[Choice of initial regimen for antiretroviral-naïve HIV patients: Analysis of motivation]. / Analyse des motivations du choix des antirétroviraux (ARV) prescrits chez des patients infectés par le VIH (PVVIH) naïfs.

OBJECTIVE: Several therapeutic combination antiretroviral therapy regimen are available for initial treatment in naïve HIV infected patients. The choice of a particular regimen remains often subjective. The aim of this study was to determine factors associated with the choice of molecules in initial ARV prescriptions. METHODS: From 01/01 to 30/10/2014, every initial cART prescription was analyzed regarding patients and physicians characteristics. Then, prescriptions were evaluated by an independent committee of ART prescribers. RESULTS: One hundred and thirty two consecutive initial prescriptions by 34 physicians of 11 medical centers were included: 71 M, migrants: 57 %, MSM: 21 %, CD4<200/mm3: 26 %, HIV RNA>100 000 cp/mL (33 %). cART regimen were: NRTI/PI (43 %), NRTI/NNRTI (29.5 %), NRTI/integrase inhibitor (23 %). 75 % of initial cART regimen were consistent with expert guidelines recommendations. The choice of initial cART was not influenced by the type of HIV contamination risk group, patient's geographic origin, CD4 levels. In contrast, working or not (P=0.007), pregnancy wish (P=0.07), pregnancy (P=0.001), HIV RNA levels (P=0.02) and HIV primary infection (P=0.049) influenced the initial choice. Neither physician's age, nor physician's experience influenced this choice. The prescription's non accordance to 2013 French guidelines was mainly related to integrase inhibitor utilisation (P= 0.0001). CONCLUSION: Overall, cART initial choice is mostly consistent with guidelines. Primary HIV infection, procreation features and high viral load are the main factors influencing this choice. New regimen with better tolerability is prescribed even if it is not yet included in the guidelines.

[Retrospective analysis of neonatal data in a monocentric cohort of 170 newborns of polydrug-using mothers, Île-de-France, 1999-2008]. / Analyse rétrospective des données de 170 nouveau-nés de mères consommatrices de substances psychoactives.

OBJECTIVES: To analyze neonatal morbidity in a single-center retrospective cohort (1999-2008) according to the mothers' polydrug use and to the social and demographic context. MATERIAL AND METHODS: One hundred and seventy newborns were identified whose mothers used two or more substances (such as heroin, cocaine, opioid maintenance treatment, tobacco, alcohol, hashish, amphetamines, benzodiazepines, or other psychotropics) at the beginning of their pregnancies. The database included 168 sociodemographic variables describing mothers' living conditions and their drug-abuse characteristics; perinatal variables such as gestational age, weight, neonatal abstinence syndrome, and modalities of discharge; and correlations with the main neonatal morbidities. RESULTS: The mothers' mean age at delivery was 31.6yrs. It was the first pregnancy for 35.2% of the mothers but the mean number of previous abortions was 1.14 and 16.3% already had previous children in foster care. At delivery only 8.2% used only one product, 52.9% 2 or 3 products, and 37.6% four or more substances. All sociodemographic variables, the deprivation score, the number of previous abortions and miscarriages, and poor prenatal monitoring were significantly different for the mothers using four products or more. The uses changed along the years of study: fewer mothers used heroin but more used hashish, combined with other substances. The medical care also changed: greater participation on the part of mothers in neonatal care, more frequent breastfeeding, less medication for neonatal abstinence syndrome with the same severity score: i.e., 45.5% of infants with a Lipsitz score between 8 and 12 received a morphine treatment in 1999-2000 versus only 5.5% in 2005-2006 and none in 2007-2008. The mean gestational age was 38.1weeks. Preterm births (22.2%) and intrauterine growth restriction (18% with birth weight <10th percentile) were mainly correlated with the number of substances at delivery (17.3% preterm if three substances or less and 31.3% if four substances or more; p<0.001), social deprivation, poor prenatal care, and mothers having gained less than 5kg in weight during pregnancy (57.1% of intrauterine growth restriction versus 14.5%). Birth weight, height, and head circumference were significantly different for mothers having drunken alcohol. Among the newborns, seven showed complete fetal alcohol syndrome. The neonatal abstinence syndrome severity (23% with a Lipsitz score>9, one-quarter of whom were medicated with morphine) was correlated with an in-utero exposure to opiates, mainly in combination with benzodiazepines, and with the use of four or more substances. The mean age of infants at discharge was 18.1days (SD 3.39): 21.1% stayed 30 days or more in the hospital, mainly because of prematurity or intrauterine growth restriction, a high neonatal abstinence syndrome score, maternal polydrug use, psychosocial deprivation, or foster care placement decisions. Decisions for foster care placement (15%) applied to polydrug users, with social deprivation, undermonitored pregnancies, or bonding difficulties. CONCLUSION: The main factors correlated with poor neonatal results were polydrug use, maternal psychiatric pathologies, and social deprivation. Overall, prenatal and postnatal care such as rooming-in improved the results.

