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In the current mpox outbreak, infections are usually self-limited. We describe 3 patients with uncontrolled HIV and mpox infections lasting months, causing debilitating lesions, complications, and death, despite initiating anti-mpox and antiretroviral therapy. Delayed treatment of mpox with antiviral agents may contribute to poor outcomes in severely immunocompromised patients., Competing Interests: Potential conflicts of interest. C. D. E. reports unpaid roles on the Board of Directors for Dallas County Medical Society and an unpaid role as an executive board member of the CV Roman Medical Society (DFW Chapter of the National Medical Association); receipt of drugs given to their institution for use in the patient from Dallas County Health and Human Services (from the CDC) for tecovirimat and VIGIV and from the Food and Drug Administration (FDA) for brincidofovir. A. G. reports receipt of drugs given to their institution for use in the patient from Dallas County Health and Human Services (from the CDC) for tecovirimat and VIGIV. J. Y. C. reports grants or contracts from Gilead Sciences for Investigator Sponsored Research unrelated to the topic of this manuscript and receipt of drugs given to their institution for use in the patient from Dallas County Health and Human Services (from the CDC) for tecovirimat and VIGIV. S. M. L. reports grants or contracts from Gilead Sciences as Site Principal Investigator for a Purpose 2 clinical trial regarding lenacapavir as pre-exposure prophylaxis (PrEP; payment to institution) and receipt of drugs given to their institution for use in the patient from Dallas County Health and Human Services (from the CDC) for tecovirimat and VIGIV. M. K. J. reports grants or contracts to the institution from Gilead Sciences, GSK/ViiV, Merck, and Janssen and receipt of drugs given to their institution for use in the patient from Dallas County Health and Human Services (from the CDC) for tecovirimat and VIGIV and from FDA for brincidofovir. E. K. reports receipt of drugs given to their institution for use in the patient from Dallas County Health and Human Services (from the CDC) for tecovirimat and VIGIV and from FDA for brincidofovir. T. M. P. reports receipt of drugs given to their institution for use in the patient from Dallas County Health and Human Services (from the CDC) for tecovirimat and VIGIV. N. S. U. reports receipt of drugs given to their institution for use in the patient from Dallas County Health and Human Services (from the CDC) for tecovirimat and VIGIV and from FDA for brincidofovir. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The oral and esophageal mucosa have been identified as possible sites of HIV/SIV entry following oral infection. Here, gamma/delta (gammadelta) T cells, a multi-functional T cell subset, were assessed at oral/esophageal mucosa and lymphoid sites at the earliest times (1-14 days) post-oral SIV inoculation utilizing quantitative RT-PCR. During these earliest times post-infection, decreased gammadelta TCR mRNA levels were observed at the oral gingiva and esophageal mucosa, while increased levels were observed within regional lymph nodes (cervical and retropharyngeal). Higher lymph node gammadelta TCR levels were associated with increased mRNA expression of the lymphoid homing chemokine/receptor (CCL21/CCR7) pair in these lymph nodes. In contrast to gammadelta TCR levels, CD4 mRNA expression remained relatively stable through 4 days post-infection, and depletion of CD4 T cells was only evident after 7 or 14 days post-infection. The decrease of gammadelta T cell mRNA from mucosal sites and the corresponding increase at lymphoid sites suggest a rapid redistribution of these immune cells at these earliest times post-SIV infection.

The objective of this study was to functionally assess gamma/delta (gammadelta) T cells following pathogenic human immunodeficiency virus (HIV) infection of humans and nonpathogenic simian immunodeficiency virus (SIV) infection of sooty mangabeys. gammadelta T cells were obtained from peripheral blood samples from patients and sooty mangabeys that exhibited either a CD4-healthy (>200 CD4(+) T cells/mul blood) or CD4-low (<200 CD4 cells/mul blood) phenotype. Cytokine flow cytometry was utilized to assess production of Th1 cytokines tumor necrosis factor alpha and gamma interferon following ex vivo stimulation with either phorbol myristate acetate/ionomycin or the Vdelta2 gammadelta T-cell receptor agonist isopentenyl pyrophosphate. Sooty mangabeys were observed to have higher percentages of gammadelta T cells in their peripheral blood than humans did. Following stimulation, gammadelta T cells from SIV-positive (SIV(+)) mangabeys maintained or increased their ability to express the Th1 cytokines regardless of CD4(+) T-cell levels. In contrast, HIV-positive (HIV(+)) patients exhibited a decreased percentage of gammadelta T cells expressing Th1 cytokines following stimulation. This dysfunction is primarily within the Vdelta2(+) gammadelta T-cell subset which incurred both a decreased overall level in the blood and a reduced Th1 cytokine production. Patients treated with highly active antiretroviral therapy exhibited a partial restoration in their gammadelta T-cell Th1 cytokine response that was intermediate between the responses of the uninfected and HIV(+) patients. The SIV(+) sooty mangabey natural hosts, which do not proceed to clinical AIDS, provide evidence that gammadelta T-cell dysfunction occurs in HIV(+) patients and may contribute to HIV disease progression.

Abstract We present a rare case of pathology-proven CMV pneumonitis in a patient with HIV infection after presenting with cough and fever. This presentation was complicated by recurrence of symptoms after treatment in the setting of continued uncontrolled HIV infection. This case raised the importance of further discussion regarding best treatment guidelines for CMV pneumonitis for patients with HIV.

