Msellati P

Postnatal transmission of human immunodeficiency virus type 1 from mother to infant -- a prospective cohort study in Kigali Rwanda.

Abstract Background. Although transmission of human immunodeficiency virus type 1 (HIV-1 ) from mother to infant has been well documented during pregnancy and delivery, little is known about the possible transmission of HIV-1 during the postnatal period. Methods. We conducted a prospective cohort study in Kigali, Rwanda, of 212 mother—infant pairs who were seronegative for HIV-1 at delivery. All the infants were breast-fed. The subjects were followed at three-month intervals, with Western blot assays for antibodies to HIV-1 and testing of mononuclear cells by a double polymerase chain reaction (PCR) using three sets of primers. To evaluate potential risk factors, each mother who seroconverted was matched with three seronegative control women. Results. After a mean follow-up of 16.6 months, 16 of the 212 mothers became seropositive for HIV-1. Of their 16 infants, 9 became seropositive. One infant was excluded from the analysis because of a positive test by PCR on the blood sample obtained at birth. Postnat...

18-month mortality and perinatal exposure to zidovudine in West Africa.

ObjectivesTo study mortality in African children born to HIV-1-infected mothers exposed peripartum to zidovudine. MethodsA randomized placebo-controlled trial in Abidjan and Bobo-Dioulasso. Pregnant women received either 300 mg zidovudine twice daily from 36–38 weeks’ gestation, 600 mg during labour, and 300 mg twice daily for 7 days post-partum or a matching placebo. Determinants of mortality were studied up to 18 months, overall and among the infected children: treatment, centre, timing of infection, mother and child HIV disease. ResultsThere were 75 infant deaths among 407 live births. The risk of death at 18 months was 176/1000 in the zidovudine arm and 221 for placebo. Relative hazard (RH, zidovudine versus placebo) was 0.47 [95% confidence interval (CI) 0.2–1.0] up to 230 days of life. Maternal CD4 lymphocyte count < 200/mm3 (RH 2.92; CI 1.4–6.1) and child HIV-1 infection (RH 12.6; CI 6.6–24.3) increased mortality of all children born to HIV-1-infected mothers. There were 101 children infected (40 in the zidovudine group), and 51 died. Their 18 month probability of death was 590/1000 in the zidovudine group and 510 in the placebo group. Among infected children, maternal zidovudine reduced the risk of death on or before day 230 (RH 0.18; CI 0.1–0.5). Maternal CD4 lymphocyte count < 200/mm3 (RH 3.25; CI 1.3–8.4), maternal death (RH 9.65; CI 1.7–56.0), diagnosis of paediatric infection on or before day 12 (RH 18.1; CI 4.8–69.0) and between days 13 and 45 (RH 7.63; CI 2.0–29.5), clinical paediatric AIDS (RH 5.37; CI 2.3–12.7) were risk factors for death in HIV-1-infected children. ConclusionMother-to-child transmission reduction by zidovudine is safe and beneficial to African children. The mortality of HIV-1-infected children is high. Peripartum maternal zidovudine exerts a protective effect for at least 8 months.

Perinatal transmission of HIV-1: lack of impact of maternal HIV infection on characteristics of livebirths and on neonatal mortality in Kigali, Rwanda.

We present the baseline results of a prospective cohort study on the perinatal transmission of HIV-1 in Kigali, Rwanda. HIV-1-antibody testing was offered to all women of urban origin delivering a live newborn at the maternity ward of the Centre Hospitalier de Kigali from November 1988 to June 1989; 218 newborns of 215 HIV-positive mothers were matched to 218 newborns of 216 HIV-negative mothers. The matching criteria were maternal age and parity. No differences in socioeconomic characteristics were observed between HIV-positive and HIV-negative women. HIV-positive mothers more frequently reported a history of at least one death of a previously born child (P less than 0.01) and a history of abortion (P less than 0.001). Most of the HIV-positive women were asymptomatic, but 72.4% of them had a CD4; CD8 ratio less than 1 versus 10.1% in the HIV-negative group (P less than 0.001). The frequency of signs and symptoms was not statistically different in the two groups, except for a history of herpes zoster or chronic cough, which was more frequent among HIV-positive women. The rates of prematurity, low birth weight, congenital malformations and neonatal mortality were comparable in the two groups. However, infants of HIV-positive mothers had a mean birth weight 130 g lower than the infants of HIV-negative mothers (P less than 0.01). The impact of maternal HIV-1 infection on the infant seems limited during the neonatal period.

