Human Immunodeficiency Virus Cohort Research Articles

A Treatment-as-Prevention Trial to Eliminate Hepatitis C Among Men Who Have Sex With Men Living With Human Immunodeficiency Virus (HIV) in the Swiss HIV Cohort Study.

In 2016, the World Health Organization (WHO) introduced global targets for the elimination of hepatitis C virus (HCV) by 2030. We conducted a nationwide HCV micro-elimination program among men who have sex with men (MSM) living with human immunodeficiency virus (HIV) from the Swiss HIV Cohort Study (SHCS) to test whether the WHO goals are achievable in this population. During phase A (10/2015-06/2016), we performed a population-based and systematic screening for HCV-RNA among MSM from the SHCS. During phase B (06/2016-02/2017) we offered treatment with HCV direct-acting antiviral (DAA) agents to MSM identified with a replicating HCV infection. During phase C (03/2017-11/2017), we offered rescreening to all MSM for HCV-RNA and initiated DAA treatment in MSM with replicating infections. We screened 3715/4640 (80%) MSM and identified 177 with replicating HCV infections (4.8%); 150 (85%) of whom started DAA treatment and 149 (99.3%) were cured. We rescreened 2930/3538 (83%) MSM with a prior negative HCV-RNA and identified 13 (0.4%) with a new HCV infection. At the end of the micro-elimination program, 176/190 MSM (93%) were cured, and the HCV incidence rate declined from .53 per 100 patient-years (95% CI, .35-.83) prior to the intervention to .12 (95% CI, .03-.49) by the end of 2019. A systematic, population-based HCV micro-elimination program among MSM living with HIV was feasible and resulted in a strong decline in HCV incidence and prevalence. Our study can serve as a model for other countries aiming to achieve the WHO HCV elimination targets. NCT02785666.

Telomere Length, Traditional Risk Factors, Factors Related to Human Immunodeficiency Virus (HIV) and Coronary Artery Disease Events in Swiss Persons Living With HIV.

Leukocyte telomere length (TL) shortens with age and is associated with coronary artery disease (CAD) events in the general population. Persons living with human immunodeficiency virus (HIV; PLWH) may have accelerated atherosclerosis and shorter TL than the general population. It is unknown whether TL is associated with CAD in PLWH. We measured TL by quantitative polymerase chain reaction (PCR) in white Swiss HIV Cohort Study participants. Cases had a first CAD event during 1 January 2000 to 31 December 2017. We matched 1-3 PLWH controls without CAD events on sex, age, and observation time. We obtained univariable and multivariable odds ratios (OR) for CAD from conditional logistic regression analyses. We included 333 cases (median age 54 years; 14% women; 83% with suppressed HIV RNA) and 745 controls. Median time (interquartile range) of TL measurement was 9.4 (5.9-13.8) years prior to CAD event. Compared to the 1st (shortest) TL quintile, participants in the 5th (longest) TL quintile had univariable and multivariable CAD event OR = 0.56 (95% confidence interval [CI], .35-.91) and OR = 0.54 (95% CI, .31-.96). Multivariable OR for current smoking was 1.93 (95% CI, 1.27-2.92), dyslipidemia OR = 1.92 (95% CI, 1.41-2.63), and for recent abacavir, cumulative lopinavir, indinavir, and darunavir exposure was OR = 1.82 (95% CI, 1.27-2.59), OR = 2.02 (95% CI, 1.34-3.04), OR = 3.42 (95% CI, 2.14-5.45), and OR = 1.66 (95% CI, 1.00-2.74), respectively. The TL-CAD association remained significant when adjusting only for Framingham risk score, when excluding TL outliers, and when adjusting for CMV-seropositivity, HCV-seropositivity, time spent with detectable HIV viremia, and injection drug use. In PLWH, TL measured >9 years before, is independently associated with CAD events after adjusting for multiple traditional and HIV-related factors.

Multiple-Imputation Variance Estimation in Studies With Missing or Misclassified Inclusion Criteria.

