Nearly all young children newly infected with HIV are infected through mother-to-child transmission (MTCT); about 86% of the estimated 160,000 children newly infected with HIV in 2018 were in the WHO African Region. [6] With a PMTCT of HIV coverage of 46%, Nigeria harbours about 27 % of the global burden of mother-to-child transmission of HIV and is one of UNAIDS’s 23 priority countries for PMTCT. [7] There is geographic disparity in PMTCT of HIV coverage among states and within regions in Nigeria. [8]

Early infant diagnosis uses Dried blood spot samples of HIV-exposed infants to detect HIV-DNA using the polymerase chain reaction technique in infants postpartum. Early Infant Diagnosis facilitates early linkage of HIV-infected infants to treatment care and support. [9] [10] Early initiation of antiretroviral therapy (ART) in the first 3 months of life reduces early infant mortality by 76% and HIV disease progression by 75%. [11] Globally, in 2018, only an estimated 59% of HIV-exposed infants received early infant diagnostic (EID) nucleic acid test by age 2 months, and only 54% of children living with HIV received ART. [12] In Nigeria, EID coverage has remained low; it has increased from 15% in 2015 to 27% in 2019. [7] EID programs require coordination and management of multiple separate health facilities/systems as well as significant logistical, financial, and human investments thus making it complex process with multiple challenges, requiring effective specimen transport, laboratory testing and results delivery, and potential loss of HIV-exposed infants at many points along the EID cascade. [13] Low demand for EID, inefficient procedures to follow up; infrastructure constraints especially power supply; stock out of EID commodities; EID backlogs, inconsistencies in sample pick up, loss of EID results long turnaround time of test results have been identified as some of the myriad of issues facing the EID programme in Nigeria. [8] [14]

To guide Quality PMTCT implementation at all levels of health care, Nigeria has transitioned through seven PMTCT guidelines from 2001 through to 2020 with Single-dose Nevirapine to mother and Nevirapine prophylaxis to the infant as the first ARV in preventing vertical transmission of HIV. [15] Currently, more efficacious cART with viral load determination is the standard of care for all HIV-positive pregnant women with ARV prophylaxis and EID for their exposed infants. [16]

The MTCT rate provides a measure of the effectiveness of the programme for preventing infant infections in pregnant women living with HIV. [17] The earliest PMTCT effectiveness studies [18] - [23] conducted in Nigeria reported MTCT rates of between 2.4% [24] and 22%. [25]

Transitioning to more efficacious cART for PMTCT between 2010 and 2012, several studies [26] - [42] in the country reported MTCT rates of between 0% [43] [44] and 9.7% [45] . Most recent reports from Sokoto, [46] FCT/Nasarawa state, [47] Delta, [48] Rivers [49] and Imo state [50] showed MTCT rates of 0.9%, 1%, 4%, 1.1%, and 3.7% respectively. A very large subregional report of EID of HEI by Dakum et al. [51] reported a MTCT rate of 5.2% at 12 weeks postpartum. Khamofu et al. reported declining MTCT rates with more efficacious cART in Nigeria. [52]

While most of these MTCT rates were determined at 6 - 8 weeks, in breastfeeding women in small sample sizes and short-duration reports, they no doubt were significant contributions to the PMTCT effort in the country. The current 2020 National HIV guideline [16] recommends that all HIV-exposed infants should have DNA PCR testing or NAT at birth, 6 - 8 weeks of age, 9 months and 8 - 12 weeks after complete cessation of breastfeeding. If the baby is not being breastfed, DNA PCR testing should be done at birth and 6 weeks.

The aim of this study was to report HIV infection in HIV-exposed infants from 5 states in the North East and North Central regions of Nigeria from 2009 to 2020.

Table 1 shows that 9,823 PCR DNA results were analysed during the study period. There was an over-all declining trend in the MTCT rate from 3.8% in 2009

X²: 84.047, p < 0.001.

to 0.8% in 2020 with blips in 2011 and 2016. Of the 9823 HIV DNA PCR results, 9568 (97.4%) had Negative DNA PCR while 255 (2.6%) were Positive.

Table 2 shows the distribution of maternal ARVs and Infant HIV DNA status; 6120 (62.3%) of HIV + mothers were receiving ART before pregnancy; 25.2 % (2475) started ART in pregnancy; 747 (7.6%) and 285 (2.9%) of HIV positive pregnant women did not receive and had unknown ARV status respectively. Regimen received by HIV-positive women was AZT + 3TC at 34 - 36 weeks gestation, AZT from 14 weeks gestation and single dose NVP in labour. Table 2 shows that 86 (11.5%) infants whose HIV-positive mothers received no ARVS were HIV DNA PCR positive; 98/6120 (1.6%) of mothers;32/2475 (1.3%); 10/98 (10.4%); 3/69 (4.5%) and 26/285 (9.1%) of infants whose HIV positive mothers had ART before pregnancy; ART during pregnancy; AZT mono-therapy; NVP Mono-therapy and those with unknown ARV status were HIV DNA PCR positive respectively (p = 0.001).

