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.

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BACKGROUND & AIMS: Interferon(IFN)-based hepatitis C virus (HCV) therapy has been replaced by direct-acting antivirals (DAAs).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.

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.

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.

A Lower CD4 Count Predicts Most Causes of Death except Cardiovascular Deaths. The Austrian HIV Cohort Study.

(1) Objective: To investigate changes in mortality rates and predictors of all-cause mortality as well as specific causes of death over time among HIV-positive individuals in the combination antiretroviral therapy (cART) era. (2) Methods: We analyzed all-cause as well as cause-specific mortality among the Austrian HIV Cohort Study between 1997 and 2014. Observation time was divided into five periods: Period 1: 1997-2000; period 2: 2001-2004; period 3: 2005-2008; period 4: 2009-2011; and period 5: 2012-2014. Mortality rates are presented as deaths per 100 person-years (d/100py). Potential risk factors associated with all-cause mortality and specific causes of death were identified by using multivariable Cox proportional hazard models. Models were adjusted for time-updated CD4, age and cART, HIV transmission category, population size of residence area and country of birth. To assess potential nonlinear associations, we fitted all CD4 counts per patient using restricted cubic splines with truncation at 1000 cells/mm3. Vital status of patients was cross-checked with death registry data. (3) Results: Of 6848 patients (59,704 person-years of observation), 1192 died: 380 (31.9%) from AIDS-related diseases. All-cause mortality rates decreased continuously from 3.49 d/100py in period 1 to 1.40 d/100py in period 5. Death due to AIDS-related diseases, liver-related diseases and non-AIDS infections declined, whereas cardiovascular diseases as cause of death remained stable (0.27 d/100py in period 1, 0.10 d/100py in period 2, 0.16 d/100py in period 3, 0.09 d/100py in period 4 and 0.14 d/100py in period 5) and deaths due to non-AIDS-defining malignancies increased. Compared to latest CD4 counts of 500 cells/mm3, lower CD4 counts conferred a higher risk of deaths due to AIDS-related diseases, liver-related diseases, non-AIDS infections and non-AIDS-defining malignancies, whereas no significant association was observed for cardiovascular mortality. Results were similar in sensitivity analyses where observation time was divided into two periods: 1997-2004 and 2005-2014. (4) Conclusions: Since the introduction of cART, risk of death decreased and causes of death changed. We do not find evidence that HIV-positive individuals with a low CD4 count are more likely to die from cardiovascular diseases.

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.

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.

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.

Virologic and immunologic outcomes of treatment with integrase inhibitors in a real-world setting: The RESPOND cohort consortium.

OBJECTIVES: To compare virologic and immunologic outcomes of integrase inhibitor (INSTI)-containing, contemporary boosted protease inhibitor (PI/b)-containing and non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens in a real-life setting. METHODS: Using logistic regression, virologic and immunologic outcomes of INSTI use were compared to outcomes of PI/b or NNRTI treatment 12 months after treatment start or switch, for participants in the RESPOND cohort consortium. A composite treatment outcome (cTO) was used, defining success as viral load (VL) <200 copies/mL and failure as at least one of: VL ≥200 copies/mL, unknown VL in the time window, any changes of antiretroviral therapy (ART) regimen, AIDS, or death. In addition, on-treatment analysis including only individuals with known VL and no regimen changes was performed. Favorable immunologic response was defined as a 25% increase in CD4 count or as reaching ≥750 CD4 cells/µL. RESULTS: Between January 2012 and January 2019, 13,703 (33.0% ART-naïve) individuals were included, of whom 7,147 started/switched to a regimen with an INSTI, 3,102 to a PI/b and 3,454 to an NNRTI-containing regimen. The main reason for cTO failure in all treatment groups were changes in ART regimen. Compared to INSTIs, the adjusted odds ratio (aOR) of cTO success was significantly lower for PI/b (0.74 [95% confidence interval, CI 0.67-0.82], p <0.001), but similar for NNRTIs (1.07 [CI 0.97-1.17], p = 0.11). On-treatment analysis and sensitivity analyses using a VL cut-off of 50 copies/mL were consistent. Compared to INSTIs, the aORs of a 25% increase in CD4 count were lower for NNRTIs (0.80 [CI 0.71-0.91], p<0.001) and PI/b (0.87 [CI 0.76-0.99], p = 0.04). CONCLUSION: In this large analysis of a real-world population, cTO and on-treatment success were similar between INSTIs and NNRTIs, but lower for PI/b, though residual confounding cannot be fully excluded. Obtaining favorable immunologic outcomes were more likely for INSTIs than the other drug classes.

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.

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.

