HIV viraemia and mother-to-child transmission risk after antiretroviral therapy initiation in pregnancy in Cape Town, South Africa.

OBJECTIVES: Maternal HIV viral load (VL) drives mother-to-child HIV transmission (MTCT) risk but there are few data from sub-Saharan Africa, where most MTCT occurs. We investigated VL changes during pregnancy and MTCT following antiretroviral therapy (ART) initiation in Cape Town, South Africa. METHODS: We conducted a prospective study of HIV-infected women initiating ART within routine antenatal services in a primary care setting. VL measurements were taken before ART initiation and up to three more times within 7 days postpartum. Analyses examined VL changes over time, viral suppression (VS) at delivery, and early MTCT based on polymerase chain reaction (PCR) testing up to 8 weeks of age. RESULTS: A total of 620 ART-eligible HIV-infected pregnant women initiated ART, with 2425 VL measurements by delivery (median gestation at initiation, 20 weeks; median pre-ART VL, 4.0 log10 HIV-1 RNA copies/mL; median time on ART before delivery, 118 days). At delivery, 91% and 73% of women had VL ≤ 1000 and ≤ 50 copies/mL, respectively. VS was strongly predicted by time on therapy and pre-ART VL. The risk of early MTCT was strongly associated with delivery VL, with risks of 0.25, 2.0 and 8.5% among women with VL < 50, 50-1000 and > 1000 copies/mL at delivery, respectively (P < 0.001). CONCLUSIONS: High rates of VS at delivery and low rates of MTCT can be achieved in a routine care setting in sub-Saharan Africa, indicating the effectiveness of currently recommended ART regimens. Women initiating ART late in pregnancy and with high VL appear substantially less likely to achieve VS and require targeted research and programmatic attention.

Birth prevalence of congenital cytomegalovirus among infants of HIV-infected women on prenatal antiretroviral prophylaxis in South Africa.

BACKGROUND: A high rate of congenital cytomegalovirus (CMV) has been documented in human immunodeficiency virus (HIV)-exposed infants in industrialized settings, both in the pre- and post-highly active antiretroviral therapy (HAART) era. Only limited data on the birth prevalence of congenital CMV among infants of HIV-infected women on prenatal antiretroviral (ARV) prophylaxis are available from sub-Saharan Africa, despite a high prevalence of both infections. We evaluated the prevalence of congenital CMV in HIV-exposed infants in the Western Cape, South Africa. METHODS: HIV-infected mothers were recruited in the immediate postnatal period at a referral maternity hospital between April and October 2012. Maternal and infant clinical data and newborn saliva swabs were collected. Saliva swabs were assayed by real-time polymerase chain reaction for CMV. Data were analyzed using univariate and multivariate logistic regression analyses to determine specific demographic, maternal, and newborn characteristics associated with congenital CMV. RESULTS: CMV was detected in 22 of 748 newborn saliva swabs (2.9%; 95% confidence interval [CI], 1.9%-4.4%). Overall, 96% of mothers used prenatal ARV prophylaxis (prenatal zidovudine, 43.9%; HAART, 52.1%). Maternal age, gestational age, prematurity (<37 weeks' gestation), type of ARV prophylaxis, length of ARV prophylaxis, birth weight, small for gestational age, and infant feeding choice were not significantly different between CMV-infected and -uninfected infants. Maternal CD4 count <200 cells/µL during pregnancy was independently associated with congenital CMV (adjusted odds ratio, 2.9; 95% CI, 1.2-7.3). A negative correlation between CMV load in saliva and maternal CD4 count was observed (r = -0.495, n = 22, P = .019). CONCLUSIONS: The birth prevalence of congenital CMV was high despite prenatal ARV prophylaxis, and was associated with advanced maternal immunosuppression.

Surgical manifestations of gastrointestinal cytomegalovirus infection in children: Clinical audit and literature review.

INTRODUCTION: Gastrointestinal sequelae of cytomegalovirus are rare, usually associated with significant immune compromise, and carry a high morbidity and mortality. Gastrointestinal disease frequently requires surgical intervention for diagnosis and management. AIM: The aim of the study is to evaluate the incidence, presentation and management of gastrointestinal cytomegalovirus disease in a pediatric population. METHOD: Between January 2003 and June 2011, a retrospective folder review was conducted of all symptomatic children with proven CMV disease, presenting to the surgical service. Eligible patients were identified using the surgical, histopathology and serology databases. RESULTS: Thirty-eight patients (1.8/1000 surgical admissions) were identified with a median presenting age of 5months (range 3days-12years). Esophagitis (n=18) and small bowel disease (n=16) predominated, but CMV was seen throughout the gastrointestinal tract. Risk factors included HIV infection (n=21, 55%) and recent gastrointestinal surgery or infection (n=10, 26%). Characteristic multiple jejunoileal perforations were seen in six patients. Compared to upper GIT disease, intestinal involvement was associated with younger age and doubled mortality. In HIV-infected children, median CD4 (%) was lower in intestinal compared to upper gastrointestinal disease. Morbidities included anastomotic breakdowns (5), anastomotic strictures (3), relook laparotomies (10), resistant esophageal strictures (5) and prolonged parenteral nutrition (5). Anti-CMV drugs were given in 63%. Overall mortality was 32% (12/38) and was associated with lower GIT disease. CONCLUSION: Invasive CMV gastrointestinal disease in our children was predominantly HIV-associated, or followed a major lower gastrointestinal inflammatory insult in infants younger than 6months. Successful therapy requires a high index of suspicion of active CMV disease to allow early implementation of CMV viral load control and aggressive treatment of the underlying immune impairment. Multiple surgical interventions are often required for both tissue diagnosis and management of acute and chronic complications. CMV-viral-load-tailored anti-CMV therapy is supported by recent literature.

Evolution of an adenovirus outbreak in a multidisciplinary children's hospital.

OBJECTIVE: To describe the course of an evolving adenovirus outbreak in a multidisciplinary children's hospital with a high-risk patient population. METHODS: Observational study in a 280-bed university hospital during June 2002. Active case finding identified children with adenovirus infection. Data are median (interquartile range) or n (%). Adenovirus infection was diagnosed in 49 children, median age 12 months (4-33). RESULTS: New cases were diagnosed over 26 days and peaked on day 17 (n = 15). Total infected inpatients peaked on days 17-21 (n = 36). Twenty-three infections (47%) were community-acquired and 26 (53%) hospital-acquired. Thirty-three children (67%) had a coexistent high-risk condition. Median hospital stay before and after diagnosis was 9 days (3-18) and 9 days (4-29), respectively. Twenty-two children (45%) were admitted to PICU. Overall hospital mortality was 22% (n = 11) and mortality attributed to adenoviral disease 12% (n = 6). Hospital mortality was similar between community- and hospital-acquired infections (22% compared to 23%) (P = 1.0). Twenty children (41%) received intravenous immunoglobulin (IVIG). Children treated with IVIG had a longer hospital stay (median 40 days vs 14 days) than those who did not receive IVIG (P = 0.01). Neither PICU mortality (29% vs 12%), nor hospital mortality (35% vs 14%), differed significantly between IVIG treated and untreated children (P = 0.76 and P = 0.16, respectively). CONCLUSION: The rapid spread of hospital-acquired adenovirus underlines the importance of effective infection control measures. Despite nosocomial infection amongst high-risk patients, mortality was similar to that of community-acquired infection. Administration of immunoglobulin was not associated with demonstrable benefit. A prospective randomized trial would be required to resolve this issue.