Optimizing infant HIV diagnosis with additional screening at immunization clinics in three sub-Saharan African settings : a cost-effectiveness analysis

INTRODUCTION: Uptake of early infant HIV diagnosis (EID) varies widely across sub-Saharan African settings. We evaluated the potential clinical impact and cost-effectiveness of universal maternal HIV screening at infant immunization visits, with referral to EID and maternal antiretroviral therapy (ART) initiation. METHODS: Using the CEPAC-Pediatric model, we compared two strategies for infants born in 2017 in Côte d'Ivoire (CI), South Africa (SA), and Zimbabwe: (1) existing EID programmes offering six-week nucleic acid testing (NAT) for infants with known HIV exposure (EID), and (2) EID plus universal maternal HIV screening at six-week infant immunization visits, leading to referral for infant NAT and maternal ART initiation (screen-and-test). Model inputs included published Ivoirian/South African/Zimbabwean data: maternal HIV prevalence (4.8/30.8/16.1%), current uptake of EID (40/95/65%) and six-week immunization attendance (99/74/94%). Referral rates for infant NAT and maternal ART initiation after screen-and-test were 80%. Costs included NAT ($24/infant), maternal screening ($10/mother-infant pair), ART ($5 to 31/month) and HIV care ($15 to 190/month). Model outcomes included mother-to-child transmission of HIV (MTCT) among HIV-exposed infants, and life expectancy (LE) and mean lifetime per-person costs for children with HIV (CWH) and all children born in 2017. We calculated incremental cost-effectiveness ratios (ICERs) using discounted (3%/year) lifetime costs and LE for all children. We considered two cost-effectiveness thresholds in each country: (1) the per-capita GDP ($1720/6380/2150) per year-of-life saved (YLS), and (2) the CEPAC-generated ICER of offering 2 versus 1 lifetime ART regimens (e.g. offering second-line ART;$520/500/580/YLS). RESULTS: With EID, projected six-week MTCT was 9.3% (CI), 4.2% (SA) and 5.2% (Zimbabwe). Screen-and-test decreased total MTCT by 0.2% to 0.5%, improved LE by 2.0 to 3.5 years for CWH and 0.03 to 0.07 years for all children, and increased discounted costs by $17 to 22/child (all children). The ICER of screen-and-test compared to EID was$1340/YLS (CI), $650/YLS (SA) and$670/YLS (Zimbabwe), below the per-capita GDP but above the ICER of 2 versus 1 lifetime ART regimens in all countries. CONCLUSIONS: Universal maternal HIV screening at immunization visits with referral to EID and maternal ART initiation may reduce MTCT, improve paediatric LE, and be of comparable value to current HIV-related interventions in high maternal HIV prevalence settings like SA and Zimbabwe

18-month occurrence of severe events among early diagnosed HIV-infected children before antiretroviral therapy in Abidjan, Côte d'Ivoire: A cohort study

<p>Abstract</p> <p>Objective</p> <p>To assess the 18-month field effectiveness on severe events of a pediatric package combining early HIV-diagnosis and targeted cotrimoxazole prophylaxis in HIV-infected children from age six-week before the antiretroviral era, in Abidjan, Côte d'Ivoire.</p> <p>Methods</p> <p>Data from two consecutive prevention of HIV mother-to-child transmission programs were compared: the ANRS 1201/1202 Ditrame-Plus cohort (2001–2005) and the pooled data of the ANRS 049a Ditrame randomized trial and its following open-labeled cohort (1995–2000), used as a reference group. HIV-infected pregnant women ≥ 32–36 weeks of gestation were offered a short-course peri-partum antiretroviral prophylaxis (ZDV in Ditrame, and ZDV ± 3TC+single-dose (sd) NVP in Ditrame-Plus). Neonatal prophylaxis was provided in Ditrame-Plus only: 7-day ZDV and sdNVP 48–72 h after birth. A 6-week pediatric HIV-RNA diagnosis was provided on-line in the Ditrame-Plus while it was only oriented on clinical symptoms in Ditrame. Six-week HIV-infected children received a daily cotrimoxazole prophylaxis in Ditrame-Plus while no prophylaxis was provided in Ditrame. The determinants of severe events (death or hospitalization > 1 day) were assessed in a Cox regression model.</p> <p>Results</p> <p>Between 1995 and 2003, 98 out of the 1121 live-births were diagnosed as HIV-infected in peri-partum: 45 from Ditrame-Plus and 53 from Ditrame. The 18-month Kaplan-Meier cumulative probability of presenting a severe event was 66% in Ditrame-Plus (95% confidence interval [95%CI]: 50%–81%) and 77% in Ditrame (95%CI: 65%–89%), Log Rank test: p = 0.47. After adjustment on maternal WHO clinical stage, maternal death, 6-week pediatric viral load, birth-weight, and breastfeeding exposure, the 18-month risk of severe event was lower in Ditrame-Plus than in Ditrame (adjusted Hazard Ratio (aHR): 0.55, 95%CI: 0.3–1.1), although the difference was not statistically significant; p = 0.07). Maternal death was the only variable determinant of the occurrence of severe events in children (aHR: 3.73; CI: 2.2–11.2; p = 0.01).</p> <p>Conclusion</p> <p>Early cotrimoxazole from 6 weeks of age in HIV-infected infants seemed to reduce probability of severe events but the study lacked statistical power to prove this. Even with systematic cotrimoxazole prophylaxis, infant morbidity and mortality remained high pointing towards a need for early pediatric HIV-diagnosis and antiretroviral treatment in Africa.</p