Seroincidence of HIV-1 infection in african women of reproductive age: a prospective cohort study in Kigali, Rwanda, 1988-1992

Objective:To estimate the seroincidence of HIV-1 infection among women of reproductive age in Kigali, Rwanda.Design:Fixed prospective cohort followed for 36 months between November 1988 and June 1992, as part of an ongoing study of mother-to-child transmission of HIV-1.Setting:Centre Hospitalier, Kigali, Rwanda.Subjects:A total of 216 HIV-seronegative women were enrolled at delivery between November 1988 and June 1989.Methods:A blood sample was obtained at delivery to test for HIV antibodies (by enzyme-linked immunosorbent assay and Western blot). Serum was tested every 3 months during follow-up. Incidence density rates of HIV seroconversion were estimated.Results:The follow-up rate after 3 years was 89%, assessed by the maximum person-years method. The seroincidence density rate was 3.5 per 100 women-years (95% confidence interval, 1.9–5.0). It decreased linearly from 7.6 during the first 6-months postpartum to 2.5 per 100 women-years during the last 6 months of the third year of follow-up. Maternal age did not affect HIV incidence rates. We examined the role of the cohort, counselling, and the first 6-month postpartum effects on this estimate.Conclusion:This fixed cohort provided an overall estimation of the HIV infection incidence rate and its dynamics. These figures could be used for programming future HIV preventive vaccine efficacy trials in Rwanda.

A Cohort Study of Factors Associated With Failure to Return for HIV Post-Test Counselling in Pregnant Women: Kigali, Rwanda, 1992-1993

ObjectiveTo identify factors associated with failure to return for HIV post-test counselling in pregnant women in Kigali (Rwanda). Subjects and methodsIn the context of a study on the impact of HIV infection on pregnancy, HIV-1 -antibody testing was offered to all pregnant women attending the antenatal clinic of the Centre Hospitalier de Kigali from July 1992 to August 1993. Pre-test counselling was performed after verbal informed consent was obtained. Two weeks later, we formally enrolled all HIV-positive women and a corresponding number of HIV-negative women in a cohort. At this visit, post-test counselling was given to those wishing to be informed of their HIV serostatus. Level of knowledge about modes of HIV transmission and condom use were recorded. Four months after delivery, another interview was conducted to determine the proportion of women who used condoms regularly. ResultsA total of 1233 pregnant women were screened. The HIV seroprevalence was 34.4% [95% confidence interval (CD, 31.7–37.1]; 271 (63.9%) out of 424 HIV-positive and 577 (71.3%) out of 809 HIV-negative women asked for their HIV serostatus (P= 0.008). In multivariate analysis, the only variable significantly associated with failure to return for post-test counselling was a positive HIV test result (odds ratio, 0.7; 95% CI, 0.5–0.9; P= 0.009), independently of obstetrical history and socioeconomic characteristics. Among the 848 women who had post-test counselling, 50.9% of the HIV-positive women and 94.6% of the HIV-negative women stated that they planned to inform their partner of their serostatus (P= 0.0001). More than 95% of the women interviewed knew about sexual and parenteral transmission of HIV, but half were unaware of mother-to-child transmission. More than 80% of the women had seen a condom before, but 14% only had used it at least once. Among women who were sexually active 4 months after delivery, 8.8% of the HIV-positive and 3.9% of the HIV-negative women reported using a condom (P=0.04). ConclusionInnovative approaches for HIV testing and counselling programs are needed and the importance of psychosocial and cultural factors associated with HIV testing should be emphasized in African populations.

Estimating the incubation period of paediatric AIDS in Rwanda.

