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
Linkage and retention in care soon after HIV diagnosis improves clinical outcomes. Conversely, missed visits after diagnosis are associated with increased mortality in the public care setting. We analyzed mortality among newly diagnosed HIV patients ≥18 years old in a large private care setting between 01/01/1997 and 12/31/2009, comparing patients who missed visits in their first year following diagnosis (index period) with those who did not. Patients who died during the index period were excluded. Hazard ratios (HR) for association of missed visits and mortality were obtained by Cox proportional hazards regression, adjusting for patient demographics, CD4+ counts, and AIDS-defining conditions (CDC, 1993) at diagnosis. We also evaluated risk factors of missed visits by multivariable logistic regression. 2811 patients were included, of whom 65% had ≥1 missed visit, and 226 patients died during follow-up. Patients with ≥1 missed visit had a 71% increased mortality risk (HR=1.71, p=0.001) with 12% increased rate per missed visit (HR=1.12, p<0.001). Factors associated with missed visits were younger age (OR=1.69 compared to 60+ years), Black and Latino race/ethnicity (OR=1.54, 1.48 respectively, compared to Caucasians), injection drug use (OR=2.50 compared to men who have sex with men), and lower CD4+ (OR=1.43 for CD4+ 100–199 cells/μL, OR=1.39 for 50–99 cells/μL, and OR=1.63 for CD4+ <50 cells/μL, compared with CD4+ >500 cells/μL). In an insured patient population, missed visits in the first year of HIV care are common and associated with increased mortality. Early retention in HIV care is critical to improving outcomes.
After HIV diagnosis, timely entry into HIV medical care and retention in that care are essential to the provision of effective antiretroviral therapy (ART). ART adherence is among the key determinants of successful HIV treatment outcome and is essential to minimize the emergence of drug resistance. The International Association of Physicians in AIDS Care convened a panel to develop evidence-based recommendations to optimize entry into and retention in care and ART adherence for people with HIV.
A systematic literature search was conducted to produce an evidence base restricted to randomized, controlled trials and observational studies with comparators that had at least 1 measured biological or behavioral end point. A total of 325 studies met the criteria. Two reviewers independently extracted and coded data from each study using a standardized data extraction form. Panel members drafted recommendations based on the body of evidence for each method or intervention and then graded the overall quality of the body of evidence and the strength for each recommendation.
Recommendations are provided for monitoring of entry into and retention in care, interventions to improve entry and retention, and monitoring of and interventions to improve ART adherence. Recommendations cover ART strategies, adherence tools, education and counseling, and health system and service delivery interventions. In addition, they cover specific issues pertaining to pregnant women, incarcerated individuals, homeless and marginally housed individuals, and children and adolescents, as well as substance use and mental health disorders. Recommendations for future research in all areas are also provided.
In HIV-1 infection, plasma viral load (VL) has dual implications for
pathogenesis and public health. Based on well-known patterns of HIV-1 evolution
and immune escape, we hypothesized that VL is an evolving quantitative trait
that depends heavily on duration of infection (DOI), demographic features, human
leukocyte antigen (HLA) genotypes and viral characteristics. Prospective data
from 421 African seroconverters with at least four eligible visits did show
relatively steady VL beyond 3 months of untreated infection, but host and viral
factors independently associated with cross-sectional and longitudinal VL often
varied by analytical approaches and sliding time windows. Specifically, the
effects of age, HLA-B*53 and infecting HIV-1 subtypes (A1, C and others)
on VL were either sporadic or highly sensitive to time windows. These
observations were strengthened by the addition of 111 seroconverters with
2–3 eligible VL results, suggesting that DOI should be a critical
parameter in epidemiological and clinical studies.
Africa; HIV-1; subtype; HLA; statistical models; viral load
Measuring retention in HIV primary care is complex as care includes multiple visits scheduled at varying intervals over time. We evaluated six commonly used retention measures in predicting viral load (VL) suppression and the correlation among measures.
Clinic-wide patient-level data from six academic HIV clinics were used for 12-months preceding implementation of the CDC/HRSA Retention in Care intervention. Six retention measures were calculated for each patient based upon scheduled primary HIV provider visits: count and dichotomous missed visits, visit adherence, 6-month gap, 4-month visit constancy, and the HRSA HAB retention measure. Spearman correlation coefficients and separate unadjusted logistic regression models compared retention measures to one another and with 12-month VL suppression, respectively. The discriminatory capacity of each measure was assessed with the c-statistic.
