Long-term outcomes of early initiated antiretroviral therapy in sub-Saharan children: a Cameroonian cohort study (ANRS-12140 Pediacam study, 2008-2013, Cameroon).

BACKGROUND: In most studies, the virological response is assessed during the first two years of antiretroviral treatment initiated in HIV-infected infants. However, early initiation of antiretroviral therapy exposes infants to very long-lasting treatment. Moreover, maintaining viral suppression in children is difficult. We aimed to assess the virologic response and mortality in HIV-infected children after five years of early initiated antiretroviral treatment (ART) and identify factors associated with virologic success in Cameroon. METHODS: In the ANRS-12140 Pediacam cohort study, 2008-2013, Cameroon, we included all the 149 children who were still alive after two years of early ART. Virologic response was assessed after 5 years of treatment. The probability of maintaining virologic success between two and five years of ART was estimated using Kaplan-Meier curve. The immune status and mortality were also studied at five years after ART initiation. Factors associated with a viral load < 400 copies/mL in children still alive at five years of ART were studied using logistic regressions. RESULTS: The viral load after five years of early ART was suppressed in 66.8% (60.1-73.5) of the 144 children still alive and in care. Among the children with viral suppression after two years of ART, the probability of maintaining viral suppression after five years of ART was 64.0% (54.0-74.0). The only factor associated with viral suppression after five years of ART was achievement of confirmed virological success within the first two years of ART (OR = 2.7 (1.1-6.8); p = 0.033). CONCLUSIONS: The probability of maintaining viral suppression between two and five years of early initiated ART which was quite low highlights the difficulty of parents to administer drugs daily to their children in sub-Saharan Africa. It also stressed the importance of initial viral suppression for achieving and maintaining virologic success in the long-term. Further studies should focus on identifying strategies that would enhance better retention in care and improved adherence to treatment within the first two years of ART early initiated in Sub-Saharan HIV-infected children.

Posterior urethral valves: 10 years audit of epidemiologic, diagnostic and therapeutic aspects in Yaoundé gynaeco-obstetric and paediatric hospital.

BACKGROUND: The incidence of posterior urethral valve (PUV) is estimated at 1:5000-1:8000 males. It is the most common paediatric urologic urgency and the most common cause of male obstructive uropathy and chronic renal failure in children. The study aimed to describe the experience of Yaoundé gynaeco-obstetrics and paediatric hospital in the management of PUV. METHODS: Retrospectively, medical records were retrieved over a ten year period and all data recorded and analyzed for study objectives. Patients were called and evaluated for outcomes regarding morbidity and mortality. RESULTS: A total of 18 patients all males were managed over the ten year period, given prevalence of 13 cases/100,000 admissions and an admission rate of 2 per annum. The median age at presentation was 22 months and 13 (72.2%) participants presented late. Voiding urethrocystogram was done in all the participants where it showed dilated and elongated posterior urethral valves in 16 (88.9%) of the cases. Endoscopic valve ablation resulted in the relief of obstruction in all but 3 (16.7%) participants that had residual valves and 2 (11.2%) participants that had urethral stenosis. Type I valves were most common in 14 (78.0%) participants. The mean duration of follow up was 34.56 ± 21.47 months. Complications at final follow up were: 10 (55.6%) chronic renal failure, 2 (11.2%) end-stage renal failure. The case fatality rate was 5.6%. CONCLUSION: Many patients present late in our setting with already established complications. There is the need to counsel parents/guardians on the importance of long-term follow up after relief of obstruction.

Cytomegalovirus infection in HIV-infected versus non-infected infants and HIV disease progression in Cytomegalovirus infected versus non infected infants early treated with cART in the ANRS 12140-Pediacam study in Cameroon.

