Gender Affirming Hormones Do Not Affect the Exposure and Efficacy of F/TDF or F/TAF for HIV Preexposure Prophylaxis: A Subgroup Analysis from the DISCOVER Trial.

Purpose: Transgender women are disproportionately affected by HIV and are underutilizing preexposure prophylaxis (PrEP). The lower uptake of PrEP by transgender women may be, in part, owing to the perception that taking PrEP may lower the efficacy of gender-affirming hormone therapy (GAHT) or to provider concerns that GAHT may lower the efficacy of PrEP. Methods: DISCOVER was a randomized, double-blind, noninferiority trial comparing emtricitabine (FTC, F) and tenofovir alafenamide (F/TAF) versus emtricitabine and tenofovir disoproxil fumarate (F/TDF) as PrEP among transgender women and cisgender men who have sex with men (MSM). This nested substudy of the DISCOVER trial compared the exposure of the active intracellular metabolites of FTC and tenofovir (TFV), FTC triphosphate (FTC-TP) and TFV diphosphate (TFV-DP), in peripheral blood mononuclear cells (PBMC) among transgender women receiving GAHT versus MSM within the F/TAF and F/TDF groups. Results: Our results demonstrate that TFV-DP and FTC-TP levels in PBMC were comparable between transgender women on GAHT and MSM receiving F/TAF, and between transgender women on GAHT and MSM receiving F/TDF. TFV-DP concentrations remained above the EC90 of 40 fmol/106 cells across all groups. No clinically significant drug-drug interactions of GAHT were observed with either F/TAF or F/TDF in this subanalysis. Conclusions: These findings are consistent with the clinical pharmacology of GAHT, FTC, TDF, and TAF reported in previous studies, and support the continued use of F/TAF and F/TDF for PrEP in transgender women.Clinicaltrials.gov registration number: NCT02842086.

Establishing a framework towards monitoring HCV microelimination among men who have sex with men living with HIV in Germany: A modeling analysis.

BACKGROUND: Prior to direct-acting antivirals (DAAs), HCV incidence rose among men who have sex with men (MSM) living with HIV infection in Germany despite high hepatitis C virus (HCV) treatment rates. We establish a HCV elimination modeling framework to evaluate whether existing treatment rates can achieve the World Health Organization (WHO) incidence target among MSM living with HIV in Germany. METHODS: To evaluate progress towards HCV elimination in Germany, we adapted a previously published HCV transmission model among MSM living with diagnosed HIV. We modelled HCV incidence and prevalence until 2030 (relative to 2015) under existing treatment and DAA scale-up and explored potential impacts of disruptions in treatment and behavioral risk reduction due to the COVID-19 pandemic. RESULTS: Continuing current treatment rates will result in stable HCV incidence among MSM living with HIV in Germany between 2015-2030. The WHO HCV incidence target is achievable under DAA scale-up to 100% treatment combined with treatment of those previously diagnosed and untreated (at a rate of 15%/year) and would result in greater reductions with early treatment (3 vs 6 months) reducing incidence from 4.0/100person-years to 0.8/100person-years by 2030. A 12-month disruption to HCV treatment (20% reduction) and risk behaviors (25%,50%,75% reduction) during the COVID-19 pandemic would result in a 15% relative increase in total HCV incidence in 2030 compared to that expected under the status quo. CONCLUSIONS: HCV elimination among MSM living with HIV in Germany requires further DAA scale-up among those newly diagnosed combined with efforts to treat those previously diagnosed but untreated. Prospective monitoring will establish whether Germany is on track for HCV microelimination.

Health-related quality-of-life in people living with HIV after switching to dual therapy with ritonavir-boosted darunavir + dolutegravir: a DUALIS sub-study.