Low seroprotection rate for meningococcus serogroup C in the adult HIV-1-infected population in Austria.

Current Advisory Committee on Immunization Practices (ACIP) guidelines recommend immunization of all human immunodeficiency virus (HIV)-infected patients against meningitis serotype ACWY due to recent outbreaks of meningitis C in homosexual men in the USA. Implementation of this recommendation in other countries, such as Austria is hindered by the scarce knowledge on the vaccine coverage. In this study the serostatus for meningococcus serogroup C was analyzed in 390 HIV-infected individuals residing in Austria. These individuals were representative for the Austrian HIV cohort regarding sex, age, transmission risk and HIV progression markers. Overall, 73% were on suppressive antiretroviral therapy, the mean CD4 cell count was 599 cells/µl and immunoglobulin G (IgG) seropositivity was 18% for meningococcus serogroup C. Migrants and patients who had acquired an infection via heterosexual intercourse had a higher chance for meningococcus serogroup C seropositivity. Importantly due to the well-preserved immune status of nearly all participants vaccination would be feasible in the majority of the seronegative patients. It is assumed that this measure would largely reduce the number of patients at risk for this vaccine-preventable disease.

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.

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.

Determinants of Restoration of CD4 and CD8 Cell Counts and Their Ratio in HIV-1-Positive Individuals With Sustained Virological Suppression on Antiretroviral Therapy.

BACKGROUND: An increasing number of HIV-positive individuals now start antiretroviral therapy (ART) with high CD4 cell counts. We investigated whether this makes restoration of CD4 and CD8 cell counts and the CD4:CD8 ratio during virologically suppressive ART to median levels seen in HIV-uninfected individuals more likely and whether restoration depends on gender, age, and other individual characteristics. METHODS: We determined median and quartile reference values for CD4 and CD8 cell counts and their ratio using cross-sectional data from 2309 HIV-negative individuals. We used longitudinal measurements of 60,997 HIV-positive individuals from the Antiretroviral Therapy Cohort Collaboration in linear mixed-effects models. RESULTS: When baseline CD4 cell counts were higher, higher long-term CD4 cell counts and CD4:CD8 ratios were reached. Highest long-term CD4 cell counts were observed in middle-aged individuals. During the first 2 years, median CD8 cell counts converged toward median reference values. However, changes were small thereafter and long-term CD8 cell count levels were higher than median reference values. Median 8-year CD8 cell counts were higher when ART was started with <250 CD4 cells/mm. Median CD4:CD8 trajectories did not reach median reference values, even when ART was started at 500 cells/mm. DISCUSSION: Starting ART with a CD4 cell count of ≥500 cells/mm makes reaching median reference CD4 cell counts more likely. However, median CD4:CD8 ratio trajectories remained below the median levels of HIV-negative individuals because of persisting high CD8 cell counts. To what extent these subnormal immunological responses affect specific clinical endpoints requires further investigation.

Epidemiology of Urinary Tract Infections in HIV Positive Patients at a Tertiary Care University Hospital in Central Europe (2011 - 2016).

OBJECTIVES: There is limited published data concerning the recent epidemiology of urinary tract infections (UTI) in HIV-patients, thus we analysed independent risk factors for UTI in HIV positive individuals and antimicrobial resistance rates of E. coli to antimicrobial agents commonly used in UTI. To determine the prevalence of symptomatic urinary tract infections (UTI) in HIV-patients, we performed a retrospective case-control study. METHODS: We included 313 HIV-patients, 101 with UTI and 212 age and gendermatched controls, attending the HIV outpatient clinic at the Vienna University Hospital (VUH) over a period from January 2011 to September 2016. The patients' specific data was gathered from the electronic database of the VUH. The statistical analysis was performed using SPSS Software Version 20.0. RESULTS: HIV infected individuals with CD4 count >200 cells/mm3 were less likely than HIV infected individuals with CD4 count <200 cells/mm3 to experience UTI (OR 0.811, 95% CI 0.712-0.923 vs. OR 2.555, 95% CI 1.553 - 4.205, respectively). The in vitro resistance rate of E. coli to antimicrobial agents was as follows: ciprofloxacin (41%), mecillinam (20.5%), trimethoprim (61%), ampicillin (67%), ampicillin/ clavulanic acid (23%), cefuroxime (17%), nitrofurantoin (2%), amikacin (0%) and gentamicin (9.5%). CONCLUSION: Immunological status (CD4 count) is an important parameter for risk assessment of UTIs in HIV-patients. The increased resistance rate of E. coli to commonly used antimicrobial agents needs to be considered when it comes to the management of UTI, additionally, surveillance strategies should be implemented in HIV-patients.

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.