Human immunodeficiency virus-infected individuals have benefited from improved viral suppression, but a discrepancy in end-stage renal disease risk between black and nonblack HIV-infected persons remains, in part due to continued disparities in antiretroviral use and viral suppression, and higher rates of comorbidities.
Background. Human immunodeficiency virus (HIV)-infected adults, particularly those of black race, are at high-risk for end-stage renal disease (ESRD), but contributing factors are evolving. We hypothesized that improvements in HIV treatment have led to declines in risk of ESRD, particularly among HIV-infected blacks.
Methods. Using data from the North American AIDS Cohort Collaboration for Research and Design from January 2000 to December 2009, we validated 286 incident ESRD cases using abstracted medical evidence of dialysis (lasting >6 months) or renal transplant. A total of 38 354 HIV-infected adults aged 18–80 years contributed 159 825 person-years (PYs). Age- and sex-standardized incidence ratios (SIRs) were estimated by race. Poisson regression was used to identify predictors of ESRD.
Results. HIV-infected ESRD cases were more likely to be of black race, have diabetes mellitus or hypertension, inject drugs, and/or have a prior AIDS-defining illness. The overall SIR was 3.2 (95% confidence interval [CI], 2.8–3.6) but was significantly higher among black patients (4.5 [95% CI, 3.9–5.2]). ESRD incidence declined from 532 to 303 per 100 000 PYs and 138 to 34 per 100 000 PYs over the time period for blacks and nonblacks, respectively, coincident with notable increases in both the prevalence of viral suppression and the prevalence of ESRD risk factors including diabetes mellitus, hypertension, and hepatitis C virus coinfection.
Conclusions. The risk of ESRD remains high among HIV-infected individuals in care but is declining with improvements in virologic suppression. HIV-infected black persons continue to comprise the majority of cases, as a result of higher viral loads, comorbidities, and genetic susceptibility.
end-stage renal disease (ESRD); chronic kidney disease (CKD); HIV infection/AIDS; HIV/AIDS; glomerular filtration rate (GFR)
We estimated US Department of Health and Human Services (DHHS)–approved human immunodeficiency virus (HIV) indicators. Among patients, 71% were retained in care, 82% were prescribed treatment, and 78% had HIV RNA ≤200 copies/mL; younger adults, women, blacks, and injection drug users had poorer outcomes. Interventions are needed to reduce retention- and treatment-related disparities.
HIV; quality of care; retention in care; antiretroviral therapy; HIV RNA suppression
Background. The role of active hepatitis C virus (HCV) replication in chronic kidney disease (CKD) risk has not been clarified.
Methods. We compared CKD incidence in a large cohort of HIV-infected subjects who were HCV seronegative, HCV viremic (detectable HCV RNA), or HCV aviremic (HCV seropositive, undetectable HCV RNA). Stages 3 and 5 CKD were defined according to standard criteria. Progressive CKD was defined as a sustained 25% glomerular filtration rate (GFR) decrease from baseline to a GFR < 60 mL/min/1.73 m2. We used Cox models to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).
Results. A total of 52 602 HCV seronegative, 9508 HCV viremic, and 913 HCV aviremic subjects were included. Compared with HCV seronegative subjects, HCV viremic subjects were at increased risk for stage 3 CKD (adjusted HR 1.36 [95% CI, 1.26, 1.46]), stage 5 CKD (1.95 [1.64, 2.31]), and progressive CKD (1.31 [1.19, 1.44]), while HCV aviremic subjects were also at increased risk for stage 3 CKD (1.19 [0.98, 1.45]), stage 5 CKD (1.69 [1.07, 2.65]), and progressive CKD (1.31 [1.02, 1.68]).
Conclusions. Compared with HIV-infected subjects who were HCV seronegative, both HCV viremic and HCV aviremic individuals were at increased risk for moderate and advanced CKD.
HIV; hepatitis C virus; chronic kidney disease; hepatitis C RNA; cohort study; glomerular filtration rate; injection drug use
In the last decade, timely initiation of antiretroviral therapy and resulting virologic suppression have greatly improved in North America concurrent with the development of better tolerated and more potent regimens, but significant barriers to treatment uptake remain.
