Practice Transformation in HIV Primary Care: Perspectives of Coaches and Champions in the Southeast United States.

INTRODUCTION/OBJECTIVES: Across the United States, and particularly in the South, there is an urgent need to improve health outcomes for people with HIV. In response, the Southeast AIDS Education & Training Center (AETC) conducted a 4-year Practice Transformation (PT) initiative (2015-2018) in 12 mostly primary care clinics across 4 states in the region. Drawing on the leadership of PT facilitators ("coaches") from AETC partner sites throughout the region and specific clinic staff members ("champions"), clinics worked toward self-selected organizational goals to increase their HIV care capacity and improve HIV health outcomes. METHODS: To explore coaches' and champions' experiences and perspectives of PT, we conducted 2 focus group sessions, 1 tailored for coaches (n = 5) and another for champions (n = 9). RESULTS: Content analysis of qualitative data revealed 4 major themes around coaches' and champions' experiences and perspectives of PT. These themes include Challenges, Facilitators, Successes, and Suggestions for PT Improvement. CONCLUSION: Primary care and infectious diseases/HIV clinics can help improve HIV Care Continuum outcomes through increasing their capacity to serve the needs of their clients, as facilitated through coaches and clinic champions. Since no single clinic or clinic patient population is alike, it is important work within organizations to address specific needs and leverage unique skillsets. Future PT initiatives can learn from experiences of this PT program to optimize the effectiveness of their programs.

Greater Weight Gain in Treatment-naive Persons Starting Dolutegravir-based Antiretroviral Therapy.

BACKGROUND: Recent studies have reported weight gain in virologically suppressed persons living with human immunodeficiency virus (PLWH) switched from older antiretroviral therapy (ART) to newer integrase strand transfer inhibitor (INSTI)-based regimens. In this study, we investigated whether weight gain differs among treatment-naive PLWH starting INSTI-based regimens compared to other ART regimens. METHODS: Adult, treatment-naive PLWH in the Vanderbilt Comprehensive Care Clinic cohort initiating INSTI-, protease inhibitor (PI)-, and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART between January 2007 and June 2016 were included. We used multivariable linear mixed-effects models to generate marginal predictions of weights over time, adjusting for baseline clinical and demographic characteristics. We used restricted cubic splines to relax linearity assumptions and bootstrapping to generate 95% confidence intervals. RESULTS: Among 1152 ART-naive PLWH, 351 initiated INSTI-based regimens (135 dolutegravir, 153 elvitegravir, and 63 raltegravir), 86% were male, and 49% were white. At ART initiation, median age was 35 years, body mass index was 25.1 kg/m2, and CD4+ T-cell count was 318 cells/µL. Virologic suppression at 18 months was similar between different ART classes. At all examined study time points, weight gain was highest among PLWH starting dolutegravir. At 18 months, PLWH on dolutegravir gained 6.0 kg, compared to 2.6 kg for NNRTIs (P < .05), and 0.5 kg for elvitegravir (P < .05). PLWH starting dolutegravir also gained more weight at 18 months compared to raltegravir (3.4 kg) and PIs (4.1 kg), though these differences were not statistically significant. CONCLUSIONS: Treatment-naive PLWH starting dolutegravir-based regimens gained significantly more weight at 18 months than those starting NNRTI-based and elvitegravir-based regimens.

The relationship between adverse neighborhood socioeconomic context and HIV continuum of care outcomes in a diverse HIV clinic cohort in the Southern United States.

Retention in care and viral suppression are critical to delaying HIV progression and reducing transmission. Neighborhood socioeconomic context (NSEC) may affect HIV care receipt. We therefore assessed NSEC's impact on retention and viral suppression in a diverse HIV clinical cohort. HIV-positive adults with ≥1 visit at the Vanderbilt Comprehensive Care Clinic and 5-digit ZIP code tabulation area (ZCTA) information between 2008 and 2012 contributed. NSEC z-score indices used neighborhood-level socioeconomic indicators for poverty, education, labor-force participation, proportion of males, median age, and proportion of residents of black race by ZCTA. Retention was defined as ≥2 HIV care visits per calendar year, >90 days apart. Viral suppression was defined as an HIV-1 RNA <200 copies/mL at last measurement per calendar year. Modified Poisson regression was used to estimate risk ratios (RR) and 95% confidence intervals (CI). Among 2272 and 2541 adults included for retention and viral suppression analyses, respectively, median age and CD4 count at enrollment were approximately 38 (1st and 3rd quartile: 30, 44) years and 351 (176, 540) cells/µL, respectively, while 24% were female, and 39% were black. Across 243 ZCTAs, median NSEC z-score was 0.09 (-0.66, 0.48). Overall, 79% of person-time contributed was retained and 74% was virally suppressed. In adjusted models, NSEC was not associated with retention, though being in the 4th vs. 1st NSEC quartile was associated with lack of viral suppression (RR = 0.88; 95% CI: 0.80-0.97). Residing in the most adverse NSEC was associated with lack of viral suppression. Future studies are needed to confirm this finding.

