WHO: Pretreatment HIV drug resistance exceeds 10% in many places

Among adults initiating ART, levels of pretreatment HIV drug resistance to two non-nucleoside reverse transcriptase inhibitors, or NNRTIs, exceeded 10% in 12 of 18 countries reporting data to WHO between 2014 and 2018, and resistance was particularly high in women, according to a new report.

The high levels of resistance reported to efavirenz and nevirapine support WHO guidelines published last year that recommend adopting dolutegravir-based regimens as the preferred first-line treatment for HIV, said Silvia Bertagnolio, MD, co-author of the new report on HIV drug resistance and a medical officer for WHO.

“WHO recommends to urgently move away from NNRTIs when levels of pretreatment drug resistance to efavirenz/nevirapine is more than 10%,” Bertagnolio explained to Infectious Disease News. “In circumstances where levels of NNRTI pretreatment drug resistance are high, and dolutegravir cannot be used in first-line ART due to cost or other considerations, protease inhibitors should be considered in first-line.”

According to the new report, between 2004 and 2018, 49 countries implemented HIV drug resistance surveys, and another 35 countries have plans to conduct these surveys.

The report included findings from 44 nationally representative surveys conducted in 24 low- and middle-income countries, including 18 that reported data on drug resistance to WHO between 2014 and 2018.

According to the findings, levels of pretreatment HIV drug resistance to NNRTIs were higher among women compared with those of men — 11.8% (95% CI, 9.4-14.8) vs. 7.8% (95% CI, 6.3-9.5).

This week, WHO strengthened its recommendation that dolutegravir be used as a first-line treatment for all populations, including women who are pregnant or of child-bearing age, after study results showed a significantly lower risk for neural tube defects in children born to mothers taking the integrase inhibitor than previously estimated.

“In some countries, access to dolutegravir in women was hampered by the safety concerns associated with dolutegravir in women of childbearing potential,” Bertagnolio said. “These data highlight the critical need to provide access to dolutegravir to women and strongly support new WHO guidelines which recommend the use of dolutegravir in all, including women and girls of reproductive age.”

In addition to women, individuals reinitiating first-line ART and reporting previous exposure to antiretroviral drugs also are at a high risk for pretreatment drug resistance, according to the report.

The proportion of people starting ART who also reported previous antiretroviral drug exposure ranged from 1.2% to 26.3%, and this is expected to increase with the global scale-up of ART, the authors said. Pretreatment drug resistance to efavirenz and/or nevirapine was found to be nearly three times higher among first-line ART initiators reporting prior antiretroviral drug exposure compared with antiretroviral drug-naive individuals starting ART.

The report also showed an “alarmingly high” prevalence of pretreatment drug resistance among children aged 18 months or younger. Data collected from surveys conducted in sub-Saharan Africa between 2012 and 2018 found that over half of infants newly diagnosed with HIV carried a virus resistant to efavirenz and/or nevirapine.

In some countries, levels of pretreatment drug resistance to nucleoside reverse-transcriptase inhibitors (NRTIs) also exceeded 10%, according to the report.

Nine countries reported findings on acquired drug resistance. In three of those countries, viral suppression levels among adults receiving HIV treatment between 2014 and 2018 exceeded 90%. The prevalence of acquired drug resistance ranged from 3% to 29% across all surveys.

Among virally nonsuppressed patients receiving NNRTI-based ART, levels of NNRTI resistance ranged from 50% to 97% and NRTI resistance ranged from 21% to 91%. Among patients for whom NNRTI-based first-line ART failed, dual-class resistance of both NNRTI and NRTI had an estimated range between 21% and 91%. – by Marley Ghizzone

References:

WHO. HIV drug resistance report 2019. https://www.who.int/hiv/pub/drugresistance/hivdr-report-2019/en/. Accessed July 22, 2019.

Disclosure: Bertagnolio reports no relevant financial disclosures.

Among adults initiating ART, levels of pretreatment HIV drug resistance to two non-nucleoside reverse transcriptase inhibitors, or NNRTIs, exceeded 10% in 12 of 18 countries reporting data to WHO between 2014 and 2018, and resistance was particularly high in women, according to a new report.

The high levels of resistance reported to efavirenz and nevirapine support WHO guidelines published last year that recommend adopting dolutegravir-based regimens as the preferred first-line treatment for HIV, said Silvia Bertagnolio, MD, co-author of the new report on HIV drug resistance and a medical officer for WHO.

“WHO recommends to urgently move away from NNRTIs when levels of pretreatment drug resistance to efavirenz/nevirapine is more than 10%,” Bertagnolio explained to Infectious Disease News. “In circumstances where levels of NNRTI pretreatment drug resistance are high, and dolutegravir cannot be used in first-line ART due to cost or other considerations, protease inhibitors should be considered in first-line.”

According to the new report, between 2004 and 2018, 49 countries implemented HIV drug resistance surveys, and another 35 countries have plans to conduct these surveys.

The report included findings from 44 nationally representative surveys conducted in 24 low- and middle-income countries, including 18 that reported data on drug resistance to WHO between 2014 and 2018.

According to the findings, levels of pretreatment HIV drug resistance to NNRTIs were higher among women compared with those of men — 11.8% (95% CI, 9.4-14.8) vs. 7.8% (95% CI, 6.3-9.5).

This week, WHO strengthened its recommendation that dolutegravir be used as a first-line treatment for all populations, including women who are pregnant or of child-bearing age, after study results showed a significantly lower risk for neural tube defects in children born to mothers taking the integrase inhibitor than previously estimated.

“In some countries, access to dolutegravir in women was hampered by the safety concerns associated with dolutegravir in women of childbearing potential,” Bertagnolio said. “These data highlight the critical need to provide access to dolutegravir to women and strongly support new WHO guidelines which recommend the use of dolutegravir in all, including women and girls of reproductive age.”

In addition to women, individuals reinitiating first-line ART and reporting previous exposure to antiretroviral drugs also are at a high risk for pretreatment drug resistance, according to the report.

The proportion of people starting ART who also reported previous antiretroviral drug exposure ranged from 1.2% to 26.3%, and this is expected to increase with the global scale-up of ART, the authors said. Pretreatment drug resistance to efavirenz and/or nevirapine was found to be nearly three times higher among first-line ART initiators reporting prior antiretroviral drug exposure compared with antiretroviral drug-naive individuals starting ART.

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The report also showed an “alarmingly high” prevalence of pretreatment drug resistance among children aged 18 months or younger. Data collected from surveys conducted in sub-Saharan Africa between 2012 and 2018 found that over half of infants newly diagnosed with HIV carried a virus resistant to efavirenz and/or nevirapine.

In some countries, levels of pretreatment drug resistance to nucleoside reverse-transcriptase inhibitors (NRTIs) also exceeded 10%, according to the report.

Nine countries reported findings on acquired drug resistance. In three of those countries, viral suppression levels among adults receiving HIV treatment between 2014 and 2018 exceeded 90%. The prevalence of acquired drug resistance ranged from 3% to 29% across all surveys.

Among virally nonsuppressed patients receiving NNRTI-based ART, levels of NNRTI resistance ranged from 50% to 97% and NRTI resistance ranged from 21% to 91%. Among patients for whom NNRTI-based first-line ART failed, dual-class resistance of both NNRTI and NRTI had an estimated range between 21% and 91%. – by Marley Ghizzone

References:

WHO. HIV drug resistance report 2019. https://www.who.int/hiv/pub/drugresistance/hivdr-report-2019/en/. Accessed July 22, 2019.

Disclosure: Bertagnolio reports no relevant financial disclosures.