Background. Since the mid-1990s, effective antiretroviral therapy (ART) regimens have improved in potency, tolerability, ease of use, and class diversity. We sought to examine trends in treatment initiation and resulting human immunodeficiency virus (HIV) virologic suppression in North America between 2001 and 2009, and demographic and geographic disparities in these outcomes.
Methods. We analyzed data on HIV-infected individuals newly clinically eligible for ART (ie, first reported CD4+ count <350 cells/µL or AIDS-defining illness, based on treatment guidelines during the study period) from 17 North American AIDS Cohort Collaboration on Research and Design cohorts. Outcomes included timely ART initiation (within 6 months of eligibility) and virologic suppression (≤500 copies/mL, within 1 year). We examined time trends and considered differences by geographic location, age, sex, transmission risk, race/ethnicity, CD4+ count, and viral load, and documented psychosocial barriers to ART initiation, including non–injection drug abuse, alcohol abuse, and mental illness.
Results. Among 10 692 HIV-infected individuals, the cumulative incidence of 6-month ART initiation increased from 51% in 2001 to 72% in 2009 (Ptrend < .001). The cumulative incidence of 1-year virologic suppression increased from 55% to 81%, and among ART initiators, from 84% to 93% (both Ptrend < .001). A greater number of psychosocial barriers were associated with decreased ART initiation, but not virologic suppression once ART was initiated. We found significant heterogeneity by state or province of residence (P < .001).
Conclusions. In the last decade, timely ART initiation and virologic suppression have greatly improved in North America concurrent with the development of better-tolerated and more potent regimens, but significant barriers to treatment uptake remain, both at the individual level and systemwide.
antiretroviral therapy; healthcare disparities; HIV; time factors; viral load
Because of limitations in the availability of data on primary care encounters, patient retention in human immunodeficiency virus (HIV) care is often estimated using laboratory measurement dates as proxies for clinical encounters, leading to possible outcome misclassification. This study included 83,041 HIV-infected adults from 14 clinical cohorts in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) who had ≥1 HIV primary care encounters during 2000–2010, contributing 468,816 person-years of follow-up. Encounter-based retention (REB) was defined as ≥2 encounters in a calendar year, ≥90 days apart. Laboratory-based retention (RLB) was defined similarly, using the dates of CD4-positive cell counts or HIV-1 RNA measurements. Percentage of agreement and the κ statistic were used to characterize agreement between RLB and REB. Logistic regression with generalized estimating equations and stabilized inverse-probability-of-selection weights was used to elucidate temporal trends and the discriminatory power of RLB as a predictor of REB, accounting for age, sex, race/ethnicity, primary HIV risk factor, and cohort site as potential confounders. Both REB and RLB increased from 2000 to 2010 (from 67% to 78% and from 65% to 77%, respectively), though REB was higher than RLB throughout (P < 0.01). RLB agreed well with REB (80%–86% agreement; κ = 0.55–0.62, P < 0.01) and had a strong, imperfect ability to discriminate between persons retained and not retained in care by REB (C statistic: C = 0.81, P < 0.05). As a proxy for REB, RLB had a sensitivity and specificity of 84% and 77%, respectively, with misclassification error of 18%.