ObjectiveTo estimate the distribution of the incubation period of paediatric AIDS in Rwanda. DesignData were collected between February 1984 and December 1990 at the Centre Hospitalier de Kigali (CHK), the capital city of Rwanda, Central Africa. PatientsWe used a sample of 685 AIDS cases registered consecutively in the Department of Paediatrics of the CHK, in which the proportion of perinatally acquired HIV-1 infection was estimated to be 98.6%. MethodsWe performed both non-parametric and parametric analyses. The methods of estimation were adapted to truncated data, using essentially the same methods as Auger et al. in their analysis of data from the New York City and the New York State AIDS case registries in 1988. ResultsWe found that a double Weibull model fitted the data very well and that the risk of developing AIDS was high for subjects under 18 months of age, but lower for older subjects. ConclusionsOur results were qualitatively similar to those of Auger et al.. There were quantitative differences between the two studies, but it was not possible to compare median survival periods. Parameters such as median or mean survival times cannot be validly estimated using only data from registers because these data exclude infected subjects who have not yet developed AIDS.

A novel pharmacokinetic approach to predict virologic failure in HIV-1-infected paediatric patients.

Objective:The objective of this study was to develop in children an HIV dynamic model able to predict simultaneously the viral load and CD4+ lymphocyte evolutions, and to take into account, through a composite inhibition score, the relative contribution of each drug of the combination efavirenz–didanosine–lamivudine and use this score as a predictor of treatment failure in a multidrug therapy. Design:Open phase II trial (BURKINAME – ANRS 12103) registered in the ClinicalTrials.gov database (http://clinicaltrials.gov) with the no. NCT00122538. Methods:Forty-nine children aged from 2.5 to 15 years were administered once-daily dose of lamivudine, didanosine and efavirenz. The three drugs effect was then characterized by a composite inhibition score combining the effect of each drug, according to their site and mechanism of action and their relative contribution. Results:Efavirenz was the most potent antiretroviral and was responsible for 65% of the total effect, and then didanosine for 23% and lamivudine was the less potent with 12% of the total observed effect. An EC90 for efavirenz was determined (3.3 mg/l). AUC90 was estimated for lamivudine and didanosine: 8.4 and 1.5 mg h/l, respectively. The composite inhibition score was the best predictor of virologic failure compared with the concentrations of each drug taken independently [hazard ratio (HR) 0.6 per 10% increase, 95% confidence interval (CI) 0.41–0.88]. Conclusion:The relative contributions of three combined drugs were assessed on plasma viral load and CD4+ lymphocyte count kinetics in HIV-1-infected children. Pharmacokinetics targets have been suggested for lamivudine and didanosine. A composite inhibition score has been determined to be a high predictor of treatment failure in a multidrug therapy.

Short-term virological efficacy, immune reconstitution, tolerance, and adherence of once-daily dosing of Didanosine, Lamivudine, and Efavirenz in HIV-1-infected african children : ANRS 12103 Burkiname

Access to antiretroviral therapy (ART) and routine laboratory monitoring are limited for HIV-1-infected children from sub-Saharan Africa. This trial conducted in Bobo-Dioulasso, Burkina Faso, aimed to describe the biological efficacy, tolerance, and adherence of the combination of didanosine, lamivudine, efavirenz in once-daily administration among eligible HIV-1-infected children. From February 2006 to November 2007, 51 HIV-1-infected children aged from 30 months to 15 years and eligible for ART were enrolled in a phase II open clinical trial with follow-up visits every 3 months. HIV-1 genotype testing was performed in children with plasma viral load (PVL) >1000 copies per milliliter after ART initiation. Children were followed for a median of 13.4 months [interquartile range (IQR) 12.8-14.2]. At enrollment, median CD4 count was 8% (IQR = 4.5-12). PVL was 341,032 (IQR = 127,838-761,539) copies per milliliter. At 12 months, median CD4 increased significantly by +15% (P < 10-3), and median PVL decreases significantly by −290,500 copies per milliliter (P < 10-4). Hemoglobin and platelets counts increased significantly by +1.05 g/dL (P < 10-5) and 108,500 cells per milliliter (P < 10-3), respectively. Based on pill count, mean yearly adherence was 97.3%, and 48% of the children had an adherence rate ≥95% at the four quarterly visits. Adherence was better for girls than for boys independently of other sociodemographic variables or markers of HIV disease progression. Drug-resistant mutations were found in 11 children (21.6%). This once-daily drug combination is associated with excellent virological efficacy, immune reconstitution, and good adherence. However, the high prevalence of drug resistance mutations is a matter of concern.

