US Military HIV Natural History Research Articles

Low Level Viremia Is Associated With Serious non-AIDS Events in People With HIV.

The consequences of low-level viremia in people with HIV are unclear. We used data from the US Military HIV Natural History Study to examine the association of low-level viremia (LLV) and serious non-AIDS events (SNAEs). Included participants initiated antiretroviral therapy after 1996 and had ≥3 viral loads (VLs) measured, using an assay with a lower limit of detection of <50 copies/mL, ≥6 months after antiretroviral therapy initiation. VLs were categorized as lower levels of LLV (51-199 copies/mL), higher level of low-level viremia (HLLV; 200-999 copies/mL), and (VF; ≥200 copies/mL on 2 or more successive determinations or a single VL ≥1000 copies/mL), and virologic suppression (VS; ie, VL <50 copies/mL). Viral blips (ie, VLs between 50 and 999 copies/mL that are preceded and succeeded by VL <50 copies/mL) were analyzed in the VS category. Cox proportional hazards models were used to examine the association of LLV and SNAEs, adjusted hazard ratios and 95% confidence intervals are presented. A total of 439 (17.4%) SNAEs were recorded among the 2528 participants (93% male, 40% Caucasian, 43% African American) followed for a median of 11 years. In 8.5% and 4.6% of the participants, respectively, LLV and HLLV were the highest recorded viremia strata. Compared with VS, SNAEs were associated with LLV (1.3 [1.2-1.4]), HLLV (1.6 [1.5-1.7]), and virologic failure (1.7 [1.7-1.8]). The results of this study suggest that LLV is associated with the occurrence of SNAEs and needs further study.

1573. Viral Blips While on Antiretroviral Therapy are Associated with Virologic Failure

Abstract Background Blips in HIV viral load (VL) while on antiretroviral therapy (ART) are of unclear clinical significance. In this study, we examined the association between blips and virologic failure (VF). Methods We used data from the US Military HIV Natural History Study (NHS) cohort. Included participants were diagnosed with HIV after 2006, had been on ART for ≥ 6months, and had ≥3 VLs recorded and measured using an assay with a lower limit of detection of &amp;lt; 50 copies/mL. VF was defined as two consecutive VLs ≥ 200 copies/mL spanning 90 days or a single VL ≥1000 copies/mL. Blips were defined as VL of 51-999 copies/mL, that were preceded and followed by a VL ≤ 50 copies/mL and were differentiated by magnitude as low-level (VL 51-199 copies/mL) or high-level (200-999 copies/mL). Detectable VLs that did not meet criteria for VF or blips were grouped as low-level viremia (LLV; 51-199 copies/mL), and higher low-level viremia (hLLV; 200-999 copies/mL). Cox proportional hazards models adjusted for demographic characteristics, time updated CD4 counts, ART, and viral load were used. Hazard ratios and 95% confidence intervals are presented. Results A total of 988 participants (median age 34.1 years, 96.7% male, 41.7% African American) were included, of which 55 (5.6%) experienced VF (Table 1). While 191 participants (19.3%) experienced blips, it was the highest VL status in 146 (14.8%) (Table 2). Having blips and low-level viremia was associated with increasing hazard of VF, graded by type and level of viremia (low-level blip 1.86 [1.10 – 3.14]; high-level blip 3.56 [1.13 – 11.18]; LLV 4.10 [3.06-5.51]; hLLV 10.51 [6.28-17.61]. Other factors associated with VF were African American race and higher VL at ART initiation. Whereas higher CD4 counts, and use of integrase strand transfer inhibitors (relative to Non-Nucleoside Reverse Transcriptase inhibitors) were protective (Table 3). Conclusion Detectable viremia, including blips, are associated with an increased risk of VF. The magnitude of the viremia appears important with dose-response-type impact (i.e., viral loads &amp;gt;200 copies/mL having a greater hazard of VF). These findings suggest that individuals with viral blips at a minimum should undergo evaluation for medication adherence and may benefit from more frequent VL monitoring. Disclosures All Authors: No reported disclosures