clinical encounters; clinical retention; HIV; laboratory measurements; measurement error; misclassification; proxies
Human immunodeficiency virus (HIV) is associated with increased risk for chronic obstructive pulmonary disease (COPD); yet substantial under-recognition of COPD exists. We administered a patient-completed, physician-reviewed COPD screening tool in an outpatient HIV clinic to determine whether screening is feasible or possible. Patients attending nonacute, routine HIV care visits were provided a brief COPD screening tool, which included three questions focused on age, respiratory symptoms, and smoking history. Providers were given completed forms for review and ordered spirometry at their discretion. Forms and medical records were subsequently reviewed to determine completion and results of spirometry testing. Of the 1,510 patients screened during the study period, 968 (64%) forms were completed. After excluding 79 incomplete forms, 889 (92%) unique patient forms were included in this analysis. Among these, 204 (23%) met criteria for spirometry referral, among whom physicians ordered spirometry in 64 (31%). At 6 months following study completion, 19 (30%) of the patients referred for spirometry had the test completed, with 5 (26%) demonstrating airflow obstruction. Nearly one out of four HIV patients met indication for screening spirometry and roughly one out of four undergoing spirometry had COPD. Critical drop-offs in the screening and diagnostic process occurred at questionnaire completion and spirometry ordering. Interventions tailored to these critical steps could improve the yield from COPD screening and help to optimize the identification of COPD in high-risk HIV-infected populations. COPD screening in a clinic focused on longitudinal HIV care can effectively identify COPD among those completing the screening continuum.
Continuum; diagnosis; feasible; spirometry
Screening persons living with HIV for gonorrhea and chlamydia has been recommended since 2003. We compared annual gonorrhea/chlamydia testing to syphilis and lipid testing among 19,368 adults (41% men who have sex with men, 30% heterosexual men, 29% women) engaged in HIV care. In 2004, 22%, 62%, and 70% of all patients were tested for gonorrhea/chlamydia, syphilis, and lipid levels, respectively. Despite increasing steadily (OR per year 1.14 [1.13, 1.15]), gonorrhea/chlamydia testing in 2010 remained lower than syphilis and lipid testing (39%, 77%, 76%, respectively). Interventions to improve gonorrhea/chlamydia screening are needed. A more-targeted screening approach may be warranted.
Gonorrhea; Chlamydia; Screening; Guidelines; HIV secondary prevention
The deleterious effect of delaying antiretroviral therapy is stronger among patients older than 45 years at entry into care than among younger patients. These results stress the importance of improving timely linkage to human immunodeficiency virus medical care in this population.
Background. The goal of targeted antiretroviral therapy initiation is to minimize disease progression among patients with human immunodeficiency virus while minimizing the therapeutic burden on these patients. We examine whether the effect of delaying therapy initiation from 500 cells/mm3 to 350 or 200 cells/mm3 is modified by age at entry into care.
Methods. We used the parametric g-formula to compare 10-year mortality under 3 CD4 cell count thresholds for therapy initiation among 3532 patients who entered care at 1 of 8 sites in the United States between 1998 and 2013. Results are reported separately for patients 18 to 34, 35 to 44, and 45 to 65 years of age at study entry.
Results. In the observed data, 10-year mortality was 13% (165 deaths). Mortality increased from 11% under therapy initiation at 500 cells/mm3 to 12% at 350 cells/mm3 (risk difference [RD]: 0.87; 95% confidence interval [CI]: .56, 2.17) and to 14% at 200 cells/mm3 (RD: 2.71; 95% CI: 1.79, 5.38). The effect of delaying therapy became greater with age: RDs comparing the 350-cells/mm3 threshold with the 500-cells/mm3 threshold ranged from −0.03 (95% CI: −0.15, 1.76) for patients 18 to 34 years of age to 0.99 (95% CI: −.27, 1.98) for patients 35 to 44 and to 2.30 (95% CI: 1.29, 5.42) for patients 45 to 65.
Conclusions. Delaying therapy increased 10-year mortality in the full cohort. Subgroup analysis highlights that patients entering care at older ages may be more vulnerable to the consequences of delayed ART initiation than younger patients.
HIV; antiretroviral therapy; aging; epidemiologic methods
Retention in care is important for all HIV-infected persons and is strongly associated with initiation of antiretroviral therapy and viral suppression. However, it is unclear how retention in care and age interact to effect viral suppression. We evaluated whether the association between retention and viral suppression differed by age at entry into care.