Infants who received ARV prophylaxis but whose mothers did not receive ART in pregnancy 747 (8.1%) had significantly more infection (p = 0.000) compared to infants who had received ARV with maternal ART (p = 0.971).

Table 2 shows that 7485 (76.2%) of HIV-exposed infants received NVP prophylaxis; 884 (9.1%) had no prophylaxis; 560 (5.6%) received AZT; 413 (4.2%) AZT/NVP and 481 (4.9%) of infants had unknown ARV (prophylaxis) status; 106/884 (12.0%) of HIV exposed infants who had no ARV prophylaxis; 10 (1.8%), 120/7485 (1.6%); 7/413 (1.7%) infants who received AZT mono-prophylaxis; NVP

mono-prophylaxis and AZT/NVP dual prophylaxis had positive HIV DNA PCR result. (p = 0.000)

Dried Blood Spots samples were collected in 2514 (25.6%) of HIV exposed infants at <6 weeks of age; 41.5% (4077) at 6 - 8 weeks; 5.8% (570) at >8 - 12 weeks and 27.1% (2662) at >12 weeks postpartum. Table 3 shows that (58/2514) 2.3% 1.7% (69/4077); 3.3% (19/570) and 4.1% (109/2662) were positive for HIV DNA PCR at <6 weeks of age; 6 - 8 weeks; 8 - 12 weeks and >12 weeks respectively. There was an increasing likelihood of positive DNA PCR test results with a delay in DBS sampling and this was statistically significant (p = 0.000).

Table 3 also showed that 96.4% (9469/9823) infants were ever breastfed and 3.6% (354) had never breastfed. Daily cotrimoxazole was received by 85.9% (8438/9823) of the infants. About 2.6% (246/9469) of infants that were ever breastfed were positive for HIV DNA PCR and 2.5% (9/354) of infants that were never breastfed were positive for HIV DNA PCR (P = 0.348) (Table 3). In Table 3 more male infants than females had positive DNA PCR tests and was statistically significant p = 0.001. At the time of DBS sample collection infants of mothers who were not breastfeeding were DNA PCR positive compared to infants whose mothers were breastfeeding. However, this was not statistically significant (p = 0.295)

This study showed that the HIV infection rate using the first DNA PCR at 6 - 8

weeks in HIV-exposed infants was 2.6%. This rate is less than 5% expected in breastfeeding women on ART. [4] [5] Significantly there was a trend of declining MTCT rate over the years as the country transitioned to more efficacious combination ART. This similar trend was demonstrated earlier by Itiola [45] and Khamofu [52] in the country and Olana in Ethiopia. [53] These studies however had smaller number of mother-infant pairs and shorter study duration. Efficacious cART with viral load determination is the standard of care for all HIV-positive pregnant women with ARV prophylaxis and EID for their exposed infants. [10] [15] [16]

Increased DBS samples from 2016 in this study were as a result of additional logging to our laboratory from non-functional PCR laboratories in some parts of in the country.

In this study, forty-two percent of the first DBS samples were obtained within the 6 - 8 weeks period as recommended by the National guideline; [10] [15] [16] a third of DBS were taken after this period with increasing possibility of positive DNA test result. (p = 0.01). This finding is similar to the report by Dakum et al. [51] ; however, the proportion of DBS sample obtained at 6 - 8 weeks in our study is twice as high as reported by Dakum et al. [51] and Itiola et al. [45] in the country. Reports on fairly large number of HIV-exposed infants in the country by Anoje et al., [28] Olerigbe et al., [41] Ibobo et al., [48] did not report 6 - 8 weeks age of DBS sample collection. Higher DBS collection rates at 6 - 8 weeks of 67.3%, 50%, and 79% have been reported in Ethiopia, [53] Malawi, [54] and Kenya, [55] respectively. HIV DNA PCR testing through DBS collection at 6 - 8 weeks has a very high sensitivity and is considered programmatically more efficient and therefore reported. [10] [15] [16] [56]

Overall, more than three-quarters of HIV-positive women in our report had received ART and had lower MTCT rate compared to women who had less efficacious ARV consisting of two or less ARVS. This is in agreement with the findings of Khamofu et al. [52] and Itiola et al. [45] with however much smaller sample sizes and shorter study duration. Highly Active Antiretroviral therapy or combination ART with at least three antiretroviral have more durable and sustained maternal viral suppression with reduced risk of MTCT of HIV. [23] [26] High Maternal viral load in Pregnancy is a major risk factor for MTCT. [10] [15] [16]