Trends in HIV Continuum of Care Outcomes over Ten Years of Follow-Up at a Large HIV Primary Medical Home in the Southeastern United States.

Longitudinal studies of retention in care (RIC) and viral suppression (VS) in the southeastern United States (US), a region disproportionately affected by HIV infection, are lacking. HIV-infected adults with ≥1 medical visit at the Vanderbilt Comprehensive Care Clinic (Nashville, Tennessee) from 2004 to 2013 were included. RIC was ≥2 (a) laboratory dates [CD4+ counts or HIV-1 viral loads (VLs)] or (b) provider encounters and/or laboratory dates in the year of interest, ≥90 days apart. VS was a VL of <200 copies/ml at last measurement in the year of interest. Modified Poisson regression estimated relative risk (RR) of RIC and VS, adjusting for age, race, sex, HIV transmission risk, and socioeconomic status (SES). Among 4,641 persons, 76.8% achieved RIC and 70.2% achieved VS. RIC and VS increased from 2004 to 2013 (p < .001 each). For lack of RIC, younger patients (RR = 1.2 and RR = 1.1, 18-24 and 25-34 vs. 35-44 year-olds, respectively), Blacks (RR = 1.3 vs. Whites), and injection drug users (IDUs) (RR = 1.2 vs. heterosexual contact [Hetero]) fared worse (p < .05 each); those with male-to-male sexual contact fared better (RR = 0.8 vs. Hetero, p < .05). For lack of VS, younger patients (RR = 1.3 and RR = 1.2, 18-24 and 25-34 vs. 35-44 year olds, respectively), Blacks (RR 1.3 vs. Whites), Females (RR = 1.1 vs. Males), IDUs (RR 1.3 vs. Hetero), and those with low SES (RR = 1.1 vs. not low SES) fared worse (p < .05, each). RIC and VS increased over time, suggesting that efforts to improve outcomes have been effective. However, disparities persist and resources should focus on groups most at risk.

Tuberculosis risk before and after highly active antiretroviral therapy initiation: does HAART increase the short-term TB risk in a low incidence TB setting?

OBJECTIVE: To evaluate the short-term and long-term effects of highly active antiretroviral therapy (HAART) on tuberculosis (TB) risk compared with risk without HAART in a low TB incidence setting. DESIGN: An observational cohort study among HIV-infected persons in care at the Comprehensive Care Center (Nashville, TN) between January 1998 and December 2008. METHODS: A marginal structural model was used to estimate the effect of HAART on short-term (≤180 days) and long-term (>180 days) TB risk, with CD4⁺ lymphocyte count incorporated as a time-updated covariate. RESULTS: Of 4534 HIV-infected patients, 34 developed TB (165 per 100,000 person-years; 20,581 person-years of follow-up). Seventeen cases occurred among persons not on HAART or >30 days after HAART discontinuation (212 per 100,000 person-years; 8019 person-years of follow-up). Seventeen occurred among persons on HAART (135 per 100,000 person-years; 12,562 person-years of follow-up); 10 in the first 180 days (402 per 100,000 person-years; 2489 person-years of follow-up); and 7 after more than 180 days (69 per 100,000 person-years; 10,073 person-years of follow-up). After adjusting for the most recent CD4⁺ lymphocyte count, the risk of TB in the first 180 days of HAART exposure relative to no HAART was 0.68 (0.14-3.22, P = 0.63). CONCLUSIONS: In this low TB incidence setting, the TB rate in the first 180 days of HAART was almost twice as high as persons not on HAART. However, after adjusting for most recent CD4⁺ count, there was no significant difference in TB risk between these 2 groups. This suggests that low recent CD4⁺ lymphocyte count influences TB risk during the first 180 days of HAART.

Antiretroviral therapy initiation before, during, or after pregnancy in HIV-1-infected women: maternal virologic, immunologic, and clinical response.