Cross-sectional analysis (2006-2010) involving 17,044 HIV-infected adults in 14 clinical cohorts across the U.S. and Canada. Patients contributed one year of data during their first full calendar year of clinical observation. Poisson regression examined associations between retention measures [U.S. National HIV/AIDS Strategy (NHAS), U.S. Department of Health and Human Services (DHHS), 6-month gap, and 3-month visit constancy] and viral suppression (HIV RNA ≤200 copies/mL) by age group: 18-29, 30-39, 40–49, 50–59, and ≥60 years old.
Overall, 89% of patients were retained in care using the NHAS measure, 74% with the DHHS indicator, 85% did not have a 6-month gap, and 62% had visits in 3-4 quarters of the year; 54% achieved viral suppression. For each retention measure, the association with viral suppression was significant for only the younger age groups (18-29 and 30-39 years): 18-29 [adjusted prevalence ratio (APR)=1.33, 95% confidence interval (CI)=1.03-1.70]; 30-39 (APR=1.23, CI=1.01-1.49); 40-49 (APR=1.06, CI=0.90-1.22); 50-59 (APR=0.92, CI=0.75-1.13); ≥60 years (APR=0.99, CI=0.63-1.56) using the NHAS measure as a representative example.
These results have important implications for improving viral control among younger adults, emphasizing the crucial role retention in care plays in supporting viral suppression in this population.
Retention in Care; Viral Suppression; Age; Engagement; HIV
Medication adherence is essential in HIV care, yet provider communication about adherence is often suboptimal. We designed this study to improve patient-provider communication about HIV medication adherence.
We randomized 26 providers at three HIV care sites to receive or not receive a one-hour communication skills training based on motivational interviewing principles applied to medication adherence. Prior to routine office visits, non-adherent patients of providers who received the training were coached to discuss adherence with their providers. Patients of providers who did not receive the training providers were not coached. We audio-recorded and coded patient-provider interactions using the Roter Interaction Analysis System (RIAS).
There was more dialogue about therapeutic regimen in visits with intervention patients and providers (167 vs 128, respectively, p=.004), with the majority of statements coming from providers. These visits also included more brainstorming solutions to nonadherence (41% vs. 22%, p=0.026). Intervention compared with control visit providers engaged in more positive talk (44 vs. 38 statements, p=0.039), emotional talk (26 vs. 18 statements, p<0.001), and probing of patient opinion (3 vs. 2 statements, p=0.009).
A brief provider training combined with patient coaching sessions, improved provider communication behaviors and increased dialogue regarding medication adherence.
Persons living with HIV (PLWH) and substance use/misuse experience significant barriers to engagement in HIV care at every step of the HIV care continuum including: (1) HIV testing and diagnosis (2) linkage to clinical care (3) retention in care pre-antiretroviral therapy (ART) (4) ART initiation and adherence (5) viral suppression. We qualitatively explored the facilitators of and barriers to participation in the HIV care continuum among PLWH with substance use/misuse.
We performed semi-structured in-depth interviews with 34 PLWH in care with recent substance use. The transcripts were analyzed in an iterative process using an editing style analysis. Interviews were conducted until thematic saturation was achieved.
Participants attributed an escalation in drug use at the time of diagnosis to denial of their disease and the belief that their death was inevitable and cited this as a barrier to treatment entry. In contrast, participants reported that experiencing adverse physical effects of uncontrolled HIV infection motivated them to enroll in care. Reported barriers to retention and adherence to care included forgetting medications and appointments because of drug use, prioritizing drug use over HIV treatment and side effects associated with medications. Participants described that progression of illness, development of a medication taking ritual and a positive provider-patient relationship all facilitated engagement and reengagement in care.
PLWH with substance use engaged in care describe barriers to and facilitators of optimal engagement related to and distinct from substance use. Greater understanding of the biologic, psychological and social factors that promote and impair engagement in care can inform interventions and reduce the increased morbidity and mortality experienced by PLWH with substance use.
HIV; Substance use; ART; Adherence; HIV care continuum
We examined HIV transmission potential of patients in care by analyzing the amount of person-time spent above a viral load threshold that increases risk for transmission.
Observational cohort and supplemental data.
