Olivia Zaegel-Faucher

Impact of hepatitis C virus coinfection on T-cell dynamics in long-term HIV-suppressors under combined antiretroviral therapy

Objective:The objective of this study is to evaluate the impact of hepatitis C virus (HCV) serostatus on the evolution of CD8+ cells and CD4+ : CD8+ ratio in HIV-infected patients on combined antiretroviral therapy (cART) who achieve sustained undetectable viral load (HIV-pVL). Design and methods:A longitudinal study performed in an outpatient HIV-unit following 1495 HIV-infected patients. Data of patients on cART achieving undetectable HIV-pVL for at least 3 years were collected retrospectively from our medical e-database NADIS from January 1997 to April 2005, a period defined in order to select patients who were naive of hepatitis treatment. T-cell counts were assessed every 6 months from HIV-suppression over the study period. Results:Two hundred and twenty-six HIV mono-infected (group 1) and 130 HCV-coinfected patients (group 2; genotype prevalence: 42% HCV-G1, 26% HCV-G3, 11% HCV-G4 and 21% HCV-G2) fulfilled the selection criteria. cART regimens were comparable between the groups, as were CD4+ and CD8+ cell counts at the first undetectable HIV-pVL. After 3 years, both groups displayed similar CD4+ cell reconstitution, although CD4+ percentage was higher in group 1 (30.3 ± 1.1 vs. 27 ± 1.1%; P < 0.001). HIV suppression led to a significant drop of median CD8+ cell counts in group 1 (P = 0.027), but not in group 2, which displayed higher CD8+ cell counts all through the follow-up (mean diff. = 135.71 ± 26.89 cells/&mgr;l, P < 0.001). Moreover, the fraction of patients reaching CD4+ : CD8+ ratio ≥ 1 was lower in group 2 (14 vs. 27.7%; P < 0.05). Conclusion:Despite sustained HIV suppression under cART, HCV coinfection was found to hamper CD8+ downregulation. Further studies will determine the impact of treatment with direct-acting antiviral agents on the CD8+ pool, and the advantage of systematic HCV-targeted therapy for HIV/HCV-coinfected patients.

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.

Mandibular osteonecrosis and dental exfoliation after trigeminal zoster in an HIV-infected patient: case report and review of the literature.

Mandibular osteonecrosis and dental exfoliation after trigeminal zoster in an HIV-infected patient: case report and review of the literature.

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: TAMALET et al.

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.

Sub-therapeutic darunavir concentration and garlic consumption; a «Mediterranean» drug-food interaction, about 2 cases

Plasma exposure of protease inhibitors (PI) of the human immunodeficiency virus (HIV) is correlated with both their efficacy and toxicity. PIs’ exposure depends on their bioavailability after oral uptake, which is limited by their intense metabolism through the cytochrome P450-3A4 (CYP3A4) pathway. PIs also inhibit CYP3A4, leading to frequent interactions with drugs and natural components, these latter remaining mostly unidentified. We report two cases of HIV-infected patients displaying clinically significant interactions between garlic and darunavir (DRV), which resulted in sub-therapeutic DRV plasma concentration associated with viral rebound. Patient 1 is a 27-year-oldman infected by a wild-typeHIV-1 subtype B since 2008. Patient started antiretrovirals in 2011 with tenofovir/emtricitabine 200/245 mg and ritonavirboosted DRV (DRV/r) 800/100mg QD. HIV plasma viral load (HIV-pVL) was below detection threshold (40 copies/mL) after 6 months. Twenty-four months later, HIV-pVL rebounded and an antiretroviral therapeutic drug monitoring (TDM) was performed (Fig. 1). Sub-therapeutic DRVandRTV trough concentrations (Ctrough) were found. Tenofovir Ctrough was correct. Patient declared taking drugs on time during meals. Adherence to treatment, concomitant drugs, and herbalmedicine were verified. Patient reported consuming 15 cloves of garlic per week and was advised to stop it. One month later, DRVand RTV Ctrough had reached the expected range. After 3 months, HIV-pVL became undetectable and remained controlled. Patient 2 is a 41-year-old woman infected with an HIV-1 CRF06-cpx since 2007 and receiving abacavir/lamivudine 600/300 mg QD and DRV/r 600/100 mg BID since 2010. Upon viral escape, TDM was performed and suboptimal DRVand RTVCtrough were found (Fig. 1). Adherence issues and concomitant drug-interactions were ruled-out. She declared important garlic consumption, but was unable to quantify it. One month after garlic eviction, DRVand RTVCtrough normalized. HIV-pVL declined below the threshold value after 3 months. These are the first reports of a clinically relevant interaction between garlic and DRV/r. Garlic interaction with other PIs have been reported, including another case-report with atazanavir [1]. In-vivo studies showed a significant decrease in saquinavir’s area under curve (AUC) after garlic consumption [2, 3]. A decrease in saquinavir’s bioavailability through induction of duodenal P-glycoprotein was suggested as an increase in P-glycoprotein expression was observed [3]. Invitro studies reported that garlic extracts increased DRV Pglycoprotein-mediated efflux leading to a decrease in intracellular concentration of DRV in both enterocytes and hepatocytes [4, 5]. One mechanism proposed is a positivecooperative effect due to allosteric modification of efflux transporters by garlic components. Nevertheless, efflux returned to reference values at higher concentration of DRV * Isabelle Poizot-Martin isabelle.poizot@ap-hm.fr

A Case of Undiagnosed HIV Infection in a 57-Year-Old Woman with Multiple Myeloma: Consequences on Chemotherapy Efficiency and Safety

Background. Non-AIDS-defining cancers represent a rising health issue among HIV-infected patients. Nevertheless, HIV testing is not systematic during the initial cancer staging. Here, we report a case of HIV infection diagnosed three years after chemotherapy initiation for multiple myeloma. Results. A 57-year-old woman diagnosed with multiple myeloma underwent a first round of chemotherapy by bortezomib/lenalidomide and then with bortezomib/liposomal-doxorubicine/dexamethasone, with partial remission, poor hematological tolerance, and multiple episodes of pneumococcal infection. Allogenic stem cell transplantation was proposed leading to HIV testing, which revealed seropositivity, with an HIV viral load of 5.5 Log10/mL and severe CD4 T cell depletion (24 cells/mm3). Chemotherapy by bendamustin was initiated. Multidisciplinary staff decided the initiation of antiretroviral therapy with tenofovir/emtricitabin/efavirenz and prophylaxis against opportunistic infections. After 34 months, patient achieved complete remission, sustained HIV suppression, and significant CD4 recovery (450 cells/mm3), allowing effective pneumococcal immunization without relapse. Conclusion. Our case illustrates the drawback that ignored HIV infection is still causing to cancer patients receiving chemotherapy and highlights the importance of early HIV testing in oncology. A multidisciplinary approach including oncologists/hematologists, virologists, and pharmacists is recommended in order to avoid drug interactions between chemotherapy and antiretroviral drugs. Moreover, prophylactic medication is recommended in these patients regardless of CD4+ cell count at the initiation of chemotherapy.