BACKGROUND: Pregnancy has been associated with a decreased risk of HIV disease progression in the highly active antiretroviral therapy (HAART) era. The effect of timing of HAART initiation relative to pregnancy on maternal virologic, immunologic and clinical outcomes has not been assessed. METHODS: We conducted a retrospective cohort study from 1997-2005 among 112 pregnant HIV-infected women who started HAART before (N = 12), during (N = 70) or after pregnancy (N = 30). RESULTS: Women initiating HAART before pregnancy had lower CD4+ nadir and higher baseline HIV-1 RNA. Women initiating HAART after pregnancy were more likely to receive triple-nucleoside reverse transcriptase inhibitors. Multivariable analyses adjusted for baseline CD4+ lymphocytes, baseline HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, history of ADE, prior use of non-HAART ART, type of HAART regimen, prior pregnancies, and date of HAART start. In these models, women initiating HAART during pregnancy had better 6-month HIV-1 RNA and CD4+ changes than those initiating HAART after pregnancy (-0.35 vs. 0.10 log(10) copies/mL, P = 0.03 and 183.8 vs. -70.8 cells/mm(3), P = 0.03, respectively) but similar to those initiating HAART before pregnancy (-0.32 log(10) copies/mL, P = 0.96 and 155.8 cells/mm(3), P = 0.81, respectively). There were 3 (25%) AIDS-defining events or deaths in women initiating HAART before pregnancy, 3 (4%) in those initiating HAART during pregnancy, and 5 (17%) in those initiating after pregnancy (P = 0.01). There were no statistical differences in rates of HIV disease progression between groups. CONCLUSIONS: HAART initiation during pregnancy was associated with better immunologic and virologic responses than initiation after pregnancy.

Race and sex differences in antiretroviral therapy use and mortality among HIV-infected persons in care.

BACKGROUND: There are conflicting data regarding race, sex, and mortality among persons infected with human immunodeficiency virus (HIV). We studied all-cause mortality among persons in care during the highly-active antiretroviral therapy (HAART) era. METHODS: This retrospective cohort study included patients who made>or=1 clinic visit from January 1998 through December 2005. RESULTS: Of 2605 patients (with 6657 person-years of follow-up), 38% were black and 24% were female. The percentage of time in care while receiving HAART was lower for blacks than for nonblacks (47% vs. 76%; P<.001) and for females than for males (57% vs. 71%; P=.01). There were 253 deaths (38 per 1000 person-years). After adjustment for characteristics at baseline, death was associated with black race (hazard ratio [HR], 1.33; P .04), female sex (HR, 1.53; P .007), injection drug use (IDU) as a risk factor for HIV infection (HR, 1.61; P .009), older age (HR, 1.45 per 10 years; P<.001), a lower CD4 cell count (HR, 0.59 for 200 vs. 350 cells/mm3; P<.001) and a higher HIV type 1 RNA level (HR, 1.35; P<.001). After adjustment for the length of time that HAART was received, black race (HR, 1.00; P .99) and IDU (HR, 1.37; P .09) were no longer associated with death, but female sex was (HR, 1.62; P=.002). CONCLUSIONS: Race-associated differences in mortality likely resulted from HAART use. Women had an increased risk of death even after adjustment for HAART use. Addressing racial disparities will require improved HAART utilization. Increased mortality among women requires further study.

Cross-cohort heterogeneity encountered while validating a model for HIV disease progression among antiretroviral initiators.

OBJECTIVE: To evaluate a model for predicting time to AIDS or death among HIV-infected persons initiating highly active antiretroviral therapy (HAART). STUDY DESIGN AND SETTING: The model was constructed from 1,891 HAART initiators in the Collaborations in HIV Outcomes Research/US (CHORUS) cohort. The model's predictive ability was assessed using internal bootstrap validation techniques and data from 716 HAART initiators at Johns Hopkins HIV Clinical Cohort (JHHCC) in whom HIV disease was, in general, more advanced. RESULTS: The estimated concordance statistic was 0.632 with the bootstrap method and 0.625 in JHHCC. Mean predicted and observed 3-year AIDS-free survival for JHHCC was 0.76 and 0.73 (95% confidence interval [CI], 0.69-0.77), respectively; mean predicted and observed 5-year AIDS-free survival was 0.69 and 0.57 (95% CI, 0.52-0.62), respectively. Sensitivity analyses showed that the discrepancy between predicted and observed AIDS-free survival after 3 years could be due to differences in lost-to-follow-up rates between cohorts. CONCLUSION: The model was fair at using baseline characteristics to order patients' risk of disease progression, but did not accurately predict AIDS-free survival >3 years after HAART initiation. Different variable definitions, patient characteristics, and loss to follow-up highlight the challenges of using data from one cohort to predict AIDS-free survival in an independent cohort.

Sociodemographic factors predict early discontinuation of HIV non-nucleoside reverse transcriptase inhibitors and protease inhibitors.

