Delayed antiretroviral therapy in HIV-infected individuals leads to irreversible depletion of skin- and mucosa-resident memory T cells.

People living with HIV (PLWH) are at increased risk for developing skin and mucosal malignancies despite systemic reconstitution of CD4+ T cells upon antiretroviral therapy (ART). The underlying mechanism of chronic tissue-related immunodeficiency in HIV is unclear. We found that skin CD4+ tissue-resident memory T (Trm) cells were depleted after HIV infection and replenished only upon early ART initiation. TCR clonal analysis following early ART suggested a systemic origin for reconstituting CD4+ Trm cells. Single-cell RNA sequencing in PLWH that received late ART treatment revealed a loss of CXCR3+ Trm cells and a tolerogenic skin immune environment. Human papilloma virus-induced precancerous lesion biopsies showed reduced CXCR3+ Trm cell frequencies in the mucosa in PLWH versus HIV- individuals. These results reveal an irreversible loss of CXCR3+ Trm cells confined to skin and mucosa in PLWH who received late ART treatment, which may be a precipitating factor in the development of HPV-related cancer.

The 'Viennese epidemic' of acute HCV in the era of direct-acting antivirals.

The recently reported epidemic of acute hepatitis C virus (HCV) infections -observed predominantly among men who have sex with men (MSM)-may now decline due to wide availability of direct-acting antivirals (DAAs). This study aimed to investigate the current trends of acute hepatitis C in Vienna. Patients presenting with acute hepatitis C between 01/2007 and12/2020 at the Vienna General Hospital were retrospectively enrolled and followed after virologic clearance/eradication. The introduction of unrestricted DAA access after 09/17 defined the 'DAA era', as compared to the 'pre-DAA era' prior to 09/17. We identified 134 acute hepatitis C cases in 119 patients with a mean age of 39 ± 9 years at inclusion. The majority of patients were male (92%), HIV-positive (88%) and MSM (85%). In the DAA era, a history of prior chronic HCV infection at inclusion was found in 24% (11/46) compared to 7% (5/73) in the pre-DAA era (p = .012). The annual rate of acute hepatitis C cases increased in the DAA era (17.11 per year) compared to the pre-DAA era (7.76 per year). The DAA era included an AHC-genotype-2 cluster and more HIV-negative acute hepatitis C cases (0% (0/73) vs. 30% (14/46), p < .001). Patients were followed after spontaneous clearance or sustained virologic treatment response (SVR) for a total of 251.88 patient-years (median 1.39 years per patient). In the DAA era, we recorded 15 acute hepatitis C-reinfections - corresponding to an incidence rate of 5.96 (95% CI: 3.57-9.66) reinfections per 100-patient-years. We continue to observe a high incidence of acute hepatitis C in Vienna in the DAA era-primarily among HIV-positive MSM, but increasingly also in HIV-negative MSM.

Switching to Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Virologically Suppressed Adults With Human Immunodeficiency Virus.

