Hypogonadism: a neglected comorbidity in young and middle-aged HIV-positive men on effective combination antiretroviral therapy.

OBJECTIVE: Male hypogonadism is poorly characterized in young-to-middle-aged people with HIV (PWH). We used a reliable free testosterone assay to assess the prevalence and predictive factors for male hypogonadism in PWH on effective combined antiretroviral therapy (cART). DESIGN: A French cross-sectional study from January 2013 to June 2016. METHODS: We included HIV-1-infected men aged between 18 and 50years with HIV loads of 50 RNA copies/ml or less, on effective cART for at least 6 months. Hypogonadism was defined, according to guidelines, as a mean calculated serum free testosterone concentration less than 70pg/ml (Vermeulen equation). Sociodemographic, anthropo-metric, bone-densitometry, hormonal, immunovirological, metabolic, and therapeutic parameters were collected. The IIEF-5, HAM-D, and AMS scales, respectively, assessed erectile function, depression, and quality of life. RESULTS: Overall, 240 patients were enrolled, 231 were analyzed. Low free testosterone concentrations (<70pg/ml) were recorded in 20 patients (8.7%), and were exclusively of secondary origin. In multivariable analysis, the risk factors predictive of male hypogonadism were age more than 43 years [adjusted odds ratio (aOR) 3.17, 95% confidence interval (95% CI) 1.02-9.86; P  = 0.04], total fat percentage more than 19% (aOR3.5, 95% CI 1.18-10.37; P  = 0.02), and treatment including efavirenz (aOR3.77, 95% CI 1.29-10.98; P  = 0.02). A nadir CD4+ T-cell count more than 200 cells / µl (aOR 0.22, 95% CI 0.07-0.65;P < 0.01) were protective. CONCLUSION: Male hypogonadism remains common in young-to-middle-aged PWH with stably suppressed viral replication. Treatment including efavirenz, being over 43 years old, and having a total body fat percentage greater than 19% could be used as criteria for identifying PWH at risk. Early screening for male hypogonadism might improve care by identifying patients requiring testosterone replacement.

Reduced bone mineral density among HIV-infected, virologically controlled young men: prevalence and associated factors.

OBJECTIVE: Reduced bone mineral density (BMD) is a frequent comorbidity observed in people living with HIV (PLHIV). We aimed to determine the prevalence of reduced BMD and its associated factors among young PLHIV men, virologically controlled by combination antiretroviral therapy (cART). DESIGN: A bicentric cross-sectional study. METHODS: We selected men, aged less than 50 years, treated by cART, with HIV-RNA less than 50 copies/ml. BMDs of lumbar spine and hip were measured by dual-energy X-ray absorptiometry (DXA). A Z-score at either site between -1.0 and -2.0 or -2 or less defined osteopenia or osteoporosis, respectively. Linear and polytomous logistic regression analyses were performed. RESULTS: Among 230 men with a median age of 43 [interquartile range (IQR), 36-47] years, BMI of 23.5 (21.3-25.3) kg/m(2) and median duration of cART of 4.2 (1.7-8.5) years, reduced BMD was diagnosed in 48.3%. In multivariate analyses, BMI decrease was associated with a risk of osteopenia [odds ratio (OR) = 1.17, P < 0.01] and osteoporosis (OR = 1.24, P < 0.01). Oestradiol levels decrease were associated with osteoporosis (OR = 1.32, P < 0.05) and lower lean mass with osteopenia (OR = 2.98, P < 0.01). There was a protective effect of the duration of cART (OR = 0.87, P < 0.01), which was even greater when the duration was more than 3 years (OR = 0.44, P = 0.02). CONCLUSION: There is a high prevalence of reduced BMD among young men, despite persistent virological control of HIV-infection. This observation raises the question of extending current recommendations for BMD assessment to PLHIV aged < 50 years for whom BMD has stabilized after cART initiation, i.e. treated for more than three years.

Recurrent obstructive acute pyelonephritis: A rare form of Actinotignum (Actinobaculum) schaalii infection in a HIV-1 infected patient.

