Background

Evidence about the effect of initiating efavirenz-containing combination antiretroviral therapy (ART) as the first-line therapy on suicidal thoughts remains conflicting.

Methods

Using data from a cohort of HIV-infected adults enrolled in routine care across 5 sites in the United States, we included participants with a baseline patient-reported outcome measure and detectable viral load who initiated ART between 2011 and 2014. Participants were followed until the earliest of the following: first suicidal thoughts, discontinuation of initial ART regimen, death, loss to care (>12 months with no HIV appointments), or administrative censoring (2014-2015). Suicidal thoughts were measured using a Patient Health Questionnaire-9 item. We used weighted marginal structural Cox models to estimate the effect of initiating efavirenz-containing ART, versus efavirenz-free ART, on the hazard of active or passive suicidal thoughts after ART initiation, accounting for confounding by channeling bias.

Results

Overall, 597 participants were followed for a median of 19 months (13,132 total person-months); 147 (25%) initiated efavirenz-containing ART. At ART initiation, 38% of participants reported suicidal thoughts or depressive symptoms. Initiating efavirenz-based ART was associated with a hazard ratio (HR) for suicidal thoughts below the null in the crude analysis [HR, 0.88; 95% confidence interval (CI): 0.53 to 1.45] and above the null in the weighted analysis (HR, 1.21; 95% CI: 0.66 to 2.28). Among those with a prior mental health issue, the weighted HR was 1.76 (95% CI: 0.45 to 6.86).

Conclusions

After accounting for measured channeling bias, we observed no strong evidence that initiating efavirenz-containing ART increased the hazard of suicidal thoughts.

Background

Transgender women (TW) are disproportionately affected by both HIV and cardiovascular disease (CVD).

Objectives

We aim to quantify prevalence of elevated predicted CVD risk for TW compared to cisgender women (CW) and cisgender men (CM) in HIV care and describe the impact of multiple operationalizations of CVD risk score calculations for TW.

Design

We conducted a cross-sectional analysis of patients engaged in HIV care between October 2014 and February 2018.

Setting

The Centers for AIDS Research Network of Integrated Clinical Systems, a collaboration of 8 HIV clinical sites in the United States contributed data for this analysis.

Patients

221 TW, 2983 CW, and 13467 CM.

Measurements

The measure of interest is prevalence of elevated 10-year cardiovascular disease risk based on ACC/AHA Pooled Cohort Risk Assessment equations (PCE) and the Framingham Risk Score (FRS), calculated for TW by: birth-assigned sex (male); history of exogenous sex hormone use (female/male); and current gender (female).

Results

Using birth-assigned sex, the adjusted prevalence ratio (aPR) was 2.52 (95% CI: 1.08,5.86) and 2.58 (95% CI: 1.71,3.89) comparing TW to CW, by PCE and FRS, respectively. It was 1.25 (95% CI: 0.54,2.87) and 1.25 (95% CI: 0.84,1.86) comparing TW to CM, by PCE and FRS, respectively. If TW were classified according to current gender versus birth-assigned sex, their predicted CVD risk scores were lower.

Limitations

PCE and FRS have not been validated in TW with HIV. Few adjudicated CVD events in the data set precluded analyses based on clinical outcomes.

Conclusions

After adjustment for demographics and history of HIV care, prevalence of elevated CVD risk in TW was similar to CM and equal to or higher than in CW, depending operationalization of the sex variable. Future studies with CVD outcomes are needed to help clinicians accurately estimate CVD risk among TW with HIV.

Objective

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.

Design

Retrospective observational cohort study.

Methods

The primary endpoint was absolute change in TG levels measured using the last TG value pretreatment and the first TG value posttreatment. A pre-post quasi-experimental design was used to estimate the change in TG because of 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.

Results

A total of 493 patients (mean age, 46 years; 95% male) were included (46 patients receiving gemfibrozil; 80, fenofibrate; 291, atorvastatin; and 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).

Conclusions

In HIV-infected patients in routine clinical care, fish oil is less effective than fibrates (but not atorvastatin) at lowering TG values. Fish oil may still represent an attractive alternative for patients with moderately elevated TGs, particularly among patients who may not want or tolerate fibrates.

Background

Rates of early syphilis in US women are steadily increasing, but predictors of infection in this group are not clearly defined.