BACKGROUND: Bictegravir (B)/emtricitabine (F)/tenofovir alafenamide (TAF) is guideline-recommended treatment for human immunodeficiency virus type 1 (HIV-1). We evaluated whether people receiving dolutegravir (DTG) plus F/TAF or F/TDF (tenofovir disoproxil fumarate) with viral suppression can switch to B/F/TAF without compromising safety or efficacy, regardless of preexisting nucleoside reverse transcriptase inhibitor (NRTI) resistance. METHODS: In this multicenter, randomized, double-blinded, active-controlled, noninferiority trial, we enrolled adults who were virologically suppressed for ≥6 months before screening (with documented/suspected NRTI resistance) or ≥3 months before screening (with no documented/suspected NRTI resistance) on DTG plus either F/TDF or F/TAF. We randomly assigned (1:1) participants to switch to B/F/TAF or DTG + F/TAF once daily for 48 weeks, each with matching placebo. The primary endpoint was proportion of participants with plasma HIV-1 RNA ≥50 copies/mL at week 48 (snapshot algorithm); the prespecified noninferiority margin was 4%. RESULTS: Five hundred sixty-seven adults were randomized; 565 were treated (284 B/F/TAF, 281 DTG + F/TAF). At week 48, B/F/TAF was noninferior to DTG + F/TAF, as 0.4% (1/284) vs 1.1% (3/281) had HIV-1 RNA ≥50 copies/mL (difference, -0.7% [95.001% confidence interval {CI}, -2.8% to 1.0%]). There were no significant differences in efficacy among participants with suspected or confirmed prior NRTI resistance (n = 138). No participant had treatment-emergent drug resistance. Median weight change from baseline at week 48 was +1.3 kg (B/F/TAF) vs +1.1 kg (DTG + F/TAF) (P = .46). Weight change differed by baseline NRTIs (+2.2 kg [F/TDF] and +0.6 kg [F/TAF], P < .001), with no differences between B/F/TAF and DTG + F/TAF. CONCLUSIONS: The single-tablet regimen B/F/TAF is a safe, effective option for people virologically suppressed on DTG plus either F/TDF or F/TAF, including in individuals with preexisting resistance to NRTIs. CLINICAL TRIALS REGISTRATION: NCT03110380.

Epidemiological trends of HBV and HDV coinfection among Viennese HIV+ patients.

BACKGROUND AND AIMS: Despite vaccination recommendations, hepatitis B (HBV) and D (HDV) coinfections are common in HIV+individuals. METHODS: HBV immunization status (anti-HBs) as well as HBV (HBsAg/HBV-DNA) and HDV (anti-HDV) coinfection rates were assessed in 1870 HIV+individuals at HIV diagnosis (baseline, BL) and last follow-up (FU). RESULTS: Sixty-eight (3.6%) HIV patients were never tested for HBV. At BL, 89/1802 (4.9%) HIV patients were HBV coinfected. Four hundred and fifteen (23.0%) showed virological HBV clearance [HBsAg(-)/anti-HBc(+)/anti-HBs(+)] and 210 (11.7%) presented with anti-HBc(+) only. Seven hundred and ten (39.4%) were HBV naïve [HBsAg(-)/anti-HBs(-)/anti-HBc(-)/HBV-DNA(-)], but only 378 (21.0%) received vaccinations with detectable anti-HBs(+) titres. Among the 89 HBV/HIV-coinfected patients, only 52 (58.4%) were tested for HDV: 11/49 (22.4%) had anti-HDV(+) and 3/12 (25.0%) showed HDV-RNA viraemia. During a median FU of 6.5 (IQR 7.2) years, 44 (4.6%) of the 953 retested BL HBV-negative patients acquired new HBV infection (including 15/304, 4.9% of vaccinated patients). Of the 89 patients, 22 (24.7%) patients cleared their HBsAg, resulting in 60/1625 (3.7%) HIV/HBV individuals at FU: 34 (56.7%) showed HBV-DNA suppression and 15 (25.0%) were HBV viraemic, while 12/89 (13.5%) remained without a FU test. Vaccinations induced anti-HBs(+) in 137 of the retested 649 (21.1%) BL HBV-naïve patients. CONCLUSION: HBV testing is well established among Viennese HIV+patients with HBV coinfection rates around 4%-5%. HBV vaccinations are insufficiently implemented since anti-HBs titres were detected in only 21.1% of HBV-naive HIV(+) patients and new HBV infections occurred in previously vaccinated patients. HDV testing is not systematically performed despite up to 25% of HIV/HBV patients may show HDV coinfection.

HIV infection as a risk factor for vaginal dysbiosis, bacterial vaginosis, and candidosis in pregnancy: A matched case-control study.