In observational studies using routinely collected data, a variable with a high level of missingness or misclassification may determine whether an observation is included in the analysis. In settings where inclusion criteria are assessed after imputation, the popular multiple-imputation variance estimator proposed by Rubin ("Rubin's rules" (RR)) is biased due to incompatibility between imputation and analysis models. While alternative approaches exist, most analysts are not familiar with them. Using partially validated data from a human immunodeficiency virus cohort, we illustrate the calculation of an imputation variance estimator proposed by Robins and Wang (RW) in a scenario where the study exclusion criteria are based on a variable that must be imputed. In this motivating example, the corresponding imputation variance estimate for the log odds was 29% smaller using the RW estimator than using the RR estimator. We further compared these 2 variance estimators with a simulation study which showed that coverage probabilities of 95% confidence intervals based on the RR estimator were too high and became worse as more observations were imputed and more subjects were excluded from the analysis. The RW imputation variance estimator performed much better and should be employed when there is incompatibility between imputation and analysis models. We provide analysis code to aid future analysts in implementing this method.

Impact of Viral Load Monitoring on Retention and Viral Suppression: A Regression Discontinuity Analysis of South Africa's National Laboratory Cohort.

South African guidelines recommend repeat viral load testing within 6 months when human immunodeficiency virus (HIV) viral loads exceed 1,000 copies/mL. We assessed whether South African facilities follow viral load monitoring guidelines and whether guidelines improve HIV-related outcomes, using a regression discontinuity design in a national HIV cohort of 174,574 patients (2013-2015). We assessed whether patients with viral loads just above versus just below 1,000 copies/mL were more likely to receive repeat testing in 6 months, and we compared differences in clinic transfers, retention, and viral suppression. The majority (67%) of patients with viral loads of >1,000 copies/mL did not receive repeat testing within 6 months, and these patients were 8.0% (95% confidence interval (CI): 6.2, 9.7) more likely to receive repeat testing compared with ≤1,000 copies/mL. Eligibility for repeat testing (>1,000 copies/mL) was associated with greater 12-month retention (risk difference = 2.9%, 95% CI: 0.6, 5.2) and combined suppression and retention (risk difference = 5.8%, 95% CI: 3.0, 8.6). Patients with viral loads of >1,000 copies/mL who actually received repeat testing were 85.2% more likely to be both retained and virally suppressed at 12 months (95% CI: 35.9, 100.0). Viral load monitoring might improve patient outcomes, but most patients with elevated viral loads do not receive monitoring within recommended timelines.

Prevalence of Potential Drug-Drug Interactions in Patients of the Swiss HIV Cohort Study in the Era of HIV Integrase Inhibitors.

Prevalence of potential drug-drug interactions (PDDIs) between antiretroviral drugs (ARVs) and co-medications was high in 2008 in a Swiss HIV Cohort Study (SHCS) survey. We reassessed the prevalence of PDDIs in the era of human immunodeficiency virus (HIV) integrase inhibitors (INIs), characterized by more favorable interaction profiles. The prevalence of PDDIs in treated HIV-positive individuals was assessed for the period 01-12/2018 by linkage of the Liverpool HIV drug interactions and SHCS databases. PDDIs were categorized as harmful (red flagged), of potential clinical relevance (amber flagged), or of weak clinical significance (yellow flagged). In 9298 included individuals, median age was 51 years (IQR, 43-58), and 72% were males. Individuals received unboosted INIs (40%), boosted ARVs (30%), and nonnucleoside reverse transcriptase inhibitor (NNRTIs) (32%)-based regimens. In the entire cohort, 68% received ≥1 co-medication, 14% had polypharmacy (≥5 co-medications) and 29% had ≥1 PDDI. Among individuals with co-medication, the prevalence of combined amber and yellow PDDIs was 43% (33% amber-mostly with cardiovascular drugs-and 20% yellow-flagged PDDIs) compared to 59% in 2008. Two percent had red-flagged PDDIs (mostly with corticosteroids), the same as in the 2008 survey. Compared with 2008, fewer individuals received boosted ARVs (-24%) and NNRTIs (-13%) but the use of co-medications was higher. Prevalence of PDDIs was lower with more widespread use of INIs in 2018 than in 2008. Continued use of boosted regimens and increasing needs for co-medications in this aging population impeded lower rates of PDDIs.

