Increasing HIV Drug Resistance in Newly Diagnosed Infants

According to data published in BMC Infectious Diseases, nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance has increased among newly diagnosed infants who live in a high HIV prevalence setting where maternal antiretroviral therapy (ART) coverage increased across years.

Researchers conducted a sub-study of 3 nationally representative cross-sectional surveys in South Africa in 2010, 2011 to 2012, and 2012 to 2013 to address several questions surrounding mother to child transmission of HIV. One goal was to determine the prevalence of drug resistance among infants aged 4 to 8 weeks who tested positive for HIV via polymerase chain reaction (PCR). Researchers used dried blood spot samples from 220 infants who had a positive HIV PCR and analyzed for HIV drug resistance at the National Institute of Communicable Diseases in South Africa.

Researchers detected HIV-1 drug resistance in 51% (95% CI, 45%-58%) of all infants with a positive HIV PCR. In 2010, 2011, and 2012, respectively, drug resistance, specifically to the NNRTI drug class, was 37% (95% CI, 28%-46%), 64% (95% CI, 53%-74%) and 63% (95% CI, 48%-77%; P <.0001). In a pooled analysis across all surveys, infants whose mothers received ART showed the highest prevalence of resistance at 74%, compared with 26% of infants who had a positive HIV PCR had no or undocumented ART drug exposure—either via their own treatment or via maternal treatment with ART.

The reliance on self-reporting of maternal and infant programs to prevent mother to child transmission prophylaxis during the time of data collection for the current pregnancy and lack of information on possible program exposure during any prior pregnancies were limitations of the study. Investigators also noted that conventional specimen sequencing strategies were used, and it can be expected that more sensitive strategies will increase the frequency of drug resistance mutation detection. Further, the study could not provide an understanding of the effect of prolonged daily nevirapine exposure or option B+ prophylaxis on the prevalence of HIV-1 drug resistance in infants beyond age 8 weeks.

According to investigators, the data “illustrate the complex drug-resistance challenges that arise as more efficacious [ART] is introduced and at earlier time points.”

Researchers also recommended that programs to prevent mother to child transmission should aim for optimal care, adherence counseling, and virologic suppression for pregnant women to reduce the risk for transmission, especially of drug-resistant strains of virus. Investigators also stated that in the context of mother to child transmission prevention programs Option B+, “more data are needed on the relationships between maternal ART duration, maternal ART adherence and the transmission of resistant virus to the infant [vs] transformation of virus into a resistant form due to infant drug exposure.”

Reference 

Hunt GM, Ledwaba J, Salimo A, et al. Prevalence of HIV-1 drug resistance amongst newly diagnosed HIV-infected infants age 4-8 weeks, enrolled in three nationally representative PMTCT effectiveness surveys, South Africa: 2010, 2011-12 and 2012-13. BMC Infect Dis. 2019;19(Suppl 1):787.