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Introduction: In 2011, Malawi implemented “Option B+,” a test-and-treat strategy for the prevention of maternal to child transmission of HIV (PMTCT); however limited data on viral load (VL) suppression exist. We describe VL suppression in HIV-infected women at four to twenty-six weeks postpartum, factors associated with VL suppression and the impact of VL suppression levels on MTCT. Methods: HIV-positive mothers at four to twenty-six weeks postpartum were enrolled in a nested cross-sectional study within the “National Evaluation of Malawi’s PMTCT Programme” cohort study between October 2014 and May 2016. HIV-exposed infants received HIV-1 DNA testing and venous samples determined maternal VL, classified as unsuppressed (>1000 copies/mL), low-detectable (40 to 1000 copies/mL) or undetectable (<40 copies/mL). Socio-demographic and PMTCT indicators were collected. Suboptimal adherence was defined as self-reported ≥2 days missed ART in the month prior to visit. Results: Of the 1274 women, 1191 (93.5%) knew their HIV status and 1154/1191 (96.9%) were on ART. VL was available for 1124/1154 (97.4%) of women on ART: 988/1124 (87.9%) had VL suppression of whom 86 (8.7%) had low-detectable and 902 (91.3%) undetectable VL. Suboptimal adherence was associated with unsuppressed VL (vs. suppressed VL; aOR 3.1, 95% CI 2.0 to 4.9; p < 0.001). Women with low-detectable VL were more likely to be adolescent (vs. undetectable VL; aOR 3.0, 95% CI 1.4 to 6.6), on ART <6 months (aOR 4.4, 95% CI 2.3 to 8.6), report suboptimal adherence (aOR 2.1, 95% CI 1.1 to 3.8; p = 0.02), and less likely to have primary or secondary education (vs. none; aOR 0.3, 95% CI 0.2 to 0.7 or aOR 0.3, 95% 0.1 to 0.6). MTCT ratios among women on ART who had undetectable VL, low-detectable VL and unsuppressed VL were 0.9% (8/902; 95% CI 0.3 to 1.5), 7.0% (6/86; 95% CI 1.5 to 12.5) and 14.0% (19/136; 95% CI 8.1 to 20.0). Unsuppressed VL and low-detectable VL (vs. undetectable VL) increased the risk of MTCT 17-fold (aOR 17.4, 95% CI 7.4 to 41.1; p = 0.002) and ninefold (aOR 8.5, 95% CI 2.9 to 25.2; p < 0.001). Conclusions: Unsuppressed and low-detectable VL was strongly predictive of MTCT among women on ART and associated with suboptimal adherence. This urges further consideration of optimal VL monitoring and target levels to reach elimination of paediatric infection.
This is a nested cross‐sectional study of HIV‐infected mothers presenting with their four to twenty‐six week old infants at outpatient clinics who were enrolled in longitudinal follow‐up in the National Evaluation of the Malawi PMTCT Programme (NEMAPP) study between October 2014 and May 2016. NEMAPP used a multistage cluster design to sample 54 sites across Malawi 13 and this sub‐set was derived using probability proportionate‐to‐size sampling methods to select 13 sites across the eight districts from the original sites. Women in these selected sites were simultaneously consented for enrolment in both the main study and in this subset for intensive clinical and laboratory monitoring. All mother‐infant pairs were followed up at 12 and 24 months. The study period occurred three years after the national implementation of “Option B+” PMTCT guidelines in Malawi which provided lifelong ART (i.e. tenofovir/lamivudine/efavirenz) for all pregnant and breastfeeding women. Mothers (or guardians) with four to twenty‐six week infants were screened for HIV infection by the study team and 3456 HIV‐positive mothers (or guardians) with HIV‐exposed infants were consented for enrolment in the main study. A sample of 1324 HIV‐positive mothers was calculated to estimate VL suppression based on an estimated 50% suppression rate, 50% loss to follow‐up at 24 months and a precision of 2.5% with a 95% confidence interval (95% CI) and an assumed design effect of 2.0. Guardians were excluded from the current analysis (Figure 1). Flow chart of mother‐infant pairs excluded and included in the study. Included mothers were interviewed using structured questionnaires by trained health facility staff to obtain information about age, parity, education, HIV status at screening, uptake PMTCT/ART, adherence to treatment (self‐reported number of days missed ARVs in the last month), birthweight of infant, uptake of infant nevirapine prophylaxis and breastfeeding practices. When possible, mothers’ health booklets were checked for accuracy of responses. A qualitative HIV‐1 DNA polymerase chain reaction (COBAS AmpliPrep/COBAS TaqMan Qualitative Assay Version 2.0, detection level 221 copies/mL; Roche Diagnostics, USA) test was performed on all HIV‐exposed infant dried blood spot (DBS) samples to determine HIV infection at the time of enrolment into NEMAPP (as part of study procedures and outside of national PMTCT programme testing). Within this subset, maternal HIV viral load (VL) testing was conducted at enrolment on venous samples (Abbott Real‐Time HIV‐1 Assay, Abbott Laboratories, Chicago, IL) of all women regardless of ART status. VL suppression is defined as HIV 1‐RNA <1000 copies/mL as per the Malawi national HIV guidelines 1. We further categorized VL results as “undetectable” (1000 copies/mL), (with “suppressed VL” being the inverse, i.e. all women with <1000 copies/mL). Missing data were treated as additional categories. Crude percentages were calculated and comparisons between groups made using chi‐square tests for categorical variables and non‐parametric tests for medians, using normal approximations (Wald) methods to calculate confidence intervals. Multivariable logistic regression analysis was used to identify characteristics associated with unsuppressed versus suppressed VL, with low‐detectable versus undetectable VL, and with MTCT. Univariate odds ratios (OR) with 95% CI were calculated for each variable in the model using normal approximation (Wald) methods. Adjusted OR (aOR) with 95% CI were calculated for each model after adjustment for age, parity, education, time on ART, number of days missed ARV's in last month and exposure to PMTCT in a previous pregnancy. In addition, birthweight, uptake of infant nevirapine, exclusive breastfeeding and VL categories were included in the model for MTCT. All variables were simultaneously entered in the logistic regression model and tested for removal through backward stepwise selection. A 0.05 significance level was set for all statistical testing. Analyses were conducted using IBM SPSS Statistics 24 (IBM, Armonk, NY, USA). Ethical approval was received from Malawi's National Health Sciences Research Committee (#1262) and the University of Toronto (#30448). The US Centers for Disease Control and Prevention (CDC) reviewed and approved as research according to human research protection procedures (#2014‐054‐7), but was not engaged. All participants provided written informed consent. The funding source for this study was the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) and they had no direct role in study design, implementation, analysis or preparation/submission of this manuscript. The author acknowledges full access to all the data and final responsibility for submission.
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