Background Cardiovascular disease risk prediction models underestimate CVD risk in people living with HIV (PLWH). Our goal is to derive a risk score based on protein biomarkers that could be used to predict CVD in PLWH. Methods and Results In a matched case–control study, we analyzed normalized protein expression data for participants enrolled in 1 of 4 trials conducted by INSIGHT (International Network for Strategic Initiatives in Global HIV Trials). We used dimension reduction, variable selection and resampling methods, and multivariable conditional logistic regression models to determine candidate protein biomarkers and to generate a protein score for predicting CVD in PLWH. We internally validated our findings using bootstrap. A protein score that was derived from 8 proteins (including HGF [hepatocyte growth factor] and interleukin‐6) was found to be associated with an increased risk of CVD after adjustment for CVD and HIV factors (odds ratio: 2.17 [95% CI: 1.58–2.99]). The protein score improved CVD prediction when compared with predicting CVD risk using the individual proteins that comprised the protein score. Individuals with a protein score above the median score were 3.10 (95% CI, 1.83–5.41) times more likely to develop CVD than those with a protein score below the median score. Conclusions A panel of blood biomarkers may help identify PLWH at a high risk for developing CVD. If validated, such a score could be used in conjunction with established factors to identify CVD at‐risk individuals who might benefit from aggressive risk reduction, ultimately shedding light on CVD pathogenesis in PLWH.

The human immunodeficiency virus (HIV) workforce continues to face a crisis, particularly in the southern United States. Adding to known issues of administrative burden and less competitive compensation, recent anti- lesbian, gay, bisexual, transgender and queer (LGBTQ+) legislation threatens the already strained HIV workforce. HIV care providers advocate for all aspects of their patient's lives, including those needing gender-affirming care. The recent legislative targets against transgender patients, which involves many people with HIV, will clearly add to the burden on individual HIV care providers and therefore the HIV workforce. Recruitment and retention efforts in states impacted by these laws will become increasingly difficult without advocacy for the patients we serve. The HIV workforce must work together with LGBTQ+ populations to address these recent laws and promote the well-being of all our patients and colleagues. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) RNA and hepatitis B core‐related antigen (HBcrAg), reflecting transcriptional activity of covalently closed circular DNA, are gaining traction as important markers to assess viral activity. Whether their expression differs under viral suppression by HIV co‐infection status is unknown. Among adults with chronic HBV on antiviral therapy, we sought to determine if the expression of HBV markers (specialized and well‐established) differs between HBV‐HIV co‐infection vs. HBV mono‐infection. We compared HBV marker levels among 105 participants in the Hepatitis B Research Network (HBRN) HBV‐HIV Ancillary Study and 105 participants in the HBRN mono‐infected Cohort Study, matched for HBeAg status and HBV DNA suppression on therapy. Among HBeAg+ participants (N = 58 per group), after adjusting for age, sex, race, ALT and HBV DNA, viral markers were higher (p <.05) in the HBV‐HIV versus the HBV‐only sample (HBeAg: 1.05 vs. 0.51 log10 IU/mL; HBsAg: 3.85 vs. 3.17 log10 IU/mL; HBV RNA: 5.60 vs. 3.70 log10 U/mL; HBcrAg: 6.59 vs. 5.51 log10 U/mL). Conversely, among HBeAg(−) participants (N = 47 per group), HBsAg (2.00 vs. 3.04 log10 IU/mL) and HBV RNA (1.87 vs. 2.66 log10 U/mL) were lower (p <.05) in HBV‐HIV vs. HBV‐only; HBcrAg levels were similar (4.14 vs. 3.64 log10 U/mL; p =.27). Among adults with chronic HBV with suppressed viremia on antiviral therapy, viral markers tracked with HIV co‐infection status and associations differed inversely by HBeAg status. The greater sensitivity and specificity of HBV RNA compared to HBcrAg allows for better discrimination of transcriptional activity regardless of HBeAg status. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) increases morbidity and mortality among people with HIV (PWH). We retrospectively analyzed HBV incidence among 5785 PWH. Fourteen had newly positive hepatitis B s antigen (mean 5.2 person-years of follow-up, 46.4/100 000 infections/year). These data show gaps in HBV vaccination and in the preventative efficacy of HBV-specific antiretroviral therapy. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection is one of the leading causes of hepatocellular carcinoma and mortality among people living with HIV (PLWH). HBV vaccination provides protection from infection; however, vaccination rates are low. We conducted a retrospective analysis at three HIV centres in Texas to determine the proportion of PLWH who received the recommended 3 doses of hepatitis B vaccine within 1 year. Factors associated with vaccination completion were explored. In our sample of three sites in a state with high HIV transmission and high rates of liver disease from 2011 to 2021, showed low rates of hepatitis B vaccination. Among eligible PLWH, only 9% completed the 3‐dose hepatitis B vaccine series in 1 year. There is an urgent need to improve HBV vaccination to reach 2030 target for hepatitis B elimination. [ABSTRACT FROM AUTHOR]

While we have the tools to achieve this goal, the persistent barriers to healthcare services experienced by too many individuals will need to be addressed to make significant progress and improve the health and quality of life of all people with human immunodeficiency virus (HIV). The necessary structural changes require actions by federal, state, and local policymakers and range from ensuring universal access to healthcare services to optimizing care delivery to ensuring a robust and diverse infectious diseases and HIV workforce. In this article, we outlines 10 key principles for policy reforms that, if advanced, would make ending the HIV epidemic in the United States possible and could have much more far-reaching effects in improving the health of our nation. [ABSTRACT FROM AUTHOR]

