On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection.

BACKGROUND: Antiretroviral preexposure prophylaxis has been shown to reduce the risk of human immunodeficiency virus type 1 (HIV-1) infection in some studies, but conflicting results have been reported among studies, probably due to challenges of adherence to a daily regimen. METHODS: We conducted a double-blind, randomized trial of antiretroviral therapy for preexposure HIV-1 prophylaxis among men who have unprotected anal sex with men. Participants were randomly assigned to take a combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or placebo before and after sexual activity. All participants received risk-reduction counseling and condoms and were regularly tested for HIV-1 and HIV-2 and other sexually transmitted infections. RESULTS: Of the 414 participants who underwent randomization, 400 who did not have HIV infection were enrolled (199 in the TDF-FTC group and 201 in the placebo group). All participants were followed for a median of 9.3 months (interquartile range, 4.9 to 20.6). A total of 16 HIV-1 infections occurred during follow-up, 2 in the TDF-FTC group (incidence, 0.91 per 100 person-years) and 14 in the placebo group (incidence, 6.60 per 100 person-years), a relative reduction in the TDF-FTC group of 86% (95% confidence interval, 40 to 98; P=0.002). Participants took a median of 15 pills of TDF-FTC or placebo per month (P=0.57). The rates of serious adverse events were similar in the two study groups. In the TDF-FTC group, as compared with the placebo group, there were higher rates of gastrointestinal adverse events (14% vs. 5%, P=0.002) and renal adverse events (18% vs. 10%, P=0.03). CONCLUSIONS: The use of TDF-FTC before and after sexual activity provided protection against HIV-1 infection in men who have sex with men. The treatment was associated with increased rates of gastrointestinal and renal adverse events. (Funded by the National Agency of Research on AIDS and Viral Hepatitis [ANRS] and others; ClinicalTrials.gov number, NCT01473472.).

Assessment of HIV Screening Tests for Use in Preexposure Prophylaxis Programs.

Preexposure prophylaxis programs involve frequent human immunodeficiency virus (HIV) testing. We evaluated the sensitivity of 2 antigen/antibody immunoassays (Architect and Bioplex), 2 antibody-based rapid tests (Vikia-HIV-1/2 and Autotest-VIH), and 1 antigen/antibody rapid test (Alere HIV Combo) for the diagnosis of HIV infection. Among the 31 HIV-1-infected participants in the ANRS-IPERGAY trial, HIV-1 RNA was detected alone in only 2. The sensitivities of the Architect and Bioplex assays were 83% (95% confidence interval [CI], 76%-99%) and 82% (95% CI, 63%-94%), respectively. The sensitivities of the Vikia, Autotest, and Alere tests were 54% (95% CI, 34%-72%), 50% (95% CI, 31%-69%), and 78% (95% CI, 58%-91%), respectively. Antigen/antibody tests should be preferred to avoid missing cases of acute HIV infection and to decrease the related risks of viral transmission and emergence of drug resistance.

Fluctuating anaemia in treated HIV patients: could be a PICA?

HIV infected patients are frequently exposed to anaemia, due to antiretroviral agents and/or prophylactic treatment of opportunistic infections. Anemia due to PICA, unusually evoked in our western countries, could be a more frequent situation than imagined. We report two cases of fluctuating anemia with no HIV or iatrogenic origin, observed in two HIV infected women, 47 years old and 33 years old respectively, coming from Africa and treated with antiretroviral agents. The anemia was explained by a culturally sanctioned practice of kaolin ingestion, in the broader context of PICA and resolved after the withdrawal of kaolin ingestion. PICA, and in particular kaolin ingestion, must be investigated when HIV infected patients came from Africa and presented significative unexplained anemia.

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.

Evaluation of Drug Abuse by Hair Analysis and Self-Reported Use Among MSM Under PrEP: Results From a French Substudy of the ANRS-IPERGAY Trial.

