Enteral administration of crushed rilpivirine in a patient with HIV: A case report.

Antiretroviral therapy administration is challenging in patients with HIV requiring enteral nutrition. There are limited pharmacokinetic data available regarding the absorption of crushed rilpivirine (RPV) and its impact on drug bioavailability, plasma concentrations and, consequently, the efficacy of treatment. We present the case of a 60-year-old woman with HIV diagnosed with squamous cell carcinoma who needed enteral administration of antiretroviral therapy following the insertion of a gastrotomy tube in September 2018. Initially, the patient was treated with a daily dose of RPV 25 mg, dolutegravir 50 mg and emtricitabine 200 mg. The treatment was later intensified with darunavir boosted with ritonavir. RPV and dolutegravir were crushed, dissolved in water and administered via a percutaneous endoscopic gastrostomy tube. Therapeutic drug and viral load monitoring determined the adequacy of enteral antiretroviral dosing. RPV plasma concentrations remained within the expected therapeutic range of 43-117 ng/mL, with only 1 below the currently used 50 ng/mL efficacy threshold. After the treatment intensification with darunavir boosted with ritonavir, the patient achieved an undetectable viral load. While we observed satisfactory RPV plasma concentrations, it is essential to maintain strict monitoring of administration method, plasma concentrations and virological responses when initiating treatment with crushed RPV. Hence, additional pharmacokinetic data are necessary to ensure the effective enteral administration of RPV and to establish the best antiretroviral dosing regimens.

Low-level viral loads and virological failure in the integrase strand transfer era.

OBJECTIVES: To analyse the occurrence of virological failure (VF) in patients starting ART with an integrase strand transfer inhibitor (INSTI)-based regimen in recent years, in relation with previous episodes of low-level viral load (LLVL). PATIENTS AND METHODS: Patients starting a first ART between 1 January 2015 and 31 December 2020 based on two NRTIs and one INSTI were included if after virological control (two measures of VL < 50 copies/mL) they had a minimum of two additional VL measurements. Cox models adjusted for sex, age, acquisition group, hepatitis B or C coinfection, place of birth, year of ART initiation, CD4+ T cells and VL at ART initiation, duration of known HIV infection and of ART regimen were used to assess the association between the time to VF and the occurrence of LLVL. ART regimen was evaluated as time-varying covariate. RESULTS: LLVL was described in 13.7% and VF in 11% of the 3302 patients. LLVL was associated with VF [adjusted HR (aHR) 1.76, 95% CI 1.28-2.41], as well as age (aHR 0.97/year, 95% CI 0.96-0.98), CD4+ T cell count at ART initiation (aHR 0.93, 95% CI 0.87-0.98), heterosexual transmission (aHR 1.76, 95% CI 1.30-2.37) and being born abroad (aHR 1.50, 95% CI 1.17-1.93). CONCLUSIONS: LLVL was related to VF. Even in the absence of subsequent failure, LLV episodes have a cost. Thus any VL value above 50 copies/mL should lead to enhanced adherence counselling.

Missed opportunities for HIV pre-exposure prophylaxis among people with recent HIV infection: The French ANRS 95041 OMaPrEP study.

OBJECTIVES: Our objective was to identify missed opportunities for the use of pre-exposure prophylaxis (PrEP) in people with recently acquired HIV, factors associated with PrEP knowledge, and reasons for not using PrEP. DESIGN: This was a French national cross-sectional multicentre study enrolling people diagnosed with recent HIV (incomplete Western blot or negative HIV test in the previous 6 months) in 28 HIV clinical centres. Data were gathered using a self-administered questionnaire (SAQ). METHOD: We analysed missed opportunities for PrEP use via a retrospective prep cascade. Factors associated with prior knowledge of PrEP and reasons for PrEP non-use among those who knew about PrEP were described using univariate and multivariate logistic regression models. RESULTS: Of the 224 eligible patients, 185 completed the SAQ and 168 (91%) were eligible for PrEP. Of these, 90% reported seeing at least one physician during the previous year, 26% received information about PrEP, and 5% used PrEP. Factors independently associated with a higher probability of knowing about PrEP were being a man who has sex with men, being aged 25-30 years (vs older), undergoing HIV screening at least once every semester (vs less often; odds ratio [OR] 4.11; 95% confidence interval [CI] 2.00-8.45), and practicing chemsex (OR 3.19; 95% CI 1.12-9.10). Fear of side effects and a low perceived risk of HIV infection were the two most common reasons for not using PrEP (N = 40 [33.33%] and N = 34 [28.3%], respectively). CONCLUSIONS: We found two gaps in the retrospective PrEP cascade: insufficient provision of PrEP information by healthcare providers (mainly general practitioners) and low PrEP acceptability by informed, eligible patients. More diverse healthcare providers need to be involved in PrEP prescription, and at-risk people need to be sensitized to the risk of HIV infection.