BACKGROUND: The outcome of CMV/HIV co-infection in infants treated early with combined antiretroviral therapy (cART) in resource-limited settings has not been described. We aimed to estimate the prevalence and identify factors associated with early CMV infection in HIV-infected and non-infected infants included in a study in Cameroon, and to compare HIV disease progression and survival after 1 year of early cART, following infants' CMV status. METHODS: HIV-infected infants followed from birth or from HIV diagnosis before 7 months old and HIV-uninfected infants born to HIV-infected or uninfected mothers were tested for CMV at a median age of 4.0 months [Interquartile range (IQR): 3.4-4.9]. Multivariable logistic regression was performed to identify factors associated with CMV infection. Early cART was offered to HIV-infected infants: mortality, immunological and virological outcomes were assessed. RESULTS: Three hundred and sixty-nine infants were tested. The proportion of infants infected with CMV at baseline was significantly higher in HIV-infected than in HIV-uninfected groups (58.9% (86/146) vs 30.0% (67/223), p < 0.001). At baseline, median CMV viral load was higher in HIV-infected (3.7 log copies/ml [IQR; 3.1-4.3]) than in HIV-uninfected infants (2.8 log copies [IQR; 2.1-3.4], p < 0.001). cART was initiated in 90% of HIV-infected infants (132/146) at a median age of 4.0 months (IQR; 3.2-5.9); in this sub-group CMV infection was independently associated with being followed from the time of HIV diagnosis rather than from birth (aOR = 3.1, 95%CI [1.2-8.0]), born to a non-single mother (aOR = 3.4[1.4-8.1]), and breastfeeding (aOR = 7.3 [2.7-19.4]). HIV-infected infants were retested after a median of 7.1 months [4.8-9.5]: CMV was undetectable in 37 of the 61 (60.7%) initially CMV-infected cases and became detectable in 8 of the 38 (21.1%) initially CMV-negative cases. After 1 year of cART, the probability of death (0.185 vs 0.203; p = 0.75), the proportion of cases with HIV RNA viral load <400 copies/ml (75.5% vs 61.5%; p = 0.17) and the mean CD4 percentage increase (10.97% vs 6.88%; p = 0.15) did not differ between CMV+ and CMV- infants. CONCLUSIONS: We observed a high prevalence of CMV infection among HIV-infected infants. Early initiation of cART may have limited the negative impact of CMV even in the absence of specific anti-CMV treatment.

Different factors associated with loss to follow-up of infants born to HIV-infected or uninfected mothers: observations from the ANRS 12140-PEDIACAM study in Cameroon.

BACKGROUND: Loss to follow-up (LTFU) is a cause of potential bias in clinical studies. Differing LTFU between study groups may affect internal validity and generalizability of the results. Understanding reasons for LTFU could help improve follow-up in clinical studies and thereby contribute to goals for prevention, treatment, or research being achieved. We explored factors associated with LTFU of mother-child pairs after inclusion in the ANRS 12140-Pediacam study. METHODS: From November 2007 to October 2010, 4104 infants including 2053 born to HIV-infected mothers and 2051 born to HIV-uninfected mothers matched individually on gender and study site were enrolled during the first week of life in three referral hospitals in Cameroon and scheduled for visits at 6, 10 and 14 weeks of age. Visits were designated 1, 2 and 3, in chronological order, irrespective of the child's age at the time of the visit. Mother-child pairs were considered lost to follow-up if they never returned for a clinical visit within the first six months after inclusion. Uni- and multivariable logistic regression were adjusted on matching variables to identify factors associated with LTFU according to maternal HIV status. RESULTS: LTFU among HIV-unexposed infants was four times higher than among HIV-exposed infants (36.7% vs 9.8%, p < 0.001). Emergency caesarean section (adjusted Odds Ratio (aOR) = 2.46 95% Confidence Interval (CI) [1.47-4.13]), young maternal age (aOR = 2.29, 95% CI [1.18-4.46]), and absence of antiretroviral treatment for prophylaxis (aOR = 3.45, 95% CI [2.30-5.19]) were independently associated with LTFU among HIV-exposed infants. Factors associated with LTFU among HIV-unexposed infants included young maternal age (aOR = 1.96, 95% CI [1.36-2.81]), low maternal education level (aOR = 2.77, 95% CI [1.95-3.95]) and housewife/unemployed mothers (aOR = 1.56, 95% CI [1.16-2.11]). CONCLUSION: Failure to return for at least one scheduled clinical visit is a problem especially among HIV-unexposed infants included in studies involving HIV-exposed infants. Factors associated with this type of LTFU included maternal characteristics, socio-economic status, quality of antenatal care and obstetrical context of delivery. Enhanced counselling in antenatal and intrapartum services is required for mothers at high risk of failure to return for follow-up visits.

Could caregiver reporting adherence help detect virological failure in Cameroonian early treated HIV-infected infants?