2064. Incidence and Risk Factors for Microscopic Hematuria in a US Military HIV Cohort

Abstract Background Microscopic hematuria (MH) is a common finding on screening urinalyses in persons living with HIV (PLWH); however, a study in the pre-HAART era revealed that a complete urologic evaluation was generally non-diagnostic in young males with a benign history and normal renal function. Recent studies have shown a decreased incidence of hematuria in PLWH in the HAART era. We performed a nested case-control study in the prospectively enrolled US Military HIV Natural History Study (NHS) to evaluate characteristics of PLWH with and without MH. Methods We evaluated male participants diagnosed with HIV and enrolled in the NHS Jan 2007 to Dec 2019. MH cases were defined as having at least one urinalysis with ≥5 RBCs/hpf. We used descriptive statistics to compare cases and controls with respect to demographics, comorbidities, and laboratory findings to determine risk factors for MH. Cox regression models evaluated for independent associations with the development of MH since HIV diagnosis. Results Of 829 included participants, 142 (17.1%) had MH, of whom 87 (61.3%) had only one MH event. Cases had a shorter mean duration of study follow-up but more analyzable urinalyses per participant. There were no significant differences between cases and controls in demographics, CD4 count nadir, time from HIV diagnosis to HAART initiation, or inclusion of tenofovir disoproxil fumarate (TDF) in initial regimen. On univariate analysis, more cases had a history of urinary tract infection (UTI) or a hypertension diagnosis through the time of incident MH compared to controls, but were less likely to have proteinuria or pyuria at the time of MH. Cox regression models revealed that a history of UTI increased the hazard for MH (HR 2.07, p &amp;lt; 0.05). In contrast, the presence of proteinuria (HR 0.42, p&amp;lt; 0.01) and TDF use (HR 0.56, p&amp;lt; 0.05) decreased the hazard for MH compared to controls. Conclusion A history of UTI, though not concurrent pyuria, was associated with an increased hazard for MH. The use of TDF in the initial HAART regimen and the presence of proteinuria were protective against hematuria. Future studies are needed to clarify these findings; however, they provide reassurance that in a young, otherwise healthy cohort, MH is typically self-limited and unrelated to intrinsic renal pathology, comorbidity, or HIV-related factor. Disclosures All Authors: No reported disclosures.

Patients with HIV-associated cancers have evidence of increased T cell dysfunction and exhaustion prior to cancer diagnosis

BackgroundPeople living with HIV (PLWH) have increased risk of developing cancers after controlling traditional risk factors and viral suppression. This study explores whether T cells can serve as a marker...

68. Comparison of Cardiovascular Risk Assessment Calculators in the US Military HIV Natural History Study

BackgroundPeople living with HIV (PLHIV) have increased risk of cardiovascular disease (CVD), however CVD risk assessment can be challenging as HIV-related factors are not included in most calculators. We compared CVD risk calculators in US Military HIV Natural History Study (NHS) participants.MethodsThe NHS database was screened for participants enrolled between 2009-2019 who were ≥ 40 years of age with no previous history of CVD or statin use. Of the 399 participants meeting criteria, 385 (96.5%) had available data to assess 3 CVD risk calculators: Atherosclerotic CVD risk calculator (ASCVD), Framingham Risk Calculator (FRC), and the Data Collection on Adverse Effects of Anti-HIV Drugs Study (DAD) risk calculator. Risk calculators were applied cross-sectionally at the first available time point at or after age 40 years and calculators were compared using a Wilcoxon signed rank test. Demographic and HIV-related characteristics were analyzed as independent variables.ResultsParticipants were predominantly male (91.1%), mostly White (49.6%) or Black/African American (44.7%), and commonly had a history of tobacco use (38.9%). The mean age at HIV diagnosis and at CVD risk calculation was 33 and 41.8 years, respectively (Table 1). Overall, there was significant variability between calculators with mean scores of 3.66%, 2.50% and 1.38% for ASCVD, FRC, and DAD, respectively for all pairwise comparisons (p< 0.001; Table 2). When assessing those with CVD risk ≥ 7.5%, a clinically relevant threshold, the proportion of individuals with risk ≥ 7.5% varied for the ASCVD (10.4%), FRC (7.5%), and DAD (< 0.8%) calculators. Associations or trends toward higher CVD risk was observed among the various calculators for race/ethnicity and both age < 30 years and CD4 ≤ 350 cells/uL at HIV diagnosis (Table 2). ConclusionSince significant variability among CVD risk calculators was observed in the NHS cohort, it may be challenging to apply overall CVD risk calculators in a clinically relevant manner. HIV-related factors, such as duration of HIV infection and CD4 nadir, are not accounted for in CVD calculators and may be indicators of increased CVD risk. Future studies are warranted in order to determine the optimal clinical use of CVD risk calculators for PLHIV. Disclosures All Authors: No reported disclosures

Statin usage and cardiovascular risk among people living with HIV in the U.S. Military HIV Natural History Study.

