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

OBJECTIVES: To study mortality in African children born to HIV-1-infected mothers exposed peripartum to zidovudine. METHODS: A 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. RESULTS: There 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. CONCLUSION: Mother-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.

Increase in CD3+ CD4- T lymphocytes in patients with AIDS and disseminated Mycobacterium avium-intracellulare complex infection: a prospective study. GECSA. Groupe d'Epidemiologie Clinique du SIDA en Aquitaine.

In a retrospective study, an increase in double-negative (CD3+ CD4- CD8-) (DN) T lymphocytes has been shown to be an independent predictor of disseminated Mycobacterium avium complex (D.MAC) infection in patients with less than 100 CD4+ T cells per mm3. To better characterize this cell expansion, a prospective study was designed. From July 1995 to April 1997, 206 HIV-infected patients with less than 100 CD4+ T cells per mm3 were prospectively followed up and immunophenotyped. The median followup was 1.1 year (+/-0.5 year), and 14 new D.MAC infections were diagnosed among 84 first AIDS-defining events. In univariate and multivariate analyses, D.MAC infections were the only opportunistic infection with a significant increase in DN T-cell percentage (median = 6.6; range = 1.7 to 24.5, P = 0.004) compared with patients without any opportunistic infection. This alteration in T-lymphocyte count could constitute a predictor for D.MAC infection in clinical practice.

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.

A multi-center trial of the effects of oral nutritional supplementation in critically ill older inpatients. GAGE Group. Groupe Aquitain Geriatrique d'Evaluation.

The purpose of this study was to assess the effect of nutritional supplementation on dietary intake and on pressure ulcer development in critically ill older patients. The multi-center trial involved 19 wards stratified according to specialty and recruitment for critically ill older patients; 9 wards were randomly selected for nutritional intervention (nutritional intervention group), consisting of the daily distribution of two oral supplements, with each supplement containg 200 kcal, for 15 d. Pressure ulcer incidence was prospectively recorded for grades I (erythema), II (superficial broken skin), and III (subcutaneous lesion) for 15 d. Nutritional intake was monitored by using estimates in units of quarters validated by comparison with weight measurement. There were 672 subjects older than 65 y, and 295 were in the nutritional intervention group versus 377 in the control group. The patients were similar for age, sex ratio, and C-reactive protein. In comparison with the control group, the nutritional intervention group included more patients with stroke, heart failure, and dyspnea and fewer with antecedent falls, delirium, lower limb fractures, and digestive disease. The nutritional intervention group had a lower risk of pressure ulcers according to the Norton score but was less dependent (Kuntzman score) and had a lower serum albumin level. During the trial, energy and protein intakes were higher in the nutritional intervention group (day 2: 1081 +/- 595 kcal versus 957 +/- 530 kcal, P = 0.006; 45.9 +/- 27.8 g protein versus 38.3 +/- 23.8 g protein in the control group, P < 0.001). At 15 d, the cumulative incidence of pressure ulcers was 40.6% in the nutritional intervention group versus 47.2% in the control group. The proportion of grade I cases relative to the total number of cases was 90%. Multivariate analysis, taking into account all diagnoses, potential risk factors, and the intra-ward correlation, indicated that the independent risk factors of developing a pressure ulcer during this period were: serum albumin level at baseline, for 1 g/L decrease: 1.05 (95% confidence interval: 1.02 to 1.07, P < 0.001); Kuntzmann score at baseline, for 1-point increase: 1.22 (0.32 to 4.58, P = 0.003); lower limb fracture: 2.68 (1.75 to 4.11, P < 0.001); Norton score < 10 versus > 14: 1.28 (1.01 to 1.62, P = 0.04); and belonging to the control group: 1.57 (1.03 to 2.38, P = 0.04). In conclusion, it was possible to increase the dietary intake of critically ill elderly subjects by systematic use of oral supplements. This intervention was associated with a decreased risk of pressure ulcer incidence.

A prospective longitudinal study of the impact of early postnatal vs. chronic maternal depressive symptoms on child development.