The cohort included HIV patients who received care at six HIV clinics in the United States, from 1 April 2009 to 31 March 2013, and had two or more viral load tests during this interval. Person-time (in days) above a viral load of 1500 copies/ml out of the total observation time was determined by inspecting consecutive pairs of viral load results and the time intervals between those pairs. The person-time rate ratios comparing demographic and clinical subgroups were estimated with Poisson regression.
The cohort included 14 532 patients observed for a median of 1073 days with a median of nine viral load records. Ninety percent of the patients had been prescribed antiretroviral therapy. On average, viral load exceeded 1500 copies/ml during 23% of the patients’ observation time (average of 84 days per year, per patient). Percentage of person-time above the threshold was higher among patients who had more than a fourth of their viral load pairs exceeding a 6-month interval (34% of observation time), patients not on antiretroviral therapy (58% of time), new/re-engaging patients (34% of time), patients 16–39 years of age (32% of time), and patients of black race (26% of time).
HIV patients in care spent an average of nearly a quarter of their time with viral loads above 1500 copies/ml, higher among some subgroups, placing them at risk for potentially transmitting HIV to others.
cohort study; HIV; person-time; transmission; viral load
Cancer is increasingly common among HIV patients given improved survival.
To examine calendar trends in cumulative cancer incidence and hazard rate by HIV status.
North American AIDS Cohort Collaboration on Research and Design during 1996–2009
86,620 HIV-infected and 196,987 uninfected adults
We estimated cancer-type-specific cumulative incidence by age 75 years by HIV status and calendar era, and examined calendar trends in cumulative incidence and hazard rates.
Cumulative incidences (%) of cancer by age 75 (HIV+/HIV−) were: Kaposi sarcoma (KS), 4.4/0.01; non-Hodgkin’s lymphoma (NHL), 4.5/0.7; lung, 3.4/2.8; anal, 1.5/0.1; colorectal, 1.0/1.5; liver, 1.1/0.4; Hodgkin lymphoma (HL), 0.9/0.1; melanoma, 0.5/0.6; and oral cavity/pharyngeal, 0.8/0.8. Among HIV-infected subjects, we observed decreasing calendar trends in cumulative incidence and hazard rate for KS and NHL. For anal, colorectal and liver cancers, increasing cumulative incidence, but not hazard rate trends, were due to the decreasing mortality rate trend (−9% per year), allowing greater opportunity to be diagnosed with these cancer types. Despite decreasing hazard rate trends for lung, HL, and melanoma, we did not observe cumulative incidence trends due to the compensating effect of the declining mortality rate on cumulative incidence.
Secular trends in screening, smoking, and viral co-infections were not evaluated.
Our analytic approach helped disentangle the effects of improved survival and changing cancer-specific hazard rates on cumulative incidence trends among HIV patients. Cumulative cancer incidence by age 75, approximating lifetime risk in HIV patients, may have clinical utility in this population. The high cumulative incidences by age 75 for KS, NHL, and lung cancer supports early and sustained ART and smoking cessation.
Primary Funding Source
National Institutes of Health
Enhanced HIV prevention interventions, such as pre-exposure prophylaxis for high-risk individuals, require substantial investments. We sought to estimate the medical cost saved by averting one HIV infection in the United States.
We estimated lifetime medical costs in persons with and without HIV to determine the cost saved by preventing one HIV infection. We used a computer simulation model of HIV disease and treatment (CEPAC) to project CD4 cell count, antiretroviral treatment status, and mortality after HIV infection. Annual medical cost estimates for HIV-infected persons, adjusted for age, sex, race/ethnicity, and transmission risk group, were from the HIV Research Network (range $1,854–$4,545/month) and for HIV-uninfected persons were from the Medical Expenditure Panel Survey (range $73–$628/month). Results are reported as lifetime medical costs from the US health system perspective discounted at 3% (2012 US dollars).