Among 10,053 patients, 8,235 (82%) had 12-month VL measures, with 6,304 (77%) achieving suppression (VL<400 c/mL). All six retention measures were significantly associated (P<0.0001) with VL suppression (OR;95%CI, c-statistic): missed visit count (0.73;0.71–0.75,0.67), missed visit dichotomous (3.2;2.8–3.6,0.62), visit adherence (3.9;3.5–4.3,0.69), gap (3.0;2.6–3.3,0.61), visit constancy (2.8;2.5–3.0,0.63), HRSA HAB (3.8;3.3–4.4,0.59). Measures incorporating “no show” visits were highly correlated (Spearman coefficient=0.83–0.85), as were measures based solely upon kept visits (Spearman coefficient=0.72–0.77). Correlation coefficients were lower across these two groups of measures (Range=0.16–0.57).
Six retention measures displayed a wide range of correlation with one another, yet each measure had significant association and modest discrimination for VL suppression. These data suggest there is no clear gold standard, and that selection of a retention measure may be tailored to context.
Retention in care; Adherence; Engagement in care; Viral load
HIV-infected patients in the current treatment era can achieve normal life expectancies, but experience a high degree of medical and psychiatric comorbidity. Impaired physical function and pain, often in the context of mood disorders and substance abuse, are common in HIV-infected patients. The objective of this study was to investigate the relationship of pain, a modifiable condition, to functional impairment in HIV-infected patients, independent of mood disorders and substance abuse.
Participants in a prospective cohort of HIV-infected patients at the University of Alabama at Birmingham were included. Patient-reported outcome measures were used to cross-sectionally assess pain and physical function (EuroQOL), mood disorders (PHQ), and substance abuse (ASSIST). Univariate and multivariable models were built with pain as the principal independent variable of interest and 3 domains of physical function (mobility, self-care, and usual activities) as outcomes. Covariates included mood, substance abuse, age, race, sex, insurance status, HIV transmission risk factor, and CD4+ T-cell count.
Among 1903 participants, 693 (37%) reported pain; 509 (27%) had a mood disorder; and 157 (8.4%) reported current substance abuse. In multivariable models, pain was independently associated with increased odds of impairment in all three domains of physical function investigated – mobility (aOR 10.5, 95% CI 7.6–14.6), self-care (aOR 4.1, 95% CI 2.2–7.4), and usual activities (aOR 5.4, 95% CI 4.0–7.4).
Pain was associated with substantially increased odds of impairment in physical function. Pain should be an important consideration in HIV primary care. Interventions to address pain and impaired physical function should be investigated.
HIV; pain; physical function; mental health; substance abuse
The goal of this study was to compare the effectiveness of fish oil, fenofibrate, gemfibrozil, and atorvastatin on reducing triglyceride (TG) levels among a large cohort of HIV-infected patients in clinical care.
Retrospective observational cohort study
The primary endpoint was absolute change in TG levels measured using the last TG value pre-treatment and the first TG value post-treatment. A pre-post quasi-experimental design was used to estimate the change in TG due to initiating fish oil. Linear regression models examined the comparative effectiveness of treatment with fish oil versus gemfibrozil, fenofibrate, or atorvastatin for TG reduction. Models were adjusted for baseline differences in age, sex, race, CD4+ cell count, diabetes, body mass index, protease inhibitor use, and time between TG measures.
A total of 493 patients (mean age 46 years; 95% male) were included (46 receiving gemfibrozil, 80 fenofibrate, 291 atorvastatin, 76 fish oil) with a mean baseline TG of 347 mg/dL. New use of fish oil decreased TG (ΔTG -45 mg/dL 95% Confidence interval (CI):-80 to -11) in the pre-post study. Compared with fish oil (reference), fibrates were more effective (ΔTG -66; 95% CI:-120 to -12) in reducing TG levels, whereas atorvastatin was not (ΔTG -39; 95% CI:-86 to 9).
In HIV-infected patients in routine clinical care, fish oil is less effective than fibrates (but not atorvastatin) at lowering triglyceride values. Fish oil may still represent an attractive alternative for patients with moderately elevated triglycerides particularly among patients who may not want or tolerate fibrates.
fish oil; triglycerides; dyslipidemia; fibrates; HIV
HIV-infected individuals frequently experience traumatic and stressful events such as sexual and physical assault; housing instability; and major financial, employment, and legal difficulties. Past trauma history predicts poorer medication adherence and health outcomes, yet little research has examined the influence of incident stressful experiences on antiretroviral medication adherence and treatment outcomes.
