Page 249 - HIVMED_v21_i1.indb

Page 2 of 4 Scientific Letter

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be higher in persons of African descent. These higher drug (from self-report and medical records) on PMTCT regimen
levels may also impact risk of drug resistance when stopping received; dates on which ART and individual antiretrovirals
EFV-based ART. were started and stopped as well as provided blood
specimens for drug resistance and HIV-1 RNA testing.
Prior to 2015, both the World Health Organization (WHO) HIV RNA results at the point of enrolment into the Mpepu
and the Botswana programme for the prevention of study, and documented nadir CD4 counts, were retrieved
mother-to-child transmission (PMTCT) recommended that and served as baseline values.
pregnant women living with HIV with a CD4 cell count >
350 cells/mm without a WHO stage 3 or 4 illness take Prior to drug resistance testing, we first determined HIV-1 RNA
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three-drug ART in pregnancy, but discontinue the ART viral load levels with the Abbott m2000sp/rt machine (limit of
postpartum or upon breastfeeding cessation (option B). detection 40 copies/mL). Where HIV-1 RNA was detected, it
was extracted using an automated validated technique. We
6
Although both WHO and Botswana subsequently modified then performed reverse transcription using in-house one-step
guidelines to recommend lifelong ART regardless of CD4 RT-PCR technique. Polymerase chain reaction (PCR) products
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cell count or disease stage (option B+), the prior guidance were then purified and sequenced. Consensus sequences
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for pregnant women, as well as the inconsistent application were generated, and the Stanford HIV Drug Resistance
of an NRTI tail at the time of EFV cessation, offers an Database was used to identify all drug resistance mutations in
opportunity to evaluate the development of resistance and the protease and reverse transcriptase coding regions.
the performance of a TDF/FTC tail among women stopping
an EFV/TDF/FTC regimen. Because this ART regimen Statistical methods
remains widely used throughout the world, the natural
experiment afforded by prior PMTCT guidelines is Statistical Package for Social Sciences (SPSS) version 25 was
applicable to our understanding of the risk of cessation of used to perform statistical analyses, which were generally
NNRTI-based regimens generally. descriptive in nature; a two-sided Fisher’s exact test was used
to evaluate for differences in the proportion of drug resistance
Methods by the approach to ART cessation, either with a 7-day TDF/FTC
tail or with abrupt cessation of all three drugs. The small
Study population number of women with drug resistance mutations precluded

Between April 2014 and May 2015, we enrolled a subset of more detailed analysis of predictors of drug resistance.
pregnant women living with HIV participating in a trial of
infant cotrimoxazole prophylaxis in Botswana (the ‘Mpepu’ Ethical �onsiderations
study) into this resistance sub-study. Mpepu was a The Botswana Health Research Development Committee
double-blinded randomised controlled trial designed to assess and the Office of Human Research Administration at Harvard
the efficacy and safety of infant cotrimoxazole prophylaxis T. H. Chan School of Public Health approved this drug
versus placebo used daily from as early as 14 days of life resistance sub-study (HRDC 00732 and IRB13-2772), and
through 15 months among HIV-exposed uninfected infants in women provided written informed consent for participation.
Botswana. 5
Results
Women were eligible for this sub-study of drug resistance
following cessation of EFV/FTC/TDF if they were living Baseline characteristics
with HIV, had pre-treatment CD4 > 350 cells/mm without Ninety women enrolled, 74 of whom discontinued
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evidence of WHO stage 3 or 4 disease, initiated EFV/FTC/ EFV/FTC/TDF postpartum and had samples collected for
TDF in pregnancy and stopped ART postpartum according genetic resistance testing and are included in this analysis.
to Botswana guidelines at the time (at 4–6 weeks postpartum Sixteen of 90 women not included in this analysis had CD4 < 350
if formula feeding, or 6 weeks after weaning if breastfeeding). cell/mm post-delivery and had to continue ART for their own
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Per Botswana national HIV treatment guidelines, a 7-day tail health per Botswana national protocol at the time. The median
of TDF/FTC after cessation of EFV was recommended. time from cessation of EFV (whether or not a tail period
However, decisions regarding receipt and cessation of occurred) to time sample was collected for resistance testing
maternal ART occurred at government clinics (rather than was 5 weeks (range: 3–13 weeks). Median age at enrolment was
study clinics), and the 7-day tail was inconsistently applied at 29 years (range: 20–45) with median nadir CD4 count of 571
the time of ART cessation. cells/mm (range: 361–1236). Forty-seven (64%) women had no
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previous exposure to antiretrovirals, 25 (34%) reported previous
Data collection and laboratory testing exposure to antiretrovirals for PMTCT purposes in a prior
Women eligible to participate in this sub-study were pregnancy and 2 (2%) were previously exposed to
identified in the Mpepu study and scheduled for a clinic visit EFV/FTC/TDF but stopped prior to conception and then
4–6 weeks after ART cessation. Interested and eligible women re-started EFV/FTC/TDF as three-drug prophylaxis for the
consented to participate in the study and provided data index pregnancy. Thirty-two (43%) stopped ART with the

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