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A care cascade is a critical tool for evaluating delivery of care for chronic infections across sequential stages, starting with diagnosis and ending with viral suppression. However, there have been few data describing the hepatitis B virus (HBV) care cascade among people living with HIV infection who have HBV coinfection. We conducted a cross-sectional study among people living with HIV and HBV coinfection receiving care between January 1, 2012 and December 31, 2016 within 13 United States and Canadian clinical cohorts contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). We evaluated each of the steps in this cascade, including: 1) laboratory-confirmed HBV infection, 2) tenofovir-based or entecavir-based HBV therapy prescribed, 3) HBV DNA measured during treatment, and 4) viral suppression achieved via undetectable HBV DNA. Among 3,953 persons with laboratory-confirmed HBV (median age, 50 years; 6.5% female; 43.8% were Black; 7.1% were Hispanic), 3,592 (90.9%; 95% confidence interval, 90.0-91.8%) were prescribed tenofovir-based antiretroviral therapy or entecavir along with their antiretroviral therapy regimen, 2,281 (57.7%; 95% confidence interval, 56.2-59.2%) had HBV DNA measured while on therapy, and 1,624 (41.1%; 95% confidence interval, 39.5-42.6) achieved an undetectable HBV DNA during HBV treatment. Our study identified significant gaps in measurement of HBV DNA and suppression of HBV viremia among people living with HIV and HBV coinfection in the United States and Canada. Periodic evaluation of the HBV care cascade among persons with HIV/HBV will be critical to monitoring success in completion of each step.

BackgroundCancer causes significant morbidity and mortality among HIV patients in the US due to extended life expectancy with access to effective antiretroviral therapy. Low, detectable HIV RNA has been studied as a risk factor for adverse health outcomes, but its clinical impact on cancer risk remains unclear. The objective of this study was to determine whether HIV RNA 999 copies/mL. We calculated estimates of the cumulative incidence of cancer diagnosis, accounting for death as a competing event. Inverse probability of exposure and censoring weights were used to control for confounding and differential loss to follow up, respectively.ResultsCrude 10-year first cancer risk in the study sample was 7.03% (95% CI: 6.08%, 7.98%), with the highest risk observed among patients with viral loads between 200 and 999 copies/mL six months after ART initiation (10.7%). After controlling for baseline confounders, 10-year first cancer risk was 6.90% (95% CI: 5.69%, 8.12%), and was similar across viral load categories.ConclusionOverall risk of first cancer was not associated with incomplete viral suppression; however, cancer remains a significant threat to HIV patients after treatment initiation. As more HIV patients gain access to treatment in the current "treat all" era, occurrences of incomplete viral suppression will be observed more frequently in clinical practice, which supports continued study of the role of low-level HIV RNA on cancer development.

BackgroundCombination antiretroviral therapy (ART) has significantly increased survival among HIV-positive adults in the United States (U.S.) and Canada, but gains in life expectancy for this region have not been well characterized. We aim to estimate temporal changes in life expectancy among HIV-positive adults on ART from 2000-2007 in the U.S. and Canada.MethodsParticipants were from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), aged ≥20 years and on ART. Mortality rates were calculated using participants' person-time from January 1, 2000 or ART initiation until death, loss to follow-up, or administrative censoring December 31, 2007. Life expectancy at age 20, defined as the average number of additional years that a person of a specific age will live, provided the current age-specific mortality rates remain constant, was estimated using abridged life tables.ResultsThe crude mortality rate was 19.8/1,000 person-years, among 22,937 individuals contributing 82,022 person-years and 1,622 deaths. Life expectancy increased from 36.1 [standard error (SE) 0.5] to 51.4 [SE 0.5] years from 2000-2002 to 2006-2007. Men and women had comparable life expectancies in all periods except the last (2006-2007). Life expectancy was lower for individuals with a history of injection drug use, non-whites, and in patients with baseline CD4 counts