Using the American College of Cardiology/American Heart Association 2013 atherosclerotic cardiovascular disease (ASCVD) management guidelines, we conducted a retrospective cross-sectional analysis of people living with HIV in the US Military HIV Natural History Study to determine whether individuals were receiving statins when indicated. Prescription data was taken from Military Health System data. Statin eligibility was defined by ASCVD guidelines. We used the 10-year ASCVD pooled cohorts' equation to evaluate risk for each participant. Across all categories, 31.9% (n=390) of individuals met criteria for statin use, and when adding these subjects to the number of those already receiving statins (n=96), 62.1% of all eligible subjects (n=302/486) were actually receiving statin therapy. In multivariable analysis, individuals of African American race [odds ratio (OR) = 0.48, 95% confidence interval (CI): 0.31-0.73] or Hispanic ethnicity (OR = 0.42, 95% CI: 0.19-0.94) were less likely to receive statin prescriptions than white individuals. Individuals with a higher CD4 count (OR = 1.12, 95% CI: 1.05-1.20 per 100 cells/μL]) were significantly more likely to receive a statin prescription. These data highlight discrepancies between ASCVD guidelines and primary care management of people living with HIV (PLWH) in the military health system, along with important racial differences. Targeted interventions are critical to identify and treat appropriate candidates for statin therapy among PLWH in the military and other settings.

Association between depression and HIV treatment outcomes in a US military population with HIV infection

BackgroundDepression is common among HIV-infected individuals and may contribute to suboptimal adherence to antiretroviral therapy (ART) and subsequent inability to attain viral load (VL) suppression. We evaluated associations between depression, self-reported adherence, and longitudinal HIV treatment outcomes in US Military HIV Natural History Study (NHS) participants with and without depression.MethodsMale NHS participants with available ICD-9 data for mental health diagnoses, Center for Epidemiological Studies Depression (CES-D) measures, and self-reported adherence (SRA) were included. ART use was defined as ART initiation between 2006 and 2010, with follow-up through 2015. SRA was defined as taking 95% of ART doses and continuous ART was defined as longitudinal ART use with gaps < 30 days. Continuous VL suppression was defined as maintaining VLs < 200 c/mL on ART. To analyse the association between depression and HIV treatment outcomes, latent class analysis was used to create classes of depression trajectories: low depression (LD), recent onset depression (ROD) and high Depression (HD).ResultsParticipants had a mean age of 32 (± 8.3) years at HIV diagnosis, and similar proportions were Caucasian (44.3%) or African American (40.8%). Overall, older participants at HIV diagnosis had greater odds of having 95% self-reported adherence (OR 1.06, 95% CI 1.02–1.12), and African Americans had lower odds (OR 0.41, 95% CI 0.22–0.76) compared to Caucasians (OR 1.49, 95% CI 0.52–4.28). However, there was no difference in SRA by depression trajectory. Participants with HD had an increased odds of taking ART continuously (OR 1.75, 95% CI 0.99–3.09), and those with ROD had significantly higher odds of virologic failure (OR 0.58, 95% CI 0.38–0.91).ConclusionsAlthough there was no observed association between depression and SRA, participants with ROD had lower odds of attaining the HIV treatment goal of VL suppression. Continued efforts to identify and aggressively manage mental health disorders is important to success along the HIV care continuum.

High frequency of potential phosphodiesterase type 5 inhibitor drug interactions in males with HIV infection and erectile dysfunction.

We sought to determine the prevalence of phosphodiesterase type 5 inhibitor (PDE-5) mediated drug-drug interactions (DDIs) in males with HIV infection receiving antiretroviral therapy (ART) and identify factors associated with PDE-5-mediated DDIs. Male US Military HIV Natural History Study participants diagnosed with erectile dysfunction (ED) and having a PDE-5 inhibitor and potentially-interacting ART co-dispensed within 30 days were included. DDIs were defined according to criteria found in published guidelines and drug information resources. The primary outcome of interest was overall PDE-5 inhibitor-mediated DDI prevalence and episode duration. A secondary logistic regression analysis was performed on those with and without DDIs to identify factors associated with initial DDI episode. A total of 235 male participants with ED met inclusion criteria. The majority were White (50.6%) or African American (40.4%). Median age at medication co-dispensing (45 years), duration of HIV infection (14 years), and duration of ED (1 year) did not differ between the two groups (p>0.05 for all). PDE-5 inhibitors included sildenafil (n = 124), vardenafil (n = 99), and tadalafil (n = 14). ART regimens included RTV-boosted protease inhibitors (PIs) atazanavir (n = 83) or darunavir (n = 34), and COBI-boosted elvitegravir (n = 43). Potential DDIs occurred in 181 (77.0%) participants, of whom 122 (67.4%) had multiple DDI episodes. The median DDI duration was 8 (IQR 1-12) months. In multivariate analyses, non-statistically significant higher odds of DDIs were observed with RTV-boosted PIs or PI-based ART (OR 2.13, 95% CI 0.85-5.37) and in those with a diagnosis of major depressive disorder (OR 1.74, 95% CI 0.83-3.64). PDE-5-mediated DDIs were observed in the majority of males with HIV infection on RTV- or COBI-boosted ART in our cohort. This study highlights the importance of assessing for DDIs among individuals on ART, especially those on boosted regimens.