BACKGROUND: This study aimed to evaluate the vaginal microbiota of HIV-positive pregnant women relative to HIV-negative controls, and to compare their risk of vaginal dysbiosis, bacterial vaginosis, and vulvovaginal candidosis (VVC). METHODS: This is a nested matched case-control study that analyzed data from women who received pregnancy care at our center from 2003 to 2014. Women routinely underwent screening for asymptomatic vaginal infections using phase microscopy on Gram-stained smears. HIV-positive women were assigned to the case group, and HIV-negative women were assigned to the control group. Cases and controls were matched in a 1:4 ratio. Logistic regression was used to test whether HIV infection was associated with vaginal dysbiosis (Nugent score 4-6), BV (Nugent score 7-10), or VVC. RESULTS: One hundred and twenty-seven women were assigned to the case group, and 4290 were assigned to the control group (including 508 matched controls). Dysbiosis or BV was found in 29.9% of the cases and 17.6% of the controls. Women in the case group had increased risk of vaginal dysbiosis or BV (odds ratio [OR] 2.09, 95% confidence interval [CI], 1.30-3.32, P = .002). The risk of VVC was also higher in the case group (OR 2.14, 95% CI, 1.22-3.77, P = .008). The incidence of preterm birth did not differ significantly between the groups (cases: 8.7%; controls: 10%, P = .887). CONCLUSIONS: HIV-positive women are at risk of vaginal dysbiosis, BV, and VVC during pregnancy. As imbalances of the vaginal microbiota can lead to preterm birth, screening and treatment of HIV-positive pregnant women are warranted.

Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study.

BACKGROUND: The level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited compared with the evidence available for transmission risk in heterosexual couples. The aim of the second phase of the PARTNER study (PARTNER2) was to provide precise estimates of transmission risk in gay serodifferent partnerships. METHODS: The PARTNER study was a prospective observational study done at 75 sites in 14 European countries. The first phase of the study (PARTNER1; Sept 15, 2010, to May 31, 2014) recruited and followed up both heterosexual and gay serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex, whereas the PARTNER2 extension (to April 30, 2018) recruited and followed up gay couples only. At study visits, data collection included sexual behaviour questionnaires, HIV testing (HIV-negative partner), and HIV-1 viral load testing (HIV-positive partner). If a seroconversion occurred in the HIV-negative partner, anonymised phylogenetic analysis was done to compare HIV-1 pol and env sequences in both partners to identify linked transmissions. Couple-years of follow-up were eligible for inclusion if condomless sex was reported, use of pre-exposure prophylaxis or post-exposure prophylaxis was not reported by the HIV-negative partner, and the HIV-positive partner was virally suppressed (plasma HIV-1 RNA <200 copies per mL) at the most recent visit (within the past year). Incidence rate of HIV transmission was calculated as the number of phylogenetically linked HIV infections that occurred during eligible couple-years of follow-up divided by eligible couple-years of follow-up. Two-sided 95% CIs for the incidence rate of transmission were calculated using exact Poisson methods. FINDINGS: Between Sept 15, 2010, and July 31, 2017, 972 gay couples were enrolled, of which 782 provided 1593 eligible couple-years of follow-up with a median follow-up of 2·0 years (IQR 1·1-3·5). At baseline, median age for HIV-positive partners was 40 years (IQR 33-46) and couples reported condomless sex for a median of 1·0 years (IQR 0·4-2·9). During eligible couple-years of follow-up, couples reported condomless anal sex a total of 76 088 times. 288 (37%) of 777 HIV-negative men reported condomless sex with other partners. 15 new HIV infections occurred during eligible couple-years of follow-up, but none were phylogenetically linked within-couple transmissions, resulting in an HIV transmission rate of zero (upper 95% CI 0·23 per 100 couple-years of follow-up). INTERPRETATION: Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV. FUNDING: National Institute for Health Research.

Epidemiological trends in HCV transmission and prevalence in the Viennese HIV+ population.