High syphilis prevalence and incidence in people living with HIV and Preexposure Prophylaxis users: A retrospective review in the French Dat'AIDS cohort.

BACKGROUND: In the past years, we observed a sharp increase of Syphilis, especially among male who have sex with male (MSM), either HIV-infected, or on pre-exposure prophylaxis (PrEP). Our aim was to assess syphilis prevalence and incidence among people living with HIV (PLWH) and PrEP users. METHODS: PLWH were included from 2010 to 2020 and PrEP users from 2016 to 2020 from the Dat'AIDS French cohort. We calculated syphilis prevalence and incidences for first infections, re-infections, and iterative infections (> 2 times). T-Tests, Wilcoxon tests and Chi2 test were used for descriptive analysis and multivariate logistic regression models were used to estimate Odds ratios (OR) and 95% confidence intervals (95% CI) for factors associated with syphilis. RESULTS: Among the 8 583 PLWH, prevalence of subject with past or present syphilis was 19.9%. These subjects were more likely MSM or transgender and aged over 35 years, but prevalence was lower in AIDS subjects. Same pattern was seen for incident infection and re-infection. Incidence was 3.8 per 100 person-years for infection and 6.5 per 100 person-years for re-infection. Among 1 680 PrEP users, syphilis prevalence was 25.8%, with an estimated 7.2% frequency of active syphilis. Risk of syphilis infection was higher in male and increased with age. Incidence was 11.2 per 100 person-years for infection and 11.1 per 100 person-years for re-infection. CONCLUSION: Syphilis prevalence and incidence were high, especially in older MSM with controlled HIV infection and PrEP users, enhancing the need to improve syphilis screening and behavioral risk reduction counseling among high-risk subjects.

Is the use of the QPC cognitive complaints questionnaire relevant for the screening strategy of HIV-Associated neurocognitive disorders?

BACKGROUND: The screening strategy for HIV-Associated Neurocognitive Disorders (HAND) is challenging. The French Expert Report recommend the use of the Cognitive Complaints Questionnaire (QPC) and the Montreal Cognitive assessment. However, the QPC has never been studied in People Living with HIV (PLWH). This study aims to determine the degree of agreement between QPC and the presence of HAND according to Frascati criteria, established by a battery of neuropsychological tests. METHODS: Data from patients who performed both a QPC and a battery of neuropsychological tests over a six-month follow-up period were evaluated retrospectively. RESULTS: A total of 121 patients were selected, with a median age of 53.1 years old. Among participants, 92.6% had an undetectable plasma viral load, 49.6% had a nadir CD4 less than 200/mm3 and 23.1% had a CDC stage C. Median CD4 cell count was 686/mm3. Prevalence of HAND was 57%, including 28.9% of Asymptomatic Neurocognitive Impairment, 24.8% of Mild Neurocognitive Disorder and 3.3% of HIV-associated Dementia. This analyze shows no agreement between QPC and HIV-associated neurocognitive disorders (kappa = -0.007). CONCLUSIONS: The QPC is not relevant in the screening for HAND. Thus, it urges to develop a specific tool to assess cognitive complaints among PLWH.

Hepatitis C virus-microelimination program and patient trajectories after hepatitis C virus cure in an outpatient HIV clinical unit.

