High rates of drug resistance among HIV-positive infants in South Africa

Michael Carter
Published: 13 July 2014

There was a high prevalence of antiretroviral drug resistance among infants newly diagnosed with HIV in Johannesburg, investigators report in AIDS. Over half the infants exposed to treatment for the prevention of mother-to-child transmission (PMTCT) or as infant prophylaxis had resistance to drugs in the non-nucleoside reverse transcriptase inhibitor (NNRTI) class. Prevalence of drug resistance, especially to NNRTIs, was also high among the infants who were reportedly never exposed to anti-HIV drugs when used for PMTCT/infant prophylaxis.

“PMTCT history is an inadequate means of ruling out pre-treatment drug resistance,” comment the authors. “Our results support the use of protease inhibitor-based first-line treatment in HIV-infected infants and young children regardless of PMTCT history.”

The appropriate use of antiretroviral therapy can help prevent vertical (mother-to-child) HIV transmission. South African guidelines were recently changed to recommend combination antiretroviral therapy for all pregnant women and also antiretroviral infant prophylaxis. The NNRTI drug nevirapine (Viramune) is the mainstay of these regimens. If HIV transmission does occur despite this therapy, there is a high risk of the infant being infected with strains of HIV that have resistance to NNRTIs and also other types of antiretroviral drugs. This has important implications for the choice of HIV treatment for the infant.

In order to help guide the most appropriate use of HIV therapy, investigators in Johannesburg, South Africa, designed a study describing patterns of drug resistance in infants newly diagnosed with HIV none of whom had yet started HIV therapy. All were under two years of age and the study was conducted in 2011.

The study population comprised 255 infants who acquired HIV at birth. Two thirds (67%) had been exposed to maternal and/or infant therapy for PMTCT. For 89% of these children, this included a maternal antiretroviral component and 97% were exposed to infant prophylaxis. The NNRTI nevirapine and several drugs in the nucleoside reverse transcriptase inhibitor (NRTI) class were widely used.

The remaining third of children had no reported or recorded exposure to antiretrovirals.

Of the PMTCT-exposed children, 57% had resistance to NNRTIs, 15% to NRTIs and 1% to protease inhibitors. Over three-quarters (78%) of children with NRTI mutations also had resistance to NNRTIs. High-level resistance to nevirapine was present in 54% of the drug-exposed infants; 22% had high-level efavirenz resistance and 2% had resistance to etravirine.

Drug resistance was also highly prevalent in the children who were not drug exposed. A quarter had NNRTI resistance, 11% resistance to NRTIs and 1% resistance to protease inhibitors. High-level resistance to nevirapine and efavirenz was present in 17% and 7%, respectively.

“We hypothesize that poor maternal recall, lack of understanding, poor record-keeping, or failure to recall exposures in prior pregnancies may explain some of these cases,” write the investigators.

They believe their data confirm “that the majority of newly diagnosed HIV-infected infants and young people will carry NNRTI-resistant virus. Resistance mutations are also present in a considerable proportion of children with no reported or recorded antiretroviral drug exposures.” All children and young people living with HIV should therefore start HIV therapy with a regimen based on a protease inhibitor, conclude the authors.

Reference

Kuhn L et al. Drug resistance among newly diagnosed HIV-infected children in the era of more efficacious antiretroviral prophylaxis. AIDS 28: 1673-78, 2014.