Complementary feeding adequacy in relation to nutritional status among early weaned breastfed children who are born to HIV-infected mothers: ANRS 1201/1202 Ditrame Plus, Abidjan, Cote d'Ivoire.: HIV, early weaning and complementary feeding adequacy

Composition of the ANRS 1201/1202 Ditrame Plus Study Group Principal Investigators: François Dabis, Valériane Leroy, Marguerite Timite-Konan, Christiane Welffens-Ekra. Coordination in Abidjan: Laurence Bequet, Didier K. Ekouevi, Besigin Tonwe-Gold, Ida Viho. Methodology, biostatistics and data management: Gérard Allou, Renaud Becquet, Katia Castetbon, Laurence Dequae-Merchadou, Charlotte Sakarovitch, Dominique Touchard. Clinical team: Clarisse Amani-Bosse, Ignace Ayekoe, Gédéon Bédikou, Nacoumba Coulibaly, Christine Danel, Patricia Fassinou, Apollinaire Horo, Ruffin Likikouët, Hassan Toure. Laboratory team: André Inwoley, François Rouet, Ramata Touré. Psycho-social team: Héléne Agbo, Hortense Aka-Dago, Hermann Brou, Annabel Desgrées-du-Loû, Alphonse Sihé, Annick Tijou-Traoré, Benjamin Zanou. Scientific Committee: Stéphane Blanche, Jean-François Delfraissy, Philippe Lepage, Laurent Mandelbrot, Christine Rouzioux, Roger SalamonInternational audienceOBJECTIVE: In high HIV prevalence resource-constrained settings, exclusive breastfeeding with early cessation is one of the conceivable interventions aimed at the prevention of HIV through breast milk. Nevertheless, this intervention has potential adverse effects, such as the inappropriateness of complementary feeding to take over breast milk. The purpose of our study first was to describe the nature and the ages of introduction of complementary feeding among early weaned breastfed infants up to their first birthday and second was to assess the nutritional adequacy of these complementary foods by creating a child feeding index and to investigate its association with child nutritional status. METHODS: A prospective cohort study in Abidjan, C?d'Ivoire, was conducted in HIV-infected pregnant women who were willing to breastfeed and had received a perinatal antiretroviral prophylaxis. They were requested to practice exclusive breastfeeding and initiate early cessation of breastfeeding from the fourth month to reduce breast milk HIV transmission. Nature and ages of introductory complementary feeding were described in infants up to their first birthday by longitudinal compilation of 24-hour and 7-day recall histories. These recalls were done weekly until 6 weeks of age, monthly until 9 months of age, and then quarterly. We created an index to synthesize the nutritional adequacy of infant feeding practices (in terms of quality of the source of milk, dietary diversity, food, and meal frequencies) ranging from 0 to 12. The association of this feeding index with growth outcomes in children was investigated. RESULTS: Among the 262 breastfed children included, complete cessation of breastfeeding occurred in 77% by their first birthday, with a median duration of 4 months. Most of the complementary foods were introduced within the seventh month of life, except for infant food and infant formula that were introduced at age 4 months. The feeding index was relatively low (5 of 12) at age 6 months, mainly as a result of insufficient dietary diversity, but was improved in the next 6 months (8.5 of 12 at 12 months of age). Inadequate complementary feeding at age 6 months was associated with impaired growth during the next 12 months, with a 37% increased probability of stunting. CONCLUSION: Adequate feeding practices around the weaning period are crucial to achieving optimal child growth. HIV-infected women should turn to early cessation of breastfeeding only when they are counseled properly to provide adequate complementary feeding to take over breast milk. Our child feeding index could contribute to the assessment of the nutritional adequacy of complementary feeding around the weaning period and therefore help to detect children who are at risk for malnutrition