OBJECTIVE: Treatment recommendations for hepatitis C now make no distinction between HIV/HCV-coinfected and HCV-monoinfected patients. The largest challenge remained lack of effective models to eliminate HCV in people living with HIV. We report the results of a microelimination program evaluating the possibility of eradicating HCV in an HIV-outpatient clinical unit within 12 months. METHODS: This HCV-microelimination program began in February 2016 in an unit following approximately 1000 HIV-infected patients and combined screening and therapeutic components according to the French guideline. A nested cohort study evaluating the impact of HCV cure on different health outcomes was conducted through self-administered questionnaires and using generalized mixed models. RESULTS: Among 601 patients eligible for HCV serological testing, 445 were evaluated, and two HCV acute infections were diagnosed. Among the 151 patients eligible for HCV RNA quantification, 119 were evaluated, and one reinfection with HCV was diagnosed. Among the 110 patients eligible for direct-acting antiviral treatment, 51 (46.4%) initiated treatment within the 12 months program, and 35 (31.8%) after. Sustained virologic response (SVR) rate was 96.1%, and two treatments failed. At least one self-reported symptom was declared by 72.5% (n = 29) of patients. Positive impact of HCV cure was observed on various markers of physical and mental health as well as on health habits. CONCLUSION: Our program should be considered as a proof of concept, which confirmed the feasibility of a HCV-microelimination program at the scale of an HIV clinical unit. However, 12 months were not sufficient to achieve our objective despite the specific organization.

Unsupervised PrEP in routine practice: a new challenge?

Pre-exposure prophylaxis (PrEP) for the prevention of HIV infection with 300 mg daily tenofovir co-formulated with 200 mg emtricitabine is recommended as one prevention option for people who are at substantial risk of acquiring an HIV infection. We report the case of a 28-year-old man who has sex with men and who was referred to our unit for a primary HIV infection with positive p18, p24 and gp160 bands on Western blot analysis but with a low HIV plasma viral load. Although HIV misdiagnosis should always be considered in cases of atypical seroconversion pattern with a low viral burden, unsupervised PrEP should be systematically investigated.

Hepatitis C virus incidence in HIV-infected and in preexposure prophylaxis (PrEP)-using men having sex with men.

BACKGROUND & AIMS: HCV incidence still appears on the rise in HIV-infected MSM in France. We assessed the incidence of HCV infection in HIV-positive and in preexposure prophylaxis (PrEP)-using MSM. METHODS: HIV-infected, HCV-negative MSM with serological follow-up in 2016 and HIV-negative, HCV-negative PrEP-using MSM enrolled from January 2016 to May 2017 in the French Dat'AIDS cohort were analyzed to assess the incidence of a primary HCV infection. The incidence of HCV reinfection was also determined in patients having cured a previous infection. RESULTS: Among 10,049 HIV-infected MSM followed in 2016, 681 patients were already HCV-infected when entering the study (prevalence 6.8%). Serological follow-up was available in 2016 for 4,151 HCV-negative patients. Virological follow-up was available for 478 patients who had cured a previous infection. Fifty-seven HCV infections occurred in 2016 (42 primary infections, 15 reinfections). Incidence of primary HCV infection, reinfection and overall HCV infection was respectively 1.0, 3.1 and 1.2/100 person-years (PY). From January 2016 to May 2017, 930 HIV-negative subjects were enrolled for PrEP. Seventeen patients were already HCV-infected (prevalence 1.8%). Twelve HCV infections occurred during follow-up (10 primary infections, 2 reinfections) giving an incidence of primary infection of 1.0/100 PY and an overall incidence of 1.2/100 PY. CONCLUSIONS: The overall incidence of HCV infection and of a primary HCV infection in HIV-positive and in PrEP-using MSM appeared similar in France in 2016-early 2017. HIV-positive and PrEP-using MSM probably share similar at-risk practices and both should be targeted for preventative interventions. This article is protected by copyright. All rights reserved.

Risk factors associated with overweight and obesity in HIV-infected people: Aging, behavioral factors but not cART in a cross-sectional study.

Identifying risk factors associated with overweight and obesity in HIV-infected patients.A cross-sectional study analyzing data from patients attending an HIV outpatient unit. Overweight was defined as body mass index (BMI) ≥25 kg/m; <30 kg/m, obesity was ≥30 kg/m. Patients' characteristics contemporary to BMI assessment were collected. Multivariate logistic regression identified risk factors associated with overweight/obesity.Eight hundred sixty-two patients, median age 51 years, 21.5 years of HIV infection follow-up, 585 (68%) male, 829 (96%) receiving combined antiretroviral therapy (cART) for median 16.7 years, 768 (91%) HIV load <40 copies/mL, 618 (73%) CD4 ≥500 cells/mm; 266 (31%) HCV serology, 110 (13%) had detectable HCV-RNA. Overweight affected 191 (22%) patients and obesity 46 (5%). Overweight and obesity were associated with age, HIV follow-up duration, and HIV transmission risk group. Overweight was also associated with gender and HCV status. In patients with substance use data, overweight was associated with alcohol and nonsmoking status. Obesity was associated with nonsmoking and ex-smoker status. Overweight/obesity were not found associated with cART or immune cell counts.In HIV-infected people, aging, alcohol consumption, nonsmoking, and ex-smoker status, the absence of HCV coinfection and to have cleared HCV infection are associated with overweight and/or obesity. Clinicians should be aware of these trends and consider introducing weight management programs as part of routine HIV care.