Immune cell state alterations rewire HIV-1 gene expression, thereby influencing viral latency and reactivation, but the mechanisms are still unfolding. Here, using a screen approach on CD4+ T cell models of HIV-1 latency, we revealed Small Molecule Reactivators (SMOREs) with unique chemistries altering the CD4+ T cell state and consequently promoting latent HIV-1 transcription and reactivation through an unprecedented mechanism of action. SMOREs triggered rapid oxidative stress and activated a redox-responsive program composed of cell-signaling kinases (MEK-ERK axis) and atypical transcription factor (AP-1 and HIF-1α) cooperativity. SMOREs induced an unusual AP-1 phosphorylation signature to promote AP-1/HIF-1α binding to the latent HIV-1 proviral genome for its activation. Consistently, latent HIV-1 reactivation was compromised with pharmacologic inhibition of oxidative stress sensing or of cell-signaling kinases, and transcription factor's loss of expression, thus functionally linking the host redox-responsive program to viral transcriptional rewiring. Notably, SMOREs induced the redox program in primary CD4+ T cells and reactivated latent HIV-1 in aviremic patient samples alone and in combination with known latency-reversing agents, thus providing physiological relevance. Our findings suggest that manipulation of redox-sensitive pathways could be exploited to alter the course of HIV-1 latency, thus rendering host cells responsive to help achieve a sterilizing cure. [ABSTRACT FROM AUTHOR]

Objective: Half of the people living with HIV (PLWH) with hepatitis C virus (HCV) remain untreated for HCV. We examined predictors of HCV linkage to care among PLWH and the impact of HIV lost to care. Design and methods: We conducted a retrospective review of PLWH/HCV from our HIV clinics between 2014 and 2017, and examined predictors of HCV linkage to care. We used the Kaplan–Meier method to estimate the probability of HIV retention and HCV linkage over time. Results: Of 615 PLWH/HCV, 34% linked to HCV care and 21% were cured. Higher odds of linkage to HCV care were among blacks (adjusted odds ratio [aOR]: 2.95, 95% confidence interval [CI]: 1.59, 5.47), prior injection drug users (IDUs; aOR: 2.89, 95% CI: 1.39, 6.01), Medicare (aOR: 3.09, 95% CI: 1.56, 6.11), and cirrhotics (aOR: 2.80, 95% CI: 1.52, 5.14). Reduced odds for linkage were in active IDU (aOR: 0.16, 95% CI: 0.05, 0.45) and those seen by an advanced practice provider (aOR: 0.53, 95% CI: 0.30, 0.92). The main reason for failure to link to HCV care was lost to HIV care. At 3 years, the overall probability of being retained in HIV care was 53%; among those who had an HCV evaluation visit, it was 75% vs. 41% with no HCV evaluation visit. Accounting for loss to follow‐up, PLWH/HCV had a 65% probability of having an HCV evaluation at 3 years. Statement of significance: HCV is a curable infection in those with or without HIV. Yet, high proportions of people living with HIV with HCV remain untreated for HCV, leading to complications of liver disease and death. Our study found that only one‐third of HIV/HCV patients were linked to HCV care. The main reason for not linking to HCV care was that increasing numbers of patients drop out of HIV care over time. Our study suggests that early focus on HCV treatment would increase the number of patients cured, but it is unclear whether this would impact retention in HIV care. [ABSTRACT FROM AUTHOR]

Background Hepatitis B virus (HBV) and fatty liver disease (FLD) are common in human immunodeficiency virus (HIV). Correlates of FLD and its relationship with alanine aminotransferase (ALT) were examined longitudinally in HIV-HBV coinfection. Methods From 28/4/2014–7/11/2018, 114 HIV-HBV adults had liver biopsy and were followed for a median of 3 years (ancillary study of Hepatitis B Research Network). Steatohepatitis was based on presence of steatosis, ballooning, and perisinusoidal fibrosis. FLD was defined as ≥5% steatosis and/or steatohepatitis. Results Median age was 49 years, 93% were male, 51% black, 93% had HIV RNA <400 copies/mL and 83% HBV DNA <1000 IU/mL. Thirty percent had FLD (20% steatosis, 10% steatohepatitis). Those with FLD had higher median triglyceride (171 vs 100 mg/dL, P < .01) and small, dense LDL (44 vs 29 mg/dL, P < .01) and lower HDL-2-C (9 vs 12 mg/dL, P  = .001). After adjusting for age, sex, and alcohol use, white and other versus black race (ORs, 8.49 and 16.54, respectively), ALT (OR, 3.13/doubling), hypertension (OR, 10.93), hyperlipidemia (OR, 4.36), and diabetes family history (OR, 5.38) were associated with having FLD (all P <.05). Steatohepatitis or steatosis alone (vs none) was associated with higher ALT over time (1.93 and 1.34 times higher, respectively; P < .001), with adjustment for age, sex, and HBV DNA. Conclusions About 30% with HIV-HBV coinfection had FLD including 10% with steatohepatitis. FLD was associated with non-black race, metabolic risks, an atherogenic lipid profile, and elevated ALT over time. Thus, identification of FLD and management of adverse metabolic profiles are critically important in HIV-HBV coinfection. Clinical Trial Registration. NCT 01924455. [ABSTRACT FROM AUTHOR]