The DUALIS study demonstrated efficacy and safety of switching to dolutegravir plus ritonavir-boosted darunavir (DRV/r) (2DR) as compared to standard-of-care-therapy with two nucleoside reverse transcriptase inhibitors + DRV/r (3DR) in pretreated people living with HIV (PLWH), 48 weeks after switching. This DUALIS sub-study investigates health-related-quality-of-life (HrQoL) in this study-population. The Hospital Anxiety and Depression Scale (HADS) and the Medical Outcome Survey-HIV (MOS-HIV) were used assessing anxiety and depression symptoms, respectively HrQoL. Data were collected at baseline, 4, 24, and 48 weeks after randomization. Outcome scores were dichotomized and used as criteria in longitudinal models identifying differential developments. Odds ratios (ORs) with 95% confidence intervals (CIs) were computed as main measures of effects. ORs<1 indicate better results for HADS, and worse for MOS-HIV scores in the 2DR compared to 3DR group. In total, 263 subjects were randomized and treated (2DR n=131, 3DR n=132; median age 48 years). Significant different progressions could only be found for HADS-Depression scores (OR=.87, 95% CI: .78, .98, p=.02). While HADS-Depression scores decreased in the 2DR group, they increased in 3DR group. This sub-study showed no disadvantages regarding HrQoL in PLWH after switching to DTG+DRV/r. Considering lifelong requirements for antiretroviral medication, close attention to HrQL is required.

Outcomes of men with HIV and germ cell cancer: Results from an international collaborative study.

BACKGROUND: Previous studies have shown that men with HIV and germ cell cancer (HIV-GCC) have inferior overall survival (OS) in comparison with their HIV-negative counterparts. However, little information is available on treatments and outcomes of HIV-GCC in the era of combination antiretroviral therapy (cART). METHODS: This study examined men living with HIV who were 18 years old or older and had a diagnosis of histologically proven germ cell cancer (GCC). The primary outcomes were OS and progression-free survival (PFS). RESULTS: Data for 89 men with a total of 92 HIV-GCCs (2 synchronous GCCs and 1 metachronous bilateral GCC) were analyzed; among them were 64 seminomas (70%) and 28 nonseminomas (30%). The median age was 36 years, the median CD4 T-cell count at GCC diagnosis was 420 cells/µL, and 77% of the patients on cART had an HIV RNA load < 500 copies/mL. Stage I disease was found in 44 of 79 gonadal GCCs (56%). Among 45 cases with primary disseminated GCC, 78%, 18%, and 4% were assigned to the good-, intermediate-, and poor-prognosis groups, respectively, of the International Germ Cell Cancer Collaborative Group. Relapses occurred in 14 patients. Overall, 12 of 89 patients (13%) died. The causes of death were refractory GCC (n = 5), an AIDS-defining illness (n = 3), and other causes (n = 4). After a median follow-up of 6.5 years, the 5- and 10-year PFS rates were 81% and 73%, respectively, and the 5- and 10-year OS rates were 91% and 85%, respectively. CONCLUSIONS: The 5- and 10-year PFS and OS rates of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients. LAY SUMMARY: Men living with HIV are at increased risk for germ cell cancer (GCC). Previous studies have shown that the survival of men with HIV-associated germ cell cancer (HIV-GCC) is poorer than the survival of their HIV-negative counterparts. This study examined the characteristics, treatments, and outcomes of 89 men with HIV-GCC in the era of effective combination antiretroviral therapies. The long-term outcomes of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients.

Virologic outcomes of switching to boosted darunavir plus dolutegravir with respect to history of drug resistance.

OBJECTIVE: The DUALIS study showed that switching to boosted darunavir (bDRV) plus dolutegravir (DTG; 2DR) was non-inferior to continuous bDRV plus 2 nucleoside/nucleotide reverse-transcriptase inhibitors (NRTIs; 3DR) in treatment-experienced virologically suppressed people living with HIV (PLWH). We analyzed virologic outcomes with respect to treatment history and HIV drug resistance. DESIGN: Post hoc analysis of a randomized trial. METHODS: Main inclusion criteria were an HIV RNA level < 50 copies/mL for ≥ 24 weeks and no resistance to integrase strand transfer inhibitors or bDRV. Resistance-associated mutations (RAMs) were interpreted using the Stanford HIVdb mutation list. Outcomes measures were 48-week virologic response (HIV RNA < 50 copies/mL, FDA snapshot) and HIV RNA ≥ 50 copies/mL (including discontinuation due to a lack of efficacy or reasons other than adverse events and HIV RNA ≥ 50 copies/mL, referred to as snapshot non-response). RESULTS: The analysis population included 263 patients (2DR: 131, 3DR: 132): 90.1% males; median age, 48 years; CD4 + T-cell nadir < 200/µl, 47.0%; ≥ 2 treatment changes, 27.4%; NRTI, non-NRTI (NNRTI), and major protease inhibitor (PI) RAMs in 9.5%, 14.4%, and 3.4%, respectively. In patients with RAMs in the 2DR and 3DR groups, virologic response rates were 87.8% and 96.0%, respectively; the corresponding rates in those without RAMs were 85.7% and 81.8%. RAMs were unrelated to virologic non-response in either group. No treatment-emergent RAMs were observed. CONCLUSIONS: DTG + bDRV is an effective treatment option without the risk of treatment-emergent resistance for PLWH on suppressive first- or further-line treatment with or without evidence of pre-existing NRTI, NNRTI, or PI RAMs. TRIAL REGISTRATION: EUDRA-CT Number 2015-000360-34; registered 07 April 2015; https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-000360-34/DE .