Factors associated with erectile dysfunction diagnosis in men with HIV infection: a case-control study.

HIV infection is associated with increased risk of erectile dysfunction (ED); however, factors associated with ED remain unclear. We evaluated the prevalence of ED among men living with HIV and factors associated with ED diagnosis in the US Military HIV Natural History Study (NHS). A retrospective cohort study evaluated participants in the NHS, a cohort of HIV-positive active duty members and beneficiaries with HIV infection. Men with a diagnosis of ED after HIV diagnosis were included. Cohort controls without ED diagnosis were matched 2:1 by age at HIV diagnosis and duration of follow-up. Multivariate logistic regression models were used to identify factors associated with ED. A total of 543 of 5682 male participants (9.6% prevalence) had a diagnosis of ED, of whom 488 were included in the analysis. The median (interquartile range, IQR) age at ED diagnosis was 43 (37.0-49.0) years and the time from HIV diagnosis to antiretroviral therapy (ART) start was longer for cases (5.0years, IQR: 2.0-9.0) than for controls (3.0years, 1.0-6.0; P<0.01). Cases had higher proportions of multiple comorbid conditions, including depression (33.4% vs. 21.7%), tobacco use (19.7% vs. 9.0%) and sleep apnoea (14.8% vs. 4.2%) compared with controls (P<0.01 for all). Logistic regression showed increased odds of ED for delayed ART initiation>4years [odds ratio (OR) = 2.05, 95% confidence interval (CI): 1.56-2.71], protease inhibitor use≥1year (OR = 1.81, 95% CI: 1.38-2.38) and sleep apnoea (OR = 2.60, 95% CI: 1.68-4.01). Erectile dysfunction was common in men with HIV and associated factors included both HIV-related and traditional factors.

Risk Factors Associated With Chronic Liver Enzyme Elevation in Persons With HIV Without Hepatitis B or C Coinfection in the Combination Antiretroviral Therapy Era.

BackgroundAs morbidity due to viral coinfections declines among HIV-infected persons, changes in liver-related morbidity are anticipated. We examined data from the US Military HIV Natural History Study (NHS), a cohort of military beneficiaries, to evaluate incidence and risk factors associated with chronic liver enzyme elevation (cLEE) in HIV-monoinfected patients in the combination antiretroviral therapy (cART) era.MethodsParticipants who were hepatitis B virus and hepatitis C virus seronegative with follow-up after 1996 were included. We defined chronic liver enzyme elevation (cLEE) as alanine aminotransferase elevations ≥1.25 times the upper limit of normal on at least 2 visits, for a duration of ≥6 months within 2 years. We used multivariate Cox proportional hazards models to examine risk factors for cLEE.ResultsOf 2779 participants, 309 (11%) met criteria for cLEE for an incidence of 1.28/100 PYFU (1.28–1.29/100 PYFU). In an adjusted model, cLEE was associated with Hispanic/other ethnicity (reference Caucasian: hazard ratio [HR], 1.744; 95% CI, 1.270–2.395), non–nucleoside reverse transcriptase inhibitor–based cART (reference boosted protease inhibitors: HR, 2.232; 95% CI, 1.378–3.616), being cART naïve (HR, 6.046; 95% CI, 3.686–9.915), or having cART interruptions (HR, 8.671; 95% CI, 4.651–16.164). African American race (HR, 0.669; 95% CI, 0.510–0.877) and integrase strand transfer inhibitor (INSTI)–based cART (HR, 0.222; 95% CI, 0.104–0.474) were protective.ConclusionsOur findings demonstrate that initiation and continued use of cART are protective against cLEE and support the hypothesis that HIV infection directly impacts the liver. INSTI-based regimens were protective and could be considered in persons with cLEE.