Cohort-Derived Machine Learning Models for Individual Prediction of Chronic Kidney Disease in People Living With Human Immunodeficiency Virus: A Prospective Multicenter Cohort Study.

BackgroundIt is unclear whether data-driven machine learning models, which are trained on large epidemiological cohorts, may improve prediction of comorbidities in people living with human immunodeficiency virus (HIV).MethodsIn this proof-of-concept study, we included people living with HIV in the prospective Swiss HIV Cohort Study with a first estimated glomerular filtration rate (eGFR) >60 mL/minute/1.73 m2 after 1 January 2002. Our primary outcome was chronic kidney disease (CKD)—defined as confirmed decrease in eGFR ≤60 mL/minute/1.73 m2 over 3 months apart. We split the cohort data into a training set (80%), validation set (10%), and test set (10%), stratified for CKD status and follow-up length.ResultsOf 12 761 eligible individuals (median baseline eGFR, 103 mL/minute/1.73 m2), 1192 (9%) developed a CKD after a median of 8 years. We used 64 static and 502 time-changing variables: Across prediction horizons and algorithms and in contrast to expert-based standard models, most machine learning models achieved state-of-the-art predictive performances with areas under the receiver operating characteristic curve and precision recall curve ranging from 0.926 to 0.996 and from 0.631 to 0.956, respectively.ConclusionsIn people living with HIV, we observed state-of-the-art performances in forecasting individual CKD onsets with different machine learning algorithms.

Prevalence of mental health conditions amongst people living with human immunodeficiency virus in one of the most deprived localities in England.

Mental health conditions (MHCs) are often unrecognised which can result in detrimental physical health outcomes and poor quality of life. This can be compounded by the impact of deprivation. People living with human immunodeficiency virus (PLWH) are more likely to be affected by MHCs which if untreated, may result in both clinical and psychosocial adversities. To ascertain the prevalence of and factors associated with MHCs in the human immunodeficiency virus cohort of Stoke-on-Trent, which is the 13th most deprived locality in England, we conducted a cross-sectional service evaluation using electronic records of 302 PLWH attending the service between October 2018 and January 2019. The prevalence of MHCs amongst PLWH was 33.4% (101/302). Depression was the most prevalent MHC affecting 17.2% (52/302). Those of white ethnicity were at higher risk (odds ratio [OR] = 3.14; p < 0.01) of MHCs compared to black Asian and minority ethnic groups. Women were at higher risk of having an MHC (OR = 3.15; p < 0.01), and recreational drug use was also a significant factor (OR = 16.18; p = 0.01) associated with MHCs. There is sub-optimal access and heterogeneity in the modes of referral to mental health support services. Commissioning constraints will further detrimentally affect our ability to provide support in an already deprived area, thus widening health inequalities affecting the most vulnerable.

Nevirapine Use Is Associated with Higher Bone Mineral Density in HIV-1 Positive Subjects on Long-Term Antiretroviral Therapy.