The estimated discounted lifetime cost for persons who become HIV infected at age 35 is $326,500 (60% for antiretroviral medications, 15% for other medications, 25% non-drug costs). For individuals who remain uninfected but at high risk for infection, the discounted lifetime cost estimate is $96,700. The medical cost saved by avoiding one HIV infection is $229,800. The cost saved would reach $338,400 if all HIV-infected individuals presented early and remained in care. Cost savings are higher taking into account secondary infections avoided and lower if HIV infections are temporarily delayed rather than permanently avoided.
The economic value of HIV prevention in the US is substantial given the high cost of HIV disease treatment.
HIV; AIDS; health care cost; prevention; computer modeling
Among antiretroviral therapy initiators in the Centers for AIDS Research Network of Integrated Clinical Systems, 10-year all-cause mortality was significantly higher among black patients than among white men. White women and Hispanic patients had lower 10-year mortality than white men.
Background. Ensuring equal access to antiretroviral therapy (henceforth therapy) should alleviate disparities in health outcomes among persons infected with human immunodeficiency virus (HIV). However, evidence supporting the persistence of disparities in survival following therapy initiation is mixed.
Methods. Patients initiating therapy in eight academic medical centers in the Centers for AIDS Research Network of Integrated Clinical Systems between 1 January 1998 and 30 December 2011. Patients (n = 10 017) were followed from therapy initiation until death from any cause, administrative censoring at 10 years after therapy initiation or the end of follow-up on 31 December 2011. The 10-year risk of all-cause mortality was calculated from standardized Kaplan–Meier survival curves.
Results. Patients were followed for a median of 4.7 years (interquartile range: 2.2, 8.2). During 51 121 person-years of follow-up, 1224 of the 10 017 patients died. The overall 10-year mortality risk was 20.2% (95% confidence interval [CI], 19.2%, 21.3%). Black men and women experienced standardized 10-year all-cause mortality risks that were 7.2% (95% CI, 4.3%, 10.1%) and 7.9% (95% CI, 3.9%, 12.0%) larger (absolute difference) than white men. White women, Hispanic men, and Hispanic women all had lower 10-year mortality than white men.
Conclusions. These data serve as a call to action to identify modifiable mechanisms leading to these observed mortality disparities among HIV-infected black patients. Effective interventions are needed to ensure that the goal of the National HIV/AIDS Strategy to overcome health disparities becomes a reality.
HIV; health status disparities; cohort studies; survival analysis; antiretroviral therapy
Background. Elite controllers spontaneously suppress human immunodeficiency virus (HIV) viremia but also demonstrate chronic inflammation that may increase risk of comorbid conditions. We compared hospitalization rates and causes among elite controllers to those of immunologically intact persons with medically controlled HIV.
Methods. For adults in care at 11 sites from 2005 to 2011, person-years with CD4 T-cell counts ≥350 cells/mm2 were categorized as medical control, elite control, low viremia, or high viremia. All-cause and diagnostic category-specific hospitalization rates were compared between groups using negative binomial regression.
Results. We identified 149 elite controllers (0.4%) among 34 354 persons in care. Unadjusted hospitalization rates among the medical control, elite control, low-viremia, and high-viremia groups were 10.5, 23.3, 12.6, and 16.9 per 100 person-years, respectively. After adjustment for demographic and clinical factors, elite control was associated with higher rates of all-cause (adjusted incidence rate ratio, 1.77 [95% confidence interval, 1.21–2.60]), cardiovascular (3.19 [1.50–6.79]) and psychiatric (3.98 [1.54–10.28]) hospitalization than was medical control. Non–AIDS-defining infections were the most common reason for admission overall (24.1% of hospitalizations) but were rare among elite controllers (2.7%), in whom cardiovascular hospitalizations were most common (31.1%).
Conclusions. Elite controllers are hospitalized more frequently than persons with medically controlled HIV and cardiovascular hospitalizations are an important contributor.
HIV; elite control; antiretroviral therapy; hospitalization; inflammation; psychiatric disease
In the United States, 21 years is a critical age of legal and social transition, with changes in social programs such as public insurance coverage. Human immunodeficiency virus (HIV)–infected youth have lower adherence to care and medications and may be at risk of loss to follow-up (LTFU) at this benchmark age. We evaluated LTFU after the 22nd birthday for HIV-infected youth engaged in care. LTFU was defined as having no primary HIV visits in the year after the 22nd birthday.