1014. Factors Associated with Switching from Tenofovir Diproxil Phosphate to a Tenofovir Alafenamide Based Regimen in a Cohort with Unrestricted Access to Care and Medications

Background Background- Tenofovir alafenamide (TAF) is associated with fewer renal and bone toxicities than tenofovir disoproxil phosphate (TDF). Hence, most experts suggest switching to TAF. We examined factors associated with switching to TAF in the US Military HIV Natural History Study (NHS), a cohort of people living with HIV who have unrestricted access to care and medications.Methods Methods- The first formulation of TAF received FDA approval on 1 November 2015; hence, we included all NHS participants with visits between November 2015 and March 2019. Patient factors including race, gender, CD4 count, antiretroviral therapies (ART), viral load, HIV diagnosis era, presence of comorbidities (cancer, heart disease, dyslipidemia, kidney disease and obesity), were assessed for association with a switch to TAF with a logistic regression model.Results Results- Of the 1678 eligible participants, 1324 (63%) had received a TDF-based regimen. Participants who received a TDF-regimen were 94% male 44% African-American [AA], 39% Caucasians and 17% Hispanic. About half the participants who received TDF-based ART switched to a TAF-based regimen (n=682, 52%). Of the 425 (32%) participants receiving TDF/FTC co-formulated with efavirenz, 48% (n=206) switched to TAF. The proportions switching to TAF were higher in those receiving TDF/FTC co-formulated with rilpivirine [59%, n=90] or elvitegravir/cobicistat [68%, n=146]. The common ART regimens after the switch were: TAF co-formulated with elvitegravir/cobicistat (46%), rilpivirine (16%) or bictegravir (12%) and TAF/FTC combined with dolutegravir (15%). In an adjusted analysis, older participants, and participants receiving TDF/FTC in combination with efavirenz, dolutegravir, raltegravir, boosted protease inhibitors or a combination of boosted protease inhibitors and integrase inhibitors (other) were less likely to switch, table 1.Conclusion Conclusions- Despite the unrestricted access to care and ART in the NHS, only half of the participants switched to TAF. Participants on efavirenz-containing regimens were less likely to switch to a TAF-based regimen, possibly due to the lack of a co-formulated single tablet. These trends need to be followed and barriers to switching to TAF (both patient and provider) need examination.Table 1- Factors associated with switching to a Tenofovir Alafenamide Based Regimen Disclosures All Authors: No reported disclosures

185. Despite the Availability of Free Testing and Care Testing for Extragenital Sexually Transmitted Infections in a Cohort of Hiv-infected Department of Defense Beneficiaries Is Low and Similar to the Rates Observed Nationwide

Background Background- Current guidelines recommend annual extragenital [EG] testing for all sexually active men who have sex with men (MSM), and every 3−6 months for MSM at risk for sexually transmitted infections (STIs). Compliance with this guideline is low and testing rates among MSM with HIV have ranged between 30–46%. Financial disincentives (such as the lack of reimbursement for EG testing) may contribute to the lower EG testing rates. To examine if access to free testing improves EG testing rates, we used data from the US Military HIV Natural History Study (NHS), a cohort comprised of HIV-infected Department of Defense beneficiaries with access to care and free testing.Methods Methods- Among NHS participants with a follow-up visit between 1/1/2013 and 1/1/2018, genital (primarily urine samples) and EG testing rates (pharyngeal and rectal) were calculated and temporal trends examined. Multivariate logistic regression analysis was used to examine factors associated with EG testing. In a sub-set of participants who answered a risk behavior survey we examined risk-related information.Results Results- Of the 1971 male participants who had a NHS visit during the study period, 1962 (99.5%) had genital and 1419 (72%) had EG testing performed at least once. Annual genital and EG testing rates ranged between 96 - 98% and 33% - 46% respectively. No temporal trends were observed in EG testing rates. EG testing rates were higher in those with a history of gonorrhea, chlamydia or syphilis in the year prior, ranging between 50 and 67%. EG testing was more likely to occur in those who were younger and those with a prior history of STI (Table 1). In a subset of participants with risk behavior information, those who reported being MSM were more likely to be tested [Referent heterosexual; Odds Ratio 2.35 [95% CI 1.60–3.46].Conclusion Conclusion-Despite the availability of free EG testing, EG testing rates were low in the NHS and similar to those observed nationwide This contrasts with the genital testing rates which were well over 95%, suggesting provider/patient related barriers are likely driving the lower testing rates. To improve testing rates further study is required to fully characterize indications for EG testing and potential provider- and/or patient-related barriers to EG testing. Disclosures All Authors: No reported disclosures

Predictors of health-related quality of life among military HIV-infected individuals.

