Rachel Hart

Disparities in achieving and sustaining viral suppression among a large cohort of HIV-infected persons in care – Washington, DC*

ABSTRACT One goal of the HIV care continuum is achieving viral suppression (VS), yet disparities in suppression exist among subpopulations of HIV-infected persons. We sought to identify disparities in both the ability to achieve and sustain VS among an urban cohort of HIV-infected persons in care. Data from HIV-infected persons enrolled at the 13 DC Cohort study clinical sites between January 2011 and June 2014 were analyzed. Univariate and multivariate logistic regression were conducted to identify factors associated with achieving VS (viral load < 200 copies/ml) at least once, and Kaplan–Meier (KM) curves and Cox proportional hazards models were used to identify factors associated with sustaining VS and time to virologic failure (VL ≥ 200 copies/ml after achievement of VS). Among the 4311 participants, 95.4% were either virally suppressed at study enrollment or able to achieve VS during the follow-up period. In multivariate analyses, achieving VS was significantly associated with age (aOR: 1.04; 95%CI: 1.03–1.06 per five-year increase) and having a higher CD4 (aOR: 1.05, 95% CI 1.04–1.06 per 100 cells/mm3). Patients infected through perinatal transmission were less likely to achieve VS compared to MSM patients (aOR: 0.63, 95% CI 0.51–0.79). Once achieved, most participants (74.4%) sustained VS during follow-up. Blacks and perinatally infected persons were less likely to have sustained VS in KM survival analysis (log rank chi-square p ≤ .001 for both) compared to other races and risk groups. Earlier time to failure was observed among females, Blacks, publically insured, perinatally infected, those with longer standing HIV infection, and those with diagnoses of mental health issues or depression. Among this HIV-infected cohort, most people achieved and maintained VS; however, disparities exist with regard to patient age, race, HIV transmission risk, and co-morbid conditions. Identifying populations with disparate outcomes allows for appropriate targeting of resources to improve outcomes along the care continuum.

Statin Use Is Associated With Incident Diabetes Mellitus Among Patients in the HIV Outpatient Study.

Introduction:Statin therapy is effective in the prevention of cardiovascular disease in the general population but has been shown to modestly increase the risk for incident diabetes mellitus (DM). Methods:We analyzed incident DM in HIV Outpatient Study (HOPS) participants followed at 8 HIV clinic sites during 2002–2011, comparing rates among those who initiated statin therapy during that period with those who did not. Using Cox proportional hazards models, we examined the association between cumulative years of statin exposure and the risk of developing DM, after controlling for age, sex, race/ethnicity, antiretroviral history, prevalent hepatitis C, body mass index, and cumulative exposure to protease inhibitor therapy. We also adjusted for propensity scores to account for residual confounding by indication. Results:Of 4692 patients analyzed, 590 (12.6%) initiated statin therapy and 355 (7.2%) developed DM. Incident DM was independently associated with statin therapy (adjusted hazard ratio, 1.14 per year of statin use), as well as older age, Hispanic/Latino ethnicity, non-Hispanic/Latino black race, antiretroviral-naive status, prevalent hepatitis C, and body mass index ≥30 kg/m2 (P < 0.05 for all). The association of statin use with incident DM was similar in the model adjusted for propensity score. Conclusions:Statin use was associated with a modestly increased risk of incident DM in an HIV-infected population, similar to existing data for the general population. HIV-infected patients should be monitored for glucose intolerance, but statins should not be withheld if clinically indicated for cardiovascular disease risk reduction.

HIV laboratory monitoring reliably identifies persons engaged in care.

Background:Attendance at biannual medical encounters has been proposed as a minimum national standard for adequate engagement in HIV care. Using data from the HIV Outpatient Study, we analyzed how well dates of HIV-related laboratory testing correlated with attendance at biannual medical encounters. Methods:HIV Outpatient Study is an open prospective cohort study of HIV-infected patients receiving outpatient care in the United States. The data set included dates for laboratory measurements and medical encounters. We included patients with at least 1 HIV laboratory test (CD4 cell count or plasma HIV RNA viral load) during 2010–2011. An HIV laboratory test was defined as associated with a medical encounter if it occurred within 3 weeks of the encounter. We assessed the predictive value of HIV laboratory tests as a proxy for adequate engagement in clinical care, defined as having had ≥2 HIV laboratory tests within 1 year and performed >90 days apart. Results:A total of 10,321 HIV laboratory tests were recorded from 2909 patients. Adequate engagement in clinical care based on medical encounters was 88.2% and 77.3% when based on laboratory tests. Using HIV laboratory tests to assess engagement had a sensitivity of 85.7%, specificity of 86.0%, and positive and negative predictive values of 97.9% and 44.5%, respectively. Of the 22.7% classified as not engaged in care by the proxy measure, over half (55.5%) were actually engaged. Conclusions:Using laboratory monitoring reliably classified persons as engaged in care. Of the 22.7% of patients classified as not engaged in care, most were actually engaged.