We prospectively measured incident stressful and traumatic events, medication adherence, and viral load over 27 months in an 8-site, 5-state study. Using multivariable logistic and generalized estimating equation modeling, we assessed the impact of incident stressful events on 27-month changes in self-reported medication adherence and virologic failure (viral load ≥400 c/mL).
Of 474 participants on antiretroviral therapy at baseline, 289 were interviewed and still on treatment at 27 months. Participants experiencing the median number of incident stressful events (n=9) had over twice the predicted odds (OR=2.32) of antiretroviral medication non-adherence at follow-up compared to those with no events. Stressful events also predicted increased odds of virologic failure during follow-up (OR=1.09 per event).
Incident stressful events are exceedingly common in the lives of HIV-infected individuals and negatively impact antiretroviral medication adherence and treatment outcomes. Interventions to address stress and trauma are needed to improve HIV outcomes.
HIV; AIDS; Stress; Adherence; Virologic failure; Disparities
The AIDS Drug Assistance Program (ADAP) provides antiretroviral medications to low-income individuals with HIV infection.
A prospective cohort study of ADAP utilization, measured using medication possession ratio (MPR), was conducted during the 2008 calendar year at the University of Alabama at Birmingham 1917 HIV Clinic. Multivariable ordinal logistic regression evaluated factors associated with ADAP utilization.
Among 245 patients, MPR quartiles (Q) were the following: Q1<69 percent, Q2 = 69–83 percent, Q3 = 84–93 percent, Q4>93 percent. In ordinal logistic regression, younger age (OR = 0.59 per 10 years; 95 percent CI = 0.44–0.79), nonwhite males (2.18; 1.18–4.04), lower CD4 count (2.79 for <200 cells/mm3; 1.44–5.43), and a history of alcohol abuse (2.11; 1.02–4.37) were associated with poor ADAP utilization.
One quarter of ADAP enrollees had MPR below 69 percent, a level well below that associated with optimal HIV treatment outcomes, indicating a need for programmatic interventions to improve ADAP utilization.
HIV; adherence; public health
Kaposi sarcoma and lymphoma rates were highest immediately after antiretroviral therapy (ART) initiation, particularly among patients with low CD4 cell counts, whereas other cancers increased with time on ART. Calendar year of ART initiation was not associated with subsequent cancer incidence.
Cancer is an important cause of morbidity and mortality in individuals infected with human immunodeficiency virus (HIV), but patterns of cancer incidence after combination antiretroviral therapy (ART) initiation remain poorly characterized.
We evaluated the incidence and timing of cancer diagnoses among patients initiating ART between 1996 and 2011 in a collaboration of 8 US clinical HIV cohorts. Poisson regression was used to estimate incidence rates. Cox regression was used to identify demographic and clinical characteristics associated with cancer incidence after ART initiation.
At initiation of first combination ART among 11 485 patients, median year was 2004 (interquartile range [IQR], 2000–2007) and median CD4 count was 202 cells/mm3 (IQR, 61–338). Incidence rates for Kaposi sarcoma (KS) and lymphomas were highest in the first 6 months after ART initiation (P < .001) and plateaued thereafter, while incidence rates for all other cancers combined increased from 416 to 615 cases per 100 000 person-years from 1 to 10 years after ART initiation (average 7% increase per year; 95% confidence interval, 2%–13%). Lower CD4 count at ART initiation was associated with greater risk of KS, lymphoma, and human papillomavirus–related cancer. Calendar year of ART initiation was not associated with cancer incidence.
KS and lymphoma rates were highest immediately following ART initiation, particularly among patients with low CD4 cell counts, whereas other cancers increased with time on ART, likely reflecting increased cancer risk with aging. Our results underscore recommendations for earlier HIV diagnosis followed by prompt ART initiation along with ongoing aggressive cancer screening and prevention efforts throughout the course of HIV care.
HIV-associated malignancies; AIDS-defining cancer; non-AIDS-defining cancer; combination antiretroviral therapy
Many HIV-infected patients in the current treatment era have substantial symptom burden, but few HIV palliative care clinics have been described. Our objective was to describe the University of Alabama at Birmingham (UAB) HIV palliative care clinic (HPCC) and compare it to the overall HIV clinic.
We conducted a chart review of patients referred to the HPCC between April 2008 and June 2011. We evaluated the reason for referral and other issues addressed during palliative care visits. Patient Reported Outcome (PRO) data was used to assess depression (PHQ-9), anxiety (PHQ-A), and substance abuse (ASSIST).