[Maternal and obstetrical data in a retrospective cohort of 170 newborns from polydrug using mothers, in the Paris area, 1999-2008]. / Analyse des données maternelles et obstétricales dans une cohorte rétrospective de 170 nouveau-nés de mères polyconsommatrices, Île-de-France, 1999-2008.

OBJECTIVES: Polydrug use in pregnancy is harmful. This survey aimed to explore the issue of the associations of substances during pregnancy and to determine the consumer profiles. PATIENTS AND METHODS: One hundred and seventy newborns whose mothers were psychoactive substances users were identified over the period 1999 to 2008. The data relating to maternal consumption, their reproductive history, and their living environment were collated. RESULTS: At the end of their pregnancy, the mothers reported using on average 3.14 substances. Three profiles were determined: 65 women were heroin users or had consumed it in their lifetime and were currently on substitution treatment, and had a very unfavourable social living environment; 30 women were mainly consumers of alcohol, with or without benzodiazepines or other psychotropic drugs, and had a history of abortions; 75 women were mainly tobacco and cannabis smokers, with or without substitution treatment, had good social living conditions and had wanted the pregnancy. CONCLUSION: Polydrug use increases the risk for the women to avoid prenatal care and is often linked with a history of abortions.

[Consequences for the newborn of alcohol consumption during pregnancy]. / Conséquences, pour l'enfant à naître, du maintien de la consommation d'alcool pendant la grossesse.

BACKGROUND: This paper aims at showing the immediate and long-term consequences affecting newborns whose mothers did not reduce or stop their consumption of alcohol when they were pregnant; these women were chosen among women who also used psychoactive substances. METHODS: A retrospective cohort was constituted of babies who were found to have been exposed in utero to one or more legal or illegal psychoactive substance(s) and who were born or hospitalized between 1999 and 2008 in a hospital near Paris. Among the cohort of 170 babies, 56 had mothers who had not modified their alcohol consumption when they were pregnant, 30 had mothers who had reduced their alcohol consumption, and 84 had mothers who declared having been abstinent. RESULTS: The babies born to mothers who did not modify their alcohol consumption when pregnant were more likely to be premature (30%) and hospitalized in the neonatology hospital unit (60.7%). They needed specific care for durations significantly longer than the babies exposed in utero to other psychoactive substances (P<0.005). They were more often diagnosed with fetal alcohol spectrum disorders (18%) and placed in a foster family (18%). CONCLUSION: Given the negative consequences on the babies born to mothers who do not modify their alcohol consumption when pregnant, these mothers should be identified and provided with better care. The successful strategies for early therapeutic interventions used in other countries should be studied as examples. This would make it possible to reduce the enormous financial, material and human costs that are a direct consequence of alcohol consumption during pregnancy.

[Obstetrical and pediatric impact of in utero cocaine exposure]. / Conséquences obstétricales et pédiatriques de la consommation de cocaïne pendant la grossesse.

