How Can We Support the Use of Oral PrEP Among Young Women who Sell Sex? A PrEP Cascade Analysis.

BACKGROUND: We constructed self-reported pre-exposure prophylaxis (PrEP) cascades and explored factors associated with and barriers to PrEP use to inform efforts to support PrEP use among young women who sell sex. METHODS: Using self-reported data from HIV-negative young women who sell sex enrolled into a cohort study using respondent-driven sampling in Zimbabwe, we constructed PrEP cascades assessing knowledge of, ever offered, ever used, and current PrEP use in 2017 and 2019. We used logistic regression to examine factors associated with PrEP use by 2019. Through qualitative interviews with 43 women enrolled in the cohort, we investigated barriers to PrEP use. RESULTS: At enrollment, 50% of women had heard of PrEP, 12% had ever been offered PrEP, and 7% ever used PrEP. Over time, all cascade domains: 96% of women had heard of and 55% reported an active offer of PrEP. Among women retained in the study in 2019 (56%; n = 538), 34% ever took PrEP by 2019. PrEP use was associated with, at enrollment, reporting more clients in the past month (10+: 45% vs 1-3: 27% adjOR = 1.71 95% CI: 1.06 to 2.76), duration of selling sex (24% <2 years vs 38% 2-3 years; adjOR = 0.51 95% CI: 0.32 to 0.83), and having visited a female sex worker program in the past 12 months (55% vs 27%; adjOR = 2.92 95% CI: 1.91 to 4.46). Qualitative interviews revealed fear of disclosing sex work, HIV-related/ART-related stigma, and (opportunity) costs of accessing PrEP as barriers to use. CONCLUSION: PrEP use was associated with factors known to increase HIV risk. Fear of stigma, disclosure, and supply-side barriers need to be addressed to increase women's ability to use PrEP.

Intraventricular haemorrhage in a Ugandan cohort of low birth weight neonates: the IVHU study.

BACKGROUND: Globally, 15 million neonates are born prematurely every year, over half in low income countries (LICs). Premature and low birth weight neonates have a higher risk of intraventricular haemorrhage (IVH). There are minimal data regarding IVH in sub-Saharan Africa. This study aimed to examine the incidence, severity and timing of and modifiable risk factors for IVH amongst low-birth-weight neonates in Uganda. METHODS: This is a prospective cohort study of neonates with birthweights of ≤2000 g admitted to a neonatal unit (NU) in a regional referral hospital in eastern Uganda. Maternal data were collected from interviews and medical records. Neonates had cranial ultrasound (cUS) scans on the day of recruitment and days 3, 7 and 28 after birth. Risk factors were tabulated and are presented alongside odds ratios (ORs) and adjusted odds ratios (aORs) for IVH incidence. Outcomes included incidence, timing and severity of IVH and 28-day survival. RESULTS: Overall, 120 neonates were recruited. IVH was reported in 34.2% of neonates; 19.2% had low grade (Papile grades 1-2) and 15% had high grade (Papile grades 3-4). Almost all IVH (90.2%) occurred by day 7, including 88.9% of high grade IVH. Of those with known outcomes, 70.4% (81/115) were alive on day 28 and survival was not associated with IVH. We found that vaginal delivery, gestational age (GA) < 32 weeks and resuscitation in the NU increased the odds of IVH. Of the 6 neonates who received 2 doses of antenatal steroids, none had IVH. CONCLUSION: In this resource limited NU in eastern Uganda, more than a third of neonates born weighing ≤2000 g had an IVH and the majority of these occurred by day 7. We found that vaginal birth, earlier gestation and need for resuscitation after admission to the NU increased the risk of IVH. This study had a high rate of SGA neonates and the risk factors and relationship of these factors with IVH in this setting needs further investigation. The role of antenatal steroids in the prevention of IVH in LICs also needs urgent exploration.

Costs and economies of scale in the accelerated program for prevention of mother-to-child transmission of HIV in Zimbabwe.

