Arlette Simonon

Natural History of Human Immunodefiency Virus Type 1 Infection in Children: A Five-Year Prospective Study in Rwanda

Objective. To compare morbidity and mortality of human immunodeficiency virus type 1 (HIV-1)-infected and HIV-1-uninfected children and to identify predictors of acquired immunodeficiency syndrome (AIDS) and death among HIV-1-infected children in the context of a developing country. Design. Prospective cohort study. Setting. Maternal and child health clinic of the Centre Hospitalier de Kigali, Rwanda. Participants. Two hundred eighteen children born to HIV-1-seropositive mothers and 218 born to seronegative mothers of the same age and parity were enrolled at birth. Outcome Measures. Deaths, clinical AIDS, nonspecific HIV-related manifestations, and use of health care services. Results. Fifty-four infected and 347 uninfected children were followed up for a median of 27 and 51 months, respectively. With the exception of chronic cough, the risk of occurrence of nonspecific HIV-related conditions was 3 to 13 times higher in infected than in uninfected children. The recurrence rate and severity of these findings were increased systematically in infected infants. Estimated cumulative risk of developing AIDS was 28% and 35% at 2 and 5 years of age, respectively. Estimated risk of death among infected children at 2 and 5 years of age was 45% and 62%, respectively, a rate 21 times higher than in uninfected children. Median survival time after estimated infection was 12.4 months. Early infection, early onset of HIV-related conditions, failure to thrive, and generalized lymphadenopathy were associated with subsequent risk of death and/or AIDS, whereas lymphoid interstitial pneumonitis was predictive of a milder disease. Conclusions. In Africa, HIV-1-infected children develop disease manifestations early in life. Specific clinical findings are predictive of HIV-1 disease, AIDS stage, and death. Bimodal expression of HIV-1 pediatric disease is encountered in Africa, as in industrialized countries, but prognosis is poorer. human immunodeficiency virus infection, children, vertical transmission, natural history, Africa.

Growth of human immunodeficiency type 1-infected and uninfected children : a prospective cohort study in Kigali, Rwanda, 1988 to 1993

OBJECTIVE To compare the anthropometric characteristics of children with and without HIV-1 infection. METHODS In a prospective cohort study of 218 children born to HIV-1 seropositive mothers and 218 children born to HIV-1 seronegative mothers in Kigali, Rwanda, 3 groups were compared: infected children (n = 46); uninfected children born to seropositive mothers (n = 140); and uninfected children born to seronegative mothers (n = 207). Weight, height and head circumference were measured at birth, every 3 months during the first year of life and every 6 months thereafter. The weight-for-age, height-for-age, weight-for-height and head circumference-for-age mean z scores were calculated. RESULTS The weight-for-age, height-for-age and head circumference-for-age mean z scores were lower among HIV-infected children than among uninfected ones at each time period. The reduction in the weight-for-age mean z score was the greatest between 12 and 36 months. The reduction in the height-for-age mean z score of HIV-infected children was persistently below 2 SD after 9 months of age. On the other hand the weight-for-height mean z score was not consistently lower in HIV-infected children when compared with uninfected ones. The anthropometric characteristics of uninfected children born to seropositive mothers were similar to those of children born to seronegative mothers. CONCLUSIONS In this study HIV-infected children were more frequently stunted (low height-for-age) than uninfected ones. Wasting (low weight-for-height) was not common among HIV-infected children.

Maternal plasma viral load, zidovudine and mother-to-child transmission of HIV-1 in Africa: DITRAME ANRS 049a trial.

