New WHO Guidelines for Managing Pretreatment HIV Drug Resistance
In patients initiating first-line ART, patients with previous exposure to ARV are more likely to have pretreatment HIVDR to NNRTIs than patients who are ARV-naïve.
The World Health Organization (WHO) published new guidelines for managing human immunodeficiency virus drug resistance (HIVDR) in countries in which pretreatment HIVDR to non-nucleoside reverse transcriptase inhibitors (NNRTIs) is prevalent. The guidelines were presented at the 9th International AIDS Society Conference on HIV Science.1
Pretreatment HIVDR to NNRTIs, such as efavirenz and nevirapine, is increasing worldwide, according to the 2017 WHO report on HIV drug resistance. In eastern Africa, southern Africa, and Latin America, the prevalence of HIVDR is approximately 10% or higher.2
“Efavirenz and nevirapine are currently a critical component of first-line regimens in low- and middle-income countries and people with drug resistance are at risk for worse outcomes compared to those without drug resistance. Specifically, those with drug-resistant virus already present before they start first-line [antiretroviral therapy] are less likely to achieve and maintain virological suppression, more likely to stop treatment, and more likely to acquire more drug resistance mutations,” Silvia Bertagnolio, MD, from the WHO department of HIV and global hepatitis programme, told Infectious Disease Advisor.
The WHO report also found that in patients initiating first-line antiretroviral therapy (ART), patients with previous exposure to antiretroviral drugs (ARV) are more likely to have pretreatment HIVDR to NNRTIs than patients who are ARV-naïve (21.6% vs 9.3%; P <.0001). People with previous exposure to ARVs may include women who were treated with ARVs as part of the prevention of mother-to-child transmission (PMTCT) or individuals who have discontinued a prior ART regimen.2
The issue of pretreatment HIVDR is further complicated by the fact that low- and middle-income countries do not have ready access to testing for HIVDR. As a result, patients with HIVDR may go undetected and receive treatment with NNRTI regimens that are only partially effective, further exacerbating transmission of HIV and drug-resistant HIV.1
“Over the next 5 years, millions more people need to start ART and be maintained on it for life; therefore, to maximize achieving the end of AIDS as a public health threat, guidelines indicating ‘what to do' in countries observing high levels of HIVDR were necessary,” Dr Bertagnolio said.
The WHO issued new recommendations to aid national public health programs in addressing pretreatment HIVDR in countries in which HIVDR is highly prevalent. The guidelines are part of the effort to “attain and maintain the treatment target of 90% viral suppression among all people receiving first-line ART by 2020.”1
The guidelines state that non-NNRTI-containing regimens, such as those containing dolutegravir, should be considered as first-line ART in patients with pretreatment HIVDR to NNRTIs.1
In countries in which testing for HIVDR is not readily available, national public health data on pretreatment HIVDR may be used to guide public health decisions. If no nationally representative data on pretreatment HIVDR are available, efforts to collect such data via surveys should be pursued.1
If the national prevalence of pretreatment HIVDR to NNRTIs is <10%, then the use of non-NNRTI-containing regimens should be prioritized in patients who have previously received treatment with ARVs.1
In countries where the prevalence of pretreatment HIVDR to NNRTIs is ≥10%, the guidelines emphasize urgent consideration of alternative non-NNRTI regimens in all patients initiating first-line ART, regardless of prior ARV exposure history. If alternative regimens cannot be broadly implemented, then introducing pretreatment HIVDR should be considered.1
“Regardless of population-levels of HIVDR, clinicians should focus on prevention of HIVDR by doing all they can to maximize adherence to and retention on ART; support drug supply continuity; and ensure that viral load testing is consistently done in all people on ART, and that these test results are used to identify individuals failing first-line therapy who should be promptly switched to second-line ART regimens,” Dr Bertagnolio said.
- Guidelines on the public health response to pretreatment HIV drug resistance, July 2017. Geneva: World Health Organization; 2017. Licence: CC BY-NC-SA 3.0 IGO. http://apps.who.int/iris/bitstream/10665/255880/1/9789241550055-eng.pdf. Accessed July 27, 2017.
- HIV Drug Resistance Report 2017. Geneva: World Health Organization; 2017. www.who.int/hiv/pub/drugresistance/hivdr-report-2017/en/. Accessed July 27, 2017.