To determine long-term predictors of health-related quality of life (HRQOL) and evaluate the treatment effect of highly active antiretroviral therapy (HAART) on HRQOL in the US Military HIV Natural History Study (NHS) cohort. Participants were a nested cohort of the NHS who responded to the Rand Short Form 36 questionnaire administered from 2006 to 2010. Physical component summary scores (PCS) and mental component summary scores (MCS) were computed using standard algorithms. HAART-status was categorized as non-protease inhibitor-based (NPI-HAART), protease inhibitor-based (PI-HAART), HAART-naïve, or off-HAART. Mixed linear random effects models were used to estimate changes in PCS and MCS over time for treatment and covariates (including CD4 count, HIV viral load, medical and mental comorbidities). Eight hundred and twelve participants met the inclusion criteria. There was no difference in PCS or MCS between those on PI-HAART compared to NPI-HAART. Significant predictors of PCS were CD4 count < 200 cells/mm3 (β = - 2.90), CD4 count 200-499cells/mm3 (β = - 0.80), and mental comorbidity (β = - 3.23). Others were medical comorbidity, AIDS-defining illness, being on NPI-HAART, HAART-naïve, age, and rank. Those with medical comorbidities experienced yearly improvement in PCS. Predictors of MCS were CD4 count < 200cells/mm3 (β = - 2.53), mental comorbidity (β = - 4.58), and being African American (β = 2.59). HRQOL was significantly affected by low CD4 count, medical and mental comorbidities. Addressing these modifiable factors would be expected to improve the physical and mental HRQOL of the cohort. Our study did not find any treatment benefit of NPI-HAART over PI-HAART on HRQOL in the long term.

CD4 rate of increase is preferred to CD4 threshold for predicting outcomes among virologically suppressed HIV-infected adults on antiretroviral therapy.

ObjectivesImmune non-responders (INR) have poor CD4 recovery and are associated with increased risk of serious events despite antiretroviral therapy (ART). A clinically relevant definition for INR is lacking.MethodsWe conducted a retrospective analysis of three large cohorts: Infectious Disease Clinic at the Atlanta Veterans Affairs Medical Center, the US Military HIV Natural History Study and Infectious Disease Program of the Grady Health System in Atlanta, Georgia. Two-stage modeling and joint model (JM) approaches were used to evaluate the association between CD4 (or CD4/CD8 ratio) slope within two years since ART initiation and a composite endpoint (AIDS, serious non-AIDS events and death) after two years of ART. We compared the predictive capacity of four CD4 count metrics (estimated CD4 slope, estimated CD4/CD8 ratio slope during two years following ART initiation and CD4 at 1 and 2 years following ART initiation) using Cox regression models.ResultsWe included 2,422 patients. Mean CD4 slope (±standard error) during two years of ART was 102 ± 2 cells/μl/year (95% confidence interval: 98–106 cells/μl/year), this increase was uniform among the three cohorts (p = 0.80). There were 267 composite events after two years on ART. Using the JM approach, a CD4 slope ≥100 cells/μL/year or CD4/CD8 ratio slope >0.1 higher rate per year were associated with lower composite endpoint rates (adjusted hazard ratio [HR] = 0.80, p = 0.04 and HR = 0.75 p<0.01, respectively). All four CD4 metrics showed modest predictive capacity.ConclusionsUsing a complex JM approach, CD4 slope and CD4/CD8 ratio slope the first two years after ART initiation were associated with lower rates of the composite outcome. Moreover, the uniformity observed in the mean CD4 slope regardless of the cohort suggests a common CD4 response pattern independent of age or CD4 nadir. Given the consistency observed with CD4 slope, availability and ease of interpretation, this study provides strong rationale for using CD4 gains <100 cells/μl/year to identify patients at risk for adverse events.