Switching to a NRTI-free 2 drug regimen (2DR) -a sub-analysis of the 48 weeks DUALIS study on metabolic and renal changes.

Background/Aims: Switching from a three-drug regimen (3DR: boosted darunavir [bDRV] and two nucleoside reverse transcriptase inhibitors [NRTIs]) to a two-drug regimen (2DR: bDRV and dolutegravir [DTG]) demonstrated non-inferiority with regard to viral suppression in people living with HIV (PLWH) in the DUALIS study. This sub-analysis focuses on changes in metabolic and renal parameters when sparing the NRTI backbone.Methods: DUALIS was a randomized, open-label, multicenter (27) phase 3-trial. Participants were virologically suppressed (HIV-RNA < 50 copies/mL) on 3DR for at least 24 weeks. Subjects were either switched to DTG 50 mg + bDRV 800 mg (with ritonavir 100 mg) (2DR) or continued their regimen consisting of two NRTIs in combination with ritonavir-bDRV (3DR) once daily. Data of metabolic and renal parameters at baseline and week 48 were compared.Results: The LDL-fraction increased by + 13.3 (-3.0 to +31.3) mg/dL on 2DRs and was stable (-14.0 to +18.0 mg/dL) on 3DRs (p < 0.0010).PLWH gained +2.0 (-0.2 to +4.0) kg and +0.2 (-1.9 to +2.1) kg in body weight on 2DRs and 3DRs, respectively 3 (p = 0.0006).The MDRD eGFR decreased by -7,8 (-17.4 to -0.3) mL/min/1.73m2 and 0.4 (-8.8 to +5.7) mL/min/1.73m2 on 2DRs and 3DRs, respectively (p = 0.0002), while serum levels of cystatin C were stable in both arms (2DR: -0.1 to +0.1 mg/L; 3DR: 0.0 to +0.1 mg/L).Conclusions: While being non-inferior in terms of viral suppression, sparing the NRTI backbone showed a non-favorable profile in metabolic or renal parameters over 48 weeks.

Efficacy and Safety of Switching to Dolutegravir With Boosted Darunavir in Virologically Suppressed Adults With HIV-1: A Randomized, Open-Label, Multicenter, Phase 3, Noninferiority Trial: The DUALIS Study.

BACKGROUND: Dolutegravir (DTG) and boosted darunavir (bDRV) are potent antiretrovirals with a high resistance barrier and might be valuable switch options for people with HIV (PWH). METHODS: DUALIS, a randomized, open-label, phase 3b, noninferiority clinical trial, compared the switch to DTG + bDRV (2DR) with continuation of 2 nucleoside reverse transcriptase inhibitors (2NRTI) + bDRV (3DR). PWH with HIV RNA <50 copies/mL taking 2NRTI + bDRV (3DR) for ≥24 weeks (1 accepted blip <200 copies/mL) were randomized to either switch to DTG 50 mg + DRV 800 mg (boosted with 100 mg of ritonavir) or continue taking 3DR. The primary end point (PE) was the proportion of HIV RNA <50 copies/mL at week (W) 48. Change in NRTI backbone was not classified as failure. The estimated sample size for PE analysis was 292; the noninferiority margin was ≤-10.0%. RESULTS: In total, 263 subjects were randomized and treated (2DR n = 131, 3DR n = 132; 90.1% male; 89.7% Caucasian; median age [interquartile range], 48 [39-54] years). At W48, 86.3% (n = 113/131) of the 2DR subject and 87.9% (n = 116/132) of the 3DR subjects had HIV RNA <50 copies/mL; the difference between arms was -1.6% (95.48% CI, based on the adjusted alpha level accounting for the interim analysis at W24, -9.9% to +6.7%; discontinuations due to adverse events: 2DR, 4.6% [n = 6]; 3DR, 0.8% [n = 1]). Kaplan-Meier estimates of confirmed HIV RNA ≥50 copies/mL at W48 were 1.6% (n = 2) in the 2DR and 3.1% (n = 4) in the 3DR group. Development of treatment-emergent resistance was not observed. CONCLUSIONS: Switching to DTG + bDRV was noninferior to continuing 3DR in subjects already treated with bDRV.