Background Studies have demonstrated benefits of antiretroviral therapy (ART) initiation on the day of human immunodeficiency virus (HIV) testing or at first clinical visit. The hospital setting is understudied for immediate ART initiation. Methods CTN0049, a linkage-to-care randomized clinical trial, enrolled 801 persons living with HIV (PLWH) and substance use disorder (SUD) from 11 hospitals across the United States. This secondary analysis examined factors related to initiating (including reinitiating) ART in the hospital and its association with linkage to HIV care, frequency of outpatient care visits, retention, and viral suppression. Results Of 801 participants, 124 (15%) initiated ART in the hospital, with more than two-thirds of these participants (80/124) initiating ART for the first time. Time to first HIV care visit among those who initiated ART in the hospital and those who did not was 29 and 54 days, respectively (P =.0145). Hospital initiation of ART was associated with increased frequency of HIV outpatient care visits at 6 and 12 months. There was no association with ART initiation in the hospital and retention and viral suppression over a 12-month period. Participants recruited in Southern hospitals were less likely to initiate ART in the hospital (P <.001). Conclusions Previous research demonstrated benefits of immediate ART initiation, yet this approach is not widely implemented. Research findings suggest that starting ART in the hospital is beneficial for increasing linkage to HIV care and frequency of visits for PLWH and SUD. Implementation research should address barriers to early ART initiation in the hospital. [ABSTRACT FROM AUTHOR]

Background Direct-acting antivirals can cure hepatitis C virus (HCV). Persons with HCV/HIV and living with substance use are disadvantaged in benefiting from advances in HCV treatment. Methods In this randomized controlled trial, participants with HCV/HIV were randomized between February 2016 and January 2017 to either care facilitation or control. Twelve-month follow-up assessments were completed in January 2018. Care facilitation group participants received motivation and strengths-based case management addressing retrieval of HCV viral load results, engagement in HCV/HIV care, and medication adherence. Control group participants received referral to HCV evaluation and an offer of assistance in making care appointments. Primary outcome was number of steps achieved along a series of 8 clinical steps (eg, receiving HCV results, initiating treatment, sustained virologic response [SVR]) of the HCV/HIV care continuum over 12 months postrandomization. Results Three hundred eighty-one individuals were screened and 113 randomized. Median age was 51 years; 58.4% of participants were male and 72.6% were Black/African American. Median HIV-1 viral load was 27 209 copies/mL, with 69% having a detectable viral load. Mean number of steps completed was statistically significantly higher in the intervention group vs controls (2.44 vs 1.68 steps; χ 2 [1] = 7.36, P  = .0067). Men in the intervention group completed a statistically significantly higher number of steps than controls. Eleven participants achieved SVR with no difference by treatment group. Conclusions The care facilitation intervention increased progress along the HCV/HIV care continuum, as observed for men and not women. Study findings also highlight continued challenges to achieve individual-patient SVR and population-level HCV elimination. Clinical Trials Registration NCT02641158. [ABSTRACT FROM AUTHOR]

Background New therapies to achieve hepatitis B surface antigen (HBsAg) clearance are under development. However, gaps in knowledge exist in understanding the incidence and predictors of HBsAg clearance in a racially diverse HIV population. Methods We examined the incidence and risk of HBsAg clearance in a retrospective cohort of people with HIV/hepatitis B virus (HBV). Included patients had sufficient data to establish chronic infection based on Centers for Disease Control and Prevention guidelines. We examined the incident rate for HBsAg loss and hazard rate ratios to evaluate predictors for HBsAg clearance in a multivariable model. Results Among 571 HIV/HBV patients, 87% were male, 61% were Black, 45% had AIDS, 48% were HBeAg positive, and the median follow-up was 88 months. Incident HBsAg clearance was 1.5 per 100 person-years. In the multivariate model, those with AIDS at baseline (adjusted hazard ratio [aHR], 2.43; 95% CI, 1.37–4.32), Hispanics (aHR, 3.57; 95% CI, 1.33–9.58), and those with injection drug use as an HIV risk factor (aHR, 3.35; 95% CI, 1.26–8.89) were more likely to lose HBsAg, whereas those who were HBeAg positive (aHR, 0.34; 95% CI, 0.19–0.63) were less likely to lose HBsAg. The median change in CD4 cell count during the observation period was 231 cells/mm3 in those with HBsAg loss vs 112 cells/mm3 in those with HBsAg persistence (P  = .004). Conclusions HBsAg loss occurs in about 10% of those with chronic HBV infection. Being Hispanic, having AIDS at baseline, having an injection drug use history, and having HBeAg-negative status at baseline predicted the likelihood of HBsAg loss. Immune restoration may be a mechanism through which HBsAg loss occurs in HIV patients. [ABSTRACT FROM AUTHOR]

Persons living with HIV (PLWH) with substance use disorders (SUD) remain a population difficult to engage in HIV care. Project HOPE (Hospital Visits as an Opportunity for Prevention and Engagement), a randomized controlled trial testing patient navigation with/without contingency management for PLWH with SUD, aimed to address this disparity. PLWH with SUD who were out of care were recruited from 11 hospitals across the United States from 2012 to 2014. Baseline socioeconomic factors, medical mistrust scores, and perceived discrimination surveys were collected at enrollment and evaluated for effects on linkage to care at the 6-month follow-up assessment. Linkage to care (attending an outpatient visit for HIV care), early linkage to care (attending first visit within 30 days of enrollment), and engagement in care (two HIV visits within the 6-month period) were determined by medical record abstraction, supplemented by self-report. Among 801 participants enrolled in the study (mean age 45 years, 33% women, and 73% African American), those who did not complete high school and with severe food insecurity had lower odds of being linked to care at 6 months. Those with high levels of medical mistrust, recent drug use, and who did not complete high school had lower odds of early linkage to care. Early linkage was associated with higher odds of engagement at 6 months and was mitigated by both patient navigator interventions (all p < .05). Addressing social determinants of health is critical to correct the disparity seen in HIV outcomes among PLWH with SUD. Identifying factors that alter the effect of interventions could help identify patients who would benefit most. [ABSTRACT FROM AUTHOR]