BACKGROUND: Despite a growing body of literature on HIV service costs in sub-Saharan Africa, only a few studies have estimated the facility-level cost of prevention of Mother-to-Child Transmission (PMTCT) services, and even fewer provide insights into the variation of PMTCT costs across facilities. In this study, we present the first empirical costs estimation of the accelerated program for the prevention of mother-to-child transmission of HIV in Zimbabwe and investigate the determinants of heterogeneity of the facility-level average cost per service. To understand such variation, we explored the association between average costs per service and supply-and demand-side characteristics, and quality of services. One aspect of the supply-side we explore carefully is the scale of production-which we define as the annual number of women tested or the yearly number of HIV-positive women on prophylaxis. METHODS: We collected rich data on the costs and PMTCT services provided by 157 health facilities out of 699 catchment areas in five provinces in Zimbabwe for 2013. In each health facility, we measured total costs and the number of women covered with PMTCT services and estimated the average cost per woman tested and the average cost per woman on either ARV prophylaxis or ART. We refer to these facility-level average costs per service as unitary costs. We also collected information on potential determinants of the variation of unitary costs. On the supply-side, we gathered data on the scale of production, staff composition and on the types of antenatal and family planning services provided. On the demand side, we measured the total population at the catchment area and surveyed eligible pairs of mothers and infants about previous use of HIV testing and prenatal care, and on the HIV status of both mothers and infants. We explored the determinants of unitary cost variation using a two-stage linear regression strategy. RESULTS: The average annual total cost of the PMTCT program per facility was US$16,821 (median US$8,920). The average cost per pregnant woman tested was US$80 (median US$47), and the average cost per HIV-positive pregnant woman initiated on ARV prophylaxis or treatment was US$786 annually (median US$420). We found substantial heterogeneity of unitary costs across facilities regardless of facility type. The scale of production was a strong predictor of unitary costs variation across facilities, with a negative and statistically significant correlation between the two variables (p<0.01). CONCLUSIONS: These findings are the first empirical estimations of PMTCT costs in Zimbabwe. Unitary costs were found to be heterogeneous across health facilities, with evidence consistent with economies of scale.

Effects of Maternal Suicidal Ideation on Child Cognitive Development: A Longitudinal Analysis.

This study aimed to assess the association between suicidal ideation among mothers living with HIV in Zimbabwe and the cognitive development of their children. Participants were mother-child dyads recruited from two rural districts in Zimbabwe. Data were collected at baseline and 12 months follow-up. Suicidal ideation was assessed using item-10 from the Edinburgh postnatal depression scale. Mixed-effects linear regression was used to assess the association of child cognitive outcomes at follow-up (using the Mullen scales of early learning) with maternal suicidal ideation. Mothers with suicidal ideation at baseline (n = 171) tended to be younger, unmarried, experienced moderate to severe hunger, had elevated parental stress and depression symptoms compared with non-suicidal mothers (n = 391). At follow-up, emerging maternal suicidal ideation was associated with poorer child cognitive outcomes (adjusted mean difference - 6.1; 95% CI - 10.3 to - 1.8; p = 0.03). Suicidal ideation affects child cognitive development and should be addressed, particularly in HIV positive mothers.

Motor performance and cognitive correlates in children cooled for neonatal encephalopathy without cerebral palsy at school age.

AIM: To investigate whether motor performance in school-age children without cerebral palsy (CP), cooled for neonatal encephalopathy, is associated with perinatal factors and 18-month developmental scores and to explore relationships between school-age motor and cognitive performance. METHODS: Motor and cognitive performance was assessed in 29 previously cooled children at six to eight years using the Movement Assessment Battery for Children-2 (MABC-2) and the Wechsler Intelligence Scale for Children (WISC-IV). Associations between MABC-2 scores less than/equal (≤) 15th centile and perinatal factors, social/family background, 18-month Bayley-III scores and WISC-IV scores were explored. RESULTS: Eleven of the 29 (38%) children had MABC-2 scores ≤15th centile including 7 (24%) ≤5th centile. No significant perinatal or socio-economic risk factors were identified. Motor scores <85 at 18 months failed to identify children with MABC-2 scores ≤15th centile. MABC-2 scores ≤15th centile were associated with lower Full Scale IQ (p = 0.045), Working Memory (p = 0.03) and Perceptual Reasoning (p = 0.005) scores at six to eight years and receiving greater support in school (p = 0.01). CONCLUSION: A third of cooled children without CP had MABC-2 scores indicating motor impairment at school age that was not identified at 18 months by Bayley-III. Most children with low MABC scores needed support at school. Sub-optimal MABC-2 scores indicate need for detailed school-age cognitive evaluation.

Evaluating the effectiveness of a multi-component intervention on early childhood development in paediatric HIV care and treatment programmes: a randomised controlled trial.