HIV-1-infected adults over the age of 50 years progress to AIDS more rapidly than adults in their twenties or thirties. In addition, HIV-1-infected individuals receiving antiretroviral therapy (ART) present with clinical diseases, such as various cancers and liver disease, more commonly seen in older uninfected adults. These observations suggest that HIV-1 infection in older persons can have detrimental immunological effects that are not completely reversed by ART. As naïve T-cells are critically important in responses to neoantigens, we first analyzed two subsets (CD45RA(+)CD31(+) and CD45RA(+)CD31(-)) within the naïve CD4(+) T-cell compartment in young (20-32 years old) and older (39-58 years old), ART-naïve, HIV-1 seropositive individuals within 1-3 years of infection and in age-matched seronegative controls. HIV-1 infection in the young cohort was associated with lower absolute numbers of, and shorter telomere lengths within, both CD45RA(+)CD31(+)CD4(+) and CD45RA(+)CD31(-)CD4(+) T-cell subsets in comparison to age-matched seronegative controls, changes that resembled seronegative individuals who were decades older. Longitudinal analysis provided evidence of thymic emigration and reconstitution of CD45RA(+)CD31(+)CD4(+) T-cells two years post-ART, but minimal reconstitution of the CD45RA(+)CD31(-)CD4(+) subset, which could impair de novo immune responses. For both ART-naïve and ART-treated HIV-1-infected adults, a renewable pool of thymic emigrants is necessary to maintain CD4(+) T-cell homeostasis. Overall, these results offer a partial explanation both for the faster disease progression of older adults and the observation that viral responders to ART present with clinical diseases associated with older adults.

Background: Racial/ethnic disparities during the first six months of the COVID-19 pandemic led to differences in COVID-19 testing and adverse outcomes. We examine differences in testing and adverse outcomes by race/ethnicity and sex across a geographically diverse and system-based COVID-19 cohort collaboration. Methods: Observational study among adults (≥18 years) within six US cohorts from March 1, 2020 to August 31, 2020 using data from electronic health record and patient reporting. Race/ethnicity and sex as risk factors were primary exposures, with health system type (integrated health system, academic health system, or interval cohort) as secondary. Proportions measured SARS-CoV-2 testing and positivity; attributed hospitalization and death related to COVID-19. Relative risk ratios (RR) with 95% confidence intervals quantified associations between exposures and main outcomes. Results: 5,958,908 patients were included. Hispanic patients had the highest proportions of SARS-CoV-2 testing (16%) and positivity (18%), while Asian/Pacific Islander patients had the lowest portions tested (11%) and White patients had the lowest positivity rates (5%). Men had a lower likelihood of testing (RR = 0.90 [0.89–0.90]) and a higher positivity risk (RR = 1.16 [1.14–1.18]) compared to women. Black patients were more likely to have COVID-19-related hospitalizations (RR = 1.36 [1.28–1.44]) and death (RR = 1.17 [1.03–1.32]) compared with White patients. Men were more likely to be hospitalized (RR = 1.30 [1.16–1.22]) or die (RR = 1.70 [1.53–1.89]) compared to women. These racial/ethnic and sex differences were reflected in both health system types. Conclusions: This study supports evidence of disparities by race/ethnicity and sex during the COVID-19 pandemic that persisted even in healthcare settings with reduced barriers to accessing care. Further research is needed to understand and prevent the drivers that resulted in higher burdens of morbidity among certain Black patients and men. [ABSTRACT FROM AUTHOR]

