Use of observational databases to evaluate the effectiveness of antiretroviral therapy for HIV infection: comparison of cohort studies with randomized trials. EuroSIDA, the French Hospital Database on HIV and the Swiss HIV Cohort Study Groups.

OBJECTIVES: It is important to assess the extent of bias when comparing the clinical efficacy of antiretroviral regimens in observational databases because, with the current lack of planned large trials, such analyses may represent the only means of assessing the risk of serious clinical events associated with new regimens. We aimed to compare the results from observational databases with those from randomized trials. METHODS: Three treatment comparisons from randomized trials [Delta, AIDS Clinical Trials Group (ACTG) 175, Community Programs for Clinical Research on AIDS (CPCRA) 007 and ACTC 320] were mimicked in cohorts: (i) zidovudine monotherapy versus combination regimens of two nucleoside analogues; (ii) zidovudine combined with either didanosine or zalcitabine; and (iii) a dual combination versus a triple regimen including a protease inhibitor. Data for over 10 000 patients from the French Hospital Database on HIV, the EuroSIDA study and the Swiss HIV cohort study were analysed for each of the comparisons. Progression to AIDS disease or death was analysed in Cox models, adjusting for baseline differences, and results compared with randomized trials. RESULTS: For comparison (i) the adjusted relative risk estimates from cohorts were between 0.61 and 0.84, favouring combinations over monotherapy, compared with 0.57 to 0.63 for trials. For comparison (ii) relative risk estimates from cohorts ranged from 0.81 to 1.01 compared with 0.77 to 0.92 for trials. For comparison (iii), two of the cohorts showed similar results to the ACTG 320 trial but one indicated a higher risk of progression on triple therapy [relative risk 1.20, 95% confidence interval (CI) 1.01-1.441, in direct contrast to the trial result (relative risk 0.50, 95% CI 0.33-0.76). CONCLUSION: Serious biases can be present when comparing outcomes from the use of antiretroviral regimens in observational studies. However, such bias is not inevitable and careful interpretation of the results from several observational studies considered together is likely to be informative, guiding the design of new trials.

Survival improvement of AIDS-related progressive multifocal leukoencephalopathy in the era of protease inhibitors. Clinical Epidemiology Group. French Hospital Database on HIV.

OBJECTIVE: To estimate the change in survival of patients with AIDS-related progressive multifocal leukoencephalopathy (PML), in relation to the introduction of protease inhibitors (PI). DESIGN: The French Hospital Database on HIV (FHDH) is a prospective cohort of 70 224 HIV-infected subjects. This study included the patients diagnosed with PML between 1 July 1995 and 30 June 1997. PML diagnosis was both presumptive and confirmed. We compared the survival probability according to the diagnosis period (period 1 or 2, before or after introduction of PI in France on 1 April 1996). Cox's model was used to calculate the relative hazards of death according to the antiretroviral regimen. RESULTS: The study included 246 patients, 109 diagnosed during period 1 and 137 during period 2. In all, 131 patients received an antiretroviral combination that included PI. By 31 December 1997, a total of 131 deaths had been reported. The probability of survival at 6 months for patients from period 2 was nearly twice as high as for patients from period 1 (60.5 versus 34.5%). In comparison with patients receiving no treatment, the risk of death in patients on combination therapy not including PI was reduced by 38% [relative hazard (RH) 0.62, 95% confidence interval (CI) (0.41; 0.95), P = 0.026] and in patients on combination therapy with PI, by 63% [RH 0.37, 95% CI (0.22; 0.64), P = 0.0004]. CONCLUSION: This study of a large cohort of patients diagnosed with PML (n = 246), provides evidence that a combination antiretroviral regimen, especially one including PI, confers marked survival benefits.

Increased risk of cervical disease among human immunodeficiency virus-infected women with severe immunosuppression and high human papillomavirus load(1).