Actinobaculum schaalii is a rarely reported, anaerobic, Gram-positive bacterium which role as uropathogen is emerging. We report here the case of a 47 year old HIV-1 infected woman presented with five recurrent episodes of obstructive pyelonephritis in the context of multiple renal stones. No bacteria was found until the fifth episode, during which prolonged urinary cultures as well as 16S rDNA sequencing allowed the diagnosis of A. schaalii infection. She had developed a life-threatening condition with severe renal failure. A right nephrectomy was performed and found that the intrarenal stones were attributed to the antiretroviral therapy. The renal parenchyma corresponded to an end-stage renal disease with chronic pyelonephritis without abcesses or granules. The situation improved after six months of amoxicillin therapy.

Identification of Variants of Hepatitis C Virus (HCV) Entry Factors in Patients Highly Exposed to HCV but Remaining Uninfected: An ANRS Case-Control Study.

Hepatitis C virus (HCV) causes persistent infection in 75% of cases and is a major public health problem worldwide. More than 92% of intravenous drug users (IDU) infected by human immunodeficiency virus type 1 (HIV-1) are seropositive for HCV, and it is conceivable that some HIV-1-infected IDU who remain uninfected by HCV may be genetically resistant.Here we conducted a case-control study to identify mutations in HCV entry coreceptors in HIV-infected IDU who remained uninfected by HCV. We recruited 138 patients, comprising 22 HIV+ HCV- case IDU and 116 HIV+ HCV+ control IDU. We focused on coreceptors in which point mutations are known to abolish HCV infectivity in vitro. Our previous study of the Claudin-1 gene revealed no specific variants in the same case population. Here we performed direct genomic sequencing of the Claudin-6, Claudin-9, Occludin and Scavenger receptor-B1 (SCARB1) gene coding regions. Most HIV+ HCV- IDU had no mutations in HCV coreceptors. However, two HIV+ HCV- patients harbored a total of four specific mutations/variants of HCV entry factors that were not found in the HIV+ HCV+ controls. One case patient harbored heterozygous variants of both Claudin-6 and Occludin, and the other case patient harbored two heterozygous variants of SCARB1. This suggests that HCV resistance might involve complex genetic events and factors other than coreceptors, a situation similar to that reported for HIV-1 resistance.

Claudin-1 gene variants and susceptibility to hepatitis C infection in HIV-1 infected intravenous drug users (an ANRS case-control study).

Hepatitis C virus (HCV) seroprevalence is highly diverse among human immunodeficiency virus-1 (HIV-1) infected patients, ranging between 10% of HIV-1 infected homo-bisexuel men, to >92% in patients infected with HIV-1 who acquired HIV-1 through intravenous drug use. Thus, being HCV-free while having acquired HIV-1 via intravenous drug use is a rare situation. Claudin-1 is a protein involved in intracellular tight-junctions and has been identified as a major cellular co-receptor for HCV infection. Our objective was to determine whether Claudin-1 gene (CLDN1) mutations might be involved in natural resistance to HCV infection. We conducted a case-control study. All recruited patients acquired HIV-1 infection via intravenous drug use route before 1995. The case study patients remained free from HCV infection (negative anti-HCV antibodies and HCV-RNA). The control study patients was co-infected with HCV (positive anti-HCV antibodies). Direct genomic sequencing of the CLDN1 gene coding region and adjacent intron/exons junctions was performed from peripheral blood mononuclear cells. A total of 138 Caucasian patients were enrolled. Twenty-two patients (cases) were free from HCV infection and 116 (controls) were co-infected with HCV. We found single nucleotide polymorphisms (SNPs) described previously with no significant differences in allele frequencies between cases and controls. In conclusion, despite being a major cellular co-receptor for HCV entry in vitro, we did not identify any specific substitution in CLDN1 gene coding region in our study patients highly exposed but resistant to HCV infection in vivo. Other cellular co-factors involved in HCV infection should be investigated in this highly-exposed intravenous drug users patients.