BCG vaccination in children born to HIV-positive mothers.

Dr. Athale and colleagues from Lusaka (Aug 15 p434) have suggested that in countries of high HIV prevalence BCG (bacillus Calmette-Guerin) vaccination should be given only to children over 12 months of age because of the risk of disseminated BCG infection. By that age it should be clear which children are infected. In a prospective study in Zaire of children born to HIV positive and negative mothers (seroprevalence 3.8% vertical transmission rate 23%) all received BCG at birth. During follow-up of 2 years 9 of 21 HIV-infected children developed tuberculosis which was disseminated in only 1 and 7 had a family contact. None had BCG adenitis. All responded well to short- course chemotherapy (avoiding thiacetazone). In the 2 matched control groups uninfected by HIV 12 developed tuberculosis--4 born to 21 HIV- positive mothers and 8 born to 21 HIV-negative mothers. None of these had disseminated infection and 1 had BCG adenitis (mother seronegative). The HIV-infected and noninfected groups did not differ significantly. In the past 10 years we have had only 1 case of probable disseminated BCG infection in a child of 5 months. He was vaccinated at 3 months and developed suppurating axillary BCG adenitis. His weight curve was static and he had persistent fever. Radiography showed typical miliary lesions and he responded well to short-course therapy. His mother was seropositive for HIV and he had no family tuberculosis contacts. We agreed that many cases of tuberculosis in children infected with HIV simulate the adult form with cavitation and extensive pneumonias but only in children over 2 years old. We suggest that this finding is probably due to progression of the primary focus rather than reactivation or progression of BCG vaccination. Such children respond well to short-course therapy but tend to relapse and have persisting problems because of lung damage (bronchiectasis). HIV infection in infants has a bimodal presentation. The early presenters will have symptoms by 12 months but only a few late presenters will have them. We would not expect nursing staff at a busy clinic or vaccination center to have time to pick out these with mildly symptomatic HIV infection. Although there is some evidence that BCG at 3 months produces a larger induration more frequent scar formation and less lymphadenopathy than if it is given at birth we suggest that in African countries this is not the time to change the policy of giving BCG near birth. Attendance at vaccination clinics falls off strikingly after the measles vaccine at 9 months and therefore many healthy children would not receive BCG. However a good case could be made for chemoprophylaxis for children for HIV-positive mothers who have had active tuberculosis in the previous 2 years. (full text)

24-Month adherence, tolerance and efficacy of once-a-day antiretroviral therapy with didanosine, lamivudine, and efavirenz in African HIV-1 infected children: ANRS 12103/12167.

BACKGROUND There is no data on long-term benefit of once-a-day antiretroviral therapy (ART) with combination of DDI, 3TC and EFV to allow its use in future therapeutic strategies. OBJECTIVES To assess 24-month immuno-virological, adherence, tolerance, and effectiveness of a once-a-day ART with DDI, 3TC and EFV. METHODS A phase 2 open trial including 51 children aged from 30 months to 15 years, monitored a once-a-day regimen for 24 months from 2006 to 2008 in the Departement de Pediatrie du CHUSS, at Bobo-Dioulasso in Burkina Faso. We tested immunological and virological response, adherence, tolerance and resistance of the treatment. RESULTS Children with CD4 >25% at 24 months were 67.4% (33/49) CI 95% [54%, 80%]. The proportion of children with viral plasma RNA <300 cp / ml at 24 months of treatment was 81.6 % (40/49) CI [68.0% 91.2%]. Good adherence was obtained with more than 88% adherence > 95% over the 24 months. Drugs were well tolerated. CONCLUSIONS Given the limited number of antiretroviral drugs available in Africa and the inadequacy of laboratory monitoring in support program, once-a-day treatment and especially the DDI-based combination strategies could be an attractive operational option.