Methods

This retrospective analysis focused on women enrolled in the US CFAR Network of Integrated Clinical Systems cohort between January 2005 and December 2016 with syphilis testing performed. The primary outcome of incident syphilis infection was defined serologically as a newly positive test with positive confirmatory testing after a negative test or a 2-dilution increase in rapid plasma regain titer. Infection rates were calculated for each woman-year in care with testing. Predictors of syphilis were sought among sociodemographics, clinical information, and self-reported behaviors. Multivariable logistic regression models were created; a subgroup analysis assessed predictors in women of reproductive age.

Results

The annual rate of incident syphilis among 4416 women engaged in human immunodeficiency virus (HIV) care and tested during the 12-year study period was 760/100 000 person-years. Independent predictors of infection were injection drug use as a risk factor for HIV acquisition (aOR, 2.2; 95% CI, 1.3-3.9), hepatitis C infection (aOR, 1.9; 95% CI, 1.1-3.4), black race (aOR, 2.2; 95% CI, 1.3-3.7 compared with white race), and more recent entry to care (since 2005 compared with 1994-2004). Predictors were similar in women aged 18-49.

Conclusions

Syphilis infection is common among US women in HIV care. Syphilis screening and prevention efforts should focus on women reporting drug use and with hepatitis C coinfection. Future studies should identify specific behaviors that mediate syphilis acquisition risk in women who use drugs.

Background

Information regarding the impact of substance use on the timing of entry into HIV care is lacking. Better understanding of this relationship can help guide approaches and policies to improve HIV testing and linkage.

Methods

We examined the effect of specific substances on stage of HIV disease at entry into care in over 5000 persons with HIV (PWH) newly enrolling in care. Substance use was obtained from the AUDIT-C and ASSIST instruments. We examined the association between early entry into care and substance use (high-risk alcohol, methamphetamine, cocaine/crack, illicit opioids, marijuana) using logistic and relative risk regression models adjusting for demographic factors, mental health symptoms and diagnoses, and clinical site.

Results

We found that current methamphetamine use, past and current cocaine and marijuana use was associated with earlier entry into care compared with individuals who reported no use of these substances.

Conclusion

Early entry into care among those with substance use suggests that HIV testing may be differentially offered to people with known HIV risk factors, and that individuals with substances use disorders may be more likely to be tested and linked to care due to increased interactions with the healthcare system.

Background.

The long-term effectiveness of human immunodeficiency virus (HIV) treatments containing integrase inhibitors is unknown.

Methods.

We use observational data from the Centers for AIDS Research Network of Integrated Clinical Systems and the Centers for Disease Control and Prevention to estimate 4-year risk of AIDS and all-cause mortality among 415 patients starting a raltegravir regimen compared to 2646 starting an efavirenz regimen (both regimens include emtricitabine and tenofovir disoproxil fumarate). We account for confounding and selection bias as well as generalizability by standardization for measured variables, and present both observational intent-to-treat and per-protocol estimates.

Results.

At treatment initiation, 12% of patients were female, 36% black, 13% Hispanic; median age was 37 years, CD4 count 321 cells/µL, and viral load 4.5 log10 copies/mL. Two hundred thirty-five patients incurred an AIDS-defining illness or died, and 741 patients left follow-up. After accounting for measured differences, the 4-year risk was similar among those starting both regimens (ie, intent-to treat hazard ratio [HR], 0.96 [95% confidence interval {CI}, .63-1.45]; risk difference, -0.9 [95% CI, -4.5 to 2.7]), as well as among those remaining on regimens (ie, per-protocol HR, 0.95 [95% CI, .59-1.54]; risk difference, -0.5 [95% CI, -3.8 to 2.9]).

Conclusions.

Raltegravir and efavirenz-based initial antiretroviral therapy have similar 4-year clinical effects. Vigilance regarding longer-term comparative effectiveness of HIV regimens using observational data is needed because large-scale experimental data are not forthcoming.

Background

Retention in care (RIC) leads to reduced HIV transmission and mortality. Few studies have investigated clinic services and RIC among people living with HIV (PLWH) in the United States. We conducted a multisite retrospective cohort study to identify clinic services associated with RIC from 2010-2016 in the United States.