BACKGROUND: HIV infection in a family may affect optimum child development. Our hypothesis is that child development outcomes among HIV-exposed infants will be improved through a complex early childhood stimulation (ECS) programme, and income and loans saving programme for HIV positive parents. METHODS: The study was a cluster-randomized controlled trial in 30 clinic sites in two districts in Zimbabwe. Clinics were randomised in a 1:1 allocation ratio to the Child Health Intervention for Development Outcomes (CHIDO) intervention or Ministry of Health standard care. The CHIDO intervention comprises three elements: a group ECS parenting programme, an internal savings and lending scheme (ISALS) and case-management home visits by village health workers. The intervention was aimed at caregiver-child dyads (child aged 0-24 months) where the infant was HIV exposed or infected. The primary outcomes were cognitive development (assessed by the Mullen Scales of Early Learning) and retention of the child in HIV care, at 12 months after enrolment. A comprehensive process evaluation was conducted. DISCUSSION: The results of this cluster-randomised trial will provide important information regarding the effects of multi-component interventions in mitigating developmental delays in HIV-exposed infants living in resource-limited environments. TRIAL REGISTRATION: This trial is registered with the Pan African Clinical Trials Registry ( www.pactr.org ), registration number PACTR201701001387209; the trial was registered on 16th January 2017 (retrospectively registered).

Postnatal Brain Growth Assessed by Sequential Cranial Ultrasonography in Infants Born <30 Weeks' Gestational Age.

BACKGROUND AND PURPOSE: Brain growth in the early postnatal period following preterm birth has not been well described. This study of infants born at <30 weeks' gestational age and without major brain injury aimed to accomplish the following: 1) assess the reproducibility of linear measures made from cranial ultrasonography, 2) evaluate brain growth using sequential cranial ultrasonography linear measures from birth to term-equivalent age, and 3) explore perinatal predictors of postnatal brain growth. MATERIALS AND METHODS: Participants comprised 144 infants born at <30 weeks' gestational age at a single center between January 2011 and December 2013. Infants with major brain injury seen on cranial ultrasonography or congenital or chromosomal abnormalities were excluded. Brain tissue and fluid spaces were measured from cranial ultrasonography performed as part of routine clinical care. Brain growth was assessed in 3 time intervals: <7, 7-27, and >27 days' postnatal age. Data were analyzed using intraclass correlation coefficients and mixed-effects regression. RESULTS: A total of 429 scans were assessed for 144 infants. Several linear measures showed excellent reproducibility. All measures of brain tissue increased with postnatal age, except for the biparietal diameter, which decreased within the first postnatal week and increased thereafter. Gestational age of ≥28 weeks at birth was associated with slower growth of the biparietal diameter and ventricular width compared with gestational age of <28 weeks. Postnatal corticosteroid administration was associated with slower growth of the corpus callosum length, transcerebellar diameter, and vermis height. Sepsis and necrotizing enterocolitis were associated with slower growth of the transcerebellar diameter. CONCLUSIONS: Postnatal brain growth in infants born at <30 weeks' gestational age can be evaluated using sequential linear measures made from routine cranial ultrasonography and is associated with perinatal predictors of long-term development.

Overlapping HIV and sex-work stigma among female sex workers recruited to 14 respondent-driven sampling surveys across Zimbabwe, 2013.

HIV stigma can inhibit uptake of HIV testing and antiretroviral therapy as well as negatively affect mental health. Efforts to reduce discrimination against people living with HIV (LWH) have contributed to greater acceptance of the infection. Female sex workers (FSW) LWH may experience overlapping stigma due to both their work and HIV status, although this is poorly understood. We examined HIV and sex-work stigma experienced by FSW LWH in Zimbabwe. Using the SAPPH-IRe cluster-randomised trial baseline survey, we analysed the data from 1039 FSW self-reporting HIV. The women were recruited in 14 sites using respondent-driven sampling. We asked five questions to assess internalised and experienced stigma related to working as a sex worker, and the same questions were asked in reference to HIV. Among all FSW, 91% reported some form of sex-work stigma. This was not associated with sociodemographic or sex-work characteristics. Rates of sex-work stigma were higher than those of HIV-related stigma. For example, 38% reported being "talked badly about" for LWH compared with 77% for their involvement in sex work. Those who reported any sex-work stigma also reported experiencing more HIV stigma compared to those who did not report sex-work stigma, suggesting a layering effect. FSW in Zimbabwe experience stigma for their role as "immoral" women and this appears more prevalent than HIV stigma. As HIV stigma attenuates, other forms of social stigma associated with the disease may persist and continue to pose barriers to effective care.