Introduction: Guidelines advocate the treatment of HCV in all HIV/HCV co-infected individuals. The aim of this randomized, open-label study (ClinicalTrials.gov identifier: NCT02707601; https://clinicaltrials.gov/ct2/show/NCT02707601) was to evaluate the safety/efficacy of ledipasvir/sofosbuvir (LDV/SOF) co-administered with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or rilpivirine/F/TAF (R/F/TAF) in HIV-1/HCV co-infected participants. Methods: Participants with HIV-1 RNA <50 copies/mL and chronic HCV-genotype (GT) 1 (HCV treatment-naïve ± compensated cirrhosis or HCV treatment-experienced non-cirrhotic) were randomized 1:1 to switch to E/C/F/TAF or R/F/TAF. If HIV suppression was maintained at Week 8, participants received 12 weeks of LDV/SOF. The primary endpoint was sustained HCV virologic response 12 weeks after LDV/SOF completion (SVR12). Results: Of 150 participants, 148 received ≥1 dose of HIV study drug and 144 received LDV/SOF (72 in each F/TAF group; 83% GT1a, 94% HCV treatment-naïve, 12% cirrhotic). Overall, SVR12 was 97% (95% confidence interval: 93–99%). Black race did not affect SVR12. Of four participants not achieving SVR12, one had HCV relapse, one had HCV virologic non-response due to non-adherence, and two missed the post-HCV Week 12 visit. Of 148 participants, 96% receiving E/C/F/TAF and 95% receiving R/F/TAF maintained HIV suppression at Week 24; no HIV resistance was detected. No participant discontinued LDV/SOF or E/C/F/TAF due to adverse events; one participant discontinued R/F/TAF due to worsening of pre-existing hypercholesterolemia. Renal toxicity was not observed in either F/TAF regimen during LDV/SOF co-administration. In conclusion, high rates of HCV SVR12 and maintenance of HIV suppression were achieved with LDV/SOF and F/TAF-based regimens. Conclusion: This study supports LDV/SOF co-administered with an F/TAF-based regimen in HIV-1/HCV-GT1 co-infected patients. [ABSTRACT FROM AUTHOR]

BACKGROUND The association between hypertension (HTN) and inflammatory biomarkers (interleukin-6 [IL-6] and high-sensitivity C-reactive protein [hsCRP]) in HIV-positive persons with CD4+ count >500 cells/mm3 is unknown. METHODS We studied HTN in participants of the Strategic Timing of AntiRetroviral Treatment (START) trial of immediate vs. deferred antiretroviral therapy (ART) in HIV-positive, ART naive adults with CD4+ count > 500 cells/mm3. HTN was defined as having a systolic blood pressure (BP) ≥140 mmHg, a diastolic BP ≥90 mmHg, or using BP-lowering therapy. Logistic and discrete Cox regression models were used to study the association between baseline biomarker levels with prevalent and incident HTN. RESULTS Among 4,249 participants with no history of cardiovascular disease, the median age was 36 years, 55% were nonwhite, and the prevalence of HTN at baseline was 18.9%. After adjustment for race, age, gender, body mass index (BMI), diabetes, smoking, HIV RNA and CD4+ levels, associations of IL-6 and hsCRP with HTN prevalence were not significant (OR per twofold higher:1.10, 95% confidence interval [CI]: 0.99, 1.20 for IL-6 and 1.05, 95% CI: 0.99, 1.10 for hsCRP). Overall incidence of HTN was 6.8 cases/100 person years. In similarly adjusted models, neither IL-6 (Hazard ratios [HR] per twofold higher IL-6 levels: 0.97, 95% CI: 0.88, 1.08) nor hsCRP (HR per twofold higher hsCRP levels: 0.97, 95% CI: 0.92, 1.02) were associated with risk of incident HTN. Associations did not differ by treatment group. Age, race, gender, and BMI were significantly associated with both the prevalence and incidence of HTN. CONCLUSIONS Traditional risk factors and not baseline levels of IL-6 or hsCRP were associated with the prevalence and incidence of HTN in START. [ABSTRACT FROM AUTHOR]

HIV disproportionately affects racial/ethnic minorities and individuals living in the southern United States, and missed clinic visits account for much of this disparity. We sought to evaluate: (1) predictors of missed initial HIV medical visits, (2) time to initial visit, and (3) the association between initial visit attendance and retention in HIV care. Chart reviews were conducted for 200 consecutive HIV-infected patients (100 in Dallas, 100 in San Antonio) completing case management (CM) intake. Of these, 52 (26%) missed their initial visit, with 22 (11%) never presenting for care. Mean age was 40 years, 85% were men, >70% were of minority race/ethnicity, and 28% had a new HIV diagnosis. Unemployment (OR [95% CI] = 2.33 [1.04-5.24], p = 0.04) and lower attendance of CM visits (OR = 3.08 [1.43-6.66], p = 0.004) were associated with missing the initial medical visit. A shorter time to visit completion was associated with CD4 ≤ 200 (HR 1.90 [1.25-2.88], p = 0.003), Dallas study site (HR = 1.48 [1.03-2.14], p = 0.04), and recent hospitalization (HR = 2.18 [1.38-3.43], p < 0.001). Patients who did not complete their initial medical visit within 90 days of intake were unlikely to engage in care. Initial medical visit attendance was associated with higher proportion of visits attended ( p = 0.04) and fewer gaps in care ( p = 0.01). Missed medical visits were common among HIV patients initiating or reinitiating care in Texas. Employment and CM involvement predicted initial medical visit attendance, which was associated with retention in care. New, early engagement strategies are needed to decrease missed visits and reduce HIV health disparities. [ABSTRACT FROM AUTHOR]