BACKGROUND: Few studies of the effects of postnatal depression on child development have considered the chronicity of depressive symptoms. We investigated whether early postnatal depressive symptoms (PNDS) predicted child developmental outcome independently of later maternal depressive symptoms. METHODS: In a prospective, longitudinal study, mothers and children were followed-up from birth to 2 years; repeated measures of PNDS were made using the Edinburgh Postnatal Depression Scale (EPDS); child development was assessed using the Bayley Scales II. Multilevel modelling techniques were used to examine the association between 6 week PNDS, and child development, taking subsequent depressive symptoms into account. RESULTS: Children of mothers with 6 week PNDS were significantly more likely than children of non-symptomatic mothers to have poor cognitive outcome; however, this association was reduced to trend level when adjusted for later maternal depressive symptoms. CONCLUSION: Effects of early PNDS on infant development may be partly explained by subsequent depressive symptoms.

Predictive factors of occurrence of cytomegalovirus disease and impact on survival in the Aquitaine Cohort in France, 1985 to 1994. Groupe d'Epidémiologie Clinique du SIDA en Aquitaine.

Our objectives were to determine the factors associated with the occurrence of a first episode of cytomegalovirus (CMV) disease in an HIV-infected population and to estimate the overall impact of CMV disease on survival. The study population consisted of the 3525 patients included in the Aquitaine Cohort between 1985 and December 31, 1993. Eligible patients (n = 1868) must have had at least one CD4+ lymphocyte count of <200 cells/mm3 during follow-up, which represents the baseline period. CMV disease manifestations were investigated using standardized definitions. A Cox proportional hazards regression analysis was used to determine the factors independently associated with the probability of developing a first episode of CMV infection and the probability of death. During follow-up, 111 patients presented with a first episode of CMV disease. Four factors were independently associated with the onset of CMV disease: older age at baseline (risk ratio [RR] = 1.03 by a 1-year increase; 95% confidence interval [CI] = 1.02-1.05), homosexuality (RR = 1.90; CI = 1.18-3.02), the progression to a CD4+ lymphocyte count <50/mm3 (RR = 10.58; CI = 5.58-20.05), and the occurrence of toxoplasmosis (RR = 3.00; CI = 1.97-4.57) or a neurologic disease (RR = 2.59; CI = 1.38-4.86) during follow-up. After other predictors were controlled for, CMV disease was associated with a high risk of death in the cohort (RR = 1.58; CI = 1.24-1.94). The development of prophylactic strategies for CMV disease for selected groups of HIV-infected patients must be a priority to improve their quality of life.

Dual nucleoside regimens in nonadvanced HIV infection: prospective follow-up of 130 patients, Aquitaine Cohort, 1996 to 1998. Groupe d'Epidémiologie Clinique du SIDA en Aquitaine (GECSA).

OBJECTIVE: To describe the response to combinations of two nucleoside reverse transcriptase inhibitors (NRTIs) initiated early in the course of HIV infection under routine circumstances and to research prognostic factors indicating good virologic response. SETTING: Patients of the Aquitaine Cohort, a hospital-based open cohort that had been recruiting since 1987 in five public hospitals of the Aquitaine region in southwestern France. METHODS: Prospective cohort study of antiretroviral-naive patients with CD4+ cell counts >0.350 x 10(9)/L who started dual NRTI therapy between January 1996 and June 1997. Intent-to-treat analysis and multivariate logistic regression were used with data collected up to March 31, 1998. RESULTS: In this study, 130 patients were enrolled with a median follow-up of 14 months. At the time of first prescription, 79% were in U. S. Centers for Disease Control and Prevention (CDC) group A, 16% in group B, and 5% in group C; median CD4+ cell count was 0.466 x 10(9)/L and median HIV RNA level was 4.52 log10 copies/ml. The two main combinations used were zidovudine (AZT) plus zalcitabine (ddC; 38%) and AZT plus didanosine (ddI; 37%). At week 52, median CD4+ and HIV RNA responses were, respectively, +80 cells and -1.6 log; the proportions of patients with HIV RNA level <5000 and <500 copies/ml were 70% and 45%, respectively, and 96% of the patients had a CD4+ cell count >0.350 x 10(9)/L at that time. At their last follow-up, 3 patients had reached been diagnosed with full-blown AIDS and the AIDS-free survival probability at 1 year was 98.2% (95% confidence interval [CI], 93.1-99.6); 1 death had occurred. The only significant variable associated with an undetectable HIV RNA level at 1 year was a lower HIV RNA level at the first prescription of dual therapy. CONCLUSION: Our data indicate that dual nucleoside combinations could be a therapeutic option for patients diagnosed and observed during follow-up in the early course of HIV infection.