We assessed bone mineral density (BMD) in a cohort of human immunodeficiency virus (HIV)-positive patients after a median of 11 years of combination antiretroviral therapy (cART) and evaluated the respective role of HIV infection and antiretroviral drugs (ARVs). A cross-sectional study of 162 participants (131 male) from the ANRS-C08 cohort was performed with bone dual-energy X-ray absorptiometry (DXA) scans and renal assessment. The window of exposure to ARVs was defined as an exposure of more than six cumulative months during the last 3 years before the DXA evaluation to account for a cumulative exposure that could affect bone remodeling. The association with low BMD (Z-score < -2) was assessed by a multiple logistic regression model. The study population was 50 years (median), hepatitis C virus (HCV) (18%), and hepatitis B virus (HBV) (8%) coinfection with HIV-RNA <50 c/mL in 89%, median CD4 of 619/mm3. Prevalence of low BMD was 18% in males and 6% in females. The factors associated with a Z-score < -2 in males were uric acid renal loss [adjusted odds ratio (aOR): 6.1; 95% confidence interval (CI): 1.2-31.5; p = .03], HCV coinfection (aOR: 4.0; 95% CI: 1.3-12.2; p = .02), and less frequent window of exposure to nevirapine (NVP) (aOR: 0.1; 95% CI: 0.02-0.6; p = .01). For the full study sample, there was a strong positive association between duration of exposure to NVP and lumbar spine Z-score (p = .004). HIV-positive patients exposed to long-term cART have a high incidence of low BMD. Tenofovir disoproxil fumarate and ritonavir-boosted protease inhibitors did not seem to be associated with increased risk of low BMD, whereas NVP exposure appeared to have an independent positive association.

Phylogenetic Cluster Analysis Identifies Virological and Behavioral Drivers of Human Immunodeficiency Virus Transmission in Men Who Have Sex With Men.

Identifying local outbreaks and their drivers is a key step toward curbing human immunodeficiency virus (HIV) transmission and potentially achieving HIV elimination. Such outbreaks can be identified as transmission clusters extracted from phylogenetic trees constructed of densely sampled viral sequences. In this study, we combined phylogenetic transmission clusters with extensive data on virological suppression and behavioral risk of cluster members to quantify the drivers of ongoing transmission over 10 years. Using the comprehensive Swiss HIV Cohort Study and its drug-resistance database, we reconstructed phylogenetic trees for each year between 2007 and 2017. We identified HIV transmission clusters dominated by men who have sex with men (MSM) and determined their annual growth. We used Poisson regression to assess if cluster growth was associated with a per-cluster infectivity and behavioral risk score. Both infectivity and behavioral risk scores were significantly higher in growing MSM transmission clusters compared to nongrowing clusters (P ≤ .01). The fraction of transmission clusters without infectious members acquiring new infections increased significantly over the study period. The infectivity score was significantly associated with per-capita incidence of MSM transmission clusters in 8 years, while the behavioral risk score was significantly associated with per-capita incidence of MSM transmission clusters in 3 years. We present a phylogenetic method to identify hotspots of ongoing transmission among MSM. Our results demonstrate the effectiveness of treatment as prevention at the population level. However, the significantly increasing number of new infections among transmission clusters without infectious members highlights a relative shift from diagnosed to undiagnosed individuals as drivers of HIV transmission in Swiss MSM.

The Role of Human Immunodeficiency Virus (HIV) Asymptomatic Status When Starting Antiretroviral Therapy on Adherence and Treatment Outcomes and Implications for Test and Treat: The Swiss HIV Cohort Study.

Since the advent of universal test-and-treat , more people living with human immunodeficiency virus (PLHIV) initiating antiretroviral therapy (ART) are asymptomatic with a preserved immune system. We explored the impact of asymptomatic status on adherence and clinical outcomes. PLHIV registered in the Swiss HIV Cohort Study (SHCS) between 2003 and 2018 were included. We defined asymptomatic as Centers for Disease Control and Prevention stage A within 30 days of starting ART, non-adherence as any self-reported missed doses and viral failure as two consecutive viral load>50 copies/mL after >24 weeks on ART. Using logistic regression models, we measured variables associated with asymptomatic status and adherence and Cox proportional hazard models to assess association between symptom status and viral failure. Of 7131 PLHIV, 76% started ART when asymptomatic and 1478 (22%) experienced viral failure after a median of 1.9 years (interquartile range, 1.1-4.2). In multivariable models, asymptomatic PLHIV were more likely to be younger, men who have sex with men, better educated, have unprotected sex, have a HIV-positive partner, have a lower viral load, and have started ART more recently. Asymptomatic status was not associated with nonadherence (odds ratio, 1.03 [95% confidence interval {CI}, .93-1.15]). Asymptomatic PLHIV were at a decreased risk of viral failure (adjusted hazard ratio, 0.87 [95% CI, .76-1.00]) and less likely to develop resistance (14% vs 27%, P < .001) than symptomatic PLHIV. Despite concerns regarding lack of readiness, our study found no evidence of adherence issues or worse clinical outcomes in asymptomatic PLHIV starting ART.