The contribution of the novel biomarkers, hepatitis B virus (HBV) RNA and HBV core-related antigen (HBcrAg), to characterization of HBV-human immunodeficiency virus (HIV) coinfection is unclear. We evaluated the longitudinal dynamics of HBV RNA and HBcrAg and their association with classical HBV serum biomarkers and liver histology and viral staining. HBV-HIV co-infected adults from 8 North American centers entered a National Institutes of Health-funded prospective cohort study. Demographic, clinical, serological, and virological data were collected at entry and every 24 to 48 weeks for up to 192 weeks. Participants with HBV RNA and HBcrAg measured ≥2 times (N = 95) were evaluated; 56 had paired liver biopsies obtained at study entry and end of follow-up. Participants had a median age of 50 years; 97% were on combination anti-viral therapy. In hepatitis B e antigen (HBeAg)+ participants, there were significant declines in HBV RNA and HBcrAg over 192 weeks that tracked with declines in HBeAg, hepatitis B surface antigen, HBV DNA, and hepatitis B core antigen (HBcAg) hepatocyte staining grade (all P <.05). In HBeAg− participants, there were not significant declines in HBV RNA (P =.49) and HBcrAg (P =.63), despite modest reductions in hepatitis B surface antigen (P <.01) and HBV DNA (P =.03). HBV serum biomarkers were not significantly related to change in hepatic activity index, Ishak fibrosis score, or hepatocyte HBcAg loss (all P >.05). In HBV-HIV coinfected adults on suppressive dually active antiviral therapy, the use of novel HBV markers reveals continued improvement in suppression of HBV transcription and translation over time. The lack of further improvement in HBV serum biomarkers among HBeAg− patients suggests limits to the benefit of combination anti-viral therapy and provide rationale for additional agents with distinct mechanisms of action. [ABSTRACT FROM AUTHOR]

Background. In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts and human immunodeficiency virus (HIV) RNA between the study arms. Methods. Incident malignancies in START were categorized into infection-related and infection-unrelated cancer.We used Cox models to assess factors associated with both cancer categories. We used sequential adjustment for baseline covariates, cancer risk factors, and HIV-specific variables to investigate potential mediators of cancer risk reduction with immediate cART. Results. There were 14 cancers among persons randomized to immediate cART (6 infection-related and 8 infection-unrelated) and 39 cancers in the deferred arm (23 infection-related and 16 infection-unrelated); hazard ratios of immediate vs deferred cART initiation were 0.26 (95% confidence interval [CI], .11-.64) for infection-related and 0.49 (95% CI, .21-1.15) for infection-unrelated cancer. Independent predictors of infection-related cancer were older age, higher body mass index, low- to middle-income region, HIV RNA, and baseline CD8 cell count. Older age and baseline CD8 cell count were independent predictors of infection-unrelated cancer. Adjustment for latest HIV RNA level had little impact on the protective effect of immediate cART on infection-related cancer. Adjustment for latest HIV RNA level, but not for CD4 cell count or cancer risk factors, attenuated the effect of immediate cART on infection-unrelated cancer. Conclusions. Immediate cART initiation significantly reduces risk of cancer. Although limited by small sample size, this benefit does not appear to be solely attributable to HIV RNA suppression and may be also mediated by other mechanisms. [ABSTRACT FROM AUTHOR]

Importance: Substance use is a major driver of the HIV epidemic and is associated with poor HIV care outcomes. Patient navigation (care coordination with case management) and the use of financial incentives for achieving predetermined outcomes are interventions increasingly promoted to engage patients in substance use disorders treatment and HIV care, but there is little evidence for their efficacy in improving HIV-1 viral suppression rates. Objective: To assess the effect of a structured patient navigation intervention with or without financial incentives to improve HIV-1 viral suppression rates among patients with elevated HIV-1 viral loads and substance use recruited as hospital inpatients. Design, Setting, and Participants: From July 2012 through January 2014, 801 patients with HIV infection and substance use from 11 hospitals across the United States were randomly assigned to receive patient navigation alone (n = 266), patient navigation plus financial incentives (n = 271), or treatment as usual (n = 264). HIV-1 plasma viral load was measured at baseline and at 6 and 12 months. Interventions: Patient navigation included up to 11 sessions of care coordination with case management and motivational interviewing techniques over 6 months. Financial incentives (up to $1160) were provided for achieving targeted behaviors aimed at reducing substance use, increasing engagement in HIV care, and improving HIV outcomes. Treatment as usual was the standard practice at each hospital for linking hospitalized patients to outpatient HIV care and substance use disorders treatment. Main Outcomes and Measures: The primary outcome was HIV viral suppression (≤200 copies/mL) relative to viral nonsuppression or death at the 12-month follow-up. Results: Of 801 patients randomized, 261 (32.6%) were women (mean [SD] age, 44.6 years [10.0 years]). There were no differences in rates of HIV viral suppression versus nonsuppression or death among the 3 groups at 12 months. Eighty-five of 249 patients (34.1%) in the usual-treatment group experienced treatment success compared with 89 of 249 patients (35.7%) in the navigation-only group for a treatment difference of 1.6% (95% CI, -6.8% to 10.0%; P = .80) and compared with 98 of 254 patients (38.6%) in the navigation-plus-incentives group for a treatment difference of 4.5% (95% CI -4.0% to 12.8%; P = .68). The treatment difference between the navigation-only and the navigation-plus-incentives group was -2.8% (95% CI, -11.3% to 5.6%; P = .68). Conclusions and Relevance: Among hospitalized patients with HIV infection and substance use, patient navigation with or without financial incentives did not have a beneficial effect on HIV viral suppression relative to nonsuppression or death at 12 months vs treatment as usual. These findings do not support these interventions in this setting. Trial Registration: clinicaltrials.gov Identifier: NCT01612169. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B coinfection is common in HIV-positive individuals and as antiretroviral therapy has made death due to AIDS less common, hepatitis has become increasingly important. Several drugs are available to treat hepatitis B. The most potent and the one with the lowest risk of resistance appears to be tenofovir (TDF). However there are several questions that remain unanswered regarding the use of TDF, including the proportion of patients that achieves suppression of HBV viral load and over what time, whether suppression is durable and whether prior treatment with other HBV-active drugs such as lamivudine, compromises the efficacy of TDF due to possible selection of resistant HBV strains. Methods: A systematic review and meta-analysis following PRISMA guidelines and using multilevel mixed effects logistic regression, stratified by prior and/or concomitant use of lamivudine and/or emtricitabine. Results: Data was available from 23 studies including 550 HBV/HIV coinfected patients treated with TDF. Follow up was for up to seven years but to ensure sufficient power the data analyses were limited to three years. The overall proportion achieving suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three years, respectively. No effect of prior or concomitant 3TC/FTC was shown. Virological rebound on TDF treatment was rare. Interpretation: TDF suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected patients with the proportion fully suppressed continuing to increase during continuous treatment. Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The use of combination treatment with 3TC/FTC offers no significant benefit over TDF alone. [ABSTRACT FROM AUTHOR]

