Switching to emtricitabine, tenofovir and rilpivirine as single tablet regimen in virologically suppressed HIV-1-infected patients: a cohort study.

OBJECTIVES: Emtricitabine/tenofovir/rilpivirine as a single-tablet regimen (STR) is widely used without licence in treatment-experienced patients. The purpose of this retrospective observational study was to assess viral suppression of ART-experienced patients switching to STR. METHODS: We assessed 131 pretreated patients switching to STR with HIV RNA <400 HIV-1 RNA copies/mL. The primary outcome measure was the proportion of patients at week 24 with HIV RNA <40 copies/mL. RESULTS: By week 24, eight patients had stopped STR: four because of adverse events and four for other reasons. Three virological failures were observed; among these, at least one patient developed cross-resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs), in particular with the E138K pattern. In intent-to-treat analysis, 92% of participants (120 of 131) achieved HIV RNA <40 copies/mL. Only grade 1 to 2 adverse events were observed, mainly consisting of increased liver enzymes (n=33). Systemic exposure to rilpivirine was above the usually observed steady-state levels for the 18 measurements assessed. CONCLUSIONS: Efficacy and tolerability are similar to those in treatment-naïve patients.

[The desire to become a parent when infected with human immunodeficiency virus, hepatitis C virus or hepatitis B virus]. / Désir d'enfant et infections virales: hépatites C et B et virus de l'immunodéficience humaine.

The French law (arrêté du 10 mai 2001) allows Assisted Reproductive Techniques (ART) in case of infection with human immunodeficiency virus, hepatitis C virus or hepatitis B virus. Our six years' experience is positive even if pluridisciplinary care needs specific equipment and human forces. Couples express high motivation. The wish to become a parent leads to a better care of the infection. ART results are excellent in case of male contamination, not as good when the female partner is infected but still encouraging. No contamination of the partner or the offspring occurred after ART. Data are already collected in France in this context. A European register should be constituted in an early future.

Poly(ADPR)polymerase expression and activity during proliferation and differentiation of rat astrocyte and neuronal cultures.

Poly(ADPR)polymerase (poly(ADPR)P) mRNA and enzymatic activity levels were investigated in primary cultures of rat astrocytes and neurons in the absence or presence of basic fibroblast growth factor (bFGF) and nerve growth factor (NGF), respectively. In cultured rat astrocytes, a biphasic increase in poly(ADPR)P mRNA, associated with enhanced nuclear poly(ADPR)P enzymatic activity, were observed. The first rise in poly(ADPR)P mRNA and enzymatic activity is at the beginning of cell proliferation and the second with the occurrence of cell differentiation. In the presence of bFGF (5 ng/ml) the mRNA peaks and the differentiation-associated poly(ADPR)P enzymatic activity undergoes a 2-fold increase. In neuronal cultures an initial high level of poly(ADPR)P mRNA is followed by a decrease while differentiation is progressively achieved. A limited increase of poly(ADPR)P activity is observed during this phase. In the presence of NGF (50 ng/ml), similar poly(ADPR)P mRNA expression and enzymatic activity patterns are observed. The results suggest that poly(ADPR)P is involved at the onset of nerve-cell proliferation and differentiation.

[Hepatitis A seroprevalence in HIV-infected patients]. / Séroprévalence de l'hépatite A chez des patients infectés par le VIH.

OBJECTIVE: The authors had for aim to prospectively study the hepatitis A seroprevalence of an HIV-infected population, followed-up in an outpatient clinic (CISIH Strasbourg). DESIGN: Blood tests were performed on all patients from September 2003 to March 2004 to screen for hepatitis A (total antibodies with Elisa). RESULTS: The overall seroprevalence was 219/514 (56.6%), similar in male and female patients. It increased with age, especially in European patients (P = 0.003). The seroprevalence was lower in European subjects: 46.3% (while it reached 100% in sub-Saharan Africans), the prevalence was similar whatever the HIV risk group (46% in homosexual as well as in heterosexual patients, 44% in intravenous drug users). Hepatitis B or C co-infection did not increase the seroprevalence of hepatitis A. The hepatitis A seroprevalence was similar in various CD4 T cell count categories. CONCLUSIONS: Our results stress the utility of hepatitis A serology in HIV-infected patients (more than 50% of European patients are non immune), and the importance of assessing hepatitis A vaccination.

