Correlates and determinants of Early Infant Diagnosis outcomes in North-Central Nigeria

Early Infant Diagnosis (EID) that yields a negative result is a desired pediatric outcome of programs designed to prevent Mother to-Child Transmission (MTCT) of HIV [1]. For their HIV-infected mothers, staying alive and retained in care with good ART adherence and periodically demonstrated enduring suppression of HIV is the end goal [2]. MTCT in Nigeria accounts for majority of new HIV infections among children worldwide. Worldwide, with about 60,000 new cases reported annually from 2009 to 2012 [3]. In 2015, Nigeria alone was responsible for almost 30% of children newly infected with HIV globally (n = 41,000 [4] of 150,000). Without antiretroviral therapy (ART), more than half of these children will die by 2 years of age [5].

Early Infant Diagnosis utilizes DNA-PCR to isolate viral nucleic acid in HIV-exposed infants (HEI) within 6 weeks of birth [6, 7] and up to 18 months of age [8] thus providing virological basis for entry into lifelong treatment for infected infants. EID impacts epidemic control by confirming non-infected HEIs and prompting timely initiation of ART in HIV-infected babies which improves treatment outcomes [9‐11]. Furthermore, the quality of communication from care providers to parents/guardians [3] and the deployment of resources for follow-up of uninfected HEIs [4] are likely to be influenced by knowledge of an EID result.

Despite the importance of EID in mitigating MTCT, its implementation has been challenging in resource-limited settings [12‐15], particularly in Nigeria, where only 6.3% and 9% of HEIs received EID in 2014 [16] and 2015 respectively, with only about 20% of those found to be eligible children actually receiving cART [17].

Evaluating current EID programs in relation to where implementation occurs is advocated [18] as this provides context-specific evidence to rethink and adapt current strategies [19]. This study presents data on the prevalence of HIV in HEI and explored the predictors of EID outcomes among HEI who received a DNA-PCR result in the high HIV prevalence settings North-Central Region of Nigeria.

A total of 14,488 DBS sample were analyzed, of which 13,738 (94.8%) returned negative results for HIV DNA-PCR. Median and mean age of HEI at first sample collection (n = 13,646) was 8 weeks (IQR 6–20) and 14.64 weeks (SD = 14.98; 95% CI 0–260) respectively as shown in Table 1.

About 41.4% of HEIs had DBS drawn up to 6 weeks, 16.3% between 6 and 8 weeks and 36.5% after 8 weeks. 42.7% (n = 6192) of assayed samples were drawn from female HEI and 88.4% (n = 12,801) of HEI were breastfed (Table 1). Most HIV positive women received combination ART (cART) before the index pregnancy (54.5%, n = 7903), 25.2% (n = 3651) had cART for the first time during the index pregnancy, those who received prophylaxis during labor were 1.1% (n = 159) while 7.0% (n = 1010) received no ART (Table 1).

Our study shows that factors like breastfeeding, maternal treatment status (cART or no ART) and age when HEI DBS, can predict the achievement of a negative DNA-PCR result following EID in the High HIV-prevalence settings of North-central Nigeria.

In this study, median age of HEIs at first DBS collection was approximately 8 weeks with only 44% of infants DBS samples taken below 6 weeks of age thereby predisposing the children to a delay in ART initiation for confirmed cases. A longer time of DBS collection and in-effect EID predicted likelihood of HEI being HIV+. For later presentation, it is plausible that symptomatic manifestation of immunologic decline in HIV infection may have prompted mothers/guardians to seek health facility and opportune HEI to EID. A study in Kenya showed that information passed to mother during pregnancy, mothers higher formal education and low experience of stigma could predict on-time (infant ≤ 6 weeks of age) EID [17].

Survival gains of commencing early infant antiretroviral therapy declines when diagnosis is late [22‐24] with rapid disease progression and mortality [25] in early life. Timely definitive diagnosis is critical in allowing early initiation of life-saving ART [26] as demonstrated in the children with HIV early antiretroviral (CHER) study [27], which reported a 76% and 75% aversion of early infant mortality and HIV progression respectively [28]. Performance of Nigeria’s EID logistics is affecting EID outcomes.

Breastfeeding is important for child survival [29, 30] and consistent with other studies in Nigeria [28, 31], was common among study mother-HEI pairs 88.9% (n = 3232). Mothers living with HIV, especially in LMIC, should breastfeed for 12 months and may continue breastfeeding for up to 24 months or longer, while being fully supported for ART adherence [32]. This is to help fight against malnutrition and death resulting from cholera due to poor hygiene. Breastfeeding should only stop once a nutritionally adequate and safe diet without breast milk can be provided [32]. Breastfeeding by HIV positive mothers was a significant predictor of HEI outcome in this study and is linked to continuing risk of postnatal infection [33], with documented MTCT rate of 13% at six weeks rising to 23% at the end of breastfeeding [34]. Data on type (exclusive or mixed), duration [35] and frequency of breastfeeding, mother’s immunological staging (HIV viral load/CD4+) and HEI testing after a 6-week window period following stop of breastfeeding [12] is required to further investigate this and is recommended.

Majority (54.5%) of HIV positive mothers were already on cART before the index pregnancy, whilst almost a third received cART for the first time. Maternal prophylaxis and cART were significant predictors of EID outcomes. Exponential rises in the chance of achieving a negative DNA-PCR result for HEI was related to the timing of cART with best results if mother started cART prior to pregnancy. This finding stands unadjusted for Mother’s cART adherence, duration of therapy or immunological status, and for the method of delivery (vaginal or operative) or timing of EID testing. It is thus deduced that aside these and other factors, substantial program-wide benefit of averting MTCT is achieved if cART for mother is ensured.

This speaks to the present MTCT issue in Nigeria where only 29% of HIV-positive pregnant women received ART [36] in 2014. Hence, as a strategy to mitigate the growing population of the 380,000 HIV-positive children residing in-country [20, 37], prevention of MTCT and EID programs in Nigeria need to urgently scale-up ART coverage for HIV infected females of reproductive age and mothers.

Nigeria adopted the WHO ‘Test and Treat’ policy in June 2016 [38] to accelerate early and universal placement on ART for all HIV positive persons [2]. In prevention of MTCT this translates to starting HIV positive pregnant women early on lifelong cART irrespective of clinical or immunological criteria (option B+) [39]. The difference in odds between the earlier placement of HIV positive mothers (previous vs index pregnancy) supports the notion that optimization of favorable pediatric outcomes is achieved at earliest cART initiation of all peripartum HIV-infected women [40].

This study was limited by the extent of variables utilized, due to non-availability of others such as baseline maternal viral load or clinical staging and follow-up HEI testing on cessation of breastfeeding. This limited our ability to explore the role of other characteristics that may be linked to EID outcomes, in addition to possible incomplete control of confounding for the associations explored. Another limitation is potential selection bias due to low EID rates among PMTCT clients which may affect generalizability of the findings. Another major challenge is the issue of missing data as request forms from the clinics are not completely filled. Clinicians needs to be aware of the importance of properly filling request forms, to enable us have a good picture of the program during evaluation.

This study showed that provision of cART for HIV infected mothers prior to and during pregnancy is associated with an increased likelihood of achieving a negative EID result. Overall program wide benefit can be optimized if lifelong cART coverage is increased for HIV positive pregnant women.