Neonatal neurological examination in well newborn term Ugandan infants.

BACKGROUND: Newborn neurological examinations have mostly been developed in high-resource settings with cohorts comprising predominantly white Caucasian infants. No comparison has been made with different populations. AIMS: To (i) establish the range of neurological findings in apparently well newborn term Ugandan infants, (ii) compare these findings to published data for equivalent term UK infants and (iii) correlate the neurological findings with perinatal characteristics and cranial ultrasound (cUS) imaging. METHODS: Low-risk term Ugandan infants were recruited from the postnatal ward at Mulago Hospital, Kampala, Uganda. Neurological examination (1) and cUS were performed. The raw data and neurological optimality scores were compared to published data from UK infants (1). Gestational age, postnatal age, sex, maternal parity and HIV status, mode of delivery, birth weight and head circumference were correlated with raw scores. RESULTS: Ugandan infants showed significantly stronger palmar grasp, better auditory and visual orientation, less irritability and less need for consoling but had poorer tone, poorer quality of spontaneous movements and more abnormal signs than UK infants. No correlation was found between raw scores and cUS findings, gestational age, sex, birth weight and head circumference. Significantly fewer Ugandan infants had optimal scores based on the UK data. CONCLUSION: The neurological status of low-risk hospital-born term Ugandan infants differs from that of low-risk UK infants. The study findings have implications for assessing normality in Ugandan infants and raise concerns about the use of this UK "optimality" score in other research settings. Further work is needed to understand fully the reasons for the differences.

The effects of hemorrhagic parenchymal infarction on the establishment of sensori-motor structural and functional connectivity in early infancy.

INTRODUCTION: The objective of the study was to characterize alterations of structural and functional connectivity within the developing sensori-motor system in infants with focal perinatal brain injury and at high risk of cerebral palsy. METHODS: Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data were used to study the developing functional and structural connectivity framework in six infants born prematurely at term equivalent age. This was first characterised in three infants without focal pathology, which was then compared to that derived from three infants with unilateral haemorrhagic parenchymal infarction and a subsequent focal periventricular white matter lesion who developed later haemiparesis. RESULTS: Functional responses to passive hand movement were in the contralateral perirolandic cortex, regardless of focal pathology. In infants with unilateral periventricular injury, afferent thalamo-cortical tracts appeared to have developed compensatory trajectories which circumvented areas of damage. In contrast, efferent corticospinal tracts showed marked asymmetry at term equivalent age following focal brain injury. Sensori-motor network analysis suggested that inter-hemispheric functional connectivity is largely preserved despite pathology and that impairment may be associated with adverse neurodevelopmental outcome. CONCLUSION: Following focal perinatal brain injury, altered structural and functional connectivity is already present and can be characterized with MRI at term equivalent age. The results of this small case series suggest that these techniques may provide valuable new information about prognosis and the pathophysiology underlying cerebral palsy.

Developmental venous anomaly in the newborn brain.

INTRODUCTION: Cerebral developmental venous anomaly (DVA) is considered a benign anatomical variant of parenchymal venous drainage; it is the most common vascular malformation seen in the adult brain. Despite its assumed congenital origin, little is known about DVA in the neonatal brain. We report here the first cohort study of 14 neonates with DVA. METHODS: Fourteen infants (seven preterm) with DVA diagnosed neonatally using cranial ultrasound (cUS) and magnetic resonance imaging (MRI) from three tertiary neonatal units over 14 years are reviewed. RESULTS: DVA was first detected on cUS in 6 and on MRI in 8 of the 14 infants. The cUS appearances of DVA showed a focal fairly uniform area of increased echogenicity, often (86 %) adjacent to the lateral ventricle and located in the frontal lobe (58 %). Blood flow in the dilated collector vein detected by Doppler ultrasound (US) varied between cases (venous flow pattern in ten and arterialized in four). The appearance on conventional MRI was similar to findings in adults. Serial imaging showed a fairly constant appearance to the DVAs in some cases while others varied considerably regarding anatomical extent and flow velocity. CONCLUSIONS: This case series underlines that a neonatal diagnosis of DVA is possible with carefully performed cUS and MRI and that DVA tends to be an incidental finding with a diverse spectrum of imaging appearances. Serial imaging suggests that some DVAs undergo dynamic changes during the neonatal period and early infancy; this may contribute to why diagnosis is rare at this age.