Antiretroviral therapy and sustained virological response to HCV therapy are associated with slower liver fibrosis progression in HIV-HCV-coinfected patients: study from the ANRS CO 13 HEPAVIH cohort.

BACKGROUND: The aim of this study was to describe changes in repeated liver stiffness (LS) measurements and to assess the determinants of increase in LS in HIV-HCV-coinfected patients. METHODS: HIV-HCV-coinfected adults enrolled in the ANRS CO 13 HEPAVIH cohort, for whom two results of LS, evaluated over ≥24 months, were available. Patients with unreliable LS results were not included. LS was measured at baseline and every year thereafter. Determinants of LS increase were assessed using linear (primary outcome: last LS minus first LS value) and logistic (secondary outcome: ≥30% increase in the initial LS value) regression analyses. RESULTS: A total of 313 patients (mean age 45 years, 67.4% male) were included. Overall, 93.9% were receiving antiretroviral treatment (ART). The mean baseline CD4(+) T-cell count was 471 cells/mm(3) and 72.2% of patients had undetectable plasma HIV RNA. The mean interval between the first and last LS measurements was 33.5 months. No significant difference was found between baseline and follow-up mean LS values (P=0.39). However, a decrease of ≥30% in LS was observed in 48 (15.3%) patients and an increase of ≥30% in 64 (20.5%) patients. In multivariate linear and logistic analyses, excessive alcohol intake (ß coefficient 6.8; P=0.0006) and high HCV viral load (OR 1.7, 95% CI 1.1, 2.5; P=0.01) were independently associated with an increase in LS, whereas time on ART>114.5 months (OR 0.5, 95% CI 0.3, 0.9; P=0.03) and achievement of sustained virological response (OR 0.1, 95% CI 0.01, 0.9; P=0.04) were independently associated with no increase in LS. CONCLUSIONS: Our findings show that long-term ART and achieving sustained virological response in HIV-HCV-coinfected patients are both significantly associated with lack of increase in LS over a 33-month period.

Insulin resistance is associated with a higher risk of hepatocellular carcinoma in cirrhotic HIV/HCV-co-infected patients: results from ANRS CO13 HEPAVIH.

BACKGROUND & AIMS: Compared to HCV-mono-infected patients, hepatocellular carcinoma (HCC) occurs at younger age in HIV/HCV-co-infected patients, is markedly more advanced at diagnosis, is less amenable to curative treatment, and has a more severe outcome. The aim of this study was to identify factors predictive of HCC occurrence in a large cohort of HIV/HCV-co-infected patients with cirrhosis. METHODS: This study involved 244 HIV/HCV-co-infected patients included in the ANRS CO13 HEPAVIH cohort, who had HCV-related cirrhosis (clinically or histologically proven cirrhosis, or liver stiffness ≥12.5 kPa) and no signs of HCC at baseline. Cox proportional hazards models were used to identify factors associated with HCC occurrence. RESULTS: During a median follow-up of 2.6 (IQR, 1.8-3.5) years, 21 patients (8.6%) developed HCC. Diagnosis of HCC was based on histology in 5 patients (24%) and non-invasive criteria in 16 patients (76%). In univariate analyses, the following factors were related to HCC occurrence: age, previous cirrhosis decompensation, a HOMA value >3.8 (patients with treated diabetes were excluded from the HOMA calculation), a lower platelet count, a lower prothrombin level, and higher alpha-fetoprotein levels. The HOMA value was >3.8 at baseline in 66.7% of patients who developed HCC and in 35.3% of the remaining patients (p=0.016). In multivariate analysis, age over 50 years (adjusted RR 3.2, 95% CI 1.2-9.0; p=0.02) and a HOMA value >3.8 (adjusted RR 3.4, 95% CI 1.1-10.3; p=0.03) remained significantly associated with HCC occurrence. CONCLUSIONS: As in HCV-mono-infected patients with HCV-related cirrhosis, insulin resistance appears to play a key role in HCC occurrence in HCV/HIV-co-infected patients with cirrhosis. This finding calls for specific screening strategies for patients with a particularly high risk of developing HCC.