OBJECTIVE: To investigate human papillomavirus (HPV) genotypes, HPV DNA load, and behavioral and sociodemographic factors in a series of human immunodeficiency virus (HIV)-seropositive women, and to correlate HPV infection with cervical disease according to immune status. METHODS: Three hundred seven HIV-seropositive women were tested for the presence of HPV DNA by polymerase chain reaction (PCR) and Southern blot hybridization. Cervical disease was assessed using Papanicolaou smears, colposcopy, and biopsies when necessary. Various risk factors for cervical intraepithelial neoplasia (CIN) were tested using multiple logistic regression analysis. RESULTS: Cervical disease was diagnosed in 83 (27.0%) of 307 women and HPV infection in 162 (52.8%). High HPV load (as detectable by Southern blot hybridization) was found in 90 (55.6%) of the 162 infected women. Potentially oncogenic or related genotypes were detected in 74 (82.2%) of these 90 cases. High-load HPV infection was twice as frequent in severely immunosuppressed women (CD4 cell count less than 200/microL) as in women with higher CD4 cell counts (P =.002). High-load HPV infection was associated with a high risk of cervical disease (adjusted odds ratio [OR] 16.8; 95% confidence interval [CI] 7.0, 40.3). The risk among severely immunosuppressed women was ten times greater than that among women with CD4 cell counts of at least 200/microL. Low-load HPV infection (detected by PCR only) was a risk factor for CIN in severely immunosuppressed women only (adjusted OR 7.4; 95% CI 1.3, 43.0). CONCLUSION: Immunosuppression favors cervical high-load HPV infection with oncogenic genotypes and its clinical expression in HIV-seropositive women.

[Long-term impact of a mass treatment by praziquantel on morbidity due to Schistosoma haematobium in two hyperendemic villages of Niger]. / Evaluation à long-terme d'un traitement de masse par praziquantel sur la morbidité due à Schistosoma haema- tobium dans deux villages hyper-endémiques du Niger.

Although it is established that the treatment by praziquantel reduces the urinary lesions due to Schistosoma haematobium, the frequency of mass treatment necessary to maintain a low morbidity level remains poorly known. The objective of this work was to study the impact over three years of a single praziquantel mass treatment on schistosomiasis morbidity in two different systems of disease transmission in Niger. The study was performed in 2 villages hyperendemic for schistosomiasis in the South-West of Niger presenting respectively 2 different systems of schistosomiasis transmission: Koutoukalé-Zéno (K Zéno), located close to an irrigated area of the Niger River Valley where the transmission is permanent, and Téguey located along a temporary pond where the transmission is seasonal. After the initial evaluation (1994), we carried out a survey 3 years later (1997) except in K. Zéno where an intermediate evaluation was performed 10 months after the initial survey (1995). Approximately 300 randomised people have been examined as follows: macroscopic examination of urine and reagent sticks for macro- and micro-haematuria, filtration and microscopic examination of urine for Schistosoma eggs, and ultrasound scan of the urinary tract for morbidity. The therapeutic coverage has reached 69.9% in K. Zéno and 78.2% in Téguey. The prevalence of infestation decreased from 74.1% to 56.4 % in K. Zéno (p < 0.001) and from 65.3% to 30.4% in Téguey (p < 0.001) at the end of the 3 years. The prevalence of heavy infestation (eggs > or = 50) went in the same time from 9.9% to 12.8% (p = 0.3) in K. Zéno and from 9.1% to 3.3% in Téguey (p = 0.01). Using ultrasound scan, the prevalence of the bladder lesions reached its previous level in both villages. However the prevalence of hydronephrosis decreased from 21.1% to 3.9% in K. éno (p < 0.001) and from 12.6% to 4.2% in Téguey (p < 0.001). Three years after the single mass treatment, the morbidity did not reach the initial level. The effectiveness of the treatment is better in the pond system where the transmission is seasonal. The lesions of the upper tract decreased more slowly than the bladder lesions, but a long time after the treatment. The re-infestation induced the re-appearance of the bladder lesions sooner than the lesions of the upper tract. The periodicity of the treatment should be variable according to the transmission system. It should occur every 2 years in irrigated areas and could be delayed (3 years) in temporary ponds. The control was beneficial in the pond system and induced a significant reduction of the severe lesions.