A Matter of Perspective: Comparison of the Characteristics of Persons with HIV Infection in the United States from the HIV Outpatient Study, Medical Monitoring Project, and National HIV Surveillance System

Comparative analyses of the characteristics of persons living with HIV infection (PLWH) in the United States (US) captured in surveillance and other observational databases are few. To explore potential joint data use to guide HIV treatment and prevention in the US, we examined three CDC-funded data sources in 2012: the HIV Outpatient Study (HOPS), a multisite longitudinal cohort; the Medical Monitoring Project (MMP), a probability sample of PLWH receiving medical care; and the National HIV Surveillance System (NHSS), a surveillance system of all PLWH. Overall, data from 1,697 HOPS, 4,901 MMP, and 865,102 NHSS PLWH were analyzed. Compared with the MMP population, HOPS participants were more likely to be older, non-Hispanic/Latino white, not using injection drugs, insured, diagnosed with HIV before 2009, prescribed antiretroviral therapy, and to have most recent CD4+ T-lymphocyte cell count ≥500 cells/mm3 and most recent viral load test<2 00 copies/mL. The MMP population was demographically similar to all PLWH in NHSS, except it tended to be slightly older, HIV diagnosed more recently, and to have AIDS. Our comparative results provide an essential first step for combined epidemiologic data analyses to inform HIV care and prevention for PLWH in the US.

Disparities in initiation of combination antiretroviral treatment and in virologic suppression among patients in the HIV outpatient study, 2000-2013

Objectives:The National HIV/AIDS Strategy emphasizes virologic suppression (VS) to reduce HIV incidence in the United States. We assessed temporal trends of and disparities in time to combination antiretroviral therapy (cART) initiation and HIV VS in a large demographically diverse cohort of HIV-infected patients. Design:We included antiretroviral-naive HIV Outpatient Study participants from 2000 to 2013 enrolled within 6 months of their HIV diagnosis who attended ≥2 HIV care–related visits. Methods:We evaluated time from HIV diagnosis to first use of cART, time from HIV diagnosis to VS, and time from first use of cART to VS. Kaplan–Meier time-to-event curves and Cox proportional hazards models were used to assess temporal trends and correlates of initiating cART and achieving HIV VS (<500 copies per milliliter). Results:Among 1156 HIV Outpatient Study patients [median age, 37 years; 43.2% non-Hispanic/Latino black (NHB), 14.1% Hispanic/Latino], estimated median times from HIV diagnosis to cART initiation and from HIV diagnosis to VS both shortened by >40% during the 13.5-year study period, reaching, respectively, 2.5 and 5.4 months. In multivariable analyses, NHB patients (as compared with non-Hispanic/Latino white) and those who had injected drugs (as compared with those who did not) initiated cART in a less timely fashion. After adjusting for CD4+ cell count and viral load at cART initiation, NHB patients and those aged <30 years (compared with ≥40 years) had lower rates of VS. Conclusions:Despite improvements in HIV treatment over time, patients who were NHB, younger, or used injection drugs had less favorable outcomes.

Antiretroviral Regimen Durability and Success in Treatment-Naive and Treatment-Experienced Patients by Year of Treatment Initiation, United States, 1996-2011.

Background:Although modern combination antiretroviral therapy (cART) regimens are better tolerated and less complex than earlier treatments, regimen modification or discontinuation remains a concern. Methods:We studied HIV Outpatient Study (HOPS) participants who initiated the first or second cART regimens during: 1996–1999, 2000–2003, 2004–2007, and 2008–2011. We analyzed regimen durability (time to regimen modification) and success (achieving undetectable plasma HIV RNA) for the first and second cART regimens using Kaplan–Meier curves and log-rank tests, and examined factors associated with durability and success of the first cART regimen using proportional hazards models. Results:Durability of cART was progressively longer for cART regimens initiated in more recent periods: median first cART regimen durations were 1.0, 1.1, 2.1, and 4.6 years in 1996–1999, 2000–2003, 2004–2007, and 2008–2011, and the median second cART durations were 0.9, 1.2, 2.8, and 3.9 years, respectively (both P < 0.001). Comparing 1996–1999 and 2008–2011, the percentage of patients who achieved an undetectable HIV RNA within 6 months of first cART initiation increased from 65% to 81% and from 63% to 80% on second cART (both P < 0.001). Among patients initiating first cART during 2008–2011, black non-Hispanic/Latino race/ethnicity and ≥twice-daily dosing were significantly associated with higher rates of regimen modification (P < 0.05), and higher baseline HIV RNA levels were associated with failure to achieve an undetectable HIV RNA (P < 0.001). Conclusions:Among HIV-infected U.S. adults in routine HIV care, durability of the first and second cART regimens and the likelihood of prompt virological suppression increased during 1996–2011, coincident with the availability of more tolerable, less complex cART options.