Methods

PLWH with ≥1 HIV primary care visit from 2010-2016 at 7 sites in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) were included. Clinic-level factors evaluated via site survey included patients per provider/trainee, navigation, RIC posters/brochures, laboratory test timing, flexible scheduling, appointment reminder methods, and stigma support services. RIC was defined as ≥2 encounters per year, ≥90 days apart, observed until death, administrative censoring (31 December 2016), or loss to follow-up (censoring at first 12-month interval without a visit with no future visits). Poisson regression with robust error variance, clustered by site adjusting for calendar year, age, sex, race/ethnicity, and HIV transmission risk factor, estimated risk ratios (RRs) and 95% confidence intervals (CIs) for RIC.

Results

Among 21 046 PLWH contributing 103 348 person-years, 67% of person-years were retained. Availability of text appointment reminders (RR, 1.13; 95% CI, 1.03-1.24) and stigma support services (RR, 1.11; 95% CI, 1.04-1.19) were associated with better RIC. Disparities persisted for age, sex, and race.

Conclusions

Availability of text appointment reminders and stigma support services was associated with higher rates of RIC, indicating that these may be feasible and effective approaches for improving RIC.

Objective

To estimate the association between immunologic response to antiretroviral therapy (ART) and non-AIDS defining cancer (NADC) incidence in HIV-infected patients.

Design

A prospective cohort including patients with at least 1 cell/μl CD4 cell count and HIV-1 RNA measure after ART initiation between 1996 and 2011 in the Centers for AIDS Research Network of Integrated Clinical Systems, a collaboration of eight HIV clinics at major academic medical centres in the United States.

Methods

Measures of immunologic response were 6-month CD4 post-ART, latest CD4 and CD4 count-years, a cumulative measure of CD4 lymphopenia. Cox regression with inverse probability-of-exposure weights was used to calculate adjusted hazard ratios of virus-related and virus-unrelated NADC incidence.

Results

Among 9389 patients at ART initiation, median CD4 cell count was 200 cells/μl [interquartile range (IQR) 60-332)], and median HIV-1 RNA was 4.8 log10 copies/ml (IQR 4.3-5.4). Median follow-up was 3.3 years (IQR 1.5-6.5). After 6 months of ART, median CD4 cell count was 304 cells/μl (IQR 163-469). One hundred and sixty-four NADCs were diagnosed during study follow-up, 65 (40%) considered virus-related. Virus-related NADCs were inversely associated with 6-month CD4 cell count (hazard ratio per 100 cells/μl increase=0.71), latest CD4 cell count (hazard ratio per 100 cells/μl increase=0.70) and CD4 cell count-years (hazard ratio per 200 cell-years/μl increase=0.91) independent of CD4 cell count at ART initiation, age and HIV-1 RNA response. No associations were found with virus-unrelated NADCs.

Conclusion

Poor CD4 cell count response was strongly associated with virus-related NADC incidence, suggesting an important role for T-cell mediated immunity in pathogenesis. Lower CD4 cell count proximal to cancer diagnosis may be a result of subclinical cancer. Intensified cancer screening should be considered for patients on ART with low CD4 cell counts.

We determined risk of virologic failure (VF) in individuals initiating tenofovir/emtricitabine/efavirenz as single versus multiple tablet regimens (MTR). We found no significant difference in the risk of VF, though did observe a trend toward more VF and M184 V mutations among persons initiating MTR. Temporal trends in care may have confounded results.

Background

Contemporary data on patterns of antiretroviral therapy (ART) use in the United States are needed to inform efforts to improve the HIV care cascade.

Methods

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/mm), demographics, psychiatric diagnoses, substance use, and engagement in continuous care (≥2 visits ≥3 months apart in 2010).

Results

Of 8633 patients at 7 sites who had ≥1 medical visit and ≥1 viral load in 2010, 94% had ever initiated ART, 89% were on ART, and 70% had an undetectable viral load at the end of 2010. Fifty percent of ART-naive patients had nadir CD4 counts >500 cells per cubic millimeter, but this group comprised just 3% of the total population. Among patients who were ART naive 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 per cubic millimeter 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.

Conclusions

Our findings suggest that ART use and viral suppression among persons in HIV care may be more common than estimated in some previous studies and increased from 2009 to 2010.