BackgroundHighly active antiretroviral treatment (HAART) has only been recently recommended for HIV-infected pregnant women requiring treatment for their own health in resource-limited settings. However, there are few documented experiences from African countries. We evaluated the short-term (4 wk) and long-term (12 mo) effectiveness of a two-tiered strategy of prevention of mother-to-child transmission of HIV (PMTCT) in Africa: women meeting the eligibility criteria of the World Health Organization (WHO) received HAART, and women with less advanced HIV disease received short-course antiretroviral (scARV) PMTCT regimens.Methods and FindingsThe MTCT-Plus Initiative is a multi-country, family-centred HIV care and treatment program for pregnant and postpartum women and their families. Pregnant women enrolled in Abidjan, Côte d'Ivoire received either HAART for their own health or short-course antiretroviral (scARV) PMTCT regimens according to their clinical and immunological status. Plasma HIV-RNA viral load (VL) was measured to diagnose peripartum infection when infants were 4 wk of age, and HIV final status was documented either by rapid antibody testing when infants were aged ≥ 12 mo or by plasma VL earlier. The Kaplan-Meier method was used to estimate the rate of HIV transmission and HIV-free survival. Between August 2003 and June 2005, 107 women began HAART at a median of 30 wk of gestation, 102 of them with zidovudine (ZDV), lamivudine (3TC), and nevirapine (NVP) and they continued treatment postpartum; 143 other women received scARV for PMTCT, 103 of them with sc(ZDV+3TC) with single-dose NVP during labour. Most (75%) of the infants were breast-fed for a median of 5 mo. Overall, the rate of peripartum HIV transmission was 2.2% (95% confidence interval [CI] 0.3%–4.2%) and the cumulative rate at 12 mo was 5.7% (95% CI 2.5%–9.0%). The overall probability of infant death or infection with HIV was 4.3% (95% CI 1.7%–7.0%) at age week 4 wk and 11.7% (95% CI 7.5%–15.9%) at 12 mo.ConclusionsThis two-tiered strategy appears to be safe and highly effective for short- and long-term PMTCT in resource-constrained settings. These results indicate a further benefit of access to HAART for pregnant women who need treatment for their own health.

HAART in pregnant African women with advanced HIV disease substantially reduced mother-to-child transmission, but was associated with LBW.

The aim was to evaluate emtricitabine (FTC) and tenofovir (TFV) neonatal ingestion through breast milk. Median TFV and FTC breast milk doses represented 0.03% and 2%, respectively, of the proposed oral infant doses. Neonatal simulated plasma concentrations were extremely low for TFV but between the half-maximal inhibitory concentration and the adult minimal expected concentration for FTC. The rare children who will acquire HIV despite TDF-FTC therapy will need to be monitored for viral resistance acquisition.For prevention of mother-to-child transmission (PMTCT) of HIV in resource-limited settings, single-dose nevirapine (sd-NVP) has been commonly administered at the start of labor up to now according to previous World Health Organization (WHO) guidelines. However, the use of sdNVP results in resistance mutations in 15 to 70% of women, at 4 to 6 weeks postpartum, compromising the success of subsequent treatments with NVP in mothers and children (1, 7). Adding a single dose of tenofovir disoproxil fumarate (TDF)-emtricitabine (FTC) reduced these resistance mutations by half (2, 10). TDF and FTC placental transfer has already been studied (4, 5), but no data were reported so far on the transfer of these drugs after birth through breast-feeding. Breast-feeding cessation or replacement feeding introduced under routine circumstances is no longer recommended by WHO, as these interventions are often associated with increased mortality and morbidity (13). Thus, it is important to assess to what extent maternal TDF and FTC are transmitted through breast milk to infants. Furthermore, TDF-FTC-based fully suppressive antiretroviral regimens represent now a recommended approach for PMTCT in pregnant, delivering, and breast-feeding women (14).Five Ivorian mothers included in the ANRS 12109 TEmAA (Tenofovir/Emtricitabine in Africa and Asia) study and who chose to exclusively breast-feed their infant were administered one tablet of NVP (200 mg) plus two tablets of TDF (300 mg)-FTC (200 mg) at the start of labor and one TDF-FTC daily tablet for 7 days postpartum. The protocol was approved by the Ethics Committee of the country (Cote d'Ivoire). The women and the children's fathers were asked to sign an informed consent form. Maternal blood and milk samples were collected concomitantly after drug administration on days 1, 2, 3, and 7 after delivery. A liquid-liquid extraction procedure was performed using 300 l of methanol-dichloromethane (10/16, vol/vol) containing 0.1% hydrochloric acid added to 100 l of milk samples. After vortexing and centrifugation at 20,000 ϫ g at ϩ4°C for 20 min, the upper phase was withdrawn and evaporated under nitrogen to dryness. The sample was then reconstituted with 100 l of mobile phase, and 40 l of the extract was injected in the analytical system. TFV and FTC concentrations were measured using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method previously described (9) and adapted for FTC. Limits of quantitation were 4.9 and 9.5 ng/ml for TFV and FTC, respectively. Maximal and minim...