BACKGROUND & AIMS: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection is common in people who inject drugs (PWIDs). Recently, 'high-risk' behaviour among men who have sex with men (MSM) has emerged as another main route of HCV transmission. We analysed temporal trends in HCV epidemiology in a cohort of Viennese HIV+ patients. METHODS: Hepatitis C virus parameters were recorded at HIV diagnosis (baseline [BL]) and last visit (follow-up [FU]) for all HIV+ patients attending our HIV clinic between January 2014 and December 2016. Proportions of HIV+ patients with anti-HCV(+) and HCV viraemia (HCV-RNA(+)) at BL/FU were assessed and stratified by route of transmission. RESULTS: In all, 1806/1874 (96.4%) HIV+ patients were tested for HCV at BL. Anti-HCV(+) was detected in 93.2% (276/296) of PWIDs and in 3.7% (31/839) of MSM. After a median FU of 6.9 years, 1644 (91.0%) patients underwent FU HCV-testing: 167 (90.3%) of PWIDs and 49 (6.7%) of MSM showed anti-HCV(+). Among 208 viraemic HCV-RNA(+) patients at BL, 30 (14.4%) had spontaneously cleared HCV, 76 (36.5%) achieved treatment-induced eradication and 89 (42.8%) remained HCV-RNA(+) at last FU. Among 1433 initially HCV-naive patients, 45 (3.5%) acquired de-novo HCV infection (11.1% PWIDs/80.0% MSM; incidence rate (IR) 0.004%; 95% confidence interval [CI] 0.0%-0.022%) and 14 had HCV reinfections (85.7% PWIDs/14.3% other; IR 0.001%; 95% CI 0.0%-0.018%) during a median FU of 6.7 years (interquartile range 7.4). CONCLUSION: Hepatitis C virus testing was successfully implemented in the Viennese HIV(+) patients. Anti-HCV(+) prevalence remained stable in HIV+ PWIDs but almost doubled in HIV+ MSM. De-novo HCV infection occurred mostly in MSM, while HCV reinfections were mainly observed in PWIDs. HCV treatment uptake was suboptimal with 42.8% remaining HCV-RNA(+) at FU.

Outcomes of coronary artery bypass grafting in patients with human immunodeficiency virus infection.

BACKGROUND: With early and effective antiretroviral therapy and improved survival for persons living with human immunodeficiency virus infection (PLHIV), this patient population now faces an increasingly elevated risk of cardiovascular disease. However, the data on outcomes after coronary artery bypass grafting (CABG) for revascularization of coronary artery disease (CAD) in HIV+ patients is limited. METHODS: We conducted a retrospective analysis of 16 patients undergoing isolated CABG at the Medical University of Vienna from 2005 to 2018, who were HIV+ on admission. The primary endpoint of the study was survival. Secondary endpoints included the components of major adverse cardiac and cerebrovascular events (MACCE): cardiovascular death, stroke, myocardial infarction (MI), and repeat revascularization. RESULTS: Patients were followed for a median of 49 months (range, 7-142 months). Survival was 100% and 90% at 1 and 3 years after CABG, respectively. There were no strokes. MI and subsequent repeat revascularization were observed in two patients. CONCLUSION: CABG provides excellent short- and midterm survival and freedom from MACCE in HIV+ patients with CAD requiring revascularization.

Prevalence of Skin-specific Autoantibodies in HIV-infected Patients and Uninfected Controls.

Various autoantibodies are detected more frequently in HIV-infected individuals than in HIV-negative controls; however, limited data exist regarding autoimmune blistering skin diseases. Using enzyme-linked immunoassay (ELISA) and indirect immunofluore-scence, no difference in the frequency and magnitude of autoantibodies against BP180, BP230, desmoglein 1 and 3 was found between 594 HIV-infected patients and 248 uninfected controls in this cross-sectional study (16.0% vs. 11.7%, respectively, for at least one positive ELISA, p = 0.11). Interestingly, reactive syphilis serology in both HIV-infected individuals and uninfected controls was associated with positive anti-BP180 ELISA results (adjusted odds ratio (OR) 2.14, 95% confidence interval (CI) 1.07-4.29, p = 0.03 and OR 4.70, CI 1.3-16.86; p = 0.0180). Our study shows a comparably low prevalence of cutaneous autoantibodies in both HIV-infected patients and uninfected controls lacking signs of autoimmune blistering skin disease. Positive BP180 ELISA in the absence of clinical signs of bullous pemphigoid should prompt further evaluation for syphilis antibodies.