336. Disparities in Cardiovascular Disease Prevention Among Persons Living with HIV in the United States Military Natural History Study

BackgroundThe use of antiretroviral therapy has reduced morbidity and mortality associated with HIV infection primarily due to the reduction of AIDS-related events. Although guidelines have aimed to standardize preventive care, disparities in prevention of cardiovascular disease remain prevalent across multiple cohorts.MethodsThe US Military HIV Natural History Study is an open cohort of Department of Defense beneficiaries. We included subjects aged 21–75 whose most recent study visit was between October 2015 and September 2016 and conducted a retrospective cross-sectional analysis of established cardiovascular disease risk factors and statin use. To determine statin eligibility we used the American College of Cardiology/American Heart Association 2013 atherosclerotic cardiovascular disease management guidelines and included subjects who had all necessary data elements for analysis.ResultsThe participants (n = 1223) were predominantly middle-aged (median 47 years, Interquartile Range [IQR] 33–55), male (95%), and were racially diverse (46% African-American, 16% Hispanic/other). The rate of tobacco use was 16%, diabetes was 11%, and 36% had hypertension. In total, 486 (40%) patients met criteria for statin therapy, with 17% of those being for secondary prevention. As of their last visit, 52 (4%) had a detectable HIV viral load. Statins were prescribed to only 302 (62%) of those with an indication, with lower prescription rates in African Americans (52%) and Hispanics (58%) than Caucasians (73%). Average blood pressure, rates of tobacco use, and prevalence of diabetes were equal between the African American and Caucasian groups.ConclusionWe found significant racial disparities in both primary and secondary cardiovascular disease mitigation within the military healthcare system. Previous studies have found similar racial differences attributed to socioeconomic factors and higher rates of intravenous drug use. As active duty service members have a stable income, open access to healthcare, and low rates of injection drug use, our findings challenge that premise. Understanding whether this is due to prescribing practices, physician-patient relationships, or healthcare uptake is critical to narrowing this major gap in care. Disclosures All authors: No reported disclosures.

335. Antiretroviral Therapy Anchor-based Trends in Body Mass Index following Treatment Initiation among Military Personnel with HIV

BackgroundWeight gain and obesity in people living with HIV have been associated with increased risk for non-AIDS-related comorbidities, and integrase strand transfer inhibitor (INSTI)-based regimens may lead to comparatively more weight gain than other regimens. We evaluated body mass index (BMI) following antiretroviral therapy (ART) initiation among participants in the US Military HIV Natural History Study (NHS).MethodsOf 961 NHS participants started on initial ART between 2006–2017, 496 men who had available baseline BMI data and were virally suppressed (< 200 c/mL) at 1 and 2 years of follow-up were included (Tables 1 and 2). ART was categorized by anchor class to include INSTIs, non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). Linear growth-curve modeling was used to predict BMI changes from ART initiation through 2 years of follow-up in participants stratified by baseline BMI (< 25 vs. ≥25 kg/m2) at ART start and anchor drug class. Demographic and HIV-related characteristics were analyzed as independent variables.ResultsOverall, the predicted BMI increased over 2 years regardless of baseline BMI (Table 3). There was a trend toward decreased BMI on ART for those with BMI ≥ 25 treated with a non-INSTI regimen (−0.63, P = 0.079). In participants with BMI < 25, all regimens were associated with overall gains in BMI except for those with high viral load (>100,000 c/mL) started on PI regimens (−1.61, P = 0.013). For those with BMI ≥ 25, only INSTI- and PI-based regimens were significantly associated with increased BMI (INSTI 0.54, P = 0.000; NNRTI 0.11, P = 0.174; PI 0.39, P = 0.006). Observed BMI increases for INSTI and PI regimens were also associated with increased time from HIV diagnosis to ART initiation (INSTI 0.35, P = 0.003; PI 0.44, P = 0.037). African Americans with BMI ≥ 25 on INSTIs had the greatest predicted gains in BMI (1.84, P = 0.007).ConclusionIn our cohort of young military members with HIV infection, those with baseline BMI < 25 experienced BMI gains across all ART classes. Among those with baseline BMI ≥ 25, African Americans on INSTI regimens had the greatest BMI gains. Further studies are needed to determine whether NNRTI regimens should be considered in certain individuals at risk for INSTI-associated weight gain. Disclosures All authors: No reported disclosures.