Background: Youth have residual thymic tissue and potentially greater capacity for immune reconstitution than adults after initiation of combination antiretroviral therapy (cART). However, youth face behavioral and psychosocial challenges that may make them more likely than adults to delay ART initiation and less likely to attain similar CD4 outcomes after initiating cART. This study compared CD4 outcomes over time following cART initiation between ART-naïve non-perinatally HIV-infected (nPHIV) youth (13–24 years-old) and adults (≥25–44 years-old). Methods: Retrospective analysis of ART-naïve nPHIV individuals 13–44 years-old, who initiated their first cART between 2008 and 2011 at clinical sites in the HIV Research Network. A linear mixed model was used to assess the association between CD4 levels after cART initiation and age (13–24, 25–34, 35–44 years), accounting for random variation within participants and between sites, and adjusting for key variables including gender, race/ethnicity, viral load, gaps in care (defined as > 365 days between CD4 tests), and CD4 levels prior to cART initiation (baseline CD4). Results: Among 2,595 individuals (435 youth; 2,160 adults), the median follow-up after cART initiation was 179 weeks (IQR 92–249). Baseline CD4 was higher for youth (320 cells/mm3) than for ages 25–34 (293) or 35–44 (258). At 239 weeks after cART initiation, median unadjusted CD4 was higher for youth than adults (576 vs. 539 and 476 cells/mm3, respectively), but this difference was not significant when baseline CD4 was controlled. Compared to those with baseline CD4 ≤200 cells/mm3, individuals with baseline CD4 of 201–500 and >500 cells/mm3 had greater predicted CD4 levels: 390, 607, and 831, respectively. Additionally, having no gaps in care and higher viral load were associated with better CD4 outcomes. Conclusions: Despite having residual thymic tissue, youth attain similar, not superior, CD4 gains as adults. Early ART initiation with minimal delay is as essential to optimizing outcomes for youth as it is for their adult counterparts. [ABSTRACT FROM AUTHOR]

Objective: To understand geographic variations in clinical retention, a central component of the HIV care continuum and key to improving individual- and population-level HIV outcomes. Design: We evaluated retention by US region in a retrospective observational study. Methods: Adults receiving care from 2000–2010 in 12 clinical cohorts of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) contributed data. Individuals were assigned to Centers for Disease Control and Prevention (CDC)-defined regions by residential data (10 cohorts) and clinic location as proxy (2 cohorts). Retention was ≥2 primary HIV outpatient visits within a calendar year, >90 days apart. Trends and regional differences were analyzed using modified Poisson regression with clustering, adjusting for time in care, age, sex, race/ethnicity, and HIV risk, and stratified by baseline CD4+ count. Results: Among 78,993 adults with 444,212 person-years of follow-up, median time in care was 7 years (Interquartile Range: 4–9). Retention increased from 2000 to 2010: from 73% (5,000/6,875) to 85% (7,189/8,462) in the Northeast, 75% (1,778/2,356) to 87% (1,630/1,880) in the Midwest, 68% (8,451/12,417) to 80% (9,892/12,304) in the South, and 68% (5,147/7,520) to 72% (6,401/8,895) in the West. In adjusted analyses, retention improved over time in all regions (p<0.01, trend), although the average percent retained lagged in the West and South vs. the Northeast (p<0.01). Conclusions: In our population, retention improved, though regional differences persisted even after adjusting for demographic and HIV risk factors. These data demonstrate regional differences in the US which may affect patient care, despite national care recommendations. [ABSTRACT FROM AUTHOR]

Objective: We sought to quantify agreement between Institute of Medicine (IOM) and Department of Health and Human Services (DHHS) retention indicators, which have not been compared in the same population, and assess clinical retention within the largest HIV cohort collaboration in the U.S. Design: Observational study from 2008–2010, using clinical cohort data in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Methods: Retention definitions used HIV primary care visits. The IOM retention indicator was: ≥2 visits, ≥90 days apart, each calendar year. This was extended to a 2-year period; retention required meeting the definition in both years. The DHHS retention indicator was: ≥1 visit each semester over 2 years, each ≥60 days apart. Kappa statistics detected agreement between indicators and C statistics (areas under Receiver-Operating Characteristic curves) from logistic regression analyses summarized discrimination of the IOM indicator by the DHHS indicator. Results: Among 36,769 patients in 2008–2009 and 34,017 in 2009–2010, there were higher percentages of participants retained in care under the IOM indicator than the DHHS indicator (80% vs. 75% in 2008–2009; 78% vs. 72% in 2009–2010, respectively) (p<0.01), persisting across all demographic and clinical characteristics (p<0.01). There was high agreement between indicators overall (κ = 0.83 in 2008–2009; κ = 0.79 in 2009–2010, p<0.001), and C statistics revealed a very strong ability to predict retention according to the IOM indicator based on DHHS indicator status, even within characteristic strata. Conclusions: Although the IOM indicator consistently reported higher retention in care compared with the DHHS indicator, there was strong agreement between IOM and DHHS retention indicators in a cohort demographically similar to persons living with HIV/AIDS in the U.S. Persons with poorer retention represent subgroups of interest for retention improvement programs nationally, particularly in light of the White House Executive Order on the HIV Care Continuum. [ABSTRACT FROM AUTHOR]