BACKGROUND: Viral load is still the marker of choice for monitoring adherence to combined antiretroviral therapy (cART) and confirming the success of HIV treatment. Unfortunately it is difficult to access in many resource-poor settings. We aimed to measure the performance of caregiver reporting adherence for detecting virological failure in routine practice during the first 2 years after cART initiation in infants. METHODS: PEDIACAM is an ongoing prospective cohort study including HIV1-infected infants diagnosed before 7 months of age between November 2007 and October 2011 in Cameroon. Adherence was assessed using a questionnaire administered every 3 months from cART initiation; the HIV-RNA viral load was determined at the same visits. Virological failure was defined as having a viral load ≥ 1000 cp/mL at 3 and 12 months after cART initiation or having a viral load ≥ 400 cp/mL at 24 months after cART initiation. The performance of each current missed and cumulative missed dose defined according to adherence as reported by caregiver was assessed using the viral load as the gold standard. RESULTS: cART was initiated at a median age of 4 months (IQR: 3-6) in the 167 infants included. The cumulative missed dose showed the best overall performance for detecting virological failure after 12 months of cART (AUC test, p = 0.005, LR + =4.4 and LR- = 0.4). Whatever the adherence reporting criterion, the negative predictive value was high (NPV ≥ 75%) 12 and 24 months after cART initiation, whereas the positive predictive value was low (PPV ≤ 50%). CONCLUSIONS: The adherence questionnaire administered by the health care provider to the infants' caregivers is not reliable for detecting virological failure in routine practice: its positive predictive value is low. However, the cumulative missed dose measurement may be a reliable predictor of virological success, particularly after 12 months of cART, given its high negative predictive value.

Trends in the epidemiology of childhood nephrotic syndrome in Africa: A systematic review.

Background: Childhood nephrotic syndrome, if left untreated, leads to progressive kidney disease or death. We quantified the prevalence of steroid-sensitive nephrotic syndrome, steroid-resistant nephrotic syndrome, and histological types as the epidemiology of nephrotic syndrome in Africa remains unknown, yet impacts outcomes. Methods: We searched MEDLINE, Embase, African Journals Online, and WHO Global Health Library for articles in any language reporting on childhood nephrotic syndrome in Africa from January 1, 1946 to July 1, 2020. Primary outcomes included steroid response, biopsy defined minimal change disease, and focal segmental glomerulosclerosis (FSGS) by both pooled and individual proportions across regions and overall. Findings: There were 81 papers from 17 countries included. Majority of 8131 children were steroid-sensitive (64% [95% CI: 63-66%]) and the remaining were steroid-resistant (34% [95% CI: 33-35%]). Of children biopsied, pathological findings were 38% [95% CI: 36-40%] minimal change, 24% [95% CI: 22-25%] FSGS, and 38% [95% CI: 36-40%] secondary causes of nephrotic syndrome. Interpretation: Few African countries reported on the prevalence of childhood nephrotic syndrome. Steroid-sensitive disease is more common than steroid-resistant disease although prevalence of steroid-resistant nephrotic syndrome is higher than reported globally. Pathology findings suggest minimal change and secondary causes are common. Scarcity of data in Africa prevents appropriate healthcare resource allocation to diagnose and treat this treatable childhood kidney disease to prevent poor health outcomes. Funding: Funding was provided by the Canadian Institute for Health Research (CIHR) and the National Institute of Health (NIH) for the H3 Africa Kidney Disease Research Network. This research was undertaken, in part, from the Canada Research Chairs program.

Seasonal pattern of hospitalization from acute respiratory infections in Yaoundé, Cameroon.

Acute respiratory infections (ARIs) are among the leading causes of childhood morbidity and mortality in Africa. The effects of climatic factors on occurrence of ARIs in the tropics are not clear. During the years 2006-07, we reviewed the clinical registers of the Chantal Biya Foundation (CBF), Yaoundé, Cameroon, paediatric hospital to investigate the association between climatic factors and ARIs in children. Our findings show that rain, high relative humidity and low temperatures are directly associated with an increase in the frequency of hospitalization from ARIs. Given the high frequency of hospitalization from ARIs we suggest that influenza vaccination campaigns should be implemented taking into account the seasonality in Cameroon.

Low rate of early vertical transmission of HIV supports the feasibility of effective implementation of the national PMTCT guidelines in routine practice of referral hospitals in Cameroon.