BACKGROUND: We used the Agence nationale de Recherches sur le sida et les hépatites virales (ANRS)-IPERGAY trial to qualitatively and quantitatively measure drug use among men who have sex with men under preexposure prophylaxis using 2 different methods, to better understand and collectively respond to risky practices. METHOD: We included 69 volunteers of the ANRS-IPERGAY trial. We measured drug use by 2 methods: (1) drug detection by hair analysis and (2) reported drug use by self-reported drug consumption. RESULTS: New psychoactive substances (NPS) and conventional drugs were detected in 53 of the 69 (77%) volunteers by hair analysis and in 39 of the 69 (57%) volunteers by questionnaires. On the 219 hair segments analyzed, the most commonly used drugs were cocaine in 47 of the 69 (68%), 3,4-methylenedioxymethamphetamine/ecstasy in 31 of the 69 (45%), and NPS in 27 of the 69 (39%). On the 1061 collected questionnaires, the most commonly used drugs were cocaine in 31 of the 69 (45%), 3,4-methylenedioxymethamphetamine/ecstasy in 29 of the 69 (42%), and NPS in 16 of the 69 (23%). Hair analysis detects more conventional drugs and/or NPS use (P < 0.05). Drug use identified by hair was significantly associated with a higher number of sexual partners in the past 2 months (P ≤ 0.001), more often casual partners (P ≤ 0.001), condomless anal sex (P ≤ 0.005), hardcore sexual practices (P ≤ 0.001), a higher number of sexually transmitted infections, and chemsex (P ≤ 0.05). CONCLUSIONS: Self-report drug use by questionnaires remains the reference tool for harm reduction at the individual level because of its feasibility and low cost. However, hair analysis is more sensitive, objectively assessing consumption, and interesting to understand uses and to be able to collectively respond to risky practices with adapted messages.

Community-Based Care in the ANRS-IPERGAY Trial: The Challenges of Combination Prevention.

ANRS-IPERGAY was a community-based randomized trial investigating the efficacy of sexual activity-based HIV pre-exposure prophylaxis (PrEP) in a population of males and transgender females who had sex with men and were at high risk of HIV infection. We qualitatively analyzed the support provided to participants by community-based health workers (CBHW) throughout the trial's double-blind and open-label extension phases. In particular, we showed that the relationship between participants and CBHW strongly influenced self-managed pill intake. The delicate construction of this relationship, balanced between trust and dependence, played an important role in PrEP adherence. CBHW had to deal with various issues surrounding participants' feelings of empowerment regarding their role in the trial, as well as related tensions between various logics and rationalities. They were essential to participants' continued involvement.

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.

HIV and hypogonadism: a new challenge for young-aged and middle-aged men on effective antiretroviral therapy.

Male hypogonadism is poorly defined in people living with HIV. Using a reliable free-testosterone assay, we examined the prevalence and risk factors of male hypogonadism among people living with HIV on effective antiretroviral therapy. Male hypogonadism was found in 12.4% of patients, twice the rate reported in the general population of the same age. Two risk thresholds, namely 5 years of antiretroviral therapy and 19% total body fat, may help to identify patients at risk.

Efficacy, safety, and effect on sexual behaviour of on-demand pre-exposure prophylaxis for HIV in men who have sex with men: an observational cohort study.

BACKGROUND: Data for on-demand pre-exposure prophylaxis (PrEP) are scarce. We implemented a cohort study to assess its efficacy, safety, and effect on sexual behaviour. METHODS: We invited men and transgender women who have sex with men, previously enrolled in the randomised placebo-controlled ANRS IPERGAY trial at seven sites (six in France and one in Canada), to participate in an open-label extension with on-demand tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) to be taken before and after sexual intercourse. We assessed the incidence of HIV and other sexually transmitted infections (STIs), PrEP adherence, safety, and sexual behaviour. Statistical analyses included comparisons of proportions and incidence between the randomised phase of the ANRS IPERGAY trial and the open-label phase, and all participants were included in safety analyses. ANRS IPERGAY is registered with ClinicalTrials.gov, number NCT01473472. FINDINGS: Between Nov 4, 2014, and Jan 27, 2015, we enrolled 361 participants. Median follow-up was 18·4 months (IQR 17·7-19·1). One participant who discontinued PrEP acquired HIV infection. HIV incidence was 0·19 per 100 person-years (95% CI 0·01-1·08), compared with 6·60 per 100 person-years (3·60-11·05) in the placebo group of the randomised study, indicating a relative reduction of 97% (95% CI 81-100) in the incidence of HIV with on-demand PrEP. Participants used a median of 18 pills of study drugs per month (IQR 11-25), and at the 6 month visit 240 (71%) of 336 participants had tenofovir detected in plasma. Drug-related gastrointestinal events were reported in 49 participants (14%) but were self-limited. Only four participants (1%) discontinued PrEP, three because of an increase in plasma creatinine. The proportion of participants reporting condomless sex at their last receptive anal intercourse significantly increased from 77% (136 of 176 participants) at baseline to 86% (66 of 77 participants) at 18 months' follow-up (p for trend=0·0004). The incidence of a first bacterial STI during this open-label phase did not change significantly compared with the randomised phase (59·0 vs 49·1 per 100 person-years, respectively; p=0·11). INTERPRETATION: On-demand oral PrEP is highly effective at preventing HIV infection among high-risk men who have sex with men and therefore represents an alternative to daily PrEP, expanding choices for HIV prevention. High rates of STIs resulting from low condom use did not undermine PrEP efficacy, but warrant frequent testing. FUNDING: ANRS (France Recherche Nord and Sud Sida-HIV Hépatites), the Canadian HIV Trials Network, Fonds Pierre Bergé-Sidaction, Gilead Sciences, and the Bill & Melinda Gates Foundation.

