Failure of pediatric AIDS prevention despite maternal HIV screening in Paris, France.
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Publications and source records attributed to S Matheron.
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In order to compare the nutritional status of tuberculosis (TB) patients who were human immunodeficiency virus (HIV)-seropositive with those who were seronegative, we carried out a cross-sectional anthropometric and biochemical assessment, together with bioelectrical impedance analysis (BIA) of the nutritional status of TB patients hospitalized in the Department of Internal Medicine, Bujumbura University Hospital, Burundi, East Africa. Of the 65 TB patients (33 pulmonary, 6 extrapulmonary, and 26 disseminated TB), 50 (76.9%) were HIV-seropositive (HIV+). When assessed according to anthropometric, BIA, and biochemical variables, HIV+ TB patients had more pronounced malnutrition than HIV- patients. Similar results were obtained when the comparison was restricted to patients with only pulmonary TB: HIV+ patients were more malnourished than HIV- patients. The results according to anthropometric measurements were: weight loss (13.5% of HIV- patients versus 26.4% of HIV+ patients, P = 0.005), body mass index (18.6 versus 15.1, P = 0.003), fat free mass (FFM) (13.9 versus 11.9, P < 0.01), and body fat (BF) (4.55 versus 3.71, P = 0.03) expressed per unit height2. BIA showed that the difference in FFM between HIV- and HIV+ TB pulmonary patients was mostly due to a decrease in body cellular mass. Measurements of albumin, prealbumin, and transferrin showed a marked decrease in all three markers in HIV+ TB pulmonary patients. The nutritional status of HIV+ patients with disseminated versus pulmonary TB was similar. The nutritional status of HIV+ TB patients is far worse than that of HIV- TB patients. In such patients, anthropometry underestimates the degree of malnutrition because it does not account for the water component of FFM. Nutritional status should be assessed and nutritional intervention should be provided in an attempt to improve the prognosis of TB patients, especially those who are infected by HIV.
BACKGROUND: A combination of two nucleoside analogues is currently the core of any antiretroviral regimen for HIV-1 infection. Stavudine plus lamivudine has shown an additive effect in vitro, as well as an absence of overlapping toxicity and cross-resistance. OBJECTIVE: To evaluate the antiviral efficacy of stavudine plus lamivudine in treatment-naive patients and in patients previously treated with other nucleoside reverse transcriptase inhibitors. DESIGN: Prospective, open-label pilot study. SETTING: Three urban clinical centers in Paris. PATIENTS: 83 patients with CD4+ cell counts between 50 and 400 cells/mm3 (42 treatment-naive and 41 treatment-experienced patients). INTERVENTIONS: Stavudine, 40 mg twice daily (30 mg twice daily in patients with a body weight < or = 60 kg), and lamivudine, 150 mg twice daily. MEASUREMENTS: Primary end points for efficacy included changes in plasma viral load and CD4+ cell count at 24 weeks compared with baseline. RESULTS: Therapy with stavudine plus lamivudine resulted in a median decrease of 1.66 log10 (10(1.66)) (range, -3.04 to -0.79 log10) in plasma HIV-1 RNA; the median increase in CD4+ cell count was 108 cells/mm3 (range, -58 to 406 cells/mm3) at week 24 in treatment-naive patients. In treatment-experienced patients, the median reduction in plasma HIV-1 RNA was 0.55 log10 (range, -2.86 to 0.52 log10), and the median increase in CD4+ cell count was 46 cells/mm3 (range, -188 to 311 cells/mm3). The percentages of patients with less than 3000 HIV-1 RNA copies/mL and less than 400 copies/mL at 24 weeks were, respectively, 57% (95% CI, 41% to 72%) and 26% (CI, 12% to 40%) among treatment-naive patients and 22% (CI, 10% to 38%) and 5% (CI, 1% to 17%) among treatment-experienced patients. Of 82 patients, 14 (17%) experienced grade 3 or 4 toxicity and 2 discontinued therapy because of intolerance toward treatment. CONCLUSION: Stavudine plus lamivudine seems to have a potent antiviral effect in treatment-naive and treatment-experienced patients. No major drug-limiting toxicity was found. This two-nucleoside combination should be considered in multidrug therapy for HIV.
We evaluated a new human immunodeficiency virus type 2 (HIV-2) DNA amplification strategy based on peripheral blood mononuclear cell long PCR (XL PCR) followed by nested PCR amplification. The primers used were located in the highly conserved long terminal repeat and in the pol regions of the genome. Five primer pairs corresponding to different regions of the HIV-2 env gene were used in the nested step. Samples from 42 patients were tested, which yielded positive amplification with at least two primer pairs in 40 (95%) samples. A primer pair (EB2/EB5) located on the V3 region succeeded in amplifying proviral DNA in 40 samples.