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

Background & AimsHuman 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.MethodsHepatitis 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.ResultsIn 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).ConclusionHepatitis 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.

Associations of Viral Seroreactivity with AIDS-Related Non-Hodgkin Lymphoma.

Infection with human immunodeficiency virus (HIV) is associated with substantially increased incidence of non-Hodgkin lymphoma (NHL). This risk may be driven, in part, by reduced immune control over viral infections in the setting of acquired immunodeficiency syndrome (AIDS), although the lymphomagenic mechanisms are not yet established. We used bead-based multiplex assays to measure antibody seroreactivity to 32 viral antigens representing 22 different viral infections (human herpesviruses 1-8, hepatitis B and C virus, human T-lymphotropic virus type-1, and human polyomaviruses) in two prospective HIV cohorts. Incident (n = 28) and prevalent (n = 38) AIDS-related NHL cases were matched by age, sex, race, and CD4 count to 67 HIV-positive control individuals without AIDS-NHL. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations of AIDS-NHL with the number of different viruses to which an individual was seropositive and seroreactivity to individual antigens. Seropositivity to an increasing number of viruses was inversely associated with AIDS-NHL (OR per virus = 0.84, 95% CI = 0.72-0.98). Seroreactivity to herpes simplex virus 2 2mgG unique antigen (OR = 0.47; 95% CI = 0.23-0.97) and to WU polyomavirus viral capsid protein (OR = 0.26, 95% CI = 0.10-0.65) was significantly lower in AIDS-NHL cases compared to controls. In this evaluation of antibodies to multiple viruses, we observed an inverse association between seropositivity to a larger number of viruses and AIDS-NHL. While in need of further evaluation, our data raise the novel hypothesis that insufficient exposures or impaired humoral immune responses to viral infections may be associated with AIDS-related lymphomagenesis.

Tuberculosis in a Spanish cohort of children living with HIV: the CHOTIS study (Childhood HIV & TB study).

BACKGROUND: Tuberculosis (TB) is the leading opportunistic infection in children with human immunodeficiency virus (HIV), but is uncommon in low prevalence regions. We aim to describe the changing epidemiology and clinical presentation of TB-HIV co-infection in a cohort of HIV-infected children in Spain.METHODS: Children diagnosed with TB between 1995 and 2016 in the paediatric HIV cohort were identified. The incidence and clinical presentation were compared in three periods: 1995-1999 (P1, before initiation of combined antiretroviral therapy, cART), 2000-2009 (P2, increase in immigration), and 2010-2016 (P3, decrease in immigration).RESULTS: We included 29 TB cases among 1183 children aged <18 years (2.4%, 243/100 000 person-years). The proportion was stable in P1 and P2 (1.3%), but decreased in P3 (0.8%). The median age at TB diagnosis was 6.4 years (IQR 4-10.6); most children in P3 were aged >10 years (20% vs. 23.1% vs. 83.3%, P = 0.01). TB was diagnosed at HIV presentation in 11/29 children (37.9%). Foreign-born children accounted for respectively 0%, 8% and 67% of the total number of children in each period (P ≤ 0.0001). One third had extrapulmonary TB; four children died (13.8%).CONCLUSION: In our cohort, the incidence of TB-HIV co-infection decreased with decline in immigration. In regions with adequate cART coverage and low TB transmission, paediatric TB-HIV coinfection is uncommon, but associated with significant morbidity. Strategies for TB surveillance, diagnosis and treatment in this vulnerable population should be reinforced.

