HIV drug resistance in infants increases with changing prevention of mother-to-child transmission regimens

Abstract

Objectives The objectives of this study were to determine HIV drug resistance prevalence in Zambian infants upon diagnosis, and to determine how changing prevention of mother-to-child transmission (PMTCT) regimens affect drug resistance. Design Dried blood spot (DBS) samples from infants in the Lusaka District of Zambia, obtained during routine diagnostic screening, were collected during four different years representing three different PMTCT treatment regimens. Methods DNA extracted from DBS samples was used to sequence a 1493 bp region of the RT gene. Sequences were analyzed via the Stanford HIV Drug Resistance (HIVDR) Database (http://hivdb.standford.edu) to screen for resistance mutations. Results HIVDR in infants increased from 21.5% in 2007/2009 to 40.2% in 2014. Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance increased steadily over the sampling period, while nucleoside reverse transcriptase inhibitor (NRTI) resistance and dual class resistance both increased more than threefold in 2014. Analysis of drug resistance scores in each group revealed increasing strength of resistance over time. In 2014, children with reported PMTCT exposure, defined as infant prophylaxis and/or maternal treatment, showed a higher prevalence and strength of resistance compared to those with no reported exposure. Conclusions HIVDR is on the rise in Zambia and presents a serious problem for successful lifelong treatment of HIV infected children. PMTCT affects both the prevalence and strength of resistance and further research is needed to determine how to mitigate its role leading to resistance.

What is new in perinatal HIV prevention?

“…As described in a 2017 meta-analyses review, 39 Boerma et al documented increasingly high rates of ARV resistance over the past decade among HIV infected infants and young children (47%) in 13 countries who failed PMTCT; as well as resistant virus among HIV infected children not reported to be exposed to PMTCT antiretrovirals (26.8%).These include studies from Southern and East Africa 40–42 as well as West Africa with the highest proportion of resistance being to nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) followed by Nucleoside Reverse Transcriptase Inhibitors (NRTIs). 43–44 Likewise HIV infected pregnant women in international settings have also shown increased rates of resistance to NNRTI and NRTIs’ with a study from KwaZulu-Natal South Africa, 45 reporting 65% of pregnant women having an NNRTI resistance and 7% with TAMS resistance using Ultra-deep sequencing (UDS) assays; and a study from Tanzania reported similar findings with drug resistance mutants in 69% of women based on UDS assays.…”

High levels of resistance to nucleoside/nucleotide reverse transcriptase inhibitors in newly diagnosed antiretroviral treatment-naive children in sub-Saharan Africa

“…Exposure of infants to antiretroviral drugs for prevention of mother-to-child transmission (PMTCT) can induce resistance to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) [1][2][3][4][5].…”

Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia

“…This may explain the high prevalence of TAMs in our study population. However, the high prevalence of TAMs was reported in an earlier study of adults failing HIV treatment in Lusaka, Zambia and other studies in the region [6,8,9,10,24]. Non the less, the poor documentation of the reasons for drug change in patient medical records remains a major limitation to interpreting the presence/absence of HIVDR mutations including TAMs.…”

“…In Johannesburg South Africa, 56.8% of 230 PMTCT-exposed but newly diagnosed children under two years had Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) HIVDR. In Zambia, a study of HIVDR in perinatally infected children showed an increasing and worsening pattern of HIVDR from 21% in 2007/9 to 40% in 2014 [10].While these studies contribute to our understanding of drug resistance, only the study in Tanzania included adolescents [11].…”

“…Another study found that 98% of 66 Zambian adults failing first line ART had HIVDR in 2009-2012 [9]. Poppe et al demonstrated an increasing prevalence of HIVDR in infants from 21.5 in 2007/2009 to 40.2% in 2014 and was mainly driven by the PMTCT practices [10]. Another study from Lusaka, Zambia showed the prevalence of NNRTI DRM prevalence was high (at or near 100%) in all first line therapy in HIV infected adult patients (age >15 years) attending the University Teaching Hospital Infectious Diseases Centre Advanced HIV Clinic [9].…”