Among 124 patients, mean age was 44 (range 27–64), and median CD4 count was 352 cells/mm3 (IQR 209–639). Depression (43, 35%), anxiety (40, 32%), and current 8 (7%) or prior 68 (56%) substance abuse occurred at higher rates than in the overall HIV clinic (p<0.05). Pain was the most common reason for referral (118, 95%); most was chronic (113, 90%) and included back pain (26, 21%) and neuropathic pain (15, 12%). Other problems commonly addressed by the palliative team included nonpain symptoms such as depression (39, 48%) and anxiety (17, 21%), insomnia (25, 30%), and constipation (26, 32%).
This is the first description of a palliative care clinic embedded within an HIV primary care clinic in a developed country that sees patients at all stages of illness. Chronic pain and nonpain symptom management in patients with psychiatric and substance abuse comorbidities are important components of ambulatory palliative care for HIV-infected patients.
Missing outcome data due to loss to follow-up occurs frequently in clinical cohort studies of HIV-infected patients. Censoring patients when they become lost can produce inaccurate results if the risk of the outcome among the censored patients differs from the risk of the outcome among patients remaining under observation. We examine whether patients who are considered lost to follow up are at increased risk of mortality compared to those who remain under observation. Patients from the US Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) who newly initiated combination antiretroviral therapy between January 1, 1998 and December 31, 2009 and survived for at least one year were included in the study. Mortality information was available for all participants regardless of continued observation in the CNICS. We compare mortality between patients retained in the cohort and those lost-to-clinic, as commonly defined by a 12-month gap in care. Patients who were considered lost-to-clinic had modestly elevated mortality compared to patients who remained under observation after 5 years (risk ratio (RR): 1.2; 95% CI: 0.9, 1.5). Results were similar after redefining loss-to-clinic as 6 months (RR: 1.0; 95% CI: 0.8, 1.3) or 18 months (RR: 1.2; 95% CI: 0.8, 1.6) without a documented clinic visit. The small increase in mortality associated with becoming lost to clinic suggests that these patients were not lost to care, rather they likely transitioned to care at a facility outside the study. The modestly higher mortality among patients who were lost-to-clinic implies that when we necessarily censor these patients in studies of time-varying exposures, we are likely to incur at most a modest selection bias.
Contemporary data on patterns of antiretroviral therapy (ART) use in the U.S. are needed to inform efforts to improve the HIV care cascade.
We conducted a cross-sectional study of patients in the Centers for AIDS Research Network of Integrated Clinical Systems cohort who were in HIV care in 2010 to assess ART use and outcomes, stratified by nadir CD4 count (≤350, 351-500, or >500 cells/mm3), demographics, psychiatric diagnoses, substance use, and engagement in continuous care (≥2 visits ≥3 months apart in 2010).
Of 8633 patients at 7 sites who had ≥1 medical visit and ≥1 viral load (VL) in 2010, 94% had ever initiated ART, 89% were on ART, and 70% had an undetectable VL at the end of 2010. Fifty percent of ART-naïve patients had nadir CD4 counts >500 cells/mm3, but this group composed just 3% of the total population. Among patients who were ART-naïve at the time of cohort entry (N=4637), both ART initiation and viral suppression were strongly associated with nadir CD4 count. Comparing 2009 and 2010, the percentages of patients with viral suppression among those with nadir CD4 counts 351-500 and >500 cells/mm3 were 44% vs. 57% and 25% vs. 33%, respectively. Engagement in care was the only factor consistently associated with ART use and viral suppression across nadir CD4 count strata.
Our findings suggest that ART use and viral suppression among persons in HIV care may be more common than estimated in some prior studies and increased from 2009 to 2010.
Antiretroviral Therapy, Highly Active; HIV Infections/drug therapy; HIV Infections/prevention & control; Patient Acceptance of Health Care/statistics & numerical data; United States
Following HIV diagnosis and linkage to care, achieving and sustaining viral load (VL) suppression has implications for patient outcomes and secondary HIV prevention. We evaluated factors associated with expeditious VL suppression and cumulative VL burden among patients establishing outpatient HIV care.
Patients initiating HIV medical care from January 2007-October 2010 at the University of Alabama at Birmingham and University of Washington were included. Multivariable Cox proportional hazards and linear regression models were used to evaluate factors associated with time to VL suppression (<50 copies/mL) and cumulative VL burden, respectively. Viremia copy-years (VCY), a novel area under the longitudinal VL curve measure, was used to estimate 2-year cumulative VL burden from clinic enrollment.