COVID-19 in people living with human immunodeficiency virus: a case series of 33 patients.

INTRODUCTION: Data on people living with human immunodeficiency virus (PLWH) in the current SARS-CoV-2 pandemic are still scarce. This case series of 33 PLWH patients with COVID-19 reveals symptoms and outcome in this special population. METHODS: Retrospective analysis of anonymized data including age, gender, HIV-associated parameters, symptoms, and outcome. RESULTS: Three out of 32 patients with documented outcomes died (9%). 91% of the patients recovered and 76% have been classified as mild cases. All patients were on antiretroviral treatment, of them 22 on tenofovir-containing regimen and 4 on the protease inhibitor darunavir. CONCLUSIONS: This preliminary case series does not support excess morbidity and mortality among symptomatic COVID-19 PLWH and with viral suppression on ART. SARS-CoV-2 infections may occur during boosted darunavir-based and/or on tenofovir-containing ART.

Indication for treatment and severity of disease in treatment-naive patients with chronic hepatitis B virus infection.

BACKGROUND AND AIMS: The prevalence of chronic hepatitis B virus (HBV) infection in Europe is poorly defined. Data on the proportion of patients eligible for therapy are lacking but are crucial to meet WHO elimination goals. The aims of our study were to provide an estimate of the need for antiviral treatment and to assess the prevalence of advanced liver disease in treatment-naive, chronic HBV-infected patients. PATIENTS AND METHODS: We performed a retrospective, cross-sectional analysis of all treatment-naive HBV-infected patients. Baseline clinical assessments included sociodemographic data, hepatitis B-specific analyses, and liver stiffness measurement (LSM). RESULTS: Between 2010 and 2017, 465 patients with chronic HBV infection were referred, with 301 (64.7%) being eligible for our analysis. Overall, 40% were female, and the mean age was 39.3±13.1 years. Moreover, 61% of patients were born outside Europe, predominantly in the Asia-Pacific region. The median HBV viral load was 1630 IU/ml (interquartile range: 240-35 000 IU/ml), 145 (48.2%) patients had an HBV viral load above 2000 IU/ml, and 14.3% were HBeAg positive.Median LSM was 5.2 kPa (interquartile range: 4.2-6.6 kPa). LSM indicating clinically significant fibrosis (≥F2) was found in 96/271 (35.0%) patients, including 20/271 (7.4%) patients with suspected advanced fibrosis/cirrhosis. Overall, 26% of patients met EASL 2017 treatment criteria. CONCLUSION: In HBV-infected patients referred to one of the largest ID clinics in Berlin, only 26% met EASL treatment criteria and 7% had suspected cirrhosis at presentation. Only in 4% of all patients, a treatment indication could not be determined by a noninvasive approach.

2016 PREP attitudes in Germany: high awareness and acceptance in MSM at risk of HIV.

PRUPOSE: To examine current risk behavior, awareness, experience, and attitudes towards pre-exposure-prophylaxis (PrEP), and to estimate a potential impact on the prevention of HIV transmission among HIV-negative MSM in Germany. PrEP was not officially licensed at the time of survey. METHODS: Web-based questionnaire from 03-06/2016. Potential participants were informed through social media, flyers, and advertisements. Risk contacts were defined as unprotected sexual intercourse under the influence of recreational drugs in the past 6 months. RESULTS: In total, 1208 subjects participated, 342 subjects were excluded for being HIV-infected or non-MSM, leaving 866 subjects to be evaluated in this analysis. Mean age was 37.0 ± 10.4 years. 593 participants (68.5%) were tested for HIV within the past 12 months. A total of 206 STDs in the past 6 months were reported by 144 (16.6%). Aware of PrEP was 748 (86.4%) respondents, while 65.1% reported willingness to use it. Risk behavior was significantly associated with higher PrEP acceptance (OR 2.90, 95% CI 2.14-3.90), as was a history of STDs (OR 1.85, 95% CI 1.17-2.91). The use of condoms would forgo 52.3% of subjects if taking PrEP. Sixty-five respondents (7.5%) reported PrEP use. Only 19 (29.2%) had accessed PrEP under medical supervision. PrEP use was reported by 14.8% with > 5 risk contacts in the past 6 months, compared to 6.3% with one risk contact (p < 0.001). CONCLUSION: We found a high PrEP awareness and acceptance, especially among subgroups of MSM at highest risk of HIV infection. Structured access and availability of PrEP to this population may have an important impact on the HIV epidemic in Germany.