BackgroundCervical cancer screening is not yet standard of care of women attending HIV care clinics in Africa and presents operational challenges that need to be addressed.MethodsA cervical cancer screening program based on visual inspection methods was conducted in clinics providing antiretroviral treatment (ART) in Abidjan, Côte d'Ivoire. An itinerant team of midwives was in charge of proposing cervical cancer screening to all HIV-positive women enrolled in ART clinics as well as to HIV-negative women who were attending the Abidjan national blood donor clinic. Positively screened women were systematically referred to a colposcopic examination. A phone-based tracking procedure was implemented to reach positively screened women who did not attend the medical consultation. The association between HIV status and cervical cancer screening outcomes was estimated using a multivariate logistic model.ResultsThe frequency of positive visual inspection was 9.0% (95% CI 8.0-10.0) in the 2,998 HIV-positive women and 3.9% (95% CI 2.7-5.1) in the 1,047 HIV-negative ones (p < 10-4). In multivariate analysis, HIV infection was associated with a higher risk of positive visual inspection [OR = 2.28 (95% CI 1.61-3.23)] as well as more extensive lesions involving the endocervical canal [OR = 2.42 (95% CI 1.15-5.08)]. The use of a phone-based tracking procedure enabled a significant reduction of women not attending medical consultation after initial positive screening from 36.5% to 19.8% (p < 10-4).ConclusionThe higher frequency of positive visual inspection among HIV-positive women supports the need to extend cervical cancer screening program to all HIV clinics in West Africa. Women loss to follow-up after being positively screened is a major concern in cervical screening programs but yet, partly amenable to a phone tracking procedure.

SUMMARY BackgroundSignificance of steatosis in HIV-HCV coinfection remains controversial.

The objectives of this study were to evaluate emtricitabine (FTC) pharmacokinetics in pregnant women and their neonates and to determine the optimal prophylactic dose for neonates after birth to prevent mother-tochild transmission of human immunodeficiency virus (HIV). A total of 38 HIV-infected pregnant women were administered tenofovir disoproxyl fumarate (300 mg)-FTC (200 mg) tablets-two tablets at the initiation of labor and one daily for 7 days postpartum. By pair, 11 maternal, one cord blood, and two neonatal FTC concentrations were measured using a high-performance liquid chromatography-tandem mass spectrometry validated method and analyzed by a population approach. Model and mean estimates (interpatient variability) were a two-compartment model for mothers, with an absorption rate constant of 0.54 h ؊1 (61%), apparent elimination and intercompartmental clearances of 23.2 (17%) and 6.04 liters ⅐ h ؊1 , and apparent central and peripheral volumes of 127 and 237 liters, respectively; an effect compartment linked to maternal circulation for cord blood and a neonatal compartment disconnected, after delivery, with a 10.6-h half-life (30%). After the 400-mg FTC administration, the median population area under the concentration-time curve and the minimal and maximal plasma FTC concentrations in pregnant women were 14.3 mg ⅐ liter ؊1 ⅐ h and 1.68 and 0.076 mg/liter, respectively. At delivery, median (range) predicted maternal and cord blood FTC concentrations were, respectively, 1.16 (0.14 to 1.99) and 0.72 (0.05 to 1.19) mg ⅐ liter ؊1 . We concluded that the 400-mg FTC administration in pregnant women produces higher exposition than does the 200-mg administration in other adults, at steady state. FTC was shown to have good placental transfer (80%). Administering 1 mg FTC/kg as soon as possible after birth or 2 mg/kg 12 h after birth should produce neonatal concentrations comparable to the concentrations observed in adults.To prevent mother-to-child transmission of human immunodeficiency virus (HIV) during delivery, a single-dose administration of nevirapine (NVP) administered at the start of labor is the most common antiretroviral regimen used in resourcelimited settings, as recommended by the World Health Organization in the Antiretroviral Drugs for Treating Pregnant Women and Preventing HIV Infection in Infants report (http: //www.who.int/hiv/pub/guidelines/pmtctguidelines3.pdf). However, the use of the single-dose administration of NVP results in resistance mutations in 15 to 70% of women, at 4 to 6 weeks postpartum, compromising the success of subsequent treatments with NVP in mother and child (7,9). A recent clinical study suggests that adding a single dose of tenofovir disoproxyl fumarate (TDF) and emtricitabine (FTC) at delivery may reduce those resistances by half (6).FTC is a potent, once-daily-administered nucleoside reverse transcriptase inhibitor approved for the treatment of HIV in adults and children older than 3 months in combination with other antiretroviral agents. The physiological changes asso...