Among 676 patients, 63% achieved VL<50 copies/mL in a median 308 days. In multivariable analysis, patients with more time-updated “no show” visits experienced delayed VL suppression (HR=0.83 per “no show” visit, 95%CI=0.76,0.91). In multivariable linear regression, visit non-adherence was independently associated with greater cumulative VL burden (log10VCY) during the first two years in care (Beta coefficient=0.11 per 10% visit non-adherence, 95%CI=0.04-0.17). Across increasing visit adherence categories, lower cumulative VL burden was observed (mean ± standard deviation log10 copy × years/mL); 0-79% adherence: 4.6 ± 0.8; 80-99% adherence: 4.3 ± 0.7; and 100% adherence: 4.1 ± 0.8 log10 copy × years/mL, respectively (P<0.01).
Higher rates of early retention in HIV care are associated with achieving VL suppression and lower cumulative VL burden. These findings are germane for a test and treat approach to HIV prevention.
HIV; Viral load; Retention in care; Adherence; Engagement in care
The generalizability of antiretroviral therapy (ART) clinical trial efficacy findings to routine care settings is not well studied. We compared the relative effectiveness of initial ART regimens estimated in AIDS Clinical Trial Group (ACTG) randomized controlled trials with that among patients receiving ART at Antiretroviral Therapy Cohort Collaboration (ART-CC) study sites.
Treatment-naive HIV-infected patients initiating identical ART regimens in ACTG trials (A5095 and A5142) and at 15 ART-CC cohort study sites were included. Virological failure (HIV-1 RNA >200 copies/ml) at 24- and 48-weeks, incident AIDS-defining events and mortality were measured according to study design (ART-CC cohort vs. ACTG trial) and stratified by 3rd drug [Abacavir (ABC), Efavirenz (EFV), and Lopinavir/r (LPV/r)]. We used logistic regression to estimate and compare odds ratios for virological failure between different regimens and study designs, and used Cox models to estimate and compare hazard ratios for AIDS and death.
Compared with patients receiving ABC, those receiving EFV had roughly half the odds of 24-week virologic failure (>200 copies/mL) in both ACTG 5095 (OR=0.53, 95% CI 0.36–0.79) and ART-CC (0.46, 0.37–0.57). Virologic superiority of EFV (vs. ABC) appeared comparable in ART-CC and ACTG 5095 (ratio of ORs 0.86, 95% CI 0.54–1.35). Odds ratios for 48-week virologic failure, comparing EFV with LPV/r, were also comparable in ACTG 5142 and ART-CC (ratio of ORs 0.87, 0.45–1.69).
Between ART regimen virologic efficacy of 3rd drugs ABC, EFV, and LPV/r observed in the ACTG 5095 and 5142 trials appear generalizable to the routine care setting of ART-CC clinical cohorts.
HIV; AIDS; Antiretroviral therapy; Comparative effectiveness; Viral load
Viremia copy-years predicted all-cause mortality independent of traditional, cross-sectional viral load measures and time-updated CD4+ T-lymphocyte count in antiretroviral therapy-treated patients suggesting cumulative human immunodeficiency virus replication causes harm independent of its effect on the degree of immunodeficiency.
Background. Cross-sectional plasma human immunodeficiency virus (HIV) viral load (VL) measures have proven invaluable for clinical and research purposes. However, cross-sectional VL measures fail to capture cumulative plasma HIV burden longitudinally. We evaluated the cumulative effect of exposure to HIV replication on mortality following initiation of combination antiretroviral therapy (ART).
Methods. We included treatment-naive HIV-infected patients starting ART from 2000 to 2008 at 8 Center for AIDS Research Network of Integrated Clinical Systems sites. Viremia copy-years, a time-varying measure of cumulative plasma HIV exposure, were determined for each patient using the area under the VL curve. Multivariable Cox models were used to evaluate the independent association of viremia copy-years for all-cause mortality.
Results. Among 2027 patients contributing 6579 person-years of follow-up, the median viremia copy-years was 5.3 log10 copy × y/mL (interquartile range: 4.9–6.3 log10 copy × y/mL), and 85 patients (4.2%) died. When evaluated separately, viremia copy-years (hazard ratio [HR] = 1.81 per log10 copy × y/mL; 95% confidence interval [CI], 1.51–2.18 per log10 copy × y/mL), 24-week VL (1.74 per log10 copies/mL; 95% CI, 1.48–2.04 per log10 copies/mL), and most recent VL (HR = 1.89 per log10 copies/mL; 95% CI: 1.63–2.20 per log10 copies/mL) were associated with increased mortality. When simultaneously evaluating VL measures and controlling for other covariates, viremia copy-years increased mortality risk (HR = 1.44 per log10 copy × y/mL; 95% CI, 1.07–1.94 per log10 copy × y/mL), whereas no cross-sectional VL measure was independently associated with mortality.