Review of recent publications about perinatal consequences of cocaine use during pregnancy points out that: - dramatic obstetrical, neonatal and developmental abnormalities, reported during 1980-90', are less frequent in recent cohort studies; - pregnant women who use cocaine or crack, also consume other psychoactive drugs (alcohol, tobacco, benzodiazepines, cannabis, opiates, ...) and have a very chaotic life-style; so, it is difficult to distinguish abnormalities caused by cocaine per se, even with numerous cohorts, control groups and multivariate analysis.

Medical and social differences between French and migrant patients consulting for the first time for HIV infection.

The objectives of the study were to describe the medical and social characteristics of patients consulting for the first time after diagnosis of HIV-infection and to compare the medical and social characteristics between French and migrant patients. From 1 January 2001 to 31 December 2002, all consecutive adults consulting for the first time for HIV infection in two HIV outpatient clinics located in the western suburb of Paris, agreed to an interview based on an administered questionnaire regarding their medical and socioeconomic characteristics. Of the 203 patients (98 women, 105 men), one-third (n=70) was of French nationality. Delay (+/-SD) in access to HIV outpatient clinic after diagnosis was shorter in migrant than in French patients, respectively 7.6+/-29.6 months (median=0.5, range=0 to 196.6) and 23.8+/-51.4 months (median=0.9, range=0 to 199.7); p=0.005. There was no significant difference in the medical characteristics between the two groups of patients on their first consultation. However, most of the migrants were living in very poor socio-economic conditions with minimal resources thus sometimes delaying initiation of HAART. The development of social facilities for HIV-positive migrants should be a public health priority.

[Perinatal drug abuse. Collaborative perinatal care for drug abusers and their infants]. / Réseaux ville-hôpital et projet social: l'expérience des réseaux périnatal et toxicomanie du nord des Hauts-de-Seine autour des femmes enceintes abusant de substances psycho-actives.

Pregnant drug abusers are a group with very high risk of perinatal morbidity. Intensive prenatal care, with substitution maintenance programs, by a medico-psycho-social team working in concert with ambulatory health and social workers, may prevent perinatal complications and mother-infant separation. The results of such a perinatal program, in a suburban low-socioeconomic population, are described. In comparison with reports in the literature, this approach appears to provide significant perinatal medical and social prognosis for pregnant abusers and their neonates.

[Neonatal withdrawal syndrome in twins born to a mother on methadone substitution]. / Syndrome de sevrage néo-natal chez des jumeaux d'une mère sous traitement de substitution par méthadone.

We report the cases of two female twins whose mother was taking methadone substitution therapy. These cases demonstrate the unpredictable nature of the neonatal withdrawal syndrome. One baby developed signs of withdrawal late 10 days after birth. She had a less severe syndrome than her twin sister who was hypotrophic and developed signs on day 1 which persisted for 6 weeks.

[Factors associated with medical management of HIV infected persons in two French districts, 1993-1995]. / Facteurs associés à la prise en charge médicale des personnes infectées par le VIH dans deux départements français, 1993-1995.

BACKGROUND: The regularity of medical followup of HIVinfected patients greatly influences the effectiveness of antiretroviral treatments and of prophylaxis of opportunistic infections. METHODS: To identify potential barriers to a regular followup, a retrospective study was conducted among the adult AIDS patients diagnosed between July 1993 and May 1995 in two French districts (Gironde and HautsdeSeine). Medical followup was described based on the frequency of CD4 counts in the medical file and on a confidential interview among patients whose HIV infection had been diagnosed at least 6 months before AIDS. Irregular followup (less than one CD4 count per year when CD4> 500/ mm(3), and per 6months when CD4< 500/ mm(3)) within the two years preceding AIDS diagnosis was analysed according to socioeconomic status and to social and behavioral factors. RESULTS: Among 290 patients, followup was irregular in 51% of the patients (injecting drug users: 66%, homo/bisexual men: 41%, patients infected through heterosexual contact: 49%, p<0.01). Factors independently associated with irregular followup were low income level (adjusted odds ratio (aOR)= 2.4; 95% confidence interval (CI), 1.44.1); absence of regular practitioner at HIV diagnosis (aOR= 1.9; 95% CI 1.13.3); imprisonment between HIV diagnosis and AIDS (aOR= 3.8; 95% CI 1.310. 9), and being non homo/bisexual male (aOR= 2.4; 95% CI 1.15.1) versus homo/bisexual male (aOR= 1.3; 95% CI 0.72.7) and female (reference). CONCLUSIONS: Results of this study show that several socioeconomic, psychological and cultural barriers to a regular preAIDS medical followup still exist. Impact of new antiretroviral therapy may only be optimal if these barriers are overcome.

