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Background: Mother-to-child HIV transmission (MTCT) has substantially declined since the scale-up of prevention programs around the world, including Rwanda. To achieve full elimination of MTCT, it is important to understand the risk factors associated with residual HIV transmission, defined as MTCT at the population-level that still occurs despite universal access to PMTCT. Methods: We performed a case control study of children born from mothers with HIV with known vital status at 18 months from birth, who were followed in three national cohorts between October and December 2013, 2014, and 2015 in Rwanda. Children with HIV were matched in a ratio of 1:2 with HIV-uninfected children and a conditional logistic regression model was used to investigate risk factors for MTCT. Results: In total, 84 children with HIV were identified and matched with 164 non-infected children. The median age of mothers from both groups was 29 years (interquartile range (IQR): 24–33). Of these mothers, 126 (51.4 %) initiated antiretroviral therapy (ART) before their pregnancy on record. In a multivariable regression analysis, initiation of ART in the third trimester (Adjusted Odds Ratio [aOR]: 9.25; 95 % Confidence Interval [95 % CI]: 2.12–40.38) and during labour or post-partum (aOR: 8.87; 95 % CI: 1.92–40.88), compared to initiation of ART before pregnancy, increased the risk of MTCT. Similarly, offspring of single mothers (aOR: 7.15; 95 % CI: 1.15–44.21), and absence of postpartum neonatal ART prophylaxis (aOR: 7.26; 95 % CI: 1.66–31.59) were factors significantly associated with MTCT. Conclusions: Late ART initiation for PMTCT and lack of postpartum infant prophylaxis are still the most important risk factors to explain MTCT in the era of universal access. Improved early attendance at antenatal care, early ART initiation, and enhancing the continuum of care especially for single mothers is crucial for MTCT elimination in Rwanda.
Since 2013, the Rwanda Biomedical Centre (RBC) conducts follow-up of children in PMTCT to monitor changes in mother-to-child HIV transmission. To allow for time trend analysis for the fiscal year that ends in June, every year the cohort comprises children born from October to December who are then followed for a period of 18 months. We performed a case-control study that was nested into three consecutive cohorts of children born to mothers with HIV in Rwanda, where cases consisted of vertically infected children and controls were non-infected children by 18 months after birth. The study population included children born to mothers with HIV between October and December 2013, 2014 and 2015 in health facilities that were providing PMTCT services. At the end of 18 months’ follow-up (time for weaning off), all children who tested HIV positive, were matched with HIV negative children at a ratio of 1:2 by year of birth and health facility to ensure balance between cases and controls. Controls were selected at random from the same facility. When matches within the same health facility were not possible, we considered a paired match from the geographically closest neighbouring health facility. Data on MTCT was collected in 67 out of 517 health facilities offering PMTCT services where we could identify children who were infected with HIV. In these 67 facilities, we selected the cases and controls and abstracted demographics and clinical and laboratory data (extent of viral load suppression at delivery) of the mother from pregnancy to the end of breastfeeding. We anonymized and keyed all data into the Open Data Kit, a free and open-source software for collecting, managing, and using data in resource-constrained countries [8]. From health facility registers, we collected data on children’s HIV status at 18 months after birth, mothers’ age at delivery, companionship by male partner during antenatal care visit, HIV status of male partner, date of antiretroviral therapy initiation for the mother (before pregnancy, during first, second, third trimester of pregnancy, or during labour), mothers’ marital status (single, married, cohabitating, divorced/separated), mothers’ occupation (employed versus not employed), mothers’ parity before the current pregnancy (first born, 1–2 children, 3 or more children), place of delivery (health facility versus home), mode of delivery (vaginal delivery versus caesarean section), maternal HIV viral load at delivery (defined as suppressed if < 1000 copies/ml, and not suppressed if ≥ 1000 copies/ml, and missing data or non-eligible), retention to treatment during antenatal care and breastfeeding, and post-natal ART prophylaxis for new born (yes/no). Retention to treatment was defined as missed drug pick up during three consecutive months from pregnancy to the end of breastfeeding period. The national guideline recommends having the first viral load test after six months on ART and every 12 months subsequently. Thus, mothers who started ART late were more likely to miss the viral load results at the time of delivery. Neonatal ART prophylaxis was defined according to national guidelines as receiving post-delivery ART prophylaxis until the end of six weeks of breastfeeding [9]. Children’s HIV status was defined as a positive or negative HIV test at 18 months after birth. The national HIV guideline recommends follow-up of all children born to mothers with HIV and mothers diagnosed with HIV during the breastfeeding period with HIV testing at 18 months at latest. The follow-up includes HIV DNA PCR test at 6 to 8 weeks and serological tests at 9 and 18 months. Once a serological test is positive, PCR testing is done for confirmation. The child is considered HIV infected if a positive PCR test result is confirmed at any time point, either 6 weeks, 9 months or 18 months after birth [9]. We provide descriptive statistics for characteristics of mothers having given birth to infected and uninfected children with confirmed HIV status at 18 months after birth. Variables that were statistically significant in the univariate analysis (p-value < 0.05) were considered for the multivariable conditional logistic regression model after testing for collinearity. We report adjusted odds ratios with 95 % confidence intervals. All analyses were conducted using Stata version 15 [10]. This study was performed in accordance with the declaration of Helsinki; the protocol was approved both by the Rwanda National Ethics Committee (reference number: 305/RNEC/2017) and the National Institute of Statistics of Rwanda (reference number: 0667/2017/10/NISR). The Ministry of Health granted approval to access to health facility data to the principal investigator (ER) for the purpose of the study. No participants were involved directly in the data collection therefore their consent was waived by the Rwanda National Ethics Committee. During data extraction, all personal identifiable information was removed to ensure confidentiality of study participants, and fully anonymous identification numbers were created.
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