Background: U.S. state AIDS Drug Assistance Programs (ADAPs) are federally funded to provide antiretroviral therapy (ART) as the payer of last resort to eligible persons with HIV infection. States differ regarding their financial contributions to and ways of implementing these programs, and it remains unclear how this interstate variability affects HIV treatment outcomes. Methods: We analyzed data from HIV-infected individuals who were clinically-eligible for ART between 2001 and 2009 (i.e., a first reported CD4+ <350 cells/uL or AIDS-defining illness) from 14 U.S. cohorts of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Using propensity score matching and Cox regression, we assessed ART initiation (within 6 months following eligibility) and virologic suppression (within 1 year) based on differences in two state ADAP features: the amount of state funding in annual ADAP budgets and the implementation of waiting lists. We performed an a priori subgroup analysis in persons with a history of injection drug use (IDU). Results: Among 8,874 persons, 56% initiated ART within six months following eligibility. Persons living in states with no additional state contribution to the ADAP budget initiated ART on a less timely basis (hazard ratio [HR] 0.73, 95% CI 0.60–0.88). Living in a state with an ADAP waiting list was not associated with less timely initiation (HR 1.12, 95% CI 0.87–1.45). Neither additional state contributions nor waiting lists were significantly associated with virologic suppression. Persons with an IDU history initiated ART on a less timely basis (HR 0.67, 95% CI 0.47–0.95). Conclusions: We found that living in states that did not contribute additionally to the ADAP budget was associated with delayed ART initiation when treatment was clinically indicated. Given the changing healthcare environment, continued assessment of the role of ADAPs and their features that facilitate prompt treatment is needed. [ABSTRACT FROM AUTHOR]

HIV-1-infected adults over the age of 50 years progress to AIDS more rapidly than adults in their twenties or thirties. In addition, HIV-1-infected individuals receiving antiretroviral therapy (ART) present with clinical diseases, such as various cancers and liver disease, more commonly seen in older uninfected adults. These observations suggest that HIV-1 infection in older persons can have detrimental immunological effects that are not completely reversed by ART. As naïve T-cells are critically important in responses to neoantigens, we first analyzed two subsets (CD45RA+CD31+ and CD45RA+CD31-) within the naïve CD4+ T-cell compartment in young (20-32 years old) and older (39-58 years old), ART-naïve, HIV-1 seropositive individuals within 1-3 years of infection and in age-matched seronegative controls. HIV-1 infection in the young cohort was associated with lower absolute numbers of, and shorter telomere lengths within, both CD45RA+CD31+CD4+ and CD45RA+CD31-CD4+ T-cell subsets in comparison to age-matched seronegative controls, changes that resembled seronegative individuals who were decades older. Longitudinal analysis provided evidence of thymic emigration and reconstitution of CD45RA+CD31+CD4+ T-cells two years post-ART, but minimal reconstitution of the CD45RA+CD31-CD4+ subset, which could impair de novo immune responses. For both ART-naïve and ART-treated HIV-1-infected adults, a renewable pool of thymic emigrants is necessary to maintain CD4+ T-cell homeostasis. Overall, these results offer a partial explanation both for the faster disease progression of older adults and the observation that viral responders to ART present with clinical diseases associated with older adults. [ABSTRACT FROM AUTHOR]