Prevalence of asymptomatic sexually transmitted infections in HIV-positive men who have sex with men in Germany: results of a multicentre cross-sectional study.

PURPOSE: Sexually transmitted infections (STIs) occur frequently in risk populations. Hereby, the role of screening-programmes remains controversial. Our study aimed to determine the prevalence of STI infections in HIV-positive men-who-have-sex-with-men (MSM). METHODS: We enrolled asymptomatic, HIV-MSM in a prospective cross-sectional study from February to August 2016 at seven German HIV-centres. All subjects were screened for Treponema-pallidum (TP) and hepatitis-B/C-infection. HIV RNA and screening for oral, rectal and urethral colonisation by Chlamydia-trachomatis (CT) and/or Neisseria-gonorrhoeae (NG) was performed. All subjects were asked to complete a sexual-risk-behaviour-questionnaire. RESULTS: In total, 296 subjects with a median age of 43.2 (36.2-49.5) years were enrolled; 99.3% were on ART for 5.5 (2.3-11.2) years. HIV RNA was < 50 copies/mL in 93.6%. Active syphilis infection was found in 5.0% of all patients, whereas 55.4% had history of infection. HCV seropositivity was found in 33 patients (13.2%) and positive HCV RNA was available in 39.4%. 66/294 (22.5%) showed negative anti-HBs-antibodies, indicating lack of immunity. Overall, 40/296 (13.5%) had positive CT/NG swabs (CT in 8.8%; 7.3% anorectal, 1.7% oropharyngeal, 1.0% urethral and NG in 6.8%; 4.5% anal, 2.0% oropharyngeal, 1.4% urethral). Time since HIV infection < 7 years (OR 2.6 (1.2-5.5); p = 0.012), the use of inhalative nitrites ("poppers") (OR 2.8 (1.3-5.9; p = 0.008) and reporting unprotected intercourse with > 20 partners within the last 6 months [OR 3.0 (1.2-7.8); p = 0.003] were significantly associated in multivariate analysis. CONCLUSION: We found high numbers of asymptomatic syphilis, hepatitis-C and CT/NG infections in HIV-MSM, remarkably in patients with shorter duration of HIV-infection with more sexual partners within last 6 months.

Highly specific reasons for nonadherence to antiretroviral therapy: results from the German adherence study.

BACKGROUND: Reasons for and frequency of nonadherence to antiretroviral therapy (ART) may have changed due to pharmacological improvements. In addition, the importance of known non-pharmacologic reasons for nonadherence is unclear. METHODS: We performed a cross-sectional, noninterventional, multicenter study to identify current reasons for nonadherence. Patients were categorized by physicians into the following adherence groups: good, unstable, or poor adherence. Co-variables of interest included age, sex, time since HIV diagnosis, ART duration, current ART regimen, HIV transmission route, comorbidity, HIV-1 RNA viral load (VL), and CD4 cell count. Patients self-reported the number of missed doses and provided their specific reasons for nonadherent behavior. Statistical analyses were performed using Fisher's extended exact test, Kruskal-Wallis test, and logistic regression models. RESULTS: Our study assessed 215 participants with good (n=162), unstable (n=36), and poor adherence (n=17). Compared to patients with good adherence, patients with unstable and poor adherence reported more often to have missed at least one dose during the last week (good 11% vs unstable 47% vs poor 63%, p<0.001). Physicians' adherence assessment was concordant with patients' self-reports of missed doses during the last week (no vs one or more) in 81% cases. Similarly, we found a strong association of physicians' assessment with viral suppression. Logistic regression analysis showed that "reduced adherence" - defined as unstable or poor - was significantly associated with patients <30 years old, intravenous drug use, history of acquired immune deficiency syndrome (AIDS), and psychiatric disorders (p<0.05). Univariate analyses showed that specific reasons, such as questioning the efficacy/dosing of ART, HIV stigma, interactive toxicity beliefs regarding alcohol and/or party drugs, and dissatisfaction with regimen complexity, correlated with unstable or poor adherence (p<0.05). CONCLUSION: Identification of factors associated with poor adherence helps in identifying patients with a higher risk for nonadherence. Reasons for nonadherence should be directly addressed in every patient, because they are common and constitute possible adherence intervention points.

Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy.

IMPORTANCE: A key factor in assessing the effectiveness and cost-effectiveness of antiretroviral therapy (ART) as a prevention strategy is the absolute risk of HIV transmission through condomless sex with suppressed HIV-1 RNA viral load for both anal and vaginal sex. OBJECTIVE: To evaluate the rate of within-couple HIV transmission (heterosexual and men who have sex with men [MSM]) during periods of sex without condoms and when the HIV-positive partner had HIV-1 RNA load less than 200 copies/mL. DESIGN, SETTING, AND PARTICIPANTS: The prospective, observational PARTNER (Partners of People on ART-A New Evaluation of the Risks) study was conducted at 75 clinical sites in 14 European countries and enrolled 1166 HIV serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex (September 2010 to May 2014). Eligibility criteria for inclusion of couple-years of follow-up were condomless sex and HIV-1 RNA load less than 200 copies/mL. Anonymized phylogenetic analysis compared couples' HIV-1 polymerase and envelope sequences if an HIV-negative partner became infected to determine phylogenetically linked transmissions. EXPOSURES: Condomless sexual activity with an HIV-positive partner taking virally suppressive ART. MAIN OUTCOMES AND MEASURES: Risk of within-couple HIV transmission to the HIV-negative partner. RESULTS: Among 1166 enrolled couples, 888 (mean age, 42 years [IQR, 35-48]; 548 heterosexual [61.7%] and 340 MSM [38.3%]) provided 1238 eligible couple-years of follow-up (median follow-up, 1.3 years [IQR, 0.8-2.0]). At baseline, couples reported condomless sex for a median of 2 years (IQR, 0.5-6.3). Condomless sex with other partners was reported by 108 HIV-negative MSM (33%) and 21 heterosexuals (4%). During follow-up, couples reported condomless sex a median of 37 times per year (IQR, 15-71), with MSM couples reporting approximately 22,000 condomless sex acts and heterosexuals approximately 36,000. Although 11 HIV-negative partners became HIV-positive (10 MSM; 1 heterosexual; 8 reported condomless sex with other partners), no phylogenetically linked transmissions occurred over eligible couple-years of follow-up, giving a rate of within-couple HIV transmission of zero, with an upper 95% confidence limit of 0.30/100 couple-years of follow-up. The upper 95% confidence limit for condomless anal sex was 0.71 per 100 couple-years of follow-up. CONCLUSIONS AND RELEVANCE: Among serodifferent heterosexual and MSM couples in which the HIV-positive partner was using suppressive ART and who reported condomless sex, during median follow-up of 1.3 years per couple, there were no documented cases of within-couple HIV transmission (upper 95% confidence limit, 0.30/100 couple-years of follow-up). Additional longer-term follow-up is necessary to provide more precise estimates of risk.

CD4+ and CD8+ T-cell kinetics in aviremic HIV-infected patients developing Hodgkin or non-Hodgkin lymphoma.

OBJECTIVE: The risk of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) is increased in HIV-infected individuals. We studied the kinetics of lymphocyte subsets in patients who subsequently developed HL or NHL while on virologically suppressive antiretroviral therapy (ART). DESIGN: Using a nested case-control design, cases of HIV+ HL or NHL were selected from two prospective clinical studies. Aviremia was defined as less than 200 HIV-RNA copies/ml for at least 6 months prior to lymphoma diagnosis. Each case was matched to three aviremic HIV+ controls without lymphoma. RESULTS: In the 81 cases (50 HL and 31 NHL), prediagnostic CD4 T cells and CD8 T cells displayed discordant kinetics compared with controls. Within the last and within the next-to-last year preceding HL diagnosis, mean CD4 T cells decreased by -168 and by -2 cells/µl, compared with an increase of +44 and +73 cells/µl in the controls, respectively. Mean CD8 T cells decreased by -352 and -115 cells/µl, compared with nonsignificant changes of -29 and ±0 cells/µl in the controls, respectively. T-cell kinetics demonstrated a marked inter-individual variability. Kinetics of CD4 and CD8 T cells were also discordant between NHL cases and controls. CONCLUSION: This study on a large number of aviremic patients developing HL and NHL who were carefully matched with controls, gives insights to prediagnostic kinetics of immune parameters. The discordant kinetics of both CD4 and CD8 T cells are already seen 1-2 years prior to lymphoma diagnosis, are more pronounced during the last year and in patients developing HL but are also seen in NHL.