Hypothermia makes cerebral resistance index a poor prognostic tool in encephalopathic newborns.

BACKGROUND: Severe neonatal encephalopathy (NE) of hypoxic-ischaemic origin may cause death or life-long disability. Acute encephalopathy may also affect cerebrovascular control. Pourcelot's cerebrovascular resistance index (RI) ≤0.55 was predictive of poor outcome in normothermic NE infants. Recent studies have questioned its predictive power during therapeutic hypothermia (HT). OBJECTIVE: To assess the predictive power of RI during HT and after rewarming. METHODS: 45 infants with NE treated with HT for 72 h had their RI calculated during early (median 11 h) and late (median 62 h) cooling and after rewarming (median 89 h). Poor outcome was defined as death or abnormalities on day 10 magnetic resonance imaging shown to predict severe neuromotor disability. RESULTS: RI ≤0.55 during cooling did not differentiate between good and poor outcome (late cooling, p = 0.08), but was powerful after rewarming (p = 0.004). RI ≤0.55 predicted true poor outcome in 43% (95% confidence interval (CI): 12, 80) during late cooling and in 100% (95% CI: 31, 100) after rewarming. RI >0.55 predicted good outcome in 86% (95% CI: 69, 95) during late cooling and in 89% (95% CI: 74, 96) after rewarming. CONCLUSIONS: Low RI is not predictive of poor outcome during HT in NE infants, but regains the predictive power seen in normothermic infants after rewarming.

Neonatal stroke.

Neonatal stroke encompasses a range of focal and multifocal ischaemic and haemorrhagic tissue injuries. This review will concentrate on focal brain injury that occurs as a consequence of arterial infarction, most frequently the left middle cerebral artery, or more rarely as a consequence of cerebral sinus venous thrombosis (CSVT). Both conditions are multifactorial in origin. The incidence of both acquired and genetic thrombophilic disorders in both mothers and infants is high although rarely causal in isolation. Neurodevelopmental morbidity occurs in over 50% of children. Specific therapy in the form of anticoagulation is currently only recommended in CSVT and needs to be carefully monitored in the presence of haemorrhage.

Predicting motor outcome and death in term hypoxic-ischemic encephalopathy.

OBJECTIVES: Central gray matter damage, the hallmark of term acute perinatal hypoxia-ischemia, frequently leads to severe cerebral palsy and sometimes death. The precision with which these outcomes can be determined from neonatal imaging has not been fully explored. We evaluated the accuracy of early brain MRI for predicting death, the presence and severity of motor impairment, and ability to walk at 2 years in term infants with hypoxic-ischemic encephalopathy (HIE) and basal ganglia-thalamic (BGT) lesions. METHODS: From 1993 to 2007, 175 term infants with evidence of perinatal asphyxia, HIE, and BGT injury seen on early MRI scans were studied. BGT, white matter, posterior limb of the internal capsule (PLIC), and cortex and brainstem abnormality were classified by severity. Motor impairment was staged using the Gross Motor Function Classification System. RESULTS: The severity of BGT lesions was strongly associated with the severity of motor impairment (Spearman rank correlation 0.77; p < 0.001). The association between white matter, cortical, and brainstem injury and motor impairment was less strong and only BGT injury correlated significantly in a logistic regression model. The predictive accuracy of severe BGT lesions for severe motor impairment was 0.89 (95% confidence interval 0.83-0.96). Abnormal PLIC signal intensity predicted the inability to walk independently by 2 years (sensitivity 0.92, specificity 0.77, positive predictive value 0.88, negative predictive value 0.85). Brainstem injury was the only factor with an independent association with death. CONCLUSION: We have shown that in term newborns with HIE and BGT injury, early MRI can be used to predict death and specific motor outcomes.

Cerebral measurements made using cranial ultrasound in term Ugandan newborns.