Acute HIV Infection Results in Subclinical Inflammatory Cardiomyopathy.

The impact of excess viral RNA on myocardial function and morphology in the setting of acute human immunodeficiency virus (HIV) infection remains unknown. In this study, 49 patients with acute HIV infection showed increased levels of N-terminal prohormone of brain natriuretic peptide, a surrogate of myocardial function, which decreased with viral suppression and normalization of systemic inflammation (79 pg/mL vs 28 pg/mL; P < .001). A comparable change was seen with levels of troponin T, a marker of morphologic myocardial damage (4.9 ng/L vs 1.5 ng/L; P < .001). In conclusion, we observed significant functional and morphological myocardial impairment during acute HIV infection, fueled by inflammatory activation and extensive viral replication, resulting in a reversible subclinical inflammatory cardiomyopathy.

Antibodies targeting BTLA or TIM-3 enhance HIV-1 specific T cell responses in combination with PD-1 blockade.

Persistent stimulation with antigens derived from viruses that establish chronic infections or tumour antigens results in the exhaustion of T cells. Coinhibitory receptors like PD-1 and CTLA-4 function as immune checkpoints on exhausted T cells. Blocking these molecules with antibodies improve immunity to cancer cells. Immune checkpoint inhibitors targeting other coinhibitory receptors might have a similar role in improving T cell function and thus also utility in cancer therapy. Using HIV-specific T cells as a model for exhaustion we have evaluated the capacity of antibodies targeting TIM-3, BTLA, CD160, LAG-3 and CTLA-4 alone or in combination with a PD-1 antibody to enhance proliferation and cytokine production in response to Gag and Nef peptides. Antibodies targeting BTLA and TIM-3 enhanced CD8 T cell proliferation. Moreover, our results indicate that blocking BTLA and TIM-3 in combination with PD-1 might be especially effective in enhancing responses of exhausted human T cells.

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.

TIM-3 does not act as a receptor for galectin-9.

T cell immunoglobulin and mucin protein 3 (TIM-3) is a type I cell surface protein that was originally identified as a marker for murine T helper type 1 cells. TIM-3 was found to negatively regulate murine T cell responses and galectin-9 was described as a binding partner that mediates T cell inhibitory effects of TIM-3. Moreover, it was reported that like PD-1 the classical exhaustion marker, TIM-3 is up-regulated in exhausted murine and human T cells and TIM-3 blockade was described to restore the function of these T cells. Here we show that the activation of human T cells is not affected by the presence of galectin-9 or antibodies to TIM-3. Furthermore, extensive studies on the interaction of galectin-9 with human and murine TIM-3 did not yield evidence for specific binding between these molecules. Moreover, profound differences were observed when analysing the expression of TIM-3 and PD-1 on T cells of HIV-1-infected individuals: TIM-3 was expressed on fewer cells and also at much lower levels. Furthermore, whereas PD-1 was preferentially expressed on CD45RA(-)CD8 T cells, the majority of TIM-3-expressing CD8 T cells were CD45RA(+). Importantly, we found that TIM-3 antibodies were ineffective in increasing anti-HIV-1 T cell responses in vitro, whereas PD-L antibodies potently reverted the dysfunctional state of exhausted CD8 T cells. Taken together, our results are not in support of an interaction between TIM-3 and galectin-9 and yield no evidence for a functional role of TIM-3 in human T cell activation. Moreover, our data indicate that PD-1, but not TIM-3, is a promising target to ameliorate T cell exhaustion.

Malignant syphilis in a HIV infected patient.