BACKGROUND/OBJECTIVE: HIV infection has a devastating impact on individual and public health, and affects populations disproportionately. Treatment with antiretroviral therapy (ART) saves lives, but long-term adherence to ART is critical to its success. We performed an observational cohort study to determine the influence of race, sex and other sociodemographic factors on early ART discontinuations among HIV-infected persons. METHODS: TennCare-enrolled adults of black or white non-Hispanic race beginning ART with either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) between 1996-2003 (N=3654) were assessed for early discontinuation. A subgroup of discontinuations was validated using the primary medical record. RESULTS: Blacks were more likely than whites to discontinue NNRTIs (37 vs. 28%; P=0.003) and PIs (36 vs. 25%; P < or = 0.001). In multivariable models adjusting for race, sex, age, early HIV-related medical encounter, urban residence and TennCare enrollment category, black race, female sex and younger age were independent predictors of discontinuation among those starting PIs. Among persons starting NNRTIs, black race, younger age and a disability-based enrollment category predicted early drug discontinuation, but female sex did not. CONCLUSIONS: Our results suggest that sociodemographic factors were associated with early NNRTI and PI discontinuation in this population, and some factors were ART class specific.

Increased detectability of plasma HIV-1 RNA after introduction of a new assay and altered specimen-processing procedures.

After changes to assay and specimen-processing methods, plasma human immunodeficiency virus type 1 (HIV-1) RNA was frequently detectable in patients who previously had well-suppressed HIV-1 RNA levels. This artifact is attributable to shipping frozen plasma in primary plasma preparation tubes and is not caused by the HIV-1 RNA detection assay; it can be avoided by shipping plasma in a secondary tube.

Pregnancy and HIV disease progression during the era of highly active antiretroviral therapy.

BACKGROUND: Before the availability of highly active antiretroviral therapy (HAART), there was no clear effect of pregnancy on human immunodeficiency virus (HIV) disease progression. This has not been assessed during the HAART era. METHODS: We conducted an observational cohort study among HIV-infected women with >or=1 outpatient clinic visit between January 1997 and December 2004. HIV disease progression was defined as the occurrence of an AIDS-defining event or death. RESULTS: Of 759 women who met the inclusion criteria, 139 (18%) had had >1 pregnancy, and 540 (71%) had received HAART. There was no difference in HAART duration by pregnancy status. Eleven pregnant (8%) and 149 nonpregnant (24%) women progressed to AIDS or death. After controlling for age, baseline CD4(+) lymphocyte count, baseline HIV-1 RNA level, and durable virologic suppression in a Cox proportional hazards model that included propensity score for pregnancy, pregnancy was associated with a decreased risk of disease progression (hazard ratio [HR], 0.40 [95% confidence interval {CI}, 0.20-0.79]; P=.009]). In a matched-pair analysis of 81 pregnant women matched to 81 nonpregnant women according to age, baseline CD4(+) lymphocyte count, receipt of HAART, and date of cohort entry, pregnant women had a lower risk of disease progression both before (HR, 0.10 [95% CI, 0.01-0.89]; P=.04) and after (HR, 0.44 [95% CI, 0.19-1.00]; P=.05) the pregnancy event. CONCLUSION: Pregnancy was associated with a lower risk of HIV disease progression in this HAART-era study. This finding could be the result of the healthier immune status of women who become pregnant or could possibly be related to a beneficial interaction between pregnancy and HAART.

Absolute count and percentage of CD4+ lymphocytes are independent predictors of disease progression in HIV-infected persons initiating highly active antiretroviral therapy.

BACKGROUND: Highly active antiretroviral therapy (HAART) is recommended when the absolute CD4(+) T lymphocyte count is <200 cells/mm(3), and it should be considered when that count is > or =200, although the optimal timing when it is > or =200 is unclear. Because preliminary data had suggested that a low CD4(+) T lymphocyte percentage (%CD4) is associated with disease progression in persons initiating HAART who have a higher absolute CD4, we sought to further characterize the predictive utility of %CD4. METHODS: We conducted an observational study of persons in Collaborations in HIV Outcomes Research/US cohort who initiated their first HAART regimen between 1997 and 2004, received > or =30 days of therapy, and had baseline values of absolute CD4, %CD4, and HIV-1 RNA. Cox proportional-hazards models determined associations between %CD4 and disease progression (to either a new AIDS-defining event [ADE] or death). RESULTS: Of 1891 persons, 11% were female and 18% were African American; the median age was 38 years. Median follow-up was 55 months (interquartile range, 23-83 months), and 468 (25%) had disease progression. Multivariable analysis including age, race, sex, HIV-1 RNA, prior antiretroviral therapy, probable route of infection, prior ADE, absolute CD4, and %CD4 was performed; prior ART (P<.0001), injection-drug use (P=.04), lower absolute CD4 (P=.002), and lower %CD4 (P=.002) predicted disease progression. CONCLUSIONS: %CD4 at initiation of the first HAART regimen predicted disease progression independent of absolute CD4; %CD4 may be used to determine the timing of HAART.