Conclusions. Viremia copy-years predicted all-cause mortality independent of traditional, cross-sectional VL measures and time-updated CD4+ T-lymphocyte count in ART-treated patients, suggesting cumulative HIV replication causes harm independent of its effect on the degree of immunodeficiency.
Among HIV-infected patients who initiated antiretroviral therapy (ART), patterns of cause-specific death varied by ART duration and were strongly related to age, sex, and transmission risk group. Deaths from non-AIDS malignancies were much more frequent than those from cardiovascular disease.
Background. Patterns of cause-specific mortality in individuals infected with human immunodeficiency virus type 1 (HIV-1) are changing dramatically in the era of antiretroviral therapy (ART).
Methods. Sixteen cohorts from Europe and North America contributed data on adult patients followed from the start of ART. Procedures for coding causes of death were standardized. Estimated hazard ratios (HRs) were adjusted for transmission risk group, sex, age, year of ART initiation, baseline CD4 count, viral load, and AIDS status, before and after the first year of ART.
Results. A total of 4237 of 65 121 (6.5%) patients died (median, 4.5 years follow-up). Rates of AIDS death decreased substantially with time since starting ART, but mortality from non-AIDS malignancy increased (rate ratio, 1.04 per year; 95% confidence interval [CI], 1.0–1.1). Higher mortality in men than women during the first year of ART was mostly due to non-AIDS malignancy and liver-related deaths. Associations with age were strongest for cardiovascular disease, heart/vascular, and malignancy deaths. Patients with presumed transmission through injection drug use had higher rates of all causes of death, particularly for liver-related causes (HRs compared with men who have sex with men: 18.1 [95% CI, 6.2–52.7] during the first year of ART and 9.1 [95% CI, 5.8–14.2] thereafter). There was a persistent role of CD4 count at baseline and at 12 months in predicting AIDS, non-AIDS infection, and non-AIDS malignancy deaths. Lack of viral suppression on ART was associated with AIDS, non-AIDS infection, and other causes of death.
Conclusions. Better understanding of patterns of and risk factors for cause-specific mortality in the ART era can aid in development of appropriate care for HIV-infected individuals and inform guidelines for risk factor management.
HIV; cause-specific mortality; antiretroviral therapy
Grounded in a socio-ecological framework, we describe salient health care system and policy factors that influence engagement in human immunodeficiency virus (HIV) clinical care. The discussion emphasizes successful programs and models of service delivery and highlights the limitations of current, fragmented health care system components in supporting effective, efficient, and sustained patient engagement across a continuum of care. A fundamental need exists for improved synergies between funding and service agencies that provide HIV testing, prevention, treatment, and supportive services. We propose a feedback loop whereby actionable, patient-level surveillance of HIV testing and engagement in care activities inform educational outreach and resource allocation to support integrated “testing and linkage to care plus” service delivery. Ongoing surveillance of programmatic performance in achieving defined benchmarks for linkage of patients who have newly diagnosed HIV infection and retention of those patients in care is imperative to iteratively inform further educational efforts, resource allocation, and refinement of service delivery.
Once-daily compared with twice-daily antiretroviral therapy regimens increased adherence; however, the difference was modest and not associated with a difference in virological suppression. In addition, higher pill burden was associated with lower rates of virological suppression, whether once- or twice-daily regimens.
Background. Contemporary antiretroviral treatment regimens are simpler than in the past, with lower pill burden and once-daily dosing frequency common. We performed a meta-analysis of randomized controlled trials (RCTs) to investigate the impact of pill burden and once-daily vs twice-daily dosing on ART adherence and virological outcomes.
Methods. A literature search of 4 electronic databases through 31 March 2013 was used. RCTs comparing once-daily vs twice-daily ART regimens that also reported on adherence and virological suppression were included. Study design, study population characteristics, intervention, outcome measures, and study quality were extracted. Study quality was rated using the Cochrane risk-of-bias tool.
