Frequency of viremic episodes in HIV-infected women initiating antiretroviral therapy during pregnancy: A cohort study

Background. The numbers of human immunodeficiency virus (HIV)-infected women initiating antiretroviral therapy (ART) in pregnancy are increasing rapidly with global policy changes. There are widespread concerns about ART adherence during pregnancy and postpartum but few data on viral suppression (VS) over time in these populations. Methods. We followed a cohort of 523 women in Cape Town, South Africa, initiating ART in pregnancy (once-daily tenofovir 300 mg, emtricitabine 200 mg, and efavirenz 600 mg) and achieving VS (<50 copies/mL). Participants provided specimens through 12 months postpartum for batched viral load (VL) testing separate from routine care. Analyses described the incidence of major (>1000 copies/mL) and minor (50-1000 copies/mL) viremic episodes (VEs) and factors associated with major VEs. Results. In the cohort (median age, 28 years; median pre-ART VL, 3.99 copies/mL; 3% previously defaulted ART; 24% with previous exposure to short-course antiretrovirals), the median time of follow-up from VS was 322 days. Overall, 70% maintained VS throughout follow-up, 8% experienced minor VEs only, and at least 1 major VE was documented in 22% of women. In women with VEs, peak viremia (median, 3.79 log10 copies/mL) was linearly related to pre-ART VL. The incidence of major VEs after initial VS was independently associated with younger age, ART initiation during the third trimester, previous defaulting on ART, and postpartum follow-up. Conclusions. Viremia appears to occur frequently, particularly postpartum, among HIV-infected women after initial VS in this setting. More intensive VL monitoring is warranted in this population; the immediate causes and long-term implications of VE require investigation. Data were drawn from the Maternal & Child Health – Antiretroviral Therapy (MCH-ART) study, an implementation science study investigating optimal ART services for pregnant and postpartum women (ClinicalTrials.gov identifier {“type”:”clinical-trial”,”attrs”:{“text”:”NCT01933477″,”term_id”:”NCT01933477″}}NCT01933477). The design and methods have been described previously [8]. In brief, between April 2013 and May 2014, we recruited a cohort of 620 consecutive ART-eligible HIV-infected pregnant women at their first antenatal care (ANC) visit at a large public-sector primary care facility and followed participants up to 12 months postpartum. From April to June 2013, ART eligibility was determined by clinical and/or immunological status (based on WHO stage III/IV disease or CD4 count ≤350 cells/µL); from July 2013 to May 2014, all HIV-infected pregnant women were ART eligible regardless of CD4 cell count or disease status (Option B+) [9]. ART initiation and clinical follow-up took place as part of routine healthcare services, with all women initiating a once-daily, fixed-dose combination of tenofovir 300 mg, emtracitabine 300 mg, and efavirenz 600 mg. In parallel, participants attended up to 9 study visits, organized separately from routine care, at regular intervals during pregnancy and postpartum. Cohort enrollment and the first study visit for all women was the day of the first ANC visit. In women making their first ANC visit at or before 30 weeks’ gestation, the next study visit was scheduled for 2 weeks after their first ANC visit, and then between 34 and 36 weeks’ gestation. For women making their first ANC visit from 31 to up to 35 weeks’ gestation, a second study visit was scheduled for between 34 and 36 weeks’ gestation. For women making their first study visit at or after 36 weeks’ gestation, there were no further antenatal study visits. Postpartum follow-up visits were carried out on a fixed schedule of 6 visits held at 7 days and 6 weeks postpartum, then every 3 months from 3 to 12 months postpartum. If participants were late or early to a scheduled study visit, we allowed visit windows up to the midpoint of the interval to the preceding or following visit, as appropriate. At study visits, participants completed brief questionnaires collecting demographic and clinical information (including age and obstetric and medical history including previous antiretroviral exposure), and additional clinical data were abstracted from routine clinic records. Separate from VL monitoring conducted as part of routine care [10], at each study visit participants provided 5 mL of venous blood for de-identified batched testing using the Abbott RealTime HIV-1 assay (Abbott Laboratories, Chicago, Illinois) conducted by the South African National Health Laboratory Service. De-identification took place through use of a participant identification number generated separately from patient clinical folder numbers or other unique identifiers, with an access-controlled identification log used to link participant data during analysis. All women provided written consent prior to enrollment, with approval from the research ethics committees of the University of Cape Town and Columbia University. Analyses were conducted using Stata software version 13.0 (StataCorp, College Station, Texas) or R version 3.2 (R Core Team, Vienna, Austria). All analyses were restricted to women with documented viral suppression (VS; defined as <50 copies/mL) during follow-up. After initial suppression, we categorized each subsequent VL measure as suppressed or elevated to minor (50–1000 copies/mL) or major (>1000 copies/mL) viremic episodes, following the guidelines used for clinical decision making in South African [10], US [11], and WHO [3] policy, and based on the observation that mother-to-child transmission risk appears to be substantially lower in patients with viral loads <1000 copies/mL [12, 13]. Sensitivity analyses modeled a binary definition of viremic episodes based on >50 copies/mL and then >400 copies/mL. The incidence of viremic episodes was estimated per 100 woman-months on ART. Product-limit methods were used to estimate the cumulative proportion of women experiencing viremia over time. Mixed-effects Poisson models compared incidence rates in subgroups of participants; results are expressed as incidence rate ratios (IRRs) with 95% confidence intervals (CIs).