July 20, 2017
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Officials warn of ‘worrying’ rise in HIV drug resistance

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On the eve of a major international AIDS conference, world health officials painted a concerning picture of rising HIV drug resistance, saying it could lead to 135,000 new deaths over the next 5 years and undermine global progress toward ending the epidemic if left unchecked.

According to a new report, six of 11 countries that have submitted surveys on pretreatment HIV drug resistance to WHO reported resistance rates of more than 10% to two of the most affordable and widely used non-nucleoside reverse transcriptase inhibitors (NNRTIs), efavirenz and nevirapine, between 2014 and 2016.

The “HIV Drug Resistance Report” was released ahead of the International AIDS Society conference in Paris. It was coauthored by WHO, the CDC and the Global Fund to Fight AIDS, Tuberculosis and Malaria.

“This new report shows a worrying picture of increasing levels of HIV drug resistance and, if unchecked, it will be a major risk to [ending the epidemic],” Marijke Wijnroks, MD, interim executive director of the Global Fund, said in a statement.

New research quantified the impact of high levels of HIV drug resistance. According to Silvia Bertagnolio, MD, a WHO medical officer in HIV treatment and care, mathematical modelling showed that NNRTI resistance levels of more than 10% in sub-Saharan Africa would lead to 135,000 deaths, 105,000 new infections and a cost of $650 million for more expensive second-line therapies over the next 5 years.

“WHO is taking the threat of HIV drug resistance very seriously because drug resistance impacts not only effective therapy at the individual level ... but also has impact at the population level,” Bertagnolio said during a teleconference.

Occurring when patients do not adhere to regular and continuous treatment, HIV drug resistance causes mutations in the genetic structure of the virus, making treatments ineffective. Pretreatment drug resistance can be acquired at the time of transmission or occur because of prior exposure to antiretroviral drugs.

“A significant proportion of those people will not be suppressed on therapy,” Bertagnolio said. “They will fail and can transmit HIV and HIV drug resistance to other individuals.”

In the new report, data from mostly low- and middle-income countries showed that the level of pretreatment drug resistance to NNRTIs has increased significantly since 2001 and has coincided with expanded ART access. The countries that reported pretreatment resistance rates of more than 10% to NNRTIs — Argentina, Guatemala, Namibia, Nicaragua, Uganda and Zimbabwe — are all located in Africa or Central America, but resistance to the drugs has increased in all regions, according to the report.

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Twenty-six countries have either completed or are currently conducting national surveys on HIV drug resistance using WHO guidance, but only 11 have submitted data on pretreatment resistance to efavirenz and nevirapine.

Photo of Gottfried Hirnschall
Gottfried Hirnschall

“Many more countries will have to do similar studies and many have already started,” said Gottfried Hirnschall, MD, MPH, director of WHO’s Department of HIV and Global Hepatitis Program.

According to Meg Doherty, MD, PhD, MPH, WHO coordinator for HIV treatment and care, new treatment guidance from WHO recommends that countries set a 10% threshold for pretreatment resistance to first-line ART regimens and use non-NNRTI-based treatments — including those with integrase inhibitors — when they reach that threshold. Integrase inhibitors like dolutegravir are affordable and have higher barriers to resistance, Doherty said.

She said a new global action plan includes five key interventions to halt the rise in HIV drug resistance rates. Among other things, it urges countries to prevent and respond to drug resistance by improving the quality of care and changing their treatment guidelines if they reach the 10% threshold.

“We need to support people who are on treatment so they can do it continuously and for life,” Hirnschall said.

The report also offered good news, including evidence of increased access to HIV prevention, testing, treatment and care around the globe. It said 36.7 million people were living with HIV in 2016, including 19.5 million who were accessing antiretroviral therapy. Hirnschall said there were 1.8 million new infections and one million HIV-related deaths last year.

However, HIV drug resistance could compromise progress toward two UNAIDS goals: achieving the 90-90-90 target — in which 90% of patients with HIV know their infection status, 90% of those patients receive sustained ART and 90% of patient on ART achieve viral suppression — and ending the HIV/AIDS epidemic by 2030. Currently, the world’s 90-90-90 numbers are 70-77-82. by Gerard Gallagher

References:

WHO. Global action plan on HIV drug resistance 2017-2021. 2017. http://www.who.int/hiv/pub/drugresistance/hivdr-action-plan-2017-2021/en/. Accessed July 20, 2017.

WHO. Guidelines on the public health response to pretreatment HIV drug resistance. 2017. http://www.who.int/hiv/pub/guidelines/hivdr-guidelines-2017/en/. Accessed July 20, 2017.

WHO. HIV drug resistance report 2017. http://www.who.int/hiv/pub/drugresistance/hivdr-report-2017/en/. Accessed July 20, 2017.

Disclosures: Bertagnolio, Doherty, Hirnschall and Wijnroks report no relevant financial disclosures.