Determinants of delayed diagnosis of HIV infection in France, 1993-1995.

OBJECTIVE: To describe the circumstances of the first HIV-positive test and to study the determinants of a delayed diagnosis of HIV infection. METHODS: In a retrospective study among adult AIDS patients diagnosed between July 1993 and May 1995 in two French districts, data on socioeconomic characteristics, circumstances of first HIV-positive test and attitudes and behaviours regarding medical care were collected in a confidential interview and analysed for potential association with a late test, defined as a first HIV-positive test within 6 months of AIDS diagnosis. RESULTS: Of the 359 AIDS patients studied, 69 (19.2%) had a late test. Late testers were more likely than other patients to have had an HIV-positive test because of clinical symptoms (89.7 versus 38.9%, P < 0.001) and not to perceive themselves as being at risk of infection with HIV (53.6 versus 39.3%, P < 0.05). The proportion of late testers was 34.6% among heterosexually infected patients, 12.7% among homo-/ bisexual men and 9.6% among injecting drug users. Factors independently associated with a late test were male gender [adjusted odds ratio (aOR), 5.6; 95% confidence interval (CI), 1.7-18.9] and absence of earned income (aOR, 5.2; 95% CI, 1.4-19) among heterosexually infected patients; high education (aOR, 3.1; 95% CI, 1.0-9.6) and having consulted a person practising alternative medicine (aOR, 3.4; 95% CI, 1.2-10) in homo-/bisexual men. CONCLUSIONS: Despite incentives to be tested for HIV, many individuals in France are still tested too late, even if they are in known high-risk groups. Efforts to test HIV-infected people as early as possible should be made by increasing the perception of HIV risk and decreasing the level of missed opportunities for testing. Current case management approaches make this recommendation critically important from both public health and an individual perspective.

[Management of drug addict pregnant women and their children]. / Prise en charge des femmes enceintes toxicomanes et de leurs enfants.

Children of substance abuse mothers have an increased risk of severe pathological disorders such as perinatal diseases (prematurity, intrauterine growth retardation, infections) with their neurological and respiratory complications and sequelae, and transmission of drug addiction related infections, ie human immunodeficiency virus, hepatitis B and C virus, syphilis. Many of these children present a drug withdrawal syndrome characterized by restlessness and jetteriness during the neonatal period. This is frequently followed by a post withdrawal period of several weeks duration with crying, excitement, sleep and feeding difficulties. Although these drug withdrawal manifestations have no incidence on the vital prognosis, it severely impairs the mother-infant interaction. Despite these disorders it appears that the outcome of these children is mainly related to their familial environment which is exposed to many risk factors: mother-child separation, violence, delinquency, precariousness, unhealthy housing, prostitution, drug dependency, parental death or imprisonment... Early medico-psycho-social intervention starting during pregnancy and a prolonged support for several years are the only way to improve their spontaneously poor outcome.

[Extrapulmonary and disseminated pneumocystosis in AIDS. A review of the literature]. / Pneumocystoses extrapulmonaires et disséminées au cours du SIDA. Une revue de la littérature.

We present a literature review about extrapulmonary and disseminated pneumocystosis in AIDS. The prevalence of such infections seems low but is probably under-estimated. Disseminated pneumocystosis occurs in patients with profound immunosuppression, who do not receive prophylaxis against Pneumocystis carinii pneumonia or are treated with aerolized pentamidine. The lack of specificity of symptoms may delay the diagnosis. Most organs may be involved. Three different presentations may be individualized: disseminated pneumocystosis, intra-thoracic only disseminated pneumocystosis, in an intra-thoracic localization alone, and localized extrapulmonary pneumocystosis. The mortality from disseminated disease is high, especially in the presence of low serum albumin level.