Emergence of uncommon HIV-1 non-B subtypes and circulating recombinant forms and trends in transmission of antiretroviral drug resistance in patients with primary infection during the 2013-2015 period in Marseille, Southeastern France.

Primary HIV-1 infections (PHI) with non-B subtypes are increasing in developed countries while transmission of HIV-1 harboring antiretroviral resistance-associated mutations (RAMs) remains a concern. This study assessed non-B HIV-1 subtypes and RAMs prevalence among patients with PHI in university hospitals of Marseille, Southeastern France, in 2005-2015 (11 years). HIV-1 sequences were obtained by in-house protocols from 115 patients with PHI, including 38 for the 2013-2015 period. On the basis of the phylogenetic analysis of the reverse transcriptase region, non-B subtypes were identified in 31% of these patients. They included 3 different subtypes (3A, 1C, 4F), 23 circulating recombinant forms (CRFs) (CRF02_AG, best BLAST hits being CRF 36_cpx and CRF30 in 7 and 1 cases, respectively), and 5 unclassified sequences (U). Non-B subtypes proportion increased significantly, particularly in 2011-2013 vs in 2005-2010 (P = .03). CRF02_AG viruses largely predominated in 2005-2013 whereas atypical strains more difficult to classify and undetermined recombinants emerged recently (2014-2015). The prevalence of protease, nucleos(t)ide reverse transcriptase, and first-generation nonnucleoside reverse transcriptase inhibitors-associated RAMs were 1.7% (World Health Organization [WHO] list, 2009/2.6% International AIDS Society [IAS] list, 2017), 5.2%/4.3%, and 5.2%/5.2%, respectively. Etravirine/rilpivirine-associated RAM (IAS) prevalence was 4.3%. Men who have sex with men (MSM) were more frequently infected with drug-resistant viruses than other patients (26% vs 7%; P = .011). The recent increase of these rare HIV-1 strains and the spread of drug-resistant HIV-1 among MSM in Southeastern France might be considered when implementing prevention strategies and starting therapies.

Frailty in HIV infected people: a new risk factor for bone mineral density loss.

OBJECTIVE: The study aims to assess the association between bone mineral density (BMD) and frailty in a cohort of HIV-infected patients. DESIGN: A cross-sectional study in an HIV outpatient unit where nearly 1000 patients are monitored. METHODS: Study participants undergoing bone densitometry were proposed an evaluation of frailty using criteria of the Cardiovascular Health Study (CHS) and the Study of Osteoporotic Fractures (SOF). Frailty markers were weight-loss, self-reported exhaustion, physical activity, grip strength, chair stands, and slow gait. Patients' characteristics were collected from an electronic medical record. Associations of frailty with BMD and osteoporosis were tested using multivariate linear and logit regression models, respectively. RESULTS: In total, 175 HIV-infected patients, 121 (69.14%) men, were analyzed. Prevalence of frailty markers, osteopenia, and osteoporosis were comparable among sexes. Despite a younger age, spinal and femoral neck BMD were lower in women (P < 0.05). Linear regression model adjusting by age, duration of HIV follow-up, BMI, smoking status, osteoarthritis, osteoporosis treatment, and the age at menopause showed a negative association of spinal and femoral BMD with frailty according to SOF criteria in women (P < 0.05). In men, SOF-defined frailty was associated with osteoporosis (odds ratio 28.79; 95% confidence interval 2.15-386.4) in a model adjusting for age, duration of HIV follow-up, CD4 nadir, CD4 T-cell count, tobacco consumption, exposure to tenofovir (TDF) and protease inhibitors. No significant associations were found between BMD and CHS-defined frailty. CONCLUSION: Our study shows that frailty according to SOF criteria is associated with low spinal BMD values in female and osteoporosis in male HIV-infected patients.