Risk of abnormal cervical cytology in HIV-infected women testing positive for both human papillomavirus and Epstein-Barr virus in genital tract specimens.

Although infection with high-risk human papillomavirus (HPV) is a prerequisite for cervical cancer development, HPV infection is not sufficient to promote cancer in the majority of infected women. We tested the hypothesis that human herpesviruses might cooperate with HPV to promote the development of cervical dysplasia, an early indicator of cervical cancer development. This study used archived specimens from a cohort of human immunodeficiency virus (HIV)-seropositive women seeking gynecological care at the Medical Center of New Orleans, Louisiana. Viral DNA was detected by PCR amplification and risk of abnormal cervical cytology was determined in relation to virus test results. Consensus human herpesvirus PCR with herpes speciation by restriction endonuclease digestion revealed Epstein-Barr virus (EBV) to be the most prevalent herpesvirus in cervicovaginal lavage specimens. Further analysis using an EBV-specific PCR assay and cervical swab specimens demonstrated an approximately fourfold increased risk of abnormal cervical cytology in women testing positive for cervical EBV and high-risk HPV compared to women testing positive for high-risk HPV alone. This relationship was independent of markers of advancing HIV disease. Cervical shedding of EBV appears to predict a greater risk of cervical dysplasia in HIV-infected women with a high-risk HPV infection.

Implementation of routine interferon-gamma release assay testing in a South London HIV cohort.

Human immunodeficiency virus (HIV) infection is a major risk factor for the development of tuberculosis (TB). Although guidelines recommend that people with HIV from high TB incidence countries and those with risk factors are screened for latent TB infection (LTBI) using interferon-gamma release assays (IGRAs), this has not been widely implemented in the UK. We introduced universal LTBI screening using IGRAs at nurse-led induction clinics for patients newly presenting, transferring or re-presenting for HIV care and conducted a prospective audit from 1 January 2018 to 30 June 2019 to identify operational challenges as well as opportunities for TB prevention. Of the 223 patients, 17 had active or previously treated TB. Of the remaining 206 individuals who were eligible for IGRA testing, 78 (38%) were not tested due to logistical issues, failure to request the test or no induction visit taking place. Of the 128 (62%) individuals who were tested for LTBI, 3 (2.3%) had a positive IGRA, 4 (3.1%) an indeterminate result and 121 (94.5%) a negative result. All seven with positive/indeterminate tests were of African/Caribbean background, had CD4 cell counts &gt;200 cells/mm3 and HIV RNA &lt;400 copies/ml. Our audit suggests that universal LTBI screening was logistically challenging and provided few opportunities for TB prevention.

Safety and efficacy of immune checkpoint inhibitors (ICIs) in cancer patients with HIV, hepatitis B, or hepatitis C viral infection

sBackgroundPatients with chronic viral infections including human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) are at increased risk of developing malignancies. The safety and efficacy of ICI therapy in patients with both cancer and chronic viral infections is not well established as most clinical trials of ICIs excluded these patient populations.MethodsWe performed a retrospective analysis of patients with advanced-stage cancers and HIV, HBV, or HCV infection treated with ICI therapy at 5 MedStar Health hospitals from January 2011 to April 2018.ResultsWe identified 50 patients including 16 HIV, 29 HBV/HCV, and 5 with concurrent HIV and either HBV or HCV. In the HIV cohort (n = 21), any grade immune-related adverse events (irAEs) were 24% with grade ≥ 3 irAEs 14%. Among 5 patients with matched pre/post-treatment results, no significant changes in HIV viral load and CD4+ T-cell counts were observed. RECIST confirmed (n = 18) overall response rate (ORR) was 28% with 2 complete responses (CR) and 3 partial responses (PR). Responders included 2 patients with low baseline CD4+ T-cell counts (40 and 77 cells/ul, respectively). In the HBV/HCV cohort (n = 34), any grade irAEs were 44% with grade ≥ 3 irAEs 29%. RECIST confirmed ORR was 21% (6 PR). Among the 6 patients with known pre/post-treatment viral titers (2 HCV and 4 HBV), there was no evidence of viral reactivation.ConclusionsOur retrospective series is one of the largest case series to report clinical outcomes among HIV, HBV and HCV patients treated with ICI therapy. Toxicity and efficacy rates were similar to those observed in patients without chronic viral infections. Viral reactivation was not observed. Tumor responses occurred in HIV patients with low CD4 T-cell counts. While prospective studies are needed to validate above findings, these data support not excluding such patients from ICI–based clinical trials or treatment.