Two-year morbidity-mortality and alternatives to prolonged breast-feeding among children born to HIV-infected mothers in Côte d'Ivoire.

International audienceBACKGROUND: Little is known about the long-term safety of infant feeding interventions aimed at reducing breast milk HIV transmission in Africa. METHODS AND FINDINGS: In 2001-2005, HIV-infected pregnant women having received in Abidjan, C?d'Ivoire, a peripartum antiretroviral prophylaxis were presented antenatally with infant feeding interventions: either artificial feeding, or exclusive breast-feeding and then early cessation from 4 mo of age. Nutritional counseling and clinical management were provided for 2 y. Breast-milk substitutes were provided for free. The primary outcome was the occurrence of adverse health outcomes in children, defined as validated morbid events (diarrhea, acute respiratory infections, or malnutrition) or severe events (hospitalization or death). Hazards ratios to compare formula-fed versus short-term breast-fed (reference) children were adjusted for confounders (baseline covariates and pediatric HIV status as a time-dependant covariate). The 18-mo mortality rates were also compared to those observed in the Ditrame historical trial, which was conducted at the same sites in 1995-1998, and in which long-term breast-feeding was practiced in the absence of any specific infant feeding intervention. Of the 557 live-born children, 262 (47%) were breast-fed for a median of 4 mo, whereas 295 were formula-fed. Over the 2-y follow-up period, 37% of the formula-fed and 34% of the short-term breast-fed children remained free from any adverse health outcome (adjusted hazard ratio [HR]: 1.10; 95% confidence interval [CI], 0.87-1.38; p = 0.43). The 2-y probability of presenting with a severe event was the same among formula-fed (14%) and short-term breast-fed children (15%) (adjusted HR, 1.19; 95% CI, 0.75-1.91; p = 0.44). An overall 18-mo probability of survival of 96% was observed among both HIV-uninfected short-term and formula-fed children, which was similar to the 95% probability observed in the long-term breast-fed ones of the Ditrame trial. CONCLUSIONS: The 2-y rates of adverse health outcomes were similar among short-term breast-fed and formula-fed children. Mortality rates did not differ significantly between these two groups and, after adjustment for pediatric HIV status, were similar to those observed among long-term breast-fed children. Given appropriate nutritional counseling and care, access to clean water, and a supply of breast-milk substitutes, these alternatives to prolonged breast-feeding can be safe interventions to prevent mother-to-child transmission of HIV in urban African settings

Field efficacy of zidovudine, lamivudine and single-dose nevirapine to prevent peripartum HIV transmission.