We compared the line probe assay (LiPA) to sequence analysis for the detection of mutations conferring resistance to nucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Plasma samples from 40 patients who had received zidovudine, dideoxyinosine, and dideoxycytosine, alone or in combination, and who were enrolled in the ALTIS 2 clinical trial (lamivudine [3TC] plus stavudine) were tested at enrollment and at week 24. RT PCR products from plasma were used for LiPA, and DNA was used for sequence analysis. LiPA gave uninterpretable results for 8.5% of the analyzed codons corresponding to 63 samples, mainly for codons 41, 69, and 70. Several minor discrepancies between the two methods occurred, mainly due to the ability of LiPA to detect mixed populations while sequence analyses detect a single homogeneous population. LiPA is suitable for detecting mixed populations and easy to implement in clinical laboratories and might be useful for epidemiological surveys of primary HIV-1 resistance.
PURPOSE: To assess the tolerability and efficacy of intravitreal injections of foscarnet in cytomegalovirus (CMV) retinitis in acquired immunodeficiency syndrome (AIDS). METHODS: Patients with CMV retinitis resistant and/or intolerant to intravenous foscarnet and ganciclovir and resistant to intravitreal ganciclovir were included. The induction therapy consisted of intravitreal injections of 2,400 micrograms of foscarnet twice a week. The assessment was performed by clinical examination and photographies of the fundus. RESULTS: Three patients (four eyes) have been included. Three eyes were administered seven and one eye eight intravitreal injections. The tolerability was good, but the efficacy was mere: the retinal lesions became less edematous, but they still extended. CONCLUSION: In these four eyes with CMV retinitis resistant to intravitreal ganciclovir, intravitreal injections of foscarnet were well tolerated but did not stop the progression of the retinitis.
Risk factor for invasive pulmonary aspergillosis in HIV-negative patients include neutropenia, corticosteroid therapy, and chemotherapy. Corresponding risk factors in HIV-positive patients have not yet been reported. A case-control study was conducted at the Bichat-Claude Bernard Teaching Hospital, Paris, France, between 1991 and 1996. Eight cases were identified. In three cases, the diagnosis was documented histologically. Of the remaining five patients, four had a de novo lung cavity with a positive bronchoscopy sample, and one had a pulmonary infiltrate with a positive bronchoscopy sample in the absence of any other potential pathogen. Each case was matched with three controls who were admitted during the same period and had CD4 counts lower than 50/mm3. Median age was 38.1 years in the cases and 38.4 years in the controls. Median CD4 counts were 12.5 +/- 19.2 in the cases versus 19.3 +/- 16.3 in the controls (P = 0.14). No case-control differences were found for AIDS duration, neutrophil counts at diagnosis or during the previous six months, history of corticosteroid therapy or chemotherapy, or number of previous opportunistic infections. Cases were more likely than controls to have a preexisting lung cavity (3/8 versus 0/24; P = 0.01) and had spent more time in the hospital during the previous year (7 +/- 4.5 versus 2.8 +/- 3.2 weeks; P = 0.02). These data do not support a role for neutropenia or immunosuppressive treatments as risk factors for invasive aspergillosis in AIDS. They suggest that AIDS patients with a lung cavity or frequent hospital stays are at increased risk for invasive aspergillosis.
We studied the propagation and the impact of zidovudine prevention on the human immunodeficiency virus-1 transmission rate from infected mothers to their infants in the French nationwide prospective cohort. Infection was diagnosed in the children on the basis of at least two positive human immunodeficiency virus-1 polymerase chain reaction tests, culture, or both. The transmission rate among treated women was compared with that among untreated women during the same period and with that among women enrolled in the cohort since 1986. The impact of zidovudine was analyzed according to the women's clinical and biologic characteristics, the mode of delivery, and use of zidovudine therapy before the pregnancy. Nearly 90% of women were treated as soon as the second half of 1994. In 1994 and 1995, 80% of mother-child pairs received at least one of the three phases of preventive treatment. Among the 663 mothers enrolled during these 2 years, only six refused the treatment. Zidovudine treatment was associated with a reduction in the transmission rate of nearly two-thirds, from 14% +/- 6% to 5% +/- 2% (p < 0.01). The degree of reduction was not influenced by the maternal CD4+ cell count or p24 antigenemia at delivery. Zidovudine treatment of the mother before the pregnancy considerably reduced the impact of preventive therapy; the transmission rate was significantly higher among pretreated mothers (20% versus 5%, p < 0.01) even after adjusting for maternal CD4+ cell count. Zidovudine prevention is now widely used in France and has had a major impact on the epidemiology of mother-child human immunodeficiency virus transmission. This justifies a policy of offering human immunodeficiency virus screening to all women before or shortly after the diagnosis of pregnancy.