ObjectiveTo study the relationship between maternal plasma RNA levels and mother-to-child transmission (MTCT) of HIV-1 in African breastfed children. DesignNested case–control study within a randomized trial assessing the efficacy of a short maternal zidovudine (ZDV) regimen to reduce MTCT. MethodsEligible women received either 300 mg of ZDV twice a day until labour, 600 mg at the beginning of labour and 300 mg twice a day for 7 days post-partum or a placebo. The diagnosis of paediatric HIV-1 infection was based on PCR tests at days 1–8, 45, 90 and 180 then on serology performed at 3 monthl intervals. Plasma HIV-1 RNA was measured at inclusion and on day 8 after delivery for all women who did transmit HIV to their children (cases) using a Chiron branched DNA assay (sensitivity 50 copies/ml) and compared with women who did not transmit (two per case) matched for phase trial, treatment allocation and site. ResultsAt inclusion, mean log10 viral load was 4.6 among 55 transmitting mothers and 3.7 among 117 non transmitters (P = 0.0001). Among transmitters, the mean difference in log10 viral load between day 8 post-partum and inclusion was −0.13 in the ZDV group (n = 23) versus 0.27 in the placebo group (n = 32;P = 0.01); among non transmitters it was −0.35 for the ZDV group (n = 47) versus 0.27 in the placebo group (n = 70;P < 10−4). In multivariate logistic regression analysis, odds ratios for MTCT were 8.7 (95% confidence interval, 3.7–20.6) for 1 log10 increase of maternal RNA at inclusion and 4.2 (95% confidence interval, 1.7–10.3) for 1 log10 increase difference from inclusion to day 8 post-partum. ConclusionHigh maternal viral load at inclusion strongly predicts MTCT of HIV in Africa. A short ZDV treatment regimen decreases significantly maternal viral load from its pretreatment level.

Evolution of human immunodeficiency virus subtype A in women seroconverting post partum and in their offspring post-natally infected by ingestion of breast milk.

The evolution of genomic RNA of human immunodeficiency virus type 1 (HIV-1), subtype A, was studied in three Rwandan mother-child pairs over a period of 12-30 months. In two pairs a homogeneous subtype A V3 sequence population was observed at seroconversion and the virus populations in the children resembled those in the mothers. One of these mother-child pairs was infected with an A/C recombinant virus (Ap17/Cp24). In the third pair, a heterogeneous V3 sequence population was observed in the maternal seroconversion sample but the V3 sequence population in the childs sample was homogeneous. In each individual the intra- and intersample variation (between the seroconversion and follow-up samples) increased over time in both the V3 region and p17gag. Independent evolution for 1-2 years did not abolish the epidemiological relationship between virus populations in mother and child.

Impact of human immunodeficiency virus type 1 subtype on HIV antibody detection in Burkina Faso.

Diagnosis of HIV infection is routinely performed by an HIV antibody detection method. Antigens play an important part in the performance of these tests. In this way sensitivity and specificity of diagnostic tests must cope with the considerable variability of HIV particularly at the level of the gene coding for the gp120 envelope glycoprotein. When 11 HIV-1 subtypes have been described with a divergence of up to 15% between them and when complex recombinant isolates are circulating the question of reliability of serodiagnostic assays arises. A study was conducted in Burkina Faso whereby five enzyme-linked immunosorbent assays (ELISA) were evaluated namely ICE HIV-1.0.2 Murex HIV-1/2 Genelavia Mixt Vironostika Uni-Form II and Enzygnost Anti HIV-1/HIV-2 Plus. 260 serum samples that were found to be positive for HIV infection underwent a serotyping assay based on the principle of ELISA and using specific peptides from the gp120 V3 loop of HIV-1 subtypes A B C D and E. Overall the results of the serotyping confirm that the diversity of HIV subtype circulating strains does not influence the sensitivity and the reliability of HIV serodiagnosis.

Timing of Mother-to Child Transmission of HIV-1 as Determinated by Nested Polymerase Chain Reaction — A Cohort Study in Kigali, Rwanda

The relative contributions of in utero, intrapartum and postnatal transmission routes of HIV-1 were estimated by PCR’ testing of 218 infants and children born to seropositive mothers, in Kigali, Rwanda. The study population consisted of 47 infected children, 139 uninfected children and 32 with indeterminate status. The infection status was established according to the clinical and serological profiles after a follow-up of 24 months (Ghent 1992). Nested PCR (two rounds of amplification) were performed on PBMCs isolated from serial blood samples. After a follow-up of two years, the estimated mother-to-child transmission rate of HIV-1 is 25.3%. Minimal and maximal estimates of in utero plus intrapartum transmission rate are 7.6% to 17.2% and of postpartum transmission rate 8.0% to 17.7%. The present study confirms that HIV-1 can be transmitted in the postnatal period through breastfeeding.