International audienceOBJECTIVES: In Africa, single-dose nevirapine (NVPsd), short regimens of zidovudine (ZDV) or ZDV + lamivudine (3TC) are recommended to prevent peripartum mother-to-child HIV transmission (PMTCT). We evaluated the 6-week field efficacy of two more PMTCT drug combinations. DESIGN: An open-label intervention cohort in Abidjan. METHODS: In 2001-2002, consenting women started oral ZDV 300 mg twice daily (bid) at > or =36 weeks of gestation, with 600 mg of ZDV + 200 mg NVPsd orally at beginning of labour. In 2002-2003, the antepartum regimen at > or =32 weeks comprised ZDV as previously + 3TC 150 mg bid; the labour dose comprised ZDV + NVPsd as previously + 300 mg 3TC orally. Neonates received ZDV syrup (2 mg/kg per 6 h) for 7 days + NVPsd syrup (2 mg/kg) on day 2 in both periods. Each woman was assisted to either use breast milk substitutes or breastfeed exclusively. Paediatric HIV infection was diagnosed by plasma HIV RNA viral load at 4 weeks, confirmed at 6 weeks. The reference group was a cohort receiving a short regimen of ZDV > or = 36-38 weeks in 1995-2000 in the same population. RESULTS: A total of 1144 HIV-infected pregnant women were included: 351 with ZDV, 420 with ZDV + NVPsd and 373 with ZDV + 3TC + NVPsd; 1010 livebirths were eligible for analysis; 79 children were HIV-infected peripartum. Six-week transmission probability was 6.5% [95% confidence interval (CI), 3.9-9.1%) with ZDV + NVPsd, a 72% reduction compared with ZDV alone (95% CI, 52-88%; P = 0.0002 adjusted on maternal CD4, clinical stage and breastfeeding). It was 4.7% (95% CI, 2.4-7.0%) with ZDV + 3TC + NVPsd (P = 0.34 compared with ZDV + NVPsd). CONCLUSIONS: A short-course of ZDV + NVPsd prevents most peripartum HIV transmission in Africa. This regimen could be added to international guidelines

Serum lactate levels in infants exposed peripartum to antiretroviral agents to prevent mother-to-child transmission of HIV: Agence Nationale de Recherches Sur le SIDA et les Hépatites Virales 1209 study, Abidjan, Ivory Coast.

International audienceBACKGROUND: Mitochondrial toxicity was described in infants exposed to long-term antiretroviral regimens containing nucleoside analogues for the prevention of mother-to-child transmission of HIV. We measured the serum lactate levels in children born to HIV-1 infected African women receiving short-term antiretroviral prevention of mother-to-child transmission of HIV regimens. METHODS: A prospective study was conducted in women-child pairs from the third trimester of pregnancy to 3 months of life. The exposed group was formed by children exposed in utero to nucleoside analog antiretroviral regimens, zidovudine or zidovudine + lamivudine from 32 to 36 weeks of amenorrhea until delivery. All of these women received nevirapine single dose at the beginning of labor. The children received zidovudine during the first 7 days of life and a nevirapine single dose at day 3. The control group was formed by infants born to HIV-1-infected women who had received nevirapine single dose only and who were not exposed to nucleoside analog antiretroviral regimens. Serum lactate levels were measured at 4, 6, and 12 weeks of life by Cobas Integra 400. RESULTS: A total of 836 blood samples from 338 infants was collected (262 exposed and 76 controls). Median lactacidemia was 1.8 mmol/L (interquartile range: 1.2-2.7 mmol/L). Overall serum lactate levels > or = 2.5 mmol/L, defining hyperlactatemia, were observed in 39 of the 292 infants who had > or = 2 serum lactate measurements. The 3-month period prevalence of hyperlactatemia did not differ between the exposed group and the control group. All of the serum lactate levels returned to normal values in all of the subsequent samples. No case of symptomatic hyperlactatemia was detected during the study period. CONCLUSIONS: Increased lactate levels were identified equally in infants whose mother received short-term nucleoside analogs or nevirapine single dose for prevention of mother-to-child transmission of HIV. Although not rare, hyperlactatemia was not related to short-term exposure to nucleoside analog antiretroviral regimens

Two-Year Probability of Remaining Free from Severe Events (Hospitalization or Death) According to the Feeding Group and Pediatric HIV Status

<p>ANRS 1201/1202 Ditrame Plus study, Abidjan, Côte d'Ivoire, 2001–2005 (<i>n</i> = 557).</p

Two-Year Probability of Remaining Free from Adverse Health Outcome (Hospitalization or Death or Validated Morbidity) According to the Feeding Group and Pediatric HIV Status

<p>ANRS 1201/1202 Ditrame Plus study, Abidjan, Côte d'Ivoire, 2001–2005 (<i>n</i> = 557).</p

Two-Year Probability of Remaining Free from Validated Morbidity (Diarrhea, Acute Respiratory Infection, or Malnutrition) According to the Feeding Group and Pediatric HIV Status

<p>ANRS 1201/1202 Ditrame Plus Study, Abidjan, Côte d'Ivoire, 2001–2005 (<i>n</i> = 557).</p