Background: Vertical (VT) transmission of HIV remains a public health concern in sub-Saharan Africa. Objective: To investigate the VT rate and factors associated with transmission in routine practice in three referral hospitals in Cameroon. Methods: All HIV-infected mothers who delivered in maternity wards or sought paediatric services during the first postnatal week from November 2007 to October 2010 were invited to participate in the ANRS-Pediacam cohort. Their infants were followed at 6, 10 and 14 weeks of life and HIV status was determined from the 6th week of life using real-time PCR. For those who were breastfed and negative at the first PCR, a second test was performed 6 weeks after breast-feeding was stopped. Logistic regression was performed to identify the independent risk factors of VT. Results: Overall, 2053 HIV-exposed infants were enrolled. Of these, 1827 were tested for HIV including 1777 before the age of 3 months, and 59 were HIV-infected, resulting in an overall early VT rate of 3.3% (CI 2.5-4.3). The VT rate was significantly associated with the type of maternal exposure to ART (0.5%, 2/439, p<0.001, CI 0.0-1.6) in mothers who commenced HAART before pregnancy, 1.9% (6/321, CI 0.7-4.0) in mothers who commenced HAART during pregnancy, 4.1% (34/837, CI 2.8-5.6) in those on short-course ART and 11.1% (17/153, CI 6.6-17.2) in mothers not receiving ART. On multivariate analysis, the type of exposure to ART remained significantly associated with being small for gestational age (aOR 5.0, CI 2.4-10.3, p < 0.001) and female gender (aOR 2.1, CI 1.2-3.8, p = 0.01). Conclusion: The successfully low rate of VT transmission of HIV in mothers who commenced HAART in early pregnancy strongly supports the need to improve access to diagnosis and early treatment of all women of childbearing age with HIV through the national PMTCT programme. Abbreviations: ANRS: French National Agency for Research on AIDS and Viral Hepatitis; ART: antiretroviral therapy; ARV: antiretroviral; AUDIPOG: Association des Utilisateurs de Dossiers Informatisés en Pédiatrie, Obstétrique et Gynécologie; CHM/MCC-CBF: The Central Hospital Maternity/Mother and Child Centre of the Chantal Biya Foundation; EHC: Essos Hospital Centre; EPI: Expanded Programme on Immunization; HAART: highly active antiretroviral therapy; HBV: hepatitis B virus; IQR: interquartile range; LH: Laquintinie Hospital; MTCT: mother-to-child transmission; NVP: nevirapine; Pediacam: Pediatrie Cameroun; PMTCT: prevention of mother-to-child transmission; SGAG: small for gestational age and gender; UNAIDS: Joint United Nations Program on HIV/AIDS; WHO: World Health Organization; ZDV: zidovudine; 3TC: lamivudine.

Early treated HIV-infected children remain at risk of growth retardation during the first five years of life: Results from the ANRS-PEDIACAM cohort in Cameroon.

BACKGROUND: Long-term growth in HIV-infected infants treated early in resource-limited settings is poorly documented. Incidence of growth retardation, instantaneous risk of death related to malnutrition and growth parameters evolution during the first five years of life of uninfected and early treated HIV-infected children were compared and associated factors with growth retardation were identified. METHODS: Weight-for-age (WAZ), weight-for-length (WLZ), and length-for-age (LAZ) Z-scores were calculated. The ANRS-PEDIACAM cohort includes four groups of infants with three enrolled during the first week of life: HIV-infected (HI, n = 69), HIV-exposed uninfected (HEU, n = 205) and HIV-unexposed uninfected (HUU, n = 196). The last group included HIV-infected infants diagnosed before 7 months of age (HIL, n = 141). The multi-state Markov model was used to describe the incidence of growth retardation and identified associated factors. RESULTS: During the first 5 years, 27.5% of children experienced underweight (WAZ<-2), 60.4% stunting (LAZ<-2) and 41.1% wasting (WLZ<-2) at least once. The instantaneous risk of death observed from underweight state (35.3 [14.1-88.2], 84.0 [25.5-276.3], and 6.0 [1.5-24.1] per 1000 person-months for 0-6 months, 6-12 months, and 12-60 months respectively) was higher than from non-underweight state (9.6 [5.7-16.1], 20.1 [10.3-39.4] and 0.3 [0.1-0.9] per 1000 person-months). Compared to HEU, HIL and HI children were most at risk of wasting (adjusted HR (aHR) = 4.3 (95%CI: 1.9-9.8), P<0.001 and aHR = 3.3 (95%CI: 1.4-7.9), P = 0.01 respectively) and stunting for HIL (aHR = 8.4 (95%CI: 2.4-29.7). The risk of underweight was higher in HEU compared to HUU children (aHR = 5.0 (CI: 1.4-10.0), P = 0.001). Others associated factors to growth retardation were chronic pathologies, small size at birth, diarrhea and CD4< 25%. CONCLUSIONS: HIV-infected children remained at high risk of wasting and stunting within the first 5 years period of follow-up. There is a need of identifying suitable nutritional support and best ways to integrate it with cART in pediatric HIV infection global care.