OBJECTIVE: To assess the reproducibility of and factors associated with HIV detection in cervicovaginal secretions (CVS). DESIGN: Longitudinal study of 43 HIV-1-infected pregnant women in Paris. METHODS: HIV DNA was detected in peripheral blood mononuclear cells (PBMC) by Amplicor and gag nested polymerase chain reaction (PCR) assays. The HIV genotype was determined by heteroduplex mobility assay. Amplicor and gag nested PCR assays were performed on serial CVS samples for HIV DNA detection, and the HIV Monitor test was used for HIV RNA detection in plasma and CVS. RESULTS: A total of 144 CVS samples were collected from the women included in the study. HIV-1 DNA was detected in 36 (25%) of the 144 samples, from 16 (37.2%) of the 43 women. Results of HIV-1 DNA detection were concordant in the first two samples in 27 (84.4%) of the 32 women with at least two CVS samples. The last CVS sample collected in each woman was HIV-1 DNA-positive in 13 (30.2%) of the 43 women. Three factors were found to be independently associated with HIV-1 DNA detection in CVS: HIV-1 subtype B, absence of zidovudine therapy, and microbial cervicovaginal infection. HIV RNA was detected in CVS from 10 (23.3%) out of 43 women and correlated with DNA detection in the same sample and HIV RNA detection in plasma. CONCLUSIONS: DNA and RNA PCR can be used to detect HIV in cells and supernatants of CVS. These techniques may be useful in cohort studies to investigate HIV transmission and to evaluate the efficacy of antiretroviral drugs to reduce HIV excretion.
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An outbreak of trichinosis caused by ingestion of horse meat occurred in December 1993 in France; more than 500 people were affected. We compared the immediate and midterm efficacy and tolerability of thiabendazole and albendazole as therapy for the 46 patients seen in our department. Forty-four patients (96%) were treated. The first 26 patients received thiabendazole therapy; the next 18 received albendazole therapy. All the patients were tested with prednisone. Eight relapses occurred (seven in the thiabendazole group and one in the albendazole group [not significant]). Side effects of treatment were reported by seven patients, all of whom were treated with thiabendazole (P = .01). Six months after treatment, 16 of the 31 patients who responded to a questionnaire still had symptoms, the most frequent of which were myalgias (81%) and fatigue (69%). No significant difference was observed between the two treatment groups. The immediate efficacy of thiabendazole and albendazole as therapy for trichinosis was comparable, but albendazole was better tolerated.
We retrospectively carried out a descriptive and prognostic study of 76 human immunodeficiency virus-infected patients with cryptococcosis diagnosed by a positive culture of cerebrospinal fluid (CSF), blood, urine, or other body fluid or tissue. We focused on the 65 patients with cryptococcal meningitis. At diagnosis, the mean CD4 lymphocyte count was 46/mm3; 86% of patients had fever; 67%, headache; 37%, stiff neck; 29%, altered mentation or confusion; 20% cranial nerve deficiency; and 48%, other focal deficiencies. Analysis of CSF specimens revealed the following results: normal (25% of the specimens), leukocyte count of < 20/mm3 (62%), positive India ink smear (87%), and positive cryptococcal antigen (92%). Twenty patients died within the first 3 months (3-month survival rate, 70%). A Cox regression model selected the following as prognostic parameters: age older than 30 years (relative risk [RR] = 2.1), CSF glucose level of < 2 mmol/L (RR = 3.7), previous admission to an intensive care unit (RR = 4.7), and mechanical ventilation (RR = 4.6). The outcome of cryptococcal meningitis in patients with AIDS remains difficult to predict at admission, and every case should be considered as potentially severe.
We describe a case of porocephalosis diagnosed in a 50 year old Gabonese male hospitalized in France for a HIV-related renal insufficiency. A standard abdominal radiography showed numerous ring-shaped calcifications, predominantly in the hepatic area. This aspect was very suggestive of the diagnosis in a patient living in Central Africa and eating occasionally meat of snake. The parasites live normally in the lungs of snakes (python, Bitis sp.). People become infected in eating undercooked snake or in handling snakes. In the majority of cases, the disease is asymptomatic and diagnosis made accidentally as in the case of our patient.