Fat distribution evaluated by computed tomography and metabolic abnormalities in patients undergoing antiretroviral therapy: preliminary results of the LIPOCO study.

BACKGROUND: Fat distribution abnormalities have been reported in patients treated with various antiretroviral drug regimens. The LIPOCO study is an ongoing observational study of unselected HIV-infected patients which aims to better characterize such disorders and their metabolic correlations. METHODS: Cross-sectional analysis of data collected at baseline in the first 154 male patients included. Investigators divided patients into four predetermined clinical categories of fat distribution: lipoatrophy, obesity, mixed condition and normal. Body composition (tetrapolar bioelectrical impedance analysis and skinfold thickness), fat distribution [computed tomography (CT) scan], plasma glucose and insulin concentrations both fasting and during an oral glucose tolerance test and endocrine and lipid profile were measured and compared between the four groups. RESULTS: Patients in the lipoatrophy group had significantly decreased abdominal and mid-thigh subcutaneous fat area values and elevated levels of plasma triglycerides. Patients in the obese and mixed groups had significantly increased intra-abdominal fat area values and elevated levels of plasma insulin and C-peptide. The CT scans identified some patients with isolated subcutaneous fat accumulation but no other alterations in fat distribution and no insulin resistance. Visceral adipose tissue measured by CT scan was positively correlated with fasting insulin and the sum of insulin levels (P < 0.0001). Fasting insulin as well as the sum of insulin levels were negatively correlated with the delta HIV-RNA (log(10)). In a multivariate logistic regression model, the use of stavudine significantly correlated with fat wasting in both nucleoside reverse transcriptase inhibitor and protease inhibitor groups: odds ratio (OR), 413 [95% confidence interval (CI), 5.2-999; P = 0.0068] and OR, 2.08 (95% CI, 0.92-7.0; P = 0.058) respectively, when compared with the use of zidovudine. Neither lamivudine or didanosine use, nor the use of protease inhibitors were significantly associated with fat distribution abnormalities or fat wasting. CONCLUSIONS: These preliminary results suggest that three major types of fat distribution abnormalities may occur in isolation or in association in HIV-infected patients undergoing active antiretroviral therapy: a fat depletion or 'lipoatrophy' syndrome which might be related to the use of stavudine; a mixed or fat redistribution syndrome related to an unusual side-product of effective virus control; and a subcutaneous adiposity syndrome reflecting increase in caloric intake.

A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy.

OBJECTIVE: To compare body composition, body fat distribution and insulin secretion in patients taking nucleoside reverse transcriptase inhibitor (NRTI) therapy. DESIGN AND SETTING: Cross-sectional study in three French AIDS clinical centres. PATIENTS: Forty-three HIV-infected patients on long-term NRTI therapy including stavudine (n = 27) or zidovudine (n = 16) and 15 therapy-naive HIV-infected patients (control group). MAIN OUTCOME MEASURES: Fat wasting was assessed by physical examination and body composition by bioelectrical impedance. Regional fat distribution was estimated using caliper measurements of skinfold thickness at four sites and evaluated by computed tomography at abdominal and mid-thigh level. Fasting glucose, insulin, C-peptide, triglyceride, cholesterol, free fatty acid, testosterone, follicle stimulating hormone, luteinizing hormone, cortisol levels, CD4 cell count and HIV viral load were determined. Daily total caloric and nutrient intake were evaluated. RESULTS: The zidovudine group and the control group had similar body composition and regional fat distribution. Stavudine therapy was associated with a significantly lower percentage of body fat (12.9% versus 15.2% in the zidovudine group; P < 0.05), markedly decreased subcutaneous to visceral fat ratio (0.90 +/- 0.63 versus 1.92 +/- 1.34, P < 0.01) and higher mean intake of fat and cholesterol (P < 0.01). Fasting plasma glucose, insulin and C-peptide levels were similar among the three groups. Triglyceride levels were significantly higher in the stavudine group than in the controls (P < 0.05), but did not differ between the stavudine and the zidovudine group or between the zidovudine and the control group. Free fatty acids tended to be higher in the stavudine group but the difference did not reach statistical significance. Lipodystrophy was observed clinically in 17 (63%) patients taking stavudine, and in three (18.75%) patients taking zidovudine after a median time of 14 months. The relative risk of developing fat wasting was 1.95 in the stavudine group as compared with the zidovudine group (95% confidence interval, 1.18-3.22). Five out of 12 patients had a major or mild improvement in their lipodystrophy after stavudine was discontinued. CONCLUSION: Lipodystrophy may be related to long-term NRTI therapy, particularly that including stavudine.