Background. The common occurrence of hepatitis B virus (HBV) infection in patients who carry the human immunodeficiency virus (HIV) demands that both viruses be recognized, evaluated, and treated when appropriate. Methods. We identified 357 HIV- and hepatitis B surface antigen-positive patients who underwent testing from 1999 to 2003; 155 patients who were new to our clinic and who initiated therapy for HIV and HBV coinfection were considered for inclusion in the study. The frequency of HIV testing (to determine HIV load and CD4+ cell count) performed during the first year of therapy was compared with the frequency of HBV measurements (to determine hepatitis B e antigen, antibody to hepatitis B e antigen, and HBV load), abdominal ultrasound examination, and measurement of levels of α-fetoprotein in serum. Results. HBV load data were obtained for only 16% of patients before initiation of antiretroviral therapy (ART), whereas HIV load was determined for 99% of patients before initiation of ART. The total number of HIV load measurements obtained during the first year after ART initiation was 497 (median number of HIV load measurements per patient, 3.0), compared with 85 measurements of HBV load (median number of HBV load measurements per patient, <1; P<.001). The percentage of patients who received any level of HBV monitoring (i.e., tests to determine hepatitis B e antigen, antibody to hepatitis B e antigen, and HBV load) after ART initiation increased from 7% in 1999 to 52% in 2001 (P<.001), whereas the percentage of patients who underwent HIV load testing remained at 80%-90% during the same period. Conclusions. Health care providers treating patients with HIV infection during the period 1999-2003 infrequently monitored HBV response in coinfected patients, but they systematically monitored HIV response after ART initiation. Improved physician adherence to guidelines that better delineate HBV treatment and monitoring for patients with HIV-HBV coinfection is needed. [ABSTRACT FROM AUTHOR]

Discerning drug hepatotoxicity from viral hepatitis flares remains an ongoing problem unique to patients coinfected with HIV and hepatitis B (HBV). We present three such coinfected patients who have been on two anti-HBV agents, lamivudine and tenofovir disoproxil fumarate simultaneously, as part of highly active antiretroviral therapy (HAART). All three developed significant aminotransferase elevations 6–12 weeks after initiation of HAART despite being on two active HBV drugs. Two of the three patients were initially thought to have drug-related hepatotoxicity from HIV medications. It seems more likely that all three patients demonstrated hepatitis B reactivation of differing severity as the result of varying degrees of immune recovery. Distinguishing clearly between drug-related hepatotoxicity and hepatitis reactivation may be difficult but is important as their clinical management differs. [ABSTRACT FROM AUTHOR]

Background: Hospital readmissions are common, costly, and potentially preventable, including among people with HIV (PWH). We present the results of an evaluation of a multicomponent intervention aimed at reducing 30-day readmissions among PWH. Methods: Demographic, socioeconomic, and clinical variables were collected from the electronic health records of PWH or those with cellulitis (control group) hospitalized at an urban safety-net hospital before and after (from September 2012 to December 2016) the implementation of a multidisciplinary HIV transitional care team. After October 2014, hospitalized PWH could receive a medical HIV consultation ± a transitional care nurse intervention. The primary outcome was readmission to any hospital within 30 days of discharge. Multivariate logistic regression and propensity score analyses were conducted to compare readmissions before and after intervention implementation in PWH and people with cellulitis. Results: Overall, among PWH, 329 of the 2049 (16.1%) readmissions occurred before and 329 of the 2023 (16.3%) occurred after the transitional care team intervention. After including clinical and social predictors, the adjusted odds ratio of 30-day readmissions for postintervention for PWH was 0.81 (95% confidence interval: 0.66 to 0.99, P = 0.04), whereas little reduction was identified for those with cellulitis (adjusted odds ratio 0.91 (95% confidence interval: 0.81 to 1.02, P = 0.10). A dose–response effect was not observed for receipt of different HIV intervention components. Conclusions: A multicomponent intervention reduced the adjusted risk of 30-day readmissions in PWH, although no dose–response effect was detected. Additional efforts are needed to reduce overall hospitalizations and readmissions among PWH including increasing HIV prevention, early diagnosis and engagement in care, and expanding the availability and spectrum of transitional care services. [ABSTRACT FROM AUTHOR]