Results. Nineteen studies met our inclusion criteria (N = 6312 adult patients). Higher pill burden was associated with both lower adherence rates (P = .004) and worse virological suppression (P < .0001) in both once-daily and twice-daily subgroups, although the association with adherence in the once-daily subgroup was not statistically significant. The average adherence was modestly higher in once-daily regimens than twice-daily regimens (weighted mean difference = 2.55%; 95% confidence interval [CI], 1.23 to 3.87; P = .0002). Patients on once-daily regimens did not achieve virological suppression more frequently than patients on twice-daily regimens (relative risk [RR] = 1.01; 95% CI, 0.99 to 1.03; P = .50). Both adherence and viral load suppression decreased over time, but adherence decreased less with once-daily dosing than with twice-daily dosing.
Conclusions. Lower pill burden was associated with both better adherence and virological suppression. Adherence, but not virological suppression, was slightly better with once- vs twice-daily regimens.
randomized controlled trials; ART; fixed-dose combination; once-daily; twice-daily
Maraviroc (MVC) use has trailed that of other post-2006 antiretroviral therapy (ART) options for treatment-experienced patients. We explored the impact of free tropism testing on MVC utilization in our cohort and explored barriers to MVC utilization. The Maraviroc Outcomes Study (MOS) is an investigator-initiated industry-sponsored trial where consecutive ART-experienced patients receiving routine care with viral loads ≥1,000 copies/ml, and whose provider requested resistance testing and received standardized resistance testing (SRT; phenotype, genotype, coreceptor/tropism). Sociodemographic, clinical, and ART characteristics of those receiving SRT were compared to a historical cohort (HC). Subsequently, providers were surveyed regarding factors influencing selection of salvage ART therapy. The HC (n=165) had resistance testing 7/08–9/09, while prospective SRT (n=83) patients were enrolled 9/09–8/10. In the HC, 92% had genotypes, 2% had tropism assays, and 62% (n=102) changed ART after resistance testing (raltegravir 37%, etravirine 25%, darunavir 24%, MVC 1%). In the SRT cohort, 57% (n=48) changed regimens after standardized resistance testing (darunavir 48%, raltegravir 40%, and etravirine 19%). CCR5-tropic virus was identified in 43% of the SRT group, and MVC was used in 10% [or 20% of R5 tropic patients who underwent a subsequent regimen change (n=25)], a statistically significant (p=0.01) increase in utilization. The factors most strongly influencing utilization were unique patient circumstances (60%), clinical experience (55%), and potential side effects (40%). The addition of routine tropism testing to genotypic/phenotypic testing was associated with increased MVC utilization, raising the possibility that tropism testing may present a barrier to MVC use; however, additional barriers exist, and merit further evaluation.
Early and regular care and treatment for human immunodeficiency virus (HIV) infection are associated with viral suppression, reductions in transmission risk and improved health outcomes for persons with HIV. We determined, on a population level, the association of care visits with time from HIV diagnosis to viral suppression.
Using data from 19 areas reporting HIV-related tests to national HIV surveillance, we determined time from diagnosis to viral suppression among 17,028 persons diagnosed with HIV during 2009, followed through December 2011, using data reported through December 2012. Using Cox proportional hazards models, we assessed factors associated with viral suppression, including linkage to care within 3 months of diagnosis, a goal set forth by the National HIV/AIDS Strategy, and number of HIV care visits as determined by CD4 and viral load test results, while controlling for demographic, clinical, and risk characteristics.
Of 17,028 persons diagnosed with HIV during 2009 in the 19 areas, 76.6% were linked to care within 3 months of diagnosis and 57.0% had a suppressed viral load during the observation period. Median time from diagnosis to viral suppression was 19 months overall, and 8 months among persons with an initial CD4 count ≤350 cells/µL. During the first 12 months after diagnosis, persons linked to care within 3 months experienced shorter times to viral suppression (higher rate of viral suppression per unit time, hazard ratio [HR] = 4.84 versus not linked within 3 months; 95% confidence interval [CI] 4.27, 5.48). Persons with a higher number of time-updated care visits also experienced a shorter time to viral suppression (HR = 1.51 per additional visit, 95% CI 1.49, 1.52).
Timely linkage to care and greater frequency of care visits were associated with faster time to viral suppression with implications for individual health outcomes and for secondary prevention.