Reduced HIV symptoms and improved health-related quality of life correlate with better access to care for HIV-1 infected women: the ELLA study.

INTRODUCTION: Global HIV-1 prevalence is 35.3 million [1]; women comprise >50% of those infected. The majority of women may lack regular care and only one-fourth are virologically suppressed [2]. ELLA is a cross-sectional, non-interventional study conducted across Europe, Latin America, Canada and Asia that describes barriers to care for HIV-infected women and associations with disease stage, symptoms and health-related quality of life (HRQoL). METHODS: HIV-infected women eligible for ELLA (≥18 years) completed: Barrier to Care Scale (BACS) comprising 12 items in four domains (Index range 0-12, Overall range 1-4, greater=more barriers, Overall score ≥2 considered severe); AIDS Clinical Trials Group (ACTG) Health Status Assessment comprising 21 items assessing 9 HRQoL domains (range 0-100, greater=better); and ACTG Symptom Distress Module comprising 20 symptoms rated on bother (range 0-4, greater=more bother). Healthcare providers documented medical history and HIV clinical data. Correlations of BACS response and last reported VL/CD4 count with HIV symptoms and HRQoL were analyzed. Spearman rank order was used to test correlations with statistical significance set at p<0.05. RESULTS: Enrollment: 1931 women from 30 countries; mean age 40 years (16.9% >50 years); 47.7% education <12 years; 36% unemployed; 82.9% urban residence. HIV was acquired heterosexually in 83.0%; 88.2% of subjects were on ART; 57.5% had VL<50 c/ml; mean CD4 was 540.5 c/µL. Mean [SD] BACS Index and Overall scores were 6.19 [3.47] (N=1818) and 2.09 [0.71] (N=1922), respectively. Stigma was a prominent barrier. Lower (better) BACS Index and Overall scores correlated with better HRQoL on all nine domains (p<0.0001). Lower VL and greater CD4 count were both correlated with better HRQoL for eight of nine domains (p<0.04, p≤0.0002, respectively) excepting pain. Lower BACS Index and Overall scores correlated with fewer symptom count and less symptom bother (p<0.0001). Fewer symptom count and less symptom bother correlated with better HRQoL on all nine domains (p<0.0001). While greater CD4 count correlated with fewer HIV symptoms and less bother (p<0.0001), VL did not significantly correlate with either. CONCLUSIONS: In HIV-infected women, reduced barriers to care correlated with fewer symptoms, less symptom bother and better HRQoL. Improved HRQoL may be mediated by greater CD4 counts and fewer symptoms. Better access to care may improve HRQoL outcomes in this population.

Acute hepatitis C virus (HCV) infection in the setting of HIV coinfection: a single-centre 10-year follow-up.

INTRODUCTION: Acute hepatitis C virus (HCV) infection has emerged as a major cause of morbidity in the HIV-infected population. Most guidelines recommend early treatment with pegylated interferon and ribavirin due to higher cure rates. The impact of acute HCV and its treatment on the outcome of the HIV-infected population is unknown. With new treatment options for HCV, early treatment of acute HCV has to be questioned. Here, we report a long-term analysis on patients with acute HCV. METHODS: Retrospective analysis from an outpatient clinic from Berlin. All patients with the diagnosis of acute HCV according to The European AIDS Treatment Network (NEAT) criteria were included in the database at their date of HCV diagnosis and followed-up until the last medical contact. Demographic data was taken from the medical file. A fibrosis estimation was performed using transient elastography (Fibroscan(®). A Fibroscan value above 7 kPa was considered as significant fibrosis, above 12.4 kPa as liver cirrhosis. The following outcomes were documented: (a) liver-related: hepatic decompensation, cirrhosis, hepatocellular carcinoma. (b) non-liver-related: death, myocardial infarction, AIDS-defining event, psychiatric hospitalisation. RESULTS: A total of 207 cases of acute HCV infection in HIV-infected patients were diagnosed between May 2002 and September 2013. All patients were male and declared homosexual contacts as their risk factor for having acquired HIV. The mean age was 39 years, 162 patients (78%) were on antiretroviral treatment, and the median CD4 cell count was 593/mm(3) (IQR 443-749). At HCV diagnosis, the highest median alanine aminotransferase (ALT) level was 408 IU/mL (159-871), the HCV viral load was 800,000 IU/mL (45x103-2.8x106). 22 cases (11%) cleared their infection spontaneously, 161 (77%) underwent interferon-based treatment. Of those treated, 58% had a sustained virological response. 36 cases of HCV reinfection were documented. All patients were followed-up over an interval of 806 patient-years. The median liver stiffness was 5.3 kPa (4-7) after a median interval of 34 months. 33 patients developed significant fibrosis, and 11 patients (6%) developed cirrhosis. Nine (5%) patients died during follow-up, and 11 developed non-liver-related endpoints. All but one deceased patients had interferon-based treatment. CONCLUSIONS: Severe hepatic disease and death rarely occurs in a highly treated HCV population. As interferon-based treatment may induce side effects, it is from now on justified to await new HCV treatment options.