Immunohistochemical evidence for neuronal and non-neuronal synthesis of GABA in the rat subcommissural organ.

In the past few years, several studies have demonstrated in the rat subcommissural organ the presence of nerve endings and modified ependymocytes showing an uptake of [(3)H]GABA. The present work was performed to demonstrate in this cerebral zone the possibility of a GABA synthesis by the immunohistochemical localization of glutamate decarboxylase (GAD). GAD-positive reaction was detected with unlabelled antibody-enzyme peroxidase anti-peroxidase. Some nerve terminals containing either clear round vesicles, or sometimes clear round vesicles and some large granular vesicles, exhibited a positive staining. These terminals could belong to GABAergic inputs in the subcommissural organ. The few reactive terminals containing some granular vesicles could be related to the serotoninergic input as suggested previously (Gamrani et al., 1981). Several ependymocytes of this structure contained GAD-like positive reaction; these cells are also capable of taking up [(3)H]GABA (Gamrani et al., 1981) and present neuronal properties with regard to GABA. However, the presence in their cytoplasm of ?? enolase, a specific glial marker, related them to glial elements. The presence of GABA in these ependymocytes suggests a modulating function of GABA on the secretory activity of the subcommissural organ.

Nail changes in patients infected with human immunodeficiency virus. A prospective controlled study.

OBJECTIVES: To study the frequency of nail changes in a population of human immunodeficiency virus (HIV)-infected patients and to evaluate the specificity of these findings by comparison with HIV-negative control subjects. DESIGN: Prospective controlled study. Nail changes were recorded by a standardized clinical examination (curvature, nail plate, color, onychomycosis). In case of clinical diagnosis of onychomycosis, mycological culture was performed. SETTING: Primary care university hospital. PATIENTS: A total of 155 HIV-1-positive patients and 103 healthy HIV-negative control subjects of comparable age and sex ratio. INTERVENTION: None. MAIN OUTCOME MEASURE: Clinical examination findings. RESULTS: Nail symptoms were present in 67.7% of HIV-positive patients vs 34.0% of controls (P << .001). The following symptoms were significantly more frequent in the HIV group: clubbing (5.8%) (P < .05), transverse lines (7.1%) (P < .01), onychoschizia (7.1%) (P < .05), leukonychia (14.3%) (P < .001), and longitudinal melanonychia (14.8%) (P < .01). The main finding was onychomycosis in 30.3% of patients vs 12.6% of controls (P < .001). Trichophyton rubrum was present in 48% of onychomycoses and unusual Candida species were also recorded. Multiple fungi were frequently cultured in a single patient. The mean CD4+ cell count was lower in patients with onychomycosis and the frequency of onychomycosis increased in advanced stages of HIV disease. Acquired total leukonychia of the 20 nails was present in 4% of patients. CONCLUSION: Nail symptoms are much more frequent in patients with HIV than in healthy controls, and some of them could be linked to the level of immunosuppression.