Influence of Pneumocystis carinii on nitrite production by rat alveolar macrophages.

Nitrite production by rat alveolar macrophages was studied to determine the role of L-arginine oxidation in the interaction between these cells and Pneumocystis carinii. Alveolar macrophages from rats obtained from two different breeders were used: rats from Janvier breeder had latent P. carinii infection, while those from Charles River breeder were bred in a germ-free environment. Pneumocystis carinii increased in vitro nitrite generation by unstimulated alveolar macrophages from Janvier rats only, and this was blocked by NG-monomethyl-L-arginine. Incubation of cells from Janvier and Charles River rats with lipopolysaccharide and/or interferon-gamma increased nitrite production to a similar extent. Pneumocystis carinii partially decreased nitrite release by activated alveolar macrophages, and this was still inhibited by NG-monomethyl-L-arginine. In the presence of P. carinii, superoxide dismutase used as a superoxide anion scavenger had no effect on nitrite production by activated cells. These results show that prior exposure to P. carinii leads to nitric oxide production by rat alveolar macrophages. Although the magnitude of this production seems to be moderate, it is of biological significance since cells of P. carinii-naive rats do not generate nitrite whereas those of latently infected rats do.

[Pigmented erythroderma in AIDS. 5 cases]. / Erythrodermies pigmentées au cours du SIDA. Cinq cas.

INTRODUCTION: We report five cases of pigmented erythroderma occurring during AIDS, noteworthy for its unusual hyperpigmented feature, its advent at the terminal stages of AIDS, and an CD8 cells dermal infiltrate. PATIENTS AND METHODS: It is a retrospective study of five patients infected with HIV: a woman infected by transfusion and four homosexual men, average 55 years old. No one was intravenous drug user. They were all severely immunocompromised; HTLV I/II serology was negative. Skin biopsies were studied with light microscopy (Hematoxylin-eosin) and immunohistochemical studies were performed on frozen sections. RESULTS: The patients had an erythroderma of particular interest because of the associated hyperpigmentation, the severe repercussion (pruritus, weight loss), and the difficulty in treating (except systemic corticosteroids). The histology demonstrated a mononuclear dermal lymphocytic infiltrate, without epidermotropism and atypical cytonuclear feature. The phenotype of the infiltrate was uniformly of the suppressor-cytotoxic subset (CD8+, CD4-). COMMENTS: Our cases are like those previously described as "Pseudo-Sezary", mimicking a lymphoma during AIDS. Numerous factors are probably the cause of this hyperpigmented erythroderma: HIV, CD8 cells... CONCLUSIONS: This severe skin disease, complicating AIDS, seems very particular, but not yet clearly defined. In practice, the problem remains the treatment of this severe erythroderma, because only the systemic corticosteroids are effective, but this is debatable during the treatment of AIDS.

Experimental evaluation of combined prophylaxis against murine pneumocystosis and toxoplasmosis.

Prophylactic efficacy of antimicrobial agents against pneumocystosis and toxoplasmosis was examined in a model of concurrent Pneumocystis carinii and Toxoplasma gondii infections in rats. Corticosteroid-treated rats naturally infected by P. carinii were challenged with the RH strain of T. gondii. Infection was assessed by counting P. carinii cysts in lung and by titration of T. gondii in tissues by tissue culture. Untreated rats died after challenge, with P. carinii infection in lungs and T. gondii infection in liver, spleen, lungs, and brain. In rats that received trimethoprim-sulfamethoxazole or pyrimethamine plus dapsone, T. gondii was eradicated and P. carinii pneumonia prevented. Roxithromycin, 200 or 400 mg/kg, provided significant protection against toxoplasmosis but had no efficacy against P. carinii. Atovaquone, 100 or 200 mg/kg, had only partial efficacy against pneumocystosis and toxoplasmosis. These results definitively confirm use of trimethoprim-sulfamethoxazole and pyrimethamine plus dapsone for prophylaxis against combined infection in immunocompromised hosts.