All HIV-infected 21-year-olds engaged in care (2002–2011) at the HIV Research Network clinics were included. We assessed the proportion LTFU and used multivariable logistic regression to evaluate demographic and clinical characteristics associated with LTFU after the 22nd birthday. We compared LTFU at other age transitions during the adolescent/young adult years.
Six hundred forty-seven 21-year-olds were engaged in care; 91 (19.8%) were LTFU in the year after turning 22 years. Receiving care at an adult versus pediatric HIV clinic (adjusted odds ratio [AOR], 2.91; 95% confidence interval [CI],1.42–5.93), having fewer than four primary HIV visits/year (AOR, 2.72; 95% CI, 1.67–4.42), and antiretroviral therapy prescription (AOR, .50; 95% CI, .41–.60) were independently associated with LTFU. LTFU was prevalent at each age transition, with factors associated with LTFU similar to that identified for 21-year-olds.
Although 19.8% of 21-year-olds at the HIV Research Network sites were LTFU after their 22nd birthday, significant proportions of youth of all ages were LTFU. Fewer than four primary HIV care visits/year, receiving care at adult clinics and not prescribed antiretroviral therapy, were associated with LTFU and may inform targeted interventions to reduce LTFU for these vulnerable patients.
Adolescents; Youth; Young adults; Loss to follow-up; Attrition; Care; HIV Research Network
Hepatitis B (HBV) and hepatitis C (HCV) co-infection are increasingly important sources of morbidity among HIV-infected persons. We determined associations between hepatitis co-infection and healthcare utilization among HIV-infected adults at four U.S. sites during 2006–2011. Outpatient HIV visits did not differ by hepatitis serostatus and decreased over time. Mental health visits were more common among HIV/HCV co-infected persons than among HIV mono-infected (IRR 1.27 [1.08–1.50]). Hospitalization rates were higher among all hepatitis-infected groups than among HIV mono-infected (HIV/HBV IRR 1.23 [1.05–1.44], HIV/HCV 1.22 [1.10–1.36], HIV/HBV/HCV 1.31 [1.02–1.68]). These findings may inform the design of clinical services and allocation of resources.
HIV; hepatitis B virus; hepatitis C virus; mental health; healthcare utilization; hospitalization
The burden of HIV disease has shifted from traditional AIDS-defining illnesses to serious non-AIDS-defining comorbid conditions. Research aimed at improving HIV-related comorbid disease outcomes requires well-defined, verified clinical endpoints. We developed methods to ascertain and verify end-stage renal disease (ESRD) and end-stage liver disease (ESLD) and validated screening algorithms within the largest HIV cohort collaboration in North America (NA-ACCORD). Individuals who screened positive among all participants in twelve cohorts enrolled between January 1996 and December 2009 underwent medical record review to verify incident ESRD or ESLD using standardized protocols. We randomly sampled 6% of contributing cohorts to determine the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ESLD and ESRD screening algorithms in a validation subcohort. Among 43,433 patients screened for ESRD, 822 screened positive of which 620 met clinical criteria for ESRD. The algorithm had 100% sensitivity, 99% specificity, 82% PPV, and 100% NPV for ESRD. Among 41,463 patients screened for ESLD, 2,024 screened positive of which 645 met diagnostic criteria for ESLD. The algorithm had 100% sensitivity, 95% specificity, 27% PPV, and 100% NPV for ESLD. Our methods proved robust for ascertainment of ESRD and ESLD in persons infected with HIV.
Latinos living with HIV in the Americas share a common ethnic and cultural heritage. In North America, Latinos have a relatively high rate of new HIV infections but lower rates of engagement at all stages of the care continuum, whereas in Latin America antiretroviral therapy (ART) services continue to expand to meet treatment needs. In this analysis, we compare HIV treatment outcomes between Latinos receiving ART in North America versus Latin America.
