Abstract:
BACKGROUND : South Africa (SA) has expanded efforts to reduce mother-to-child transmission of HIV (MTCT) to less
than 2% at six weeks after birth and to less than 5% at 18 months postpartum by 2016. Despite improved
antiretroviral regimens and coverage between 2001 and 2016, there is little data on infant HIV drug resistance. This
paper tracks the prevalence of HIV drug resistance patterns amongst HIV infected infants from three nationally
representative studies that assessed the effectiveness of national programs to prevent MTCT (PMTCT). The first study
was conducted in 2010 (under the dual therapy PMTCT policy), the second from 2011 to 12 (PMTCT Option A
policy) and the third from 2012 to 13 (PMTCT Option A policy). From 2010 to 2013, infant non-nucleoside reverse
transcriptase inhibitor (NNRTI) exposure increased from single dose to daily throughout breastfeeding; maternal
nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI exposure increased with initiation of NNRTI-and NRTIcontaining
triple antiretroviral therapy (ART) earlier in gestation and at higher CD4 cell counts.
METHODS : Three nationally representative surveys were conducted in 2010, 2011–12 and 2012–13. During the
surveys, mothers with known, unknown, or no exposure to antiretrovirals for PMTCT and their infants were
included, and MTCT was measured. For this paper, infant dried blood spots (iDBS) from HIV PCR positive infants
aged 4–8 weeks, with consent for additional iDBS testing, were analysed for HIV drug resistance at the National
Institute of Communicable Diseases (NICD), SA, using an in-house assay validated by the Centers for Disease Control
and Prevention (CDC). Total viral nucleic acid was extracted from 2 spots and amplified by nested PCR to generate
a ~ 1 kb amplicon that was sequenced using Sanger sequencing technologies. Sequence assembly and editing was
performed using RECall v3.
RESULTS : Overall, HIV-1 drug resistance was detected in 51% (95% Confidence interval (CI) [45–58%]) of HIV PCR
positive infants, 37% (95% CI [28–47%]) in 2010, 64% (95% CI [53–74%]) in 2011 and 63% (95% CI [47–77%]) in 2012
(p < 0.0001), particularly to the NNRTI drug class. Pooled analyses across all three surveys demonstrated that infants
whose mothers received ART showed the highest prevalence of resistance (74%); 26% (21/82) of HIV PCR positive
infants with no or undocumented antiretroviral drug (ARV) exposure harboured NNRTI resistance.
CONCLUSIONS : These data demonstrate increasing NNRTI resistance amongst newly-diagnosed infants in a high HIV
prevalence setting where maternal ART coverage increased across the years, starting earlier in gestation and at
higher CD4 cell counts. This is worrying as lifelong maternal ART coverage for HIV positive pregnant and lactating
women is increasing. Also of concern is that resistant virus was detected in HIV positive infants whose mothers
were not exposed to ARVs, raising questions about circulating resistant virus. Numbers in this group were too small
to assess trends over the three years.