[Emergence of resistant hepatitis B virus strains during long-term lamivudine therapy in human immunodeficiency virus co-infected patients]. / Emergence de souches résistantes de virus de l'hépatite B, sous traitement prolongé par lamivudine, chez des malades co-infectés par le virus de l'immunodéficience humaine.

Seven patients co-infected with hepatitis B virus (HBsAg and HBeAg carriers, quantifiable HBV DNA with the bDNA technic) and human immunodeficiency virus received a triple antiretroviral combination therapy, including lamivudine (150 mg twice a day). Hepatitis B viral load rapidly became undetectable in 6/7 patients. It remained below the level of detection in 2 subjects, after 20 and 22 months of treatment, with one of them achieving HBeAg/anti-HBe seroconversion. However, in the other 4 individuals, hepatitis B viremia increased again after 8 to 16 months of lamivudine-containing regimen. The last patient was a non-responder. The 4 relapsers developed a double mutation Leu(528) for Met(528) and Met(552) for Val(552), on hepatitis B virus polymerase, either concomitant (M8 and M16) with a hepatitis B virus DNA increase, or 2 months earlier (M10 and M12). The high frequency of hepatitis B virus resistance to lamivudine emphasizes the necessity of identifying more effective strategies, such as double combination therapies.

[Multicenter study of intrafamilial transmission of hepatitis C virus in human immunodeficiency virus infection]. / Etude multicentrique de la transmission intra-familiale du virus de l'hépatite C dans le contexte de l'infection par le virus de l'immunodéficience humaine.

OBJECTIVE: Intrafamilial transmission of hepatitis C virus in human immunodeficiency virus and hepatitis C virus co-infections is not well documented. This cross-sectional study evaluated the transmission of hepatitis C virus in the sexual partners of hepatitis C virus and human immunodeficiency virus co-infected patients. METHODS: Hemophiliacs and transfused hepatitis C virus and human immunodeficiency virus co-infected patients who were being seen in three French university hospitals, and their sexual partners were studied by a face-to-face interview using an epidemiological questionnaire and by biological tests: antibodies against hepatitis C virus, hepatitis C virus RNA, and ALT activity. RESULT: Fifty-two subjects were included: 26 cases and their 26 sexual partners. Three sexual partners (11.5 %) had anti-hepatitis C virus antibodies, two of whom had an undetermined RIBA test. All three had a risk factor for hepatitis C virus infection (transfusion, intra-muscular injections with re-usable needles). Two of these three partners were also human immunodeficiency virus antibody positive. Hepatitis C virus RNA was negative in all sexual partners. CONCLUSION: This study provides evidence of a low prevalence of anti-hepatitis C virus antibodies in sexual partners of hepatitis C virus and human immunodeficiency virus co-infected patients. It does not support intra-familial transmission of hepatitis C virus.

[Prevention of pneumocystosis with pentamidine aerosols]. / La prévention des pneumocystoses par la pentamidine en aérosols.

In patients with human immunodeficiency virus infection primary or secondary prevention of pulmonary pneumocystosis sometimes fails, resulting in atypical or extrarespiratory pneumocystosis. From the series found in the literature and from our own experience, it appears that such failures depend on the way aerosols are administered: they are usually due to low dosage, intervals of more than 2 weeks between aerosols, excessive particle size or poor patient's compliance. We suggest that pentamidine mesylate or isethionate should be administered forthnightly in doses of 4 mg/kg bodyweight, using an inhaler capable of delivering particles of less than 2 micrometers in diameter.

[Acrosyndromes induced by bleomycin in HIV 1 related Kaposi's disease. 5 cases]. / Acrosyndromes induits par la bléomycine au cours de la maladie de Kaposi associée au VIH 1. 5 observations.