Vascular graft infections in the intensive care unit: clinical spectrum and prognostic factors.

OBJECTIVES: To report clinical characteristics and prognosis of vascular graft infections in Intensive Care Unit (ICU). METHODS: Thirty seven patients consecutively admitted in ICU for suspected or definite vascular graft infection between January 2006 and June 2009 were included. RESULTS: Staphylococcus species (n = 18) and enterobacteriae (n = 16) were the most frequent causative organisms. Twenty six patients (70%) needed mechanical ventilation. Further surgical procedures were performed in 7 patients (19%). In case of definite infection, mortality in ICU was 33%. In non survivors, shock (92% vs 42%, p = 0.01), age > 70 years (73% vs 27%, p = 0.04), POSSUM score > 45 (73% vs 27%, p = 0.04) and extra-anatomic bypass (45% vs 14%, p = 0.05) were more frequent, intra-operative volume of red cells transfusion (6 ± 3 vs 3 ± 2 units, p = 0.006) and of fresh frozen plasma (2.8 ± 2.8 vs 0.7 ± 1.2 units, p = 0.02), and SAPS II score (58 ± 26 vs 38 ± 17, p = 0.03) were higher. Proportion of adequate initial antibiotic therapy was similar in survivors and non survivors (91% vs 100%, p = 0.4). Proportion of patients treated with an aminoglycoside tended to be higher in survivors (59% vs 27%, p = 0.07). By multivariate analysis, only shock was associated with death in ICU (AOR: 16.3; 95% CI: 1.7-152.1; p = 0.01). CONCLUSIONS: Vascular graft infection carries high morbidity and mortality rates in ICU. Extra-anatomic bypass might be associated with higher mortality. Early aminoglycoside prescription might be protective.

Impact of drug stock-outs on death and retention to care among HIV-infected patients on combination antiretroviral therapy in Abidjan, Côte d'Ivoire.

BACKGROUND: To evaluate the type and frequency of antiretroviral drug stock-outs, and their impact on death and interruption in care among HIV-infected patients in Abidjan, Côte d'Ivoire. METHODS AND FINDINGS: We conducted a cohort study of patients who initiated combination antiretroviral therapy (cART) in three adult HIV clinics between February 1, 2006 and June 1, 2007. Follow-up ended on February 1, 2008. The primary outcome was cART regimen modification, defined as at least one drug substitution, or discontinuation for at least one month due to drug stock-outs at the clinic pharmacy. The secondary outcome for patients who were on cART for at least six months was interruption in care, or death. A Cox regression model with time-dependent variables was used to assess the impact of antiretroviral drug stock-outs on interruption in care or death. Overall, 1,554 adults initiated cART and were followed for a mean of 13.2 months. During this time, 72 patients discontinued treatment and 98 modified their regimen because of drug stock-outs. Stock-outs involved nevirapine and fixed-dose combination zidovudine/lamivudine in 27% and 51% of cases. Of 1,554 patients, 839 (54%) initiated cART with fixed-dose stavudine/lamivudine/nevirapine and did not face stock-outs during the study period. Among the 975 patients who were on cART for at least six months, stock-out-related cART discontinuations increased the risk of interruption in care or death (adjusted hazard ratio [HR], 2.83; 95%CI, 1.25-6.44) but cART modifications did not (adjusted HR, 1.21; 95%CI, 0.46-3.16). CONCLUSIONS: cART stock-outs affected at least 11% of population on treatment. Treatment discontinuations due to stock-outs were frequent and doubled the risk of interruption in care or death. These stock-outs did not involve the most common first-line regimen. As access to cART continues to increase in sub-Saharan Africa, first-line regimens should be standardized to decrease the probability of drug stock-outs.