Safety analysis of raltegravir/truvada regimen in HIV/HCV co-infected patients without switchback after HCV treatment.

INTRODUCTION: Due to drug-drug interactions of HIV- and HCV-specific antivirals when initiating an HCV-therapy, the antiretroviral therapy (ART) often has to be changed. The spectrum of applicable antiretrovirals is small, therefore many patients were switched to raltegravir/truvada (RAL/TVD) in our cohort. Due to the relatively low genetic barrier of RAL, this regimen may be endangered to fail, if the NRTI backbone is not fully active because of pre-existing NRTI resistance. We investigated the long-term follow-up and safety of RAL/TVD in co-infected patients after hepatitis C virus (HCV) therapy was stopped and the protective antiretroviral effect of interferon ended. MATERIALS AND METHODS: Twenty patients initiated a direct-acting antiviral (DAA) containing HCV therapy (8x faldaprevir, 6x telaprevir, 2x daclatasvir and 4x simeprevir) between 11/2011 and 01/2013. Seventeen were switched to RAL/TVD, three patients were not treated before, but started with the regimen. Diagnosis of HIV infection was dated between 1985 and 2010. The HI-viral suppression was monitored retrospectively to date. RESULTS: Thirteen of the twenty patients (65%) remained on RAL/TVD after finishing HCV treatment, for seven patients, no data about their ART continuation was available, after HCV therapy had stopped. All remaining thirteen patients showed an HI-viral load below detection limit up to date (for 15 to 22 months, median 20 months). Only for four patients, historic resistance data were available but none showed NRTI mutations. CONCLUSIONS: Switch to RAL/TVD as HIV ART due to initiating HCV therapy was safe for the observed small cohort even in long-term follow-up without switchback or a second ART switch. However, resistance data for the cohort was little, showing no NRTI mutations, indicating a relatively safe setting. Since no further data is available, physicians should keep in mind ART history, historical therapy failure and HIV-resistance while switching ART to treat HCV in co-infected patients. Further investigation in larger cohorts is needed, especially thinking of upcoming interferon-free HCV regimen in heavily pre-treated co-infected patients.

Hepatitis C virus (HCV)-specific memory B-cell responses in transiently and chronically infected HIV positive individuals.

BACKGROUND: Antibody responses to hepatitis C virus (HCV) occur delayed and overly decline after viral clearance indicating that the B-cell response to HCV is abnormal. Virus-specific memory B-cells have recently been found in infected individuals, but the viral exposure requirements for the generation of these cells is unknown. OBJECTIVES: The primary goal of this study was to quantify and compare the HCV-specific memory B-cell response between chronic and resolved HCV-infected individuals. A secondary goal was to examine if HIV-specific memory B-cell responses are maintained during HCV co-infection. STUDY DESIGN: HCV core protein- and HIV-specific memory B-cell responses were examined in HIV/HCV-infected individuals treated 4-30 weeks after HCV diagnosis. Memory B-cell frequencies were compared between chronically and transiently infected individuals. RESULTS: Chronically infected individuals had vigorous HCV-specific memory B-cell responses and antibodies, whereas subjects with transient viremia showed low or undetectable virus-specific B-cell responses. In addition, chronically HIV/HCV-infected subjects had robust HIV-specific memory B-cell responses. CONCLUSIONS: Whereas chronic HCV infection induces virus-specific antibodies and memory B-cells, transient infection in individuals with sustained viral response to therapy does not stimulate a durable HCV-specific B-cell response indicating that the formation of long-lived virus-specific B-cells is suppressed in the early phase of infection. This may contribute to the inability to spontaneously clear HCV infection.