[Preliminary evaluation of usable indicators during a control program for urinary bilharziosis in Niger]. / Evaluation préliminaire des indicateurs utilisables au cours d'un programme de lutte contre la bilharziose urinaire au Niger.

The performance of several indirect screening tests was evaluated during the start-up phase of a urinary schistosomiasis control program in Niger. Urine tests were carried out on a total of 354 children attending 3 primary schools on five consecutive days. Tests included filtration of 10 ml of urine, search for microscopic hematuria using reagent strips, and gross examination of urine. In addition a questionnaire was administered on the first day to identify signs of dysuria and hematuria. Repeat testing had a strong effect on the epidemiological profile of urinary schistosomiasis in the 3 schools. Although day-to-day counts varied greatly, egg excretion could be considered as high in all infected subjects. The screening sensitivity of urine filtration was low when the level of endemicity was moderate (up to 55 p. 100). Microscopic hematuria was common. However the sensitivity of this method was overestimated in comparison with urine filtration alone and use of reagent strips can be inconvenient. Using carefully defined diagnostic criteria, gross examination of urine was as effective as urine filtration and easier to perform. The value of the questionnaire for evaluation of morbidity was low despite relatively good performance of the diagnostic techniques. The children's responses concerning hematuria were not objective and questions concerning dysuria were poorly understood and time-consuming. In the next phase of study, these findings will be validated by ultrasound imaging.

Simplified methods of determining treatment retention in Malawi: ART cohort reports vs. pharmacy stock cards.

SETTING: Rapid scale-up of antiretroviral therapy (ART) has challenged the health system in Malawi to monitor large numbers of patients effectively. OBJECTIVE: To compare two methods of determining retention on treatment: quarterly ART clinic data aggregation vs. pharmacy stock cards. DESIGN: Between October 2010 and March 2011, data on ART outcomes were extracted from monitoring tools at five facilities. Pharmacy data on ART consumption were extracted. Workload for each method was observed and timed. We used intraclass correlation and Bland-Altman plots to compare the agreeability of both methods to determine treatment retention. RESULTS: There is wide variability between ART clinic cohort data and pharmacy data to determine treatment retention due to divergence in data at sites with large numbers of patients. However, there is a non-significant trend towards agreeability between the two methods (intraclass correlation coefficient > 0.9; P > 0.05). Pharmacy stock card monitoring is more time-efficient than quarterly ART data aggregation (81 min vs. 573 min). CONCLUSION: In low-resource settings, pharmacy records could be used to improve drug forecasting and estimate ART retention in a more time-efficient manner than quarterly data aggregation; however, a necessary precondition would be capacity building around pharmacy data management, particularly for large-sized cohorts.

Nutritional status in adults in the pluri-ethnic population of New Caledonia. The CALDIA Study Group.

OBJECTIVE: To describe the nutritional status (body mass index (BMI) and waist-hip ratio (WHR)) of the population of New Caledonia in relation to ethnicity and urban-rural environment. DESIGN: Diabetes screening survey in two rural provinces of New Caledonia and in the suburbs of Noumea. SUBJECTS: 8875 subjects aged 30-59 y, Europeans, Melanesians and Polynesians. MEASUREMENTS: BMI, WHR. RESULTS: Obesity (BMI > or = 27 kg/m2 in men, 25 kg/m2 in women) was highly prevalent in all groups, but varied according to ethnicity: respectively, 43% and 52% in Europeans, 46% and 72% in Melanesians, 72% and 83% in Polynesians. In the urban area, mean WHR values, adjusted for age and BMI, were significantly higher than in rural areas, especially in Melanesians. CONCLUSION: Both ethnicity and urban-rural environment are linked to the amount and distribution of adiposity, which appeared worsened in the urban area in Europeans, and even more in Melanesians.