Effect of persistent moderate viremia on disease progression during HIV therapy.

OBJECTIVE: Although highly active antiretroviral therapy has been shown to lower plasma HIV-1 RNA in HIV infection, many patients do not reach the target goal of undetectable viremia. We evaluated whether risk of clinical progression varies by level of viral suppression achieved. DESIGN: Patients in the Collaborations in HIV Outcomes Research/United States cohort who maintained stable HIV-1 RNA levels of either <400, 400 to 20,000, or >20,000 copies/mL during a run-in period of at least 6 months were studied. Baseline was the first day after this period. METHODS: Proportional hazards models were used to quantify the relation between baseline HIV-1 RNA levels and risk of a new AIDS-defining diagnosis or death after adjusting for CD4 count, age, gender, ethnicity, study site, prior AIDS-defining diagnosis, and antiretroviral therapy history. RESULTS: Patients (N = 3010) were followed for up to 4.3 years after the 6-month run-in period, with 343 deaths or AIDS-defining diagnoses reported. The risk of a new AIDS-defining diagnosis or death was not significantly different in the 400 to 20,000- and <400-copies/mL groups (6% vs. 7%, hazard ratio [HR] = 1.0, 95% confidence interval [CI]: 0.7-1.4; P = 0.9) but was significantly higher in the >20,000-copies/mL group (26%, HR = 3.3, 95% CI: 2.5-4.4; P < 0.001 vs. the <400-copies/mL group). Median CD4 count changes during the first year of follow-up showed increases of 75 and 13 cells/mm for the <400- and 400 to 20,000-copies/mL groups, respectively, whereas the >20,000-copies/mL group had a decrease of 23 cells/mm. CONCLUSIONS: Patients who maintained baseline HIV-1 RNA levels of 400 to 20,000 copies/mL for at least 6 months preserved immunologic status and were no more likely to die or develop a new AIDS-defining diagnosis in the time frame studied than those with baseline levels <400 copies/mL. Patients with HIV-1 RNA levels >20,000 copies/mL at baseline had greater clinical and immunologic deterioration. These data suggest that maintenance of moderate viremia may confer clinical benefit not seen when viremia exceeds 20,000 copies/mL, and this should be taken into account when considering the risks and benefits of continuing failing therapy.

Improvements in access to care for HIV and AIDS in a statewide Medicaid managed care system.

BACKGROUND: Some experimental Medicaid managed care systems have expanded eligibility criteria for chronically ill persons, but these systems' impact on access to care remains unknown. OBJECTIVE: To determine whether initiating a statewide Medicaid managed care system (TennCare) guaranteeing universal access for persons living with HIV or AIDS (PLWHs) increased their enrollment in public sector insurance. DESIGN, SETTING, AND PARTICIPANTS: A retrospective longitudinal descriptive analysis of trends in population characteristics during the study period was performed. The study population included all PLWHs in Tennessee (1992-1997) identified by the State Health Department. These data linked with Medicaid/TennCare enrollment files identified percentages of Tennessee's HIV/AIDS population enrolled in Medicaid (1993) or TennCare (1994-1997) and eligi-bility/demographics changes during program initiation. MAIN OUTCOME MEASURE: Annual percentage of PLWHs enrolled in Medicaid/TennCare. RESULTS: Absolute numbers of PLWHs served by Medicaid/TennCare increased 475% from 1992 (n = 593) to 1997 (n = 2818). Similar increases in Tennessee's overall HIV-positive population occurred. Percentages of PLWHs enrolled in Medicaid/TennCare increased (1993 to 1997): HIV (28% to 34%) and AIDS (32% to 44%). The largest percentage of PLWHs added to the program were uninsured/uninsurable. CONCLUSIONS: Absolute numbers of PLWHs covered by Medicaid/TennCare substantially increased. Percentages of PLWHs covered increased more modestly, partly owing to large increases in overall numbers of HIV-positive Tennesseans during the study period. Increases in coverage were greatest for the AIDS population. Tennessee's broad expansion of eligibility for PLWHs resulted in improved access, but did not result in enrollment of most PLWHs. States contemplating similar Medicaid expansions should not expect all PLWHs to crowd into public sector insurance programs.