HIV-positive adults initiating ART at Caribbean, Central and South America Network for HIV (CCASAnet) sites were compared to Latino patients (based on country of origin or ethnic identity) starting treatment at North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) sites in the United States and Canada between 2000 and 2011. Cox proportional hazards models compared mortality, treatment interruption, antiretroviral regimen change, virologic failure and loss to follow-up between cohorts.
The study included 8400 CCASAnet and 2786 NA-ACCORD patients initiating ART. CCASAnet patients were younger (median 35 vs. 37 years), more likely to be female (27% vs. 20%) and had lower nadir CD4 count (median 148 vs. 195 cells/µL, p<0.001 for all). In multivariable analyses, CCASAnet patients had a higher risk of mortality after ART initiation (adjusted hazard ratio (AHR) 1.61; 95% confidence interval (CI): 1.32 to 1.96), particularly during the first year, but a lower hazard of treatment interruption (AHR: 0.46; 95% CI: 0.42 to 0.50), change to second-line ART (AHR: 0.56; 95% CI: 0.51 to 0.62) and virologic failure (AHR: 0.52; 95% CI: 0.48 to 0.57).
HIV-positive Latinos initiating ART in Latin America have greater continuity of treatment but are at higher risk of death than Latinos in North America. Factors underlying these differences, such as HIV testing, linkage and access to care, warrant further investigation.
HIV; antiretroviral therapy; highly active; mortality; Latin America; North America; cohort studies
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.
Observational study from 2008–2010, using clinical cohort data in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).
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.
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.
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.
Background: Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally.
Methods: We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitor-based regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level <500/µl in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years.
Results: After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/µl was 529/µl [95% confidence interval (CI): 517–541] in North America, 494/µl (95% CI: 429–559) in West Africa, 515/µl (95% CI: 508–522) in Southern Africa, 503/µl (95% CI: 478–528) in Asia and 437/µl (95% CI: 425–449) in East Africa.
Conclusions: CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level.
HIV; Africa; antiretroviral therapy; CD4 + T cell counts; immunological activation
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.
We evaluated retention by US region in a retrospective observational study.
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.
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).
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.
We examined hepatitis C virus screening among HIV-infected patients enrolled in care at 7 US sites between 2000 and 2011. While there is a trend toward more frequent screening over time, it remains variable among sites and high-risk MSM are screened infrequently.
Background. Human immunodeficiency virus (HIV)-infected, hepatitis C virus (HCV)-uninfected patients are at risk for incident HCV infection, but little is known about screening practices for incident HCV among HIV-infected individuals in HIV primary care clinics.
Methods. We used data from the Center for AIDS Research Network of Integrated Clinical Systems (CNICS) to investigate historical trends in screening for incident HCV infection among HIV-infected patients who were HCV-uninfected at enrollment in care. We used descriptive measures and Poisson regression to identify factors associated with screening for HCV infection (using HCV antibody or RNA), performed temporal analyses to assess changes in screening over time, and investigated the frequency with which elevated alanine aminotransferase (ALT) levels were followed by diagnostic HCV testing.
Results. Among 17 090 patients registered at CNICS sites between 2000 and 2011, 14 534 (85%) received HCV antibody screening within 3 months of enrolling in care, and 9077 met all of the inclusion criteria. Only 55.6% ever received additional HCV screening. HCV screening increased over time, but not uniformly at all sites. Only 26.7% of first-time ALT elevations to >100 IU/L were followed up within 12 months by HCV antibody or RNA testing.
Conclusions. Although most HIV-infected patients were screened for prevalent HCV infection at enrollment in care, only half who were HCV uninfected were screened again. Screening varied between sites, even when controlling for demographics and risk behaviors. Patients with new ALT elevations to >100 IU/L were seldom assessed for incident HCV infection. Guidelines are needed to help HIV providers know whom to screen, how frequently to screen, and which screening test to use.
HIV; hepatitis C; screening; men who have sex with men; incidence