OBJECTIVES: To compare the safety and efficacy or oral ganciclovir with intravenous ganciclovir for the maintenance therapy of cytomegalovirus (CMV) retinitis in AIDS patients. DESIGN: Multicenter, randomized, open-label study, with both masked and unmasked ophthalmic assessments. METHODS: Patients with AIDS and stable CMV retinitis were randomized after an induction course of intravenous ganciclovir (5 mg/kg twice daily) to receive maintenance therapy with oral ganciclovir (500 mg six times daily) or intravenous ganciclovir (5 mg/kg once daily). MAIN OUTCOME MEASURE: The primary endpoint of the study was time to progression of CMV retinitis from the start of maintenance therapy. RESULTS: The mean time to progression, evaluated by funduscopy was 109 days for the intravenous group, and 86 days for the oral group (P = 0.02). The masked photographic assessment revealed shorter time to progression for both oral and intravenous groups, as compared with funduscopy data, and showed no significant difference between the two treatment groups: 62 days for intravenous ganciclovir and 51 days for oral ganciclovir (P = 0.15). Diarrhea and neutropenia were the most frequent reported events in both groups, with the incidence of sepsis more than double in the intravenous compared with the oral ganciclovir group (3 versus 8.5%). CONCLUSIONS: Oral ganciclovir offers a reasonable alternative to intravenous ganciclovir for the maintenance therapy of CMV retinitis in AIDS patients.
OBJECTIVES: Human immunodeficiency virus (HIV) infection has greatly modified the epidemiology and clinical course of tuberculosis. The aim of this study was to analyze the characteristics of tuberculosis in African patients hospitalized in Paris by comparing clinical features in patients with and without HIV infection. METHODS: Hospital records of 71 patients from Africa hospitalized between 1989 and 1992 in Paris with a certain or probable diagnosis of tuberculosis were studied retrospectively. RESULTS: There were 30 patients (42%) with HIV infection. In 12 of them (40%) HIV positivity was discovered at diagnosis of tuberculosis. Age, sex, and duration of residence in France before diagnosis were similar between HIV+ and HIV- patients. Pulmonary tuberculosis was found in 23 patients and extrapulmonary forms (mainly lymph node involvement) were seen in 34; both in 14 patients. There was no difference in localization between HIV+ and HIV- patients except for disseminated tuberculosis which was more frequent in HIV+ patients. Skin reactions to tuberculin were positive in 76% and 97% of the HIV- and HIV+ patients respectively (p < 0.02). Drug resistance was observed in 8 patients (6 HIV+): streptomycin (n = 6), pyrazinamide (n = 2), isoniazide (n = 2), ethambutol (n = 1) and rifampicin (n = 1). Drug therapy was successful in controlling the initial manifestations of tuberculosis in both HIV+ and HIV- patients. CONCLUSION: Extrapulmonary forms of tuberculosis, especially lymph node infection was more frequent in Africans hospitalized in Paris, whether the patients were HIV positive or negative. HIV infection was associated with disseminated tuberculosis, non-excavated pulmonary tuberculosis and undesirable side effects of antituberculosis drugs.
OBJECTIVE: To assess the prevalence, presentation, and risk factors of pentamidine-induced dysglycemia. RESEARCH DESIGN AND METHODS: Blood glucose values were screened in 244 consecutive immunocompromised patients with Pneumocystis carinii pneumonia: 116 being treated with cotrimoxazole and 128 others with pentamidine. RESULTS: Two cotrimoxazole patients developed diabetes as a result of necrotizing pancreatitis (1.7%); the others remained euglycemic. Forty-eight pentamidine-treated patients (38.5%) developed severe glucose homeostasis disorders: hypoglycemia in 7, hypoglycemia and then diabetes in 18, and diabetes alone in 23 (P < 0.001 vs. the cotrimoxazole group). Hypoglycemia was early, sudden, often recurrent, and life-threatening, associated with inappropriately high insulin levels in plasma; the B-cell response to stimuli was poor. Of the 41 diabetic patients, 26 required insulin therapy; their plasma C-peptide levels were lower than normal, and the B-cell secretory responses to stimuli were poor. Islet cell antibodies, insulin antibodies, and insulitis were not detected. The pentamidine-treated dysglycemic patients differed from their euglycemic counterparts by higher pentamidine doses (P < 0.001), higher plasma creatinine levels (P < 0.001), and more severe anoxia (P < 0.05) and shock (P < 0.001). Most of them had received pentamidine mesylate parenterally (n = 36; 75%); six others received the isethionate salt and six exclusively pentamidine aerosols. CONCLUSIONS: Pentamidine-induced dysglycemic accidents are primarily due to inappropriate insulin release and toxicity to the islet B-cells. Drug accumulation due to excessive doses, iterative courses, and/or renal impairment is the determining risk factor.