OBJECTIVES: Raynaud's syndromes may be observed in HIV-infected patients, particularly those with Kaposi disease treated with bleomycin. This complication occurs in 10% of patients given bleomycin although only 7 cases have been reported in the literature. The aim of this study was to determine the frequency of certain biological abnormalities observed in HIV patients with Kaposi disease given bleomycin and who develop Raynaud's syndromes. PATIENTS AND METHODS: A survey was conducted from 1989 to 1995 among 1074 patients infected with HIV-1. There were 121 patients with Kaposi disease and 73 of these were treated with bleomycin. The clinical features and laboratory results (cryoglobulinemia, free protein-S, protein-C, anticardiolipin antibodies, von Wille-brand factor (vWF.ag) endothelin-1) were obtained in 5 patients who developed biomycin-induced Raynaud's syndrome. RESULTS: Amont the 73 patients with Kaposi disease treated with bleomycin (total mean dose = 227 mg (120-380 mg)), 5 patients (12.6%) developed a severe Raynaud's synchrome including two who suffered digital necrosis Withdrawal of bleomycin led to improved symptomatology (n = 2) or an aggravation (n = 1) in the 3 patients followed. CONCLUSION: Raynaud's syndromes are frequent (12.6%) in HIV patients with Kaposi disease treated with bleomycin. The vascular toxicity of bleomycin, demonstrated in animals, would appear to be the causal factor among others. Release of endothelial factors (vWF.ag endothelin-1) and perturbed hemostasis related to the HIV infection (protein-S deficiency, anti-cardiolipin antibodies) could be an expression of and aggravate the vascular toxicity of bleomycin.

[Reproductive options for people living with HIV: 2013 guidelines from the French expert working group]. / Désir d'enfant chez les personnes vivant avec le VIH : nouvelles recommandations 2013 du groupe d'experts français.

The desire for children is a legitimate aspiration that should be part of multidisciplinary care for all men, women or couples living with HIV. The use of effective antiretroviral therapy has revolutionized the prevention of sexual, as well as mother-to-child HIV transmission. When the HIV plasma viral load is undetectable on long-term antiretroviral therapy, the risk of mother-to-child transmission is <1% and the risk of heterosexual HIV transmission without condom use in a stable relationship is very low (estimated at less than 1/10,000) in the absence of inflammation of the genital tract. In a man with a long-term undetectable viral load, viral shedding in semen is uncommon, but may occur persistently or intermittently. The same appears true of viral shedding in the vaginal tract of women. Reproductive options are: natural conception, self-insemination when the woman is HIV-infected, assisted reproduction. Natural conception is now considered to be an acceptable option when the conditions are met, after exploring four aspects: (1) virological (viral load undetectable sustained for at least 6 months on therapy), (2) genital (absence of genital infections or lesions), (3) fertility (after appropriate evaluation) and (4) detecting the ovulation period to limit intercourse without condoms. Assisted reproduction has two objectives in the context of HIV, to allow the couple to conceive without abandoning condom use and/or to treat infertility.

[HIV and pregnancy: 2013 guidelines from the French expert working group]. / Infection par le VIH et grossesse: nouvelles recommandations 2013 du groupe d'experts français.

With effective antiretroviral therapy, the risk of mother to child transmission (MTCT) is now under 1%. The 2013 French guidelines emphasize early antiretroviral lifelong antiretroviral therapy. Thus, the current trend for women living with HIV is to take antiretroviral therapy before, during and after their pregnancies. A major issue today is the choice of antiretroviral drugs, to maximize the benefits and minimize the risks of fetal exposure. This requires interdisciplinary care. The use of effective therapies permits gradual but profound changes in obstetric practice. When maternal plasma viral load is controlled (<50 copies/ml), obstetrical care can be more similar to standards in HIV-negative women. Prophylactic cesarean section is recommended when the viral load in late pregnancy is above 400 copies/mL. Intravenous zidovudine during labor is recommended only if the last maternal viral load is>400 copies/mL or in case of complications such as preterm delivery, bleeding or chorio-amnionitis during labor. In case of premature rupture of membranes before 34 weeks, a multidisciplinary decision should be made, based on gestational age and control of maternal viral load; if the woman is under antiretroviral therapy and especially if her viral load is undetectable, steroids and antibiotics should be offered and pregnancy can be continued except in case of signs or symptoms of chorio-amnionitis. Breastfeeding is not recommended in women living with HIV in France, as in industrialized countries. Prophylaxis in the newborn is usually zidovudine for 1 month. In case of significant exposure to HIV perinatally, in particular when, maternal viral load is>1000 copies/mL, prophylactic combination therapy is recommended. Monitoring of the child is necessary to determine whether or not it is free of HIV infection and to monitor possible adverse effects of perinatal exposure to antiretroviral drugs.