Engagement in HIV care is increasingly recognized as a crucial step in maximizing individual patient outcomes. The recently updated HIV Medicine Association primary HIV care guidelines include a new recommendation highlighting the importance of extending adherence beyond antiretroviral medications to include adherence to clinical care. Beyond individual health, emphasis on a “test and treat” approach to HIV prevention highlights the public health importance of engagement in clinical care as an essential intermediary between the putative benefits of universal HIV testing (“test”) followed by ubiquitous antiretroviral treatment (“treat”). One challenge to administrators, researchers and clinicians who want to systematically evaluate HIV clinical engagement is deciding on how to measure retention in care. Measuring retention is complex as this process includes multiple clinic visits (repeated measures) occurring longitudinally over time. This article provides a synthesis of five commonly used measures of retention in HIV care, highlighting their methodological and conceptual strengths and limitations, and suggesting situations where certain measures may be preferred over others. The five measures are missed visits, appointment adherence, visit constancy, gaps in care, and the Human Resources and Services Administration HIV/AIDS Bureau (HRSA HAB) performance measure for retention in HIV care. As has been noted for antiretroviral medication adherence, there is no gold standard to measure retention in care, and consideration of the advantages and limitations of each measure, particularly in the context of the desired application, should guide selection of a retention measure.
Increases in multimorbidity and obesity have been noted in HIV infected populations in the current treatment era. Patterns of multimorbid disease clustering as well as the impact of obesity on multimorbidity are understudied in this population.
We examined obesity and multimorbidity patterns among 1844 HIV-infected patients in the UAB 1917 Clinic. Exploratory factor analysis (EFA) was used to identify the underlying factor structure responsible for clustering. Patterns among the resulting morbidity factors by body mass index (BMI) category were explored. Multivariable logistic regression models were fit to identify predictors of multimorbidity cluster patterns.
The prevalence of multimorbidity was 65% (1205/1844). Prevalence increased with progressive BMI categories from underweight (64%) to obese (79%). Three multimorbidity clusters were identified: “Metabolic” including hypertension (HTN), gout, diabetes mellitus, and chronic kidney disease (CKD) (range: 0.41 to 0.84; P<0.001); “Behavioral“ including mood disorders, dyslipidemia, chronic obstructive pulmonary disease (COPD), chronic ulcer disease, osteoarthritis, obstructive sleep apnea (OSA), and cardiac disorders (range: 0.32 to 0.57; P<0.001); “Substance Use” including alcohol abuse, substance abuse, tobacco abuse, and hepatitis C (range: 0.53 to 0.89; P<0.001). Obesity was associated with increased odds of multimorbidity (Obese vs. Normal BMI category: OR=1.52, 95%CI=1.15-2.00).
Three patterns of disease clustering were identified. Obesity was associated with a higher likelihood of multimorbidity. The management of multimorbidity and obesity will need to be addressed in future clinical practice guidelines to enhance long term outcomes of HIV-infected patients in the current treatment era.
Multimorbidity; Obesity; HIV; Factor Analysis; Tetrachoric
Aspirin for primary prevention of cardiovascular events is underutilized in human immunodeficiency virus (HIV)–infected patients. As these patients are at increased risk for events compared with HIV-negative persons, interventions are needed to increase HIV provider awareness of and adherence to existing guidelines.
Background. Individuals infected with human immunodeficiency virus (HIV) are at increased risk for cardiovascular disease (CVD) events compared with uninfected persons. However, little is known about HIV provider practices regarding aspirin (ASA) for primary prevention of CVD.
Methods. A cross-sectional study was conducted among patients attending the University of Alabama at Birmingham 1917 HIV Clinic during 2010 to determine the proportion receiving ASA for primary prevention of CVD and identify factors associated with ASA prescription. Ten-year risk for CVD events was calculated for men aged 45–79 and women aged 55–79. The 2009 US Preventive Services Task Force (USPSTF) guidelines were used to determine those qualifying for primary CVD prevention.
Results. Among 397 patients who qualified to receive ASA (mean age, 52.2 years, 94% male, 36% African American), only 66 (17%) were prescribed ASA. In multivariable logistic regression analysis, diabetes mellitus (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.28–5.27), hyperlipidemia (OR, 3.42; 95% CI, 1.55–7.56), and current smoking (OR, 1.87; 95% CI, 1.03–3.41) were significantly associated with ASA prescription. Odds of ASA prescription more than doubled for each additional CVD-related comorbidity present among hypertension, diabetes, hyperlipidemia, and smoking (OR, 2.13, 95% CI, 1.51–2.99).
Conclusions. In this HIV-infected cohort, fewer than 1 in 5 patients in need received ASA for primary CVD prevention. Escalating likelihood of ASA prescription with increasing CVD-related comorbidity count suggests that providers may be influenced more by co-occurrence of these diagnoses than by USPSTF guidelines. In the absence of HIV-specific guidelines, interventions to improve HIV provider awareness of and adherence to existing general population guidelines on CVD risk reduction are needed.