In this study, 7.6% of HIV-positive pregnant women did not receive ARVs and therefore had higher MTCT rates. This is similar to 7% reported by Dakum et al. [51] but lower than the 13% and 38.5% reported by Itiola et al. [45] and Anoje et al. [28] respectively. A much lower proportion of HIV-positive pregnant women did not receive ARVs in the report of these workers. [41] [48] While this study showed 2.9% of HIV-positive mothers with missing data on ARVs, these workers [49] [51] reported 17.4% and 12.2% respectively. Similarly, 9.1% of HIV-exposed infants did not receive ARV prophylaxis and 4.9% had missing data on ARVs. Infant HIV infection was highest in the former category in our study. A much higher proportion of 17.1% [45] and 38.2% [28] of HEI did not receive ARV prophylaxis. This infant status was not reported by Dakum et al. [51] Infant ARV prophylaxis is an indicator of the quality of PMTCT service delivery. [10] [15] [16] Increased odds of infant HIV infection with lack of Maternal ARV and infant HIV prophylaxis have also been reported. [53] [54] [55]

Missing data, unknown status and non-administration of ARVs in PMTCT programme remain significant challenges in the country traceable to gaps in training, human resource constraints, monitoring and evaluation and lack of electronic medical records. [7] [8] [12] [14]

At the time of DBS sample collection, 87% of HEI were breastfeeding and overall, 96.4% of these infants reported ever breastfed. In this study, there is a significant relationship between the duration of breastfeeding and positive DNA PCR test result with prolonged Breastfeeding increasing the risk. This relationship between prolonged breastfeeding and infant HIV infection has also been reported by workers in Nigeria [41] [45] [48] [51] and in Ethiopia [53] and Kenya. [55] . The risk of postnatal transmission through breastfeeding is associated with clinical, immunological and virological maternal factors and infant feeding patterns. [57] Maternal seroconversion during breastfeeding, low maternal CD4 cell count, increased maternal RNA viral load in plasma and breast milk are strongly associated with increased risk of transmission. Breast pathologies such as clinical and subclinical mastitis, nipple bleeding, and abscesses, fissures or lesions are also associated with a higher risk of transmission through breastfeeding. [57] Mother-to-child transmission rates of HIV through breastfeeding is 13% at six weeks rising to 23% at the end of breastfeeding. [7] Breastfeeding remains and will be the topmost item on the agenda of child survival globally and especially in low- and medium-income countries. [1] [2] [16]

There are several limitations in this study; this is the first HIV DNA PCR results analyzed and therefore we are unable to determine subsequent and final HIV infant outcomes. Our study did not report other maternal and infant characteristics like CD4 + cell count, viral load, WHO clinical stage, follow-up infant status, or cessation of breastfeeding that would affect final infant outcomes. As a retrospective study, information may have been incomplete and the MTCT rate therefore and estimation and not the actual. In spite of its limitations, the large sample size, the long duration of review and evidence of PMTCT effectiveness through different ART regime remain the strength of this study.

Mother-to-child transmission of HIV infection rate has declined with the use of efficacious combination ARV therapy in five states of Northern Nigeria.

Prolonged breastfeeding is associated with the risk of transmission of HIV especially in the absence of maternal and infant ARV.

PMTCT requires strengthening, especially the provision of maternal and infant ARV in northern Nigeria and the country in general.

Elon Warnow Isaac: Conceived of the study and study design, developed the first manuscript draft and critically reviewed all drafts of the manuscript.

Dr Iliya Jalo, Dr. Abubakar Joshua Difa, and Ms. Oyeniyi Christianah Oluwaseun: Conducted quantitative data analysis and reviewed all drafts of the manuscript.

Dr Mohammed Manga and Mr. Muhammad Danlami Hassan: Reviewed and commented on the data.

We wish to acknowledge Hajiya Fatima Y Aliyu, Hajiya Zainab Dan-Malam and Hafsat Sabo of the Data unit of Paediatrics department for extracting the data.

There was no funding received for this study.

The authors declare no conflicts of interest regarding the publication of this paper.

Isaac, E.W., Ajani, A., Iliya, J., Manga, M., Difa, A.J., Oluwaseun, O.C. and Hassan, M.D. (2023) Deoxyribonucleic Acid-Polymerase Chain Reaction Status of HIV Exposed Infants in a Sub Regional Prevention of Mother-to-Child Transmission of HIV Programme during the Period 2009-2020. Open Journal of Epidemiology, 13, 328-341. https://doi.org/10.4236/ojepi.2023.134024