Incidence and risk factors of severe hypertriglyceridaemia in the era of highly active antiretroviral therapy: the Aquitaine Cohort, France, 1996-99.

OBJECTIVE: To estimate the incidence of serum hypertriglyceridaemia > 6 mm/L (HTG) and identify associated factors in the era of highly active antiretroviral therapy (HAART). METHODS: A prospective cohort, multirisk, both genders, of HIV-infected patients was treated with several patterns of antiretrovirals. Cox's model was used to estimate the effect of explanatory variables documented at the first normal triglyceride measurement (< 2 mm/L) on the subsequent occurrence of HTG. RESULTS: Among 925 patients (27% treated with a protease inhibitor (PI) containing regimen and 48% treated with other HAART combinations) followed 25 months in median with a median triglyceridaemia of 1.1 mm/L at baseline, 70 experienced an HTG, 4.2 cases per 100 person years[95% confidence interval (CI)=2,2,3,3-5]. Univariate analysis retained the following as risk factors of HTG: male gender, homosexual transmission group, greater age, higher body weight, AIDS stage, > or = 2 antiretrovirals including PI, higher triglyceride level and lower CD4+ cell count at baseline. In multivariate analysis, the risk of HTG remained associated with being male homosexual [hazard ratio (HR) = 1.68, P = 0.04], at the AIDS stage (HR = 1.84, P = 0.03), with increased triglyceride level (HR = 2.82 for 1 mm/L higher at baseline, P < 10-3), impaired CD4+ cell count (HR = 1.2 for 100 cells/microL lower, P = 0.02) and increased body weight (HR = 1.3 for 10 kg higher, P = 0.02). CONCLUSIONS: Baseline triglyceride level and being overweight are risk factors of HTG, together with advanced HIV disease, but the contribution of HAART is not demonstrated.

Estimating the efficacy of interventions to prevent mother-to-child transmission of HIV in breast-feeding populations: development of a consensus methodology.

Postnatal transmission of HIV through breast milk complicates both the design of effective interventions to prevent mother-to-child transmission of HIV (PMTCT) and their evaluation. Estimated long-term efficacy in five African trials (four with peri-partum antiretrovirals and one with artificial feeding) varied from 25 to 50 per cent. This variation may be due, at least in part, to differences in analytical methodology. To facilitate direct comparison between trials, a methodological consensus approach to the analysis and presentation of the results of PMTCT trials was developed. The initial methodology used and results presented from African trials with available long-term efficacy data were reviewed during a workshop in Bordeaux, France, in September 2000. A consensus approach for evaluating efficacy applicable across PMTCT studies was developed. There are four typical situations defined by duration of follow-up (short versus long), and the available demographic (vital status) and biological data (single versus repeat HIV testing). Efficacy can be assessed from the risk of infection directly or from HIV-free survival by combining infection and death as a single endpoint. Studies should report results in a standardized format including infection, weaning, mortality and loss to follow-up. New statistical methods that account for the unknown date when a child would first test positive for HIV, for weaning as a competing risk for HIV infection, and for increased risk of death among HIV-infected children should be used in analysing data from PMTCT studies with repeat HIV testing. All estimates should be reported with confidence intervals. This standardized methodology that allows direct comparison between studies is now being applied to four randomized clinical trials.