We present a 47 year old female white HIV-1 infected patient with multiple painless rupioid skin lesions, a CD4 count of 155 cells/mm3, positive syphilis serology and a histopathology conspicuous for malignant syphilis. She could be successfully treated with Benzathine-Benzylpenicillin (Retarpen®) 2,4 Mega I.E., 3x intramuscularly in weekly intervals.

Reversion and conversion of interferon-γ release assay results in HIV-1-infected individuals.

In this prospective study, human immunodeficiency virus type 1 (HIV-1)-infected subjects underwent QuantiFERON-TB Gold In-Tube interferon-γ release assay (IGRA) testing at baseline and after 24 months in a low tuberculosis incidence country. Concordant baseline and follow-up results were observed in 86% (n = 686 of 794) of subjects. IGRA conversions occurred in 9% (n = 63 of 718), whereas IGRA reversions were seen in 33% (n = 25 of 76) of individuals. Of the 10 active tuberculosis cases during follow-up, 5 had concordant positive IGRA results and 2 were IGRA converters. Although the clinical significance of IGRA conversions and reversions remains to be established, repeated IGRA testing seems to be of value in HIV-1-infected individuals.

Health-related quality of life and severity of fatigue in HIV/HCV co-infected patients before, during, and after antiviral therapy with pegylated interferon plus ribavirin.

UNLABELLED: The aim of this study was to prospectively assess health-related quality of life (HRQL) and severity of fatigue before, during and after antiviral therapy in HIV/HCV co-infected patients. DESIGN: 59 HIV/HCV co-infected patients receiving pegylated interferon plus ribavirin (PEGIFN+RBV) in the HIVCOPEG study were included in this substudy evaluating the secondary endpoints HRQL and severity of fatigue. METHODS: HRQL and severity of fatigue were assessed using SF36 and FSS, respectively. Advanced liver fibrosis was defined as METAVIR F3/F4 or liver stiffness >9.5 kPa. RESULTS: At baseline, advanced liver fibrosis was associated with worse physical health. Mental health was impaired in female patients and in patients with a history of intravenous drug abuse, while a history of depression was associated with higher severity of fatigue. Female gender was associated with a more pronounced relative decrease in mental health during therapy. At follow-up, 24 weeks after the end of therapy, both physical health and fatigue symptoms had improved. Virological response was associated with better physical and mental health, as well as with reduced severity of fatigue. A correlation between anemia grade and the relative impairments in physical health, mental health and fatigue was observed. CONCLUSIONS: Antiviral therapy with PEGIFN+RBV impairs physical and mental health and increases severity of fatigue, while virological response is associated with improvements in physical health and fatigue symptoms. The optimization of anemia management is essential for reducing the burden of impaired HRQL and fatigue in HIV/HCV co-infected patients receiving antiviral therapy with PEGIFN+RBV.

Pyogenic spondylodiscitis in HIV-positive patients under antiretroviral therapy: A case series.

Background: The incidence of pyogenic spondylodiscitis has been increasing in countries of Europe and North America, probably due to an increasing number of persons with risk factors for this infection. It is unclear whether HIV infection in the era of antiretroviral therapy (ART) increases the risk for spondylodiscitis. Method: We present 7 cases of pyogenic spondylodiscitis of the cervical, thoracic, and lumbar spine in six individuals living with HIV under ART with suppressed viral load. Results: All patients presented with severe non-radicular pain and elevated inflammatory markers. Diagnosis was confirmed by magnetic resonance imaging (MRI) scan and isolation of the pathogen. Staphylococcus aureus was the causative pathogen in five patients. One patient suffered from an infection with Klebsiella pneumoniae followed by a mixed infection with Cutibacterium acnes and Bacillus circulans 18 months later. All patients needed surgical intervention, and the mean duration of antibiotic treatment was 17 weeks (range 12-26). Five patients recovered fully, including two persons who also suffered from endocarditis. One patient died from multi-organ failure. Conclusion: Spondylodiscitis may be seen more frequently in persons living with HIV as they grow older and suffer from comorbidities which put them at risk for this infection. HIV physicians should be aware of the infection and its risk factors.

