-line drugs, requiring more expensive and toxic drugs to suppress it.

“Given the interconnected world we live in today, and the ability of people to move across the globe, this epidemic will not be stamped out until we can control it in places like Africa,” Li concluded.

By Anna Almendrala

Original Article