Background: Using data from a randomized trial, we evaluated the cost of HCV care facilitation that supports moving along the continuum of care for HIV/HCV co-infected individuals with substance use disorder.Methods: Participants were HIV patients residing in the community, initially recruited from eight US hospital sites. They received HCV care facilitation (n = 51) or treatment as usual (n = 62) for up to six months. We used micro-costing methods to evaluate costs from the healthcare sector and patient perspectives in 2017 USD. We conducted sensitivity analyses varying care facilitator caseloads and examined offsetting savings using participant self-reported healthcare utilization.Results: The average site start-up cost was $6320 (site range: $4320-$7000), primarily consisting of training. The mean weekly cost per participant was $20 (site range: $4-$30) for care facilitation visits and contacts, $360 (site range: $130- $700) for supervision and client outreach, and $70 (site range: $20-$180) for overhead. In sensitivity analyses applying a weekly caseload of 10 participants per care facilitator (versus 1-6 observed in the trial), the total mean weekly care facilitation cost from the healthcare sector perspective decreased to $110. Weekly participant time and travel costs averaged $7. There were no significant differences in other healthcare service costs between participants in the intervention and control arms.Conclusion: Weekly HCV care facilitation costs were approximately $450 per participant, but approximately $110 at a real-world setting maximum caseload of 10 participants per week. No healthcare cost offsets were identified during the trial period, although future savings might result from successful HCV treatment. [ABSTRACT FROM AUTHOR]

Background/Aims: HIV-infected patients now live longer and often have complications of liver disease, especially with hepatitis B or C virus coinfection. Limited data are available on those with hepatocellular carcinoma (HCC). Methods: A retrospective analysis from 1992 to 2005 in 6 centers identified 63 HIV-infected HCC patients. Controls were 226 consecutive HIV-negative HCC patients from four sites. Results: HIV-positive patients were younger than controls (52 vs. 64years, p <0.001), more commonly had chronic hepatitis B or C (97% vs. 73%, p <0.001), were more frequently symptomatic (51% vs. 38%, p =0.048), had a higher median alfa-fetoprotein level (227 vs. 51 ng/ml, p =0.005), but a similar mean Child–Turcotte–Pugh score (7.0 vs. 7.5, p =0.05) and HCC staging score (Barcelona-Clínic-Liver-Cancer stages C+D in 50% vs. 58%, p =0.24). HCC developed faster in HIV/HCV-coinfected than in HCV-monoinfected patients (mean, 26 vs. 34years after HCV infection, p =0.002). HIV-positive patients received proven therapy more often (48% vs. 31%, p =0.017), but median survival was similar (6.9 vs. 7.5 months, p =0.44). Independent factors predicting survival were symptomatic presentation (hazard ratio [HR], 0.437; p <0.001), any proven therapy (HR, 2.19; p <0.001), diagnosis after 01-Jan-2002 (HR, 1.52; p =0.010), Barcelona-Clínic-Liver-Cancer stages C+D (HR, 0.491; p <0.001), AST/ALT⩾2.00 (HR, 0.597; p =0.001), AFP⩾400 ng/mL (HR, 0.55, p =0.003), and platelets⩾100,000/mm3 (HR, 0.651; p =0.012), but not HIV-serostatus (p =0.19). In HIV-infected patients without HCC therapy (n =33), median survival was longer with undetectable HIV RNA (<400copies/mL) than with HIV viremia (6.5 vs. 2.6 months, p =0.013). Conclusions: HIV-positive HCC patients are younger and more frequently symptomatic and infected with HCV or HBV than HIV-negative patients. Tumor staging and survival are similar. In untreated patients, undetectable HIV RNA independently predicts better survival. [Copyright &y& Elsevier]

Background: People living with HIV who report substance use (PLWH-SU) face many barriers to care, resulting in an increased risk for poor health outcomes and the potential for ongoing disease transmission. This study evaluates the mechanisms by which Patient Navigation (PN) and Contingency Management (CM) interventions may work to address barriers to care and improve HIV outcomes in this population.Methods: Mediation analysis was conducted using data from a randomized, multi-site trial testing PN interventions to improve HIV care outcomes among 801 hospitalized PLHW-SU. Direct and indirect effects of PN and PN + CM were evaluated through five potential mediators-psychosocial conditions, healthcare avoidance, financial hardship, system barriers, and self-efficacy for HIV treatment adherence-on engagement in HIV care and viral suppression.Results: The PN + CM intervention had an indirect effect on improving engagement in HIV care at 6 months by increasing self-efficacy for HIV treatment adherence (β = 0.042, 95% CI = 0.008, 0.086). PN + CM also led to increases in viral suppression at 6 months (β = 0.090, 95% CI = 0.023, 0.168) and 12 months (β = 0.069, 95% CI = 0.009, 0.129) via increases in self-efficacy, although the direct effects were not significant. No mediating effects were observed for PN alone.Conclusion: PN + CM interventions for PLWH-SU can increase an individual's self-efficacy for HIV treatment adherence, which in turn improves engagement in care at 6 months and may contribute to viral suppression over 12 months. Building self-efficacy may be a key factor in the success of such interventions and should be considered as a primary goal of PN + CM in practice. [ABSTRACT FROM AUTHOR]