Exceptional genetic variability of hepatitis B virus indicates that Rwanda is east of an emerging African genotype E/A1 divide.

In Western Africa, hepatitis B virus (HBV) genotype E predominates throughout a vast crescent spanning from Senegal to Namibia and at least to the Central African Republic to the East. Although from most of the eastern parts of sub-Saharan Africa only limited sets of strains have been characterized, these belong predominantly to genotype A. To study how far the genotype E crescent extends to the East, a larger number of HBV strains from Rwanda were analyzed. Phylogenetic analysis of 45 S fragment sequences revealed strains of genotypes A (n = 30), D (n = 10), C (n = 4), and B (n = 1). Twelve genotype A sequences formed a new cluster clearly separated from the reference strains of the known sub-genotypes. Thus, with four genotypes and at least six sub-genotypes and a new cluster of genotype A strains, HBV shows an exceptional genetic variability in this small country, unprecedented in sub-Saharan Africa. Despite this exceptional genetic variability, not a single genotype E virus was found indicating that this country does not belong to the genotype E crescent, but is east of an emerging African genotype E/A1 divide.

Improved access increases postpartum uptake of contraceptive implants among HIV-positive women in Rwanda.

BACKGROUND: Long-acting reversible contraceptives (LARCs) and sterilisation are the most cost-effective methods of contraception but are rarely used in sub-Saharan Africa partly due to limited access. STUDY DESIGN: HIV-positive pregnant women attending two urban clinics in Rwanda were followed prospectively in a perinatal HIV transmission cohort study. Women attending one clinic were referred to public family planning (FP) services for all contraceptive methods (Site A) and women attending the other clinic (Site B) were offered implants and intrauterine devices (IUDs) on-site. RESULTS: Fifty three percent of the pregnant women reported an intention to use a LARC or to be sterilised after delivery. The uptake of implants was significantly higher at Site B (38%) than at Site A (6%). The IUD uptake was extremely low at both sites (2%). Twenty-eight of the 39 women at Site B who had intended to start using a LARC actually did so as compared to only one of 23 at Site A. CONCLUSION: When access to LARC was provided, a substantial number of HIV-positive women started using hormonal implants, but not IUDs, in the postpartum period. HIV and FP services should consider improving access to implants to reduce the number of unintended pregnancies.

Age-related immune reconstitution during highly active antiretroviral therapy in human immunodeficiency virus type 1-infected children.

OBJECTIVES: To evaluate the immune reconstitution in HIV-1-infected children in whom highly active antiretroviral therapy (HAART) controlled viral replication and to assess the existence of a relation between the magnitude of this restoration and age. METHODS: All HIV-1-infected children in whom a new HAART decreased plasma viral load below 400 copies/ml after 3 months of therapy were prospectively enrolled in a study of their immune reconstitution. Viral load, lymphocyte phenotyping, determination of CD4+ and CD8+ T cell receptor repertoires and proliferative responses to mitogens and recall antigens were assessed every 3 months during 1 year. RESULTS: Nineteen children were evaluated. Naive and memory CD4+ percentages were already significantly increased after 3 months of HAART. In contrast to memory CD4+ percentages, naive CD4+ percentages continued to rise until 12 months. Age at baseline was inversely correlated with the magnitude of the rise in naive CD4+ cells after 3, 6 and 9 months of therapy but not after 12 months. Although memory and activated CD8+ cells were already decreasing after 3 months, abnormalities of the CD8 T cell receptor repertoire and activation of CD8+ cells persisted at 1 year. HAART increased the response to mitogens as early as 3 months after starting therapy. CONCLUSIONS: In children the recovery of naive CD4+ cells occurs more rapidly if treatment is started at a younger age, but after 1 year of viral replication control, patients of all ages have achieved the same level of restoration. Markers of chronic activation in CD8+ cells persist after 1 year of HAART.

Breastfeeding with maternal antiretroviral therapy or formula feeding to prevent HIV postnatal mother-to-child transmission in Rwanda.

OBJECTIVE: To assess the 9-month HIV-free survival of children with two strategies to prevent HIV mother-to-child transmission. DESIGN: Nonrandomized interventional cohort study. SETTING: Four public health centres in Rwanda. PARTICIPANTS: Between May 2005 and January 2007, all consenting HIV-infected pregnant women were included. INTERVENTION: Women could choose the mode of feeding for their infant: breastfeeding with maternal HAART for 6 months or formula feeding. All received HAART from 28 weeks of gestation. Nine-month cumulative probabilities of HIV transmission and HIV-free survival were determined using the Kaplan-Meier method and compared using the log-rank test. Determinants were analysed using a Cox model analysis. RESULTS: Of the 532 first-liveborn infants, 227 (43%) were breastfeeding and 305 (57%) were formula feeding. Overall, seven (1.3%) children were HIV-infected of whom six were infected in utero. Only one child in the breastfeeding group became infected between months 3 and 7, corresponding to a 9-month cumulative risk of postnatal infection of 0.5% [95% confidence interval (CI) 0.1-3.4%; P = 0.24] with breastfeeding. Nine-month cumulative mortality was 3.3% (95% CI 1.6-6.9%) in the breastfeeding arm group and 5.7% (95% CI 3.6-9.2%) for the formula feeding group (P = 0.20). HIV-free survival by 9 months was 95% (95% CI 91-97%) in the breastfeeding group and 94% (95% CI 91-96%) for the formula feeding group (P = 0.66), with no significant difference in the adjusted analysis (adjusted hazard ratio for breastfeeding: 1.2 (95% CI 0.5-2.9%). CONCLUSION: : Maternal HAART while breastfeeding could be a promising alternative strategy in resource-limited countries.

Validation of 2006 WHO prediction scores for true HIV infection in children less than 18 months with a positive serological HIV test.

INTRODUCTION: All infants born to HIV-positive mothers have maternal HIV antibodies, sometimes persistent for 18 months. When Polymerase Chain Reaction (PCR) is not available, August 2006 World Health Organization (WHO) recommendations suggest that clinical criteria may be used for starting antiretroviral treatment (ART) in HIV seropositive children <18 months. Predictors are at least two out of sepsis, severe pneumonia and thrush, or any stage 4 defining clinical finding according to the WHO staging system. METHODS AND RESULTS: From January 2005 to October 2006, we conducted a prospective study on 236 hospitalized children <18 months old with a positive HIV serological test at the national reference hospital in Kigali. The following data were collected: PCR, clinical signs and CD4 cell count. Current proposed clinical criteria were present in 148 of 236 children (62.7%) and in 95 of 124 infected children, resulting in 76.6% sensitivity and 52.7% specificity. For 87 children (59.0%), clinical diagnosis was made based on severe unexplained malnutrition (stage 4 clinical WHO classification), of whom only 44 (50.5%) were PCR positive. Low CD4 count had a sensitivity of 55.6% and a specificity of 78.5%. CONCLUSION: As PCR is not yet widely available, clinical diagnosis is often necessary, but these criteria have poor specificity and therefore have limited use for HIV diagnosis. Unexplained malnutrition is not clearly enough defined in WHO recommendations. Extra pulmonary tuberculosis (TB), almost impossible to prove in young children, may often be the cause of malnutrition, especially in HIV-affected families more often exposed to TB. Food supplementation and TB treatment should be initiated before starting ART in children who are staged based only on severe malnutrition.