Virologic Response to Early Antiretroviral Therapy in HIV-infected Infants: Evaluation After 2 Years of Treatment in the Pediacam Study, Cameroon.

INTRODUCTION: Little is known about virologic responses to early antiretroviral therapy (ART) in HIV-infected infants in resource-limited settings. We estimated the probability of achieving viral suppression within 2 years of ART initiation and investigated the factors associated with success. METHODS: We analyzed all 190 infants from the Cameroon Pediacam who initiated ART by 12 months of age. The main outcome measure was viral suppression (<1000 copies/mL) on at least 1 occasion; the other outcome measures considered were viral suppression (<400 copies/mL) on at least 1 occasion and confirmed viral suppression (both thresholds) on 2 consecutive occasions. We used competing-risks regression for a time-to-event analysis to estimate the cumulative incidence of outcomes and univariate and multivariate models to identify risk factors. RESULTS: During the first 24 months of ART, 20.0% (38) of the infants died, giving a mortality rate of 11.9 deaths per 100 infant-years (95% confidence interval: 8.1-15.7). The probability of achieving a viral load below 1000 or 400 copies/mL was 80.0% (69.0-81.0) and 78.0% (66.0-79.0), respectively. The probability of virologic suppression (with these 2 thresholds) on 2 consecutive occasions was 67.0% (56.0-70.0) and 60.0% (49.0-64.0), respectively. Virologic success was associated with not having missed any doses of treatment before the visit, but not with socioeconomic and living conditions. CONCLUSION: Many early treated children failed to achieve virologic suppression, likely due to a combination of adherence difficulties, drug dosing and viral resistance, which highlights the need for routine viral load monitoring. The high infant mortality despite early ART initiation needs to be addressed in sub-Saharan countries.

Neurodevelopmental outcomes in HIV-infected and uninfected African children.

OBJECTIVE: HIV infection is associated with cognitive impairments, but outcomes are poorly explored in children starting antiretroviral therapy (ART) early or in those exposed but uninfected. DESIGN: Nested cross-sectional evaluation of the neurocognitive and behavioural outcomes of HIV-infected, HIV-exposed uninfected (HEU) and HIV-unexposed (HUU) Cameroonian children at age 4-9 years prospectively followed. METHODS: Cognitive development was assessed in 127 HIV-infected, 101 HEU, 110 HUU children using the KABC-II, neurologic dysfunction using the Touwen examination and behavioural difficulties using the Strength and Difficulties Questionnaire (SDQ). Analyses were adjusted for children age, sex and primary language. Contextual factors were included in a second step to assess their effects on outcomes. RESULTS: All HIV-infected children were treated before 12 months. There was a negative linear gradient in KABC-II scores from HUU children to HEU and HIV-infected children [gradient: -6.0 (-7.7; -4.3) for nonverbal index, NVI, and -8.8 (-10.7; -6.8) for mental processing index, MPI]. After adjusting for contextual factors, scores of HEU children were not significantly different from those of HUU children (all P > 0.1) and differences between HIV-uninfected and HUU children reduced [NVI: from -11.9 (-15.3; -8.5) to -3.4 (-6.8; -0.01), MPI: from -17.6 (-21.3; -13.8) to -5.5 (-9.3; -1.7)]. Compared with uninfected children, HIV-infected children had more neurological dysfunctions and higher SDQ scores (P = 0.002). CONCLUSION: Despite early ART, perinatal-HIV infection is associated with poorer neurocognitive scores and increased behavioural difficulties during childhood. Contextual factors play an important role in this association, which emphasizes the need for early nutritional and developmental interventions targeting both HIV-affected infants and their relatives.

