Early diagnosis of paediatric HIV-1 infection among African breast-fed children using a quantitative plasma HIV RNA assay.

OBJECTIVE: To evaluate the performance of a quantitative plasma HIV-1 RNA assay for HIV infection diagnosis among African breast-fed children. METHODS: Serial plasma specimens collected in the first week, at day 45-90, 6 months and 9-12 months of age from HIV-exposed children born to HIV-1-infected women enrolled in the DITRAME ANRS 049a perinatal intervention trial (Abidjan, Côte d'Ivoire) were tested for HIV-1 plasma RNA using a branched DNA (bDNA) assay. Sensitivity and specificity of this RNA test were assessed in comparison with a qualitative DNA polymerase chain reaction (PCR) performed on the same blood samples and allowing a reliable detection of the predominant subtype A. RESULTS: Among 91 samples from 53 infected children which tested positive by DNA PCR, the sensitivity of the bDNA test was 100% [95% confidence interval (CI), 96.0-100.0] at < or = 8 days (n = 19), 6-12 weeks (n = 43), 6 months (n = 26), and 9-12 months (n = 3). The median plasma HIV-1 RNA viral load ranged from 242 000 copies/ml at < or = 8 days to more than 500 000 copies/ml at day 45-90 and at 6 months. Of 106 specimens from 106 uninfected children who were DNA PCR- negative at month 3 or 6 of age, HIV-1 RNA was undetectable in 103, yielding an overall specificity for the bDNA test of 97.2% (95% CI, 92.0-99.4). The viral load in the three remaining samples with false-positive results was low (410, 937 and 3752 copies/ml, respectively). CONCLUSIONS: The quantitative bDNA assay appears a suitable tool for early, reliable and easy diagnosis of paediatric HIV-1 infection among a population of African breast-fed children.

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

OBJECTIVE: To study the relationship between maternal plasma RNA levels and mother-to-child transmission (MTCT) of HIV-1 in African breastfed children. DESIGN: Nested case-control study within a randomized trial assessing the efficacy of a short maternal zidovudine (ZDV) regimen to reduce MTCT. METHODS: Eligible 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. RESULTS: At 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 log(10) increase of maternal RNA at inclusion and 4.2 (95% confidence interval, 1.7--10.3) for 1 log(10) increase difference from inclusion to day 8 post-partum. CONCLUSION: High 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.

6-month efficacy, tolerance, and acceptability of a short regimen of oral zidovudine to reduce vertical transmission of HIV in breastfed children in Côte d'Ivoire and Burkina Faso: a double-blind placebo-controlled multicentre trial. DITRAME Study Group. DIminution de la Transmission Mère-Enfant.

BACKGROUND: Zidovudine reduces the rate of vertical transmission of HIV in non-breastfed populations. We assessed the acceptability, tolerance, and 6-month efficacy of a short regimen of oral zidovudine in African populations practising breastfeeding. METHODS: A randomised double-blind placebo-controlled trial was carried out in public clinics of Abidjan, Côte d'Ivoire, and Bobo-Dioulasso, Burkina Faso. Eligible participants were women aged 18 years or older, who had confirmed HIV-1 infection and pregnancy of 36-38 weeks duration, and who gave written informed consent. Exclusion criteria were severe anaemia, neutropenia, abnormal liver function, and sickle-cell disease. Women were randomly assigned zidovudine (n=214; 300 mg twice daily until labour, 600 mg at beginning of labour, and 300 mg twice daily for 7 days post partum) or matching placebo (n=217). The primary outcome was the diagnosis of HIV-1 infection in the infant on the basis of sequential DNA PCR tests at days 1-8, 45, 90, and 180. We compared the probability of infection at a given age in the two groups. Analyses were by intention to treat. FINDINGS: Women were enrolled between September, 1995, and February, 1998, when enrolment to the placebo group was stopped. Analysis was based on 421 women and 400 lifeborn infants. Baseline demographic, clinical, and laboratory characteristics were similar in the two groups. The Kaplan-Meier probability of HIV infection in the infant at 6 months was 18.0% in the zidovudine group (n=192) and 27.5% in the placebo group (n=197; relative efficacy 0.38 [95% CI 0.05-0.60]; p=0.027). Adjustment for centre, period of recruitment, mode of delivery, maternal CD4-cell count, duration of labour, prolonged rupture of membranes, and duration of breastfeeding did not change the treatment effect. The proportions of women taking more than 80% of the planned maximum dose were 75% before delivery, 81% during labour, and 83% post partum, without statistical difference between the groups. No major adverse biological or clinical event was reported in excess among women and children of the zidovudine group. INTERPRETATION: A short course of oral zidovudine given during the peripartum period is well accepted and well tolerated, and provides a 38% reduction in early vertical transmission of HIV-1 infection despite breastfeeding.

Human papillomavirus and human immunodeficiency virus infections: relation with cervical dysplasia-neoplasia in African women.

Our study assessed the factors associated with cervical squamous intra-epithelial lesions (SILs) and invasive cervical cancer, with special attention to human immunodeficiency virus (HIV) and human papillomavirus (HPV) infections. Women from 3 outpatient gynecology clinics of Abidjan, Côte d'Ivoire, were screened for cervical abnormalities: 151 women with low-grade SILs and 151 controls, 60 with high-grade SILs and 240 controls, and 13 with invasive cancer and 65 controls were enrolled in 3 case-control studies. Controls were chosen at random among the women without lesions, with a frequency matching for age and center. We used the PCR method for the detection of cervical HPV DNA and the restriction fragment length polymorphism analysis for HPV typing. HIV antibody testing and CD4 cell count were performed. In multivariate analyses, factors associated with cervical lesions were: for low-grade SILs, HPV positivity, HIV-1 seropositivity and parity >3; for high-grade SILs, HPV positivity, chewing tobacco, HIV-1 seropositivity and illiteracy, and for invasive cancer, HPV positivity only. We found a diversity of HPV types associated with SILs. In HIV-1-infected women, SILs occurred at an early stage of HIV disease. Women infected with both HIV-1 and HPV were at much higher risk of SILs than women infected with each of these 2 viruses separately. Invasive cancer was linked to HIV-2 infection in univariate analysis only. Our results suggest that the relation of SILs with HIV-1 infection is mainly explained by HPV infection and that HIV-1-infected African women may not often reach the invasive stage of cervical cancer.

PIP: The factors associated with cervical squamous intraepithelial lesions (SILs) and invasive cervical cancer were assessed in case-control studies of women from 3 outpatient gynecology clinics in Abidjan, Ivory Coast. Enrolled were 151 women with low-grade SILs and 151 controls, 60 women with high-grade SILs and 240 controls, and 13 women with invasive cervical cancer and 65 controls. Human papillomavirus (HPV) was detected in 75% of the high-grade SILs and cancers compared to 20% in the age-matched control groups. In the multivariate analysis, low-grade SILs were associated with HPV positivity, HIV-1 seropositivity, and parity above 3; for high-grade SIL, these risk factors were HPV positivity, chewing tobacco, HIV-1 seropositivity, and illiteracy. Cervical cancer was associated only with HPV positivity. Women infected with both HPV and HIV-1 were at a significantly higher risk of SILs than women infected with only one of these two viruses. These findings suggest that the association of SILs with HIV-1 infection is primarily explained by HPV infection and that HIV-infected African women may not live to reach the invasive stage of cervical cancer. The feasibility of cervical screening directed preferentially to African women with a low educational level or multipara merits assessment.