Prevalence of thyroid disfunctions in a large cohort of Human Immunodeficiency Virus (HIV)-Infected Patients

Prevalence of thyroid disfunctions in a large cohort of Human Immunodeficiency Virus (HIV)-Infected Patients

Liver stiffness and fibrosis-4 alone better predict liver events compared with aspartate aminotransferase to platelet ratio index in a cohort of human immunodeficiency virus and hepatitis C virus co-infected patients from ANRS CO13 HEPAVIH cohort.

HIV/hepatitis C virus (HCV) co-infection leads to major complications, and noninvasive markers developed to stage liver fibrosis could be used as prognostic markers. We aimed to compare the performances of liver stiffness (LS), fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI) to predict liver-related events in HIV/HCV co-infected patients. HIV/HCV co-infected patients from the ANRS CO13 HEPAVIH cohort were included if they had LS, FIB-4, and APRI measurements done in a window of 3 months. Primary outcome was the time between inclusion and occurrence of a liver-related event. Univariable and multivariable Fine and Gray models were performed. Predictive performances were compared by the area under the receiver operating characteristic (AUROC) differences after correction of optimistic by bootstrap samples. Best cutoffs to predict liver-related events were estimated by sensitivity and specificity maximization. A total of 998 patients were included. Overall, 70.7% were men. Their median age was 46.8 years. According to LS value, 204 (20.4%) patients had cirrhosis. Overall, 39 patients experienced at least one liver-related event. In univariable analysis, LS AUROC curve was significantly superior to FIB-4 and APRI AUROC curves, being 87.9, 78.2, and 75.0%, respectively. After adjustment on age, CD4 levels, and insulin resistance, no differences were observed. The best cutoffs to identify patients at low or high risk of liver-related events were below 8.5, 1.00, and 0.35 and above 16.5, 4.00, and 1.75 for LS, FIB-4, and APRI, respectively. To predict HCV-related events, APRI had lower performance than LS and FIB-4. FIB-4 is as good as LS to predict HCV-related events, suggesting that it can be used for the management of HIV/HCV co-infected patients and replace LS.

HIV care in Istanbul, Turkey: How far is it from the UNAIDS 90-90-90 targets?

The prevalence of human immunodeficiency virus (HIV) infection is low but it is steadily increasing in Turkey. In the current study, we aimed to assess the status of HIV infection management with the proposed 90–90–90 targets in a large HIV cohort in Istanbul, Turkey. The cohort included 2382 patients (2082 male, 300 female, mean age was 36.3 ± 11.3 years). Mean CD4 cell count was 399 cells/mm3and HIV-RNA level was 576,235 copies/ml. According to the modeling by the Modeling tool of European Center for Diseases Control Software, 72 and 74% of all HIV patients had been diagnosed in 2016 and 2017, respectively (the first target). Among 2382 patients, 2191 (92%) were on antiretroviral therapy (the second target). The third target of virally suppressing those on treatment was achieved among 70.2% of the patients. The current study suggests that both the fraction of those living with undiagnosed HIV and the proportion of those on treatment who are virally suppressed should be targeted to sustain optimal HIV care. Efforts should continue to surpass the targets of 90–90–90.

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

SummaryCurrent 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.