Low birth weight in perinatally HIV-exposed uninfected infants: observations in urban settings in Cameroon.

BACKGROUND: The consequences of maternal HIV infection for fetal growth are controversial. Here, we estimated the frequency of small for gestational age and gender (SGAG) among neonates born to HIV-infected or uninfected mothers and assessed the contribution, if any, of maternal HIV to the risk of SGAG. METHODS: The data used were obtained from the ANRS-Pediacam cohort in Cameroon. Pairs of newborns, one to a HIV-infected mother and the other to an uninfected mother, were identified during the first week of life, and matched on gender and recruitment site from 2007-2010. SGAG was defined in line with international recommendations as a birth weight Z-score adjusted for gestational age at delivery and gender more than two standard deviations below the mean (-2SD). Considering the matched design, logistic regression modeling was adjusted on site and gender to explore the effect of perinatal HIV exposure on SGAG. RESULTS: Among the 4104 mother-infant pairs originally enrolled, no data on birth weight and/or gestational age were available for 108; also, 259 were twins and were excluded. Of the remaining 3737 mother-infant pairs, the frequency of SGAG was 5.3% (95%CI: 4.6-6.0), and was significantly higher among HIV-infected infants (22.4% vs. 6.3%; p<.001) and lower among HIV-unexposed uninfected infants (3.5% vs. 6.3%; p<.001) than among HIV-exposed uninfected infants. Similarly, SGAG was significantly more frequent among HIV-infected infants (aOR: 4.1; 2.0-8.1) and less frequent among HIV-unexposed uninfected infants (aOR: 0.5; 0.4-0.8) than among HIV-exposed uninfected infants. Primiparity (aOR: 1.9; 1.3-2.7) and the presence of any disease during pregnancy (aOR: 1.4; 1.0-2.0) were identified as other contributors to SGAG. CONCLUSION: Maternal HIV infection was independently associated with SGAG for HIV-exposed uninfected infants. This provides further evidence of the need for adapted monitoring of pregnancy in HIV-infected women, especially if they are symptomatic, to minimize additional risk factors for SGAG.

Feasibility of early infant diagnosis of HIV in resource-limited settings: the ANRS 12140-PEDIACAM study in Cameroon.

BACKGROUND: Early infant diagnosis (EID) of HIV is a key-point for the implementation of early HAART, associated with lower mortality in HIV-infected infants. We evaluated the EID process of HIV according to national recommendations, in urban areas of Cameroon. METHODS/FINDINGS: The ANRS12140-PEDIACAM study is a multisite cohort in which infants born to HIV-infected mothers were included before the 8(th) day of life and followed. Collection of samples for HIV DNA/RNA-PCR was planned at 6 weeks together with routine vaccination. The HIV test result was expected to be available at 10 weeks. A positive or indeterminate test result was confirmed by a second test on a different sample. Systematic HAART was offered to HIV-infected infants identified. The EID process was considered complete if infants were tested and HIV results provided to mothers/family before 7 months of age. During 2007-2009, 1587 mother-infant pairs were included in three referral hospitals; most infants (n = 1423, 89.7%) were tested for HIV, at a median age of 1.5 months (IQR, 1.4-1.6). Among them, 51 (3.6%) were HIV-infected. Overall, 1331 (83.9%) completed the process by returning for the result before 7 months (median age: 2.5 months (IQR, 2.4-3.0)). Incomplete process, that is test not performed, or result of test not provided or provided late to the family, was independently associated with late HIV diagnosis during pregnancy (adjusted odds ratio (aOR) = 1.8, 95%CI: 1.1 to 2.9, p = 0.01), absence of PMTCT prophylaxis (aOR = 2.4, 95%CI: 1.4 to 4.3, p = 0.002), and emergency caesarean section (aOR = 2.5, 95%CI: 1.5 to 4.3, p = 0.001). CONCLUSIONS: In urban areas of Cameroon, HIV-infected women diagnosed sufficiently early during pregnancy opt to benefit from EID whatever their socio-economic, marital or disclosure status. Reduction of non optimal diagnosis process should focus on women with late HIV diagnosis during pregnancy especially if they did not receive any PMTCT, or if complications occurred at delivery.