Tolerability of HIV postexposure prophylaxis with tenofovir/emtricitabine and lopinavir/ritonavir tablet formulation.

OBJECTIVE: To evaluate the tolerability of HIV postexposure prophylaxis (PEP) with tenofovir/emtricitabine and lopinavir/ritonavir tablet formulation (TDF/FTC+LPV/r). DESIGN: Multicentric observational prospective study. METHOD: Adults with an HIV transmission risk in the past 48 h were eligible. Baseline sociodemographic characteristics, description of exposure event, and HIV serostatus of the source patient were collected. Laboratory monitoring for toxicity and a clinical evaluation were performed; adherence and side effects were recorded using a standardized form on day 0, 15, and 28. RESULTS: Between November 2006 and June 2008, 249 participants were included in 10 French hospitals. Mean age was 31.5 +/- years. Sex ratio male/female was 1.96. Exposure events are as follows: occupational exposure, 40 (16%); sexual intercourse, 204 (82%); and other, 5 (2%). Tolerability could be evaluated in 188 cases. In 22 cases, PEP was discontinued for adverse effects before day 28, including two cases of skin rash related to TDF/FTC prescription, one renal lithiasis related to LPV/r prescription, and one rhabdomyolysis. One hundred and sixty-six persons completed the 28 days of PEP with tolerability judged as good in 96 (58%) individuals. Among everyone who experienced at least one side effect, 78% reported diarrhea, 78% asthenia, and 59% nausea and/or vomiting. CONCLUSION: Considering data of previous studies performed using similar methodology, the dropout rate due to adverse events appeared significantly lower in TDF/FTC+LPV/r tablet formulation than those in zidovudine/lamivudine (ZDV/3TC)+nelfinavir (P < 0.0001), ZDV/3TC+lopinavir/ritonavir soft gel capsules (P < 0.01), and 3TC+TDF+atazanavir boosted by ritonavir (P < 0.05) and should be considered as standard of care concerning HIV PEP.

Post-exposure prophylaxis with a maraviroc-containing regimen after occupational exposure to a multi-resistant HIV-infected source person.

We report the case of a health care worker who received a post-exposure prophylaxis including an investigational drug, maraviroc, after a needle stick percutaneous injury to an HIV-infected patient with late-stage disease and harboring a multi-drug resistant virus. Post-exposure prophylaxis including maraviroc was pursued for a total of 28 days, with a weekly clinical and biological evaluation. Post-exposure prophylaxis was well tolerated, with no increase in liver function tests. The health care worker remained HIV-negative after a 6-month follow-up.

Human herpesvirus 6-associated retrobulbar optic neuritis in an HIV-infected patient: response to anti-herpesvirus therapy and long-term outcome.

Like other herpesviruses, human herpesvirus 6 (HHV-6) can reactivate in immunocompromised patients. A case is described of an HIV-1-infected patient who developed bilateral retrobulbar optic neuritis associated with HHV-6 infection. A 59-year-old woman, infected with HIV for 18 years, interrupted antiretroviral treatment because of therapeutic failure and severe metabolic complications. She presented subsequently with blurred vision and ophthalmological examination showed visual loss due to optic neuritis. Her CD4+ count was 285 cells/mm(3) and her plasma HIV-1 RNA level was 5.5 log(10) copies (cp)/ml. Magnetic resonance imaging of the brain was normal. HHV-6 loads were 3.2 log cp/ml in cerebrospinal fluid (CSF) and 6.3 log cp/10(6) peripheral blood mononuclear cells. Combined intravenous treatment was started with foscarnet and ganciclovir then changed to cidofovir and long-term valganciclovir. Her ocular condition improved gradually despite little decrease of the HHV-6 load in the CSF. Salvage antiretroviral treatment was then administered, with marked immunological and virological responses, contributing to further progressive ocular improvement. HHV-6-related optic neuritis has not been described previously in HIV-infected patients. Anti-HHV-6 treatment improved the patient's vision, but immune restoration seems to remain essential for long-term recovery.