Background We described malnutrition and the effect of age at antiretroviral therapy (ART) initiation on catch-up growth over 24 months among HIV-infected children enrolled in the IeDEA West African paediatric cohort (pWADA). Methods Malnutrition was defined at ART initiation (baseline) by a Z-score <-2 SD, according to three anthropometric indicators: Weight-for-age (WAZ) for underweight, Height-for-age (HAZ) for stunting, and Weight-for-Height/BMI-for-age (WHZ/BAZ) for wasting. Kaplan-Meier estimates for catch-up growth (Z-score ≥-2 SD) on ART, adjusted for gender, immunodeficiency and malnutrition at ART initiation, ART regimen, time period and country, were compared by age at ART initiation. Cox proportional hazards regression models determined predictors of catch-up growth on ART over 24 months. Results Between 2001 and 2012, 2004 HIV-infected children < 10 years of age were included. At ART initiation, 51% were underweight, 48% were stunted and 33% were wasted. The 24-month adjusted estimates for catch-up growth were 69% (95% confidence interval [CI]: 57;80), 61% (95%CI: 47;70), and 90% (95%CI: 76;95) for WAZ, HAZ, and WHZ/BAZ, respectively. Adjusted catch-up growth was more likely for children <5 years of age at ART initiation compared to children ≥5 years for WAZ, HAZ (P<0.001), and for WHZ/BAZ (P = 0.026). Conclusions Malnutrition among these children is an additional burden that has to be urgently managed. Despite a significant growth improvement after 24 months on ART, especially in children <5 years, a substantial proportion of children still never achieved catch-up growth. Nutritional care should be part of the global healthcare of HIV-infected children in sub-Saharan Africa.

BackgroundClinical evolution of HIV-infected children who have not yet initiated antiretroviral treatment (ART) is poorly understood in Africa. We describe severe morbidity and mortality of untreated HIV-infected children.MethodsAll HIV-infected children enrolled from 2004-2009 in a prospective HIV programme in two health facilities in Abidjan, Côte d'Ivoire, were eligible from their time of inclusion. Risks of severe morbidity (the first clinical event leading to death or hospitalisation) and mortality were documented retrospectively and estimated using cumulative incidence functions. Associations with baseline characteristics were assessed by competing risk regression models between outcomes and antiretroviral initiation.Results405 children were included at a median age of 4.5 years; at baseline, 66.9% were receiving cotrimoxazole prophylaxis, and 27.7% met the 2006 WHO criteria for immunodeficiency by age. The risk of developing a severe morbid event was 14% (95%CI: 10.7 - 17.8) at 18 months; this risk was lower in children previously exposed to any prevention of mother-to-child-transmission (PMTCT) intervention (adjusted subdistribution hazard ratio [sHR]: 0.16, 95% CI: 0.04 - 0.71) versus those without known exposure. Cumulative mortality reached 5.5% (95%CI: 3.5 - 8.1) at 18 months. Mortality was associated with immunodeficiency (sHR: 6.02, 95% CI: 1.28-28.42).ConclusionsHaving benefited from early access to care minimizes the severe morbidity risk for children who acquire HIV. Despite the receipt of cotrimoxazole prophylaxis, the risk of severe morbidity and mortality remains high in untreated HIV-infected children. Such evidence adds arguments to promote earlier access to ART in HIV-infected children in Africa and improve care interventions in a context where treatment is still not available to all.