Prevalence and dynamics of NAFLD-associated fibrosis in people living with HIV in Vienna from first presentation to last follow-up.

BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) is frequent in people living with HIV (PLWH) and may be aggravated by metabolic comorbidities and antiretroviral therapy (ART)-associated adverse effects. METHODS: We retrospectively assessed epidemiological, clinical and laboratory parameters and ART regimens at HIV diagnosis (BL) and at last follow-up (FU) in 1458 PLWH without viral hepatitis coinfection attending our HIV clinic in 2014-2016. Fibrosis was non-invasively assessed by the NAFLD fibrosis score (NFS). RESULTS: The median age of subjects was 37.8 years, 77.4% were male and 67.2% on ART, median CD4+ count was 356.0 cells/µL. At BL, 503 (34.5%) and 20 (1.4%) PLWH had dyslipidemia and diabetes, respectively. According to the NFS 16 (1.3%) showed advanced fibrosis (NFS ≥ 0.676), among which 1 (6.3%) had diabetes, 7 (43.8%) had dyslipidemia, and 5 (31.3%) were on HIV-protease inhibitors (PI). In addition, 191(15.1%) had intermediate NFS results, while fibrosis was ruled out (NFS ≤ 1.455) in 1065 (83.7%) PLWH. After a median follow-up of 6.3 years, 590 (42.8%) had dyslipidemia and 61 (4.4%) had diabetes. Also, 21 (1.6%) showed advanced fibrosis, of which 10 (47.6%) had diabetes, 4 (19.0%) had dyslipidemia, and 9 (42.9%) were on PI-based ART, 223 (17.4%) had intermediate NFS results, while 1039 (81.0%) showed no fibrosis. CONCLUSION: During FU, advanced NAFLD fibrosis occurred in 1.3-1.6% of PLWH. Dyslipidemia, diabetes, and PI-based ART were associated with advanced NAFLD fibrosis. Prospective investigations of NAFLD severity and risk factors in PLWH are warranted.

Progress of Hepatitis C elimination in Viennese people living with HIV after two decades of increasing cure rates.

BACKGROUND & AIMS: Interferon(IFN)-based hepatitis C virus (HCV) therapy has been replaced by direct-acting antivirals (DAAs). We assessed temporal trends in patient characteristics, transmission risks, treatment initiation, and cure rates in eras of IFN, restricted DAA-access, and unrestricted DAA-access in Viennese HCV/HIV-coinfected patients (HIV/HCV). METHODS: Consecutive HIV/HCV-coinfected patients starting HCV treatment at the Vienna General Hospital between 2002 and 2020 were retrospectively enrolled. RESULTS: Of all N = 508 HIV/HCV, 78% (398/508) were male and the mean age was 41.8 ± 9.5 years. 'People-who-inject-drugs' (PWID) accounted for 61% (311/508), while 31% (156/508) were 'men who have sex with men' (MSM). In the IFN-era, restricted DAA-era and unrestricted DAA-era, N = 152, N = 129, and N = 227 HCV treatments were started and 49% (74/152), 95% (122/129), and 88% (200/227) achieved sustained virologic response, respectively. Treatment during the IFN-era was a strong predictor for virologic non-response (aOR 12.69; 6.93-23.24) and loss-to-follow-up (aOR 6.12; 2.99-12.54), while virologic non-response was less common in 'MSM' (aOR 0.28; 0.13-0.62). Ninety three percent (50/54) of the observed HCV reinfections occurred in the unrestricted DAA-era. A substantial increase in 'MSM' transmission was observed since 2010 with 66% (107/161) in the DAA-era versus 15% (49/330) prior to the DAA-era. CONCLUSIONS: HCV cure rates in Viennese HIV patients increased from 49% in the IFN-era to 88-95% in the DAA-era. MSM-related risk behaviour and reinfections became the key challenges towards HCV elimination in HIV-coinfected patients.