BACKGROUND: Few cUS studies of cerebral measurements are available for normal term infants. Normative data is important for evaluating cerebral structure size in symptomatic term infants and assessing preterm brain growth by term age. OBJECTIVES: To (i) make linear measurements using cranial ultrasound (cUS) for major cerebral structures and intracranial spaces in normal newborn term infants, (ii) correlate these measurements with gestational age (GA), birth weight (BW), head circumference (HC), gender and within one infant (iii) examine inter/intra-observer variation, and (iv) compare these data with those currently available. DESIGN, SETTING AND PATIENTS: Linear cUS measurements of major cerebral structures were made in well term-born Ugandan infants at Mulago University Hospital, Kampala. Correlations between the measurements and gender, HC, BW and GA were calculated. Intra- and inter-observer agreements were assessed. RESULTS: Data from 106 infants (mean GA 39.20±1.4SD weeks) were analysed. Intra/inter-observer agreement was substantial/excellent. Significant correlations were found between HC and pons anterior-posterior diameter (p<0.01), corpus callosal (CC) length (p=0.02) and transverse cerebellar diameter (TCD, p<0.01) and between BW and CC length (p=0.02), vermis height (<0.01) and thalamo-occipital distance (p=0.03); no significant correlation was found with GA. Within infants CC length and TCD correlated significantly (p=0.019). Males had larger left ventricular indices than females (p=0.04). The data was similar to those from other populations. CONCLUSIONS: These data provide reliable reference values for linear measurements of many cerebral structures made using cUS. The data agree well with those from other populations suggesting that cerebral size is similar in different ethnic groups.

Cranial ultrasound findings in well newborn Ugandan infants.

BACKGROUND: There has been no study assessing cranial ultrasound (cUS) scans in newborn infants born in equatorial Africa. OBJECTIVE: To assess the cUS scans of apparently well newborn term Ugandan infants and to correlate the findings with perinatal data. METHODS: An observational study of apparently healthy postnatal ward term Ugandan infants at Mulago Hospital, Makerere University Hospital, Kampala, Uganda. RESULTS: Data from 112 infants scanned at a median age of 1.4 postnatal days were analysed. Only 57 (51%) infants had scans considered normal, including 30 infants with isolated focal peritrigonal white matter (WM) echogenicity that was very common, occurring in 60 (53%) of infants. More extensive WM echogencities were seen in nine (7.5%) and focal unilateral central grey matter echogenicity in eight (6.5%) infants. Haemorrhage was not common. Subependymal pseudocysts (SEP) and choroid plexus cysts (CPC) occurred in 19.6% of infants each. Four infants only had lenticulostriate vasculopathy. No correlation was found between mode of delivery, birth weight, head circumference or gestational age, maternal HIV status and any cUS abnormality. CONCLUSIONS: Apparently well term-born Ugandan infants frequently have abnormalities on cUS. These are mainly increased WM echogenicity, SEP and CPC. These may relate to the reported high incidence of congenital infections in this population but this remains to be confirmed. The observations provide baseline data for comparison with scans from sick infants from similar communities and are also important for studies in which cUS will be used to assess progress.

Increased risk of HIV-infection among school-attending orphans in rural Zimbabwe.

In Zimbabwe around 1.1 million children have been orphaned due to AIDS. We conducted a survey among school-attending youth in rural south-eastern Zimbabwe in 2003, and examined the association between orphaning and risk of HIV. We enrolled 30 communities in three provinces. All students attending Year 2 of secondary school were eligible. Each completed a questionnaire and provided a finger-prick blood specimen for testing for HIV-1 and HSV-2 antibodies. Female participants were tested for pregnancy. Six thousand seven hundred and ninety-one participants were recruited (87% of eligible); 35% had lost one or both parents (20% of participants had lost their father; 6% their mother; and 9% both parents). Orphans were not poorer than non-orphans based on reported access to income, household structure and ownership of assets. There was strong evidence that orphans, and particularly those who had lost both parents, were at increased sexual risk, being more likely to have experienced early sexual debut; to have been forced to have sex; and less likely to have used condoms. Fifty-one students were HIV positive (0.75%). Orphans were three times more likely to be HIV infected than non-orphans (adjusted odds ratio = 3.4; 95% confidence interval: 1.8-6.6). Over 60% of those HIV positive were orphaned. Among school-going youth, the rates of orphaning were very high; there was a strong association between orphaning and increased risk of HIV, and evidence of greater sexual risk taking among orphans. It is essential that we understand the mechanisms by which orphaned children are at increased risk of HIV in order to target prevention and support appropriately.