Trends in use of genotypic resistance testing and frequency of major drug resistance among antiretroviral-naive persons in the HIV Outpatient Study, 1999–2011

BACKGROUND Monitoring antiretroviral drug resistance can inform treatment recommendations; however, there are few such data from US patients before they initiate ART. METHODS We analysed data from HIV Outpatient Study (HOPS) participants from nine US HIV clinics who were diagnosed with HIV infection during 1999-2011. Using the IAS-USA December 2010 guidelines, we assessed the frequency of major drug resistance mutations (mDRMs) related to antiretroviral agents in viral isolates from patients who underwent commercial genotypic testing (GT) for resistance before initiating ART. We employed general linear regression models to assess factors associated with having undergone GT, and then factors associated with having mDRM. RESULTS Among 1531 eligible patients, 758 (49.5%) underwent GT before first ART, increasing from 15.5% in 1999-2002 to 75.9% in 2009-11 (P < 0.001). GT was carried out a median of 1.2 months after the diagnosis of HIV. In adjusted regression analyses, patients with pre-ART CD4+ T lymphocyte counts ≥200 cells/mm(3) or with HIV RNA levels >5.0 log10 copies/mL and those with a first HOPS visit in 2006 or later were significantly (P < 0.05) more likely to have undergone GT. Of the 758 patients, 114 (15.0%) had mDRMs; mutations relating to NRTIs, NNRTIs and PIs were present in 8.0%, 7.1% and 2.6%, respectively. There was no temporal change in the frequency of mDRM, and mDRMs were associated with an HIV RNA level <4.0 log10 copies/mL. CONCLUSIONS During 1999-2011, GT use among antiretroviral-naive patients became more common, but a quarter of patients in recent years remained untested. The frequency of mDRMs remained stable over time at about 15%.

CD4 cell count at initiation of ART, long-term likelihood of achieving CD4 >750 cells/mm3 and mortality risk

OBJECTIVES We sought to evaluate associations between CD4 at ART initiation (AI), achieving CD4 >750 cells/mm(3) (CD4 >750), long-term immunological recovery and survival. METHODS This was a prospective observational cohort study. We analysed data from ART-naive patients seen in 1996-2012 and followed ≥3 years after AI. We used Kaplan-Meier (KM) methods and log-rank tests to compare time to achieving CD4 >750 by CD4 at AI (CD4-AI); and Cox regression models and generalized estimating equations to identify factors associated with achieving CD4 >750 and mortality risk. RESULTS Of 1327 patients, followed for a median of 7.9 years, >85% received ART for ≥75% of follow-up time; 64 died. KM estimates evaluating likelihood of CD4 >750 during 5 years of follow-up, stratified by CD4-AI <50, 50-199, 200-349, 350-499 and 500-750, were 20%, 25%, 56%, 80% and 87%, respectively (log-rank P < 0.001). In adjusted models, CD4-AI ≥200 (versus CD4-AI <200) was associated with achievement of CD4 >750 [adjusted HR (aHR) = 4.77]. Blacks were less likely than whites to achieve CD4 >750 (33% versus 49%, aHR = 0.77). Mortality rates decreased with increasing CD4-AI (P = 0.004 across CD4 strata for AIDS causes and P = 0.009 for non-AIDS death causes). Among decedents with CD4-AI ≥50, 56% of deaths were due to non-AIDS causes. CONCLUSIONS Higher CD4-AI resulted in greater long-term CD4 gains, likelihood of achieving CD4 >750, longer survival and decreased mortality regardless of cause. Over 80% of persons with CD4-AI ≥350 achieved CD4 >750 by 4 years while 75% of persons with CD4-AI <200 did not. These data confirm the hazards of delayed AI and support early AI.

HIV Viral Load Monitoring Frequency and Risk of Treatment Failure among Immunologically Stable HIV-Infected Patients Prescribed Combination Antiretroviral Therapy

The authors sought to assess whether viral load (VL) monitoring frequency was associated with differential rates of virologic failure (VF) among HIV Outpatient Study (HOPS) participants seen during 1999 to 2013, who had maintained VL <50 copies/mL, CD4 counts ≥300 cells/mm3, and been prescribed a stable combination antiretroviral regimen for at least 2 years. The authors required VL and CD4 testing to have occurred regularly for the entire 2-year period. The authors assessed rates of VF comparing patients who maintained a frequent VL testing (≥3 VLs) to those who shifted to a less frequent schedule (2 VL) after the 2-year period. Virologic failure was observed among 116 of 573 participants. The authors did not detect statistically significant difference in frequency of VF among patients undergoing frequent (21.0%) versus less frequent VL testing (19.6%), even after multivariable adjustment. Biannual VL monitoring for stable patients with aviremia could generate substantial cost savings without the increased risk of VF.

High burden of metabolic comorbidities in a citywide cohort of HIV outpatients: evolving health care needs of people aging with HIV in Washington, DC

With the increasing impact of cardiovascular disease among populations aging with HIV, contemporary prevalence estimates for predisposing metabolic comorbidities will be important for guiding the provision of relevant lifestyle and pharmacological interventions. We estimated the citywide prevalence of hypertension, type 2 diabetes, dyslipidaemia, and obesity; examined differences by demographic subgroups; and assessed clinical correlates.