[Assisted reproductive technique for an opiates dependant couple]. / Assistance médicale à la procréation chez un couple dépendant aux opiacés.

The aim of our network "Motherhood and Addiction Alsace" is to take care of opiates addicted pregnant women in order to permit the birth of a healthy child, raised by stabilized parents both on drug use and psychosocial status. A couple, both on methadone treatment, with chronic hepatitis for the husband had access to an in vitro fertilization program thanks to the network care. The difficulties on the path to parenthood, the adequate use of painkillers, neonatal care and the use of a coordinated action of all health professionals are discussed.

[Alterations of ovarian reserve tests in Human Immunodeficiency Virus (HIV)-infected women]. / Altérations des marqueurs de la réserve ovarienne chez les femmes infectées par le virus de l'immunodéficience humaine.

OBJECTIVES: Little is known about the impact of highly active antiretroviral therapy or HIV infection itself on the ovarian function. The aim of this study was to evaluate ovarian function in HIV-infected women in comparison with normal values from non-HIV infected women. PATIENTS AND METHODS: This is a prospective pilot study using markers of ovarian function: the antral follicular count (AFC) defined between cycle days 7 and 10 and follicle-stimulating hormone (FSH), inhibin B and antimüllerian hormone (AMH) for early follicular phase hormonal assessments. A descriptive analysis according to age was performed. RESULTS: Results from 78 HIV positive women are presented. AFC shows a high rate of abnormal values (63 %) occurring surprisingly early. The hormonal markers are concordant with a 36, 57 and 23 % abnormal rate for FSH, inhibin B and AMH respectively. DISCUSSION AND CONCLUSION: In our series, HIV seropositivity was associated with stigmas of premature ovarian insufficiency. This may explain impaired fertility but also suggests premature menopause in this population that should therefore be monitored early for such changes.

[Inadequate vaccination coverage in a French cohort of HIV positive patients]. / Insuffisance de couverture vaccinale d'une cohorte française de patients séropositifs VIH.

INTRODUCTION: HIV patients have a high rate of infectious complications. Vaccination, though less efficient in case of severe immunosuppression, can prevent some of these infections. Since 2006, new vaccine recommendations have been elaborated in France. We studied the vaccine status of HIV+ patients for influenza, Streptococcus pneumoniae, tetanus, and hepatitis A and B among an alsatian HIV+ population. PATIENTS AND METHODS: From August 20, 2007 to September 15, 2007, HIV patients of the Alsace HIV center (COREVIH) were included in a prospective study, screening demographic, medical, immunovirological, and vaccination data. RESULTS: Three hundred and thirty-one patients were included, 49% of whom were asymptomatic, 29% symptomatic without AIDS, 18% at AIDS stage, and no documentation for 4%. Seventy-one patients (21.4%) were vaccinated against influenza, 11 (3.3%) against Streptococcus pneumoniae, 34 against HAV (only 16.3% of patients with a negative test before), 120 against HBV (60% of patients with no serological markers before), and 186 (56.2%) against tetanus. The most frequent reasons for non-vaccination were non-proposal by physicians, lack of expected effectiveness, and fear of an immunovirological adverse effect. CONCLUSION: Vaccination coverage for recommended vaccines of HIV infected people remains at a low level and appears sometimes inferior to the rates reached among the general French population. It is necessary to inform prescribers and HIV positive patients about the interest of vaccination.