2515. Clinical Relevance of Immune Non-Response Among Virally Suppressed Adults Living with HIV in Africa and the United States

BackgroundImmune non-response (INR) for people living with HIV (PLWH) is the inability to regain healthy CD4 counts despite viral suppression (VS) on antiretroviral therapy (ART). We identified factors associated with INR in two methodologically similar but demographically diverse cohorts with open access to care and assessed the relationship between INR and incident serious non-AIDS event (SNAE).MethodsThe US Military HIV Natural History Study (NHS) and the African Cohort Study (AFRICOS) are multisite, open cohort studies enrolling PLWH. Participants with 2 years of VS < 400 copies/mL on ART were evaluated for INR, defined as CD4 < 350 cells/µL at 2 years VS. Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for factors associated with INR. Cox proportional hazards regression produced adjusted hazard ratios (aHR) and 95% CIs for factors associated with incident SNAE (first non-AIDS cancer, cardiovascular, gastrointestinal, genitourinary, liver, musculoskeletal or respiratory event) after 2 years of VS.Results10.8% of the 1,784 NHS and 25.8% of the 984 AFRICOS subjects had INR. The AFRICOS cohort was older and had a higher proportion of females. In both cohorts, immune non-responders were significantly older and had a significantly lower CD4 at ART initiation. Those with INR also took longer to reach 2 years of VS since starting ART. Odds of INR decreased by over 60% for every 100 cell increase in baseline CD4 in both cohorts (NHS aOR = 0.31 [95% CI 0.26, 0.37]; AFRICOS aOR = 0.36 [95% CI 0.21, 0.86]). In the NHS, hazard of incident SNAE was 61% higher for those with INR (aHR = 1.61 [95% CI 1.12, 2.33]). Probability of SNAE-free survival at 15 years since 2 years of VS was approximately 20% lower comparing those with and without INR; nearly equal to the differences observed by 15-year age groups.ConclusionINR was common in two diverse cohorts with open access to care and treatment. The association with SNAEs suggests early identification of and interventions to prevent or reverse INR may improve clinical outcomes, but further study is needed. The clinical relevance of INR highlights the value of early HIV identification and treatment, and suggests CD4 monitoring at ART initiation and post-VS is important in settings where INR is prevalent. Disclosures All authors: No reported disclosures.

369. Association Between Depression and HIV Treatment Outcomes in a US Military Population with HIV Infection

BackgroundDepression is common among HIV-infected individuals and may contribute to suboptimal adherence to antiretroviral therapy (ART) and reduced rates of viral load (VL) suppression. We evaluated longitudinal HIV treatment outcomes in US Military HIV Natural History Study (NHS) participants with or without a diagnosis depression.MethodsMale NHS participants with available ICD-9 data for mental health diagnoses and self-reported adherence (SRA) were included (n = 549). Groups were defined as having a history of depression (n = 188, 34.2%), classified as major depressive disorder and/or anxiety disorder, or no history of depression (n = 361, 65.8%). Delay in ART initiation was defined as the time from HIV diagnosis to ART start greater than the group mean (4.91 ± 4.69 years). SRA was defined as taking ≥95% of ART doses and continuous ART was defined as longitudinal ART use with gaps < 30 days. Continuous VL suppression was defined as maintaining VLs < 200 c/mL on ART. Logistic regression analysis was performed comparing variables for those with and without a coded diagnosis of depression.ResultsParticipants had a mean age of 33 (±8.36) years at HIV diagnosis, and similar proportions were Caucasian (44.3%) or African American (40.8%). At ART initiation, the mean CD4 count was 370 (±154 cells/μL) and 362 (±163 cells/μL) for those with and without a history of depression, respectively. Overall, older participants at HIV diagnosis had greater odds of having high SRA (OR 1.07, 95% CI 1.03–1.11), and compared with Caucasians, African Americans had lower odds of having high SRA (OR 0.43, 95% CI 0.25–0.75; table). Participants with a history of depression had greater odds of experiencing delayed ART initiation (OR 2.12, 95% CI 1.11–4.05). However, they also had greater odds of remaining on continuous ART (OR 1.38, 95% CI 0.95–2.02) during follow-up compared with those without a history of depression.ConclusionAlthough HIV-infected individuals with depression were more likely to experience delays in ART initiation, there were no observed differences in SRA or VL suppression. Continued efforts to identify and aggressively manage mental health disorders are important to success along the HIV care continuum. Disclosures All authors: No reported disclosures.

Relationship between depression and risk behaviors in a US Military population with HIV infection

ABSTRACTThis study evaluated the relationships between depression trajectories, depression diagnosis and sexual risk behaviors in the US Military HIV Natural History Study. Risk behavior survey data, a coded diagnosis of depression, available Center for Epidemiological Studies Depression measures, and self-reported depressive symptoms (n = 662) were utilized. Latent class analysis created 3 classes of depression trajectories, namely, low depression (LD, n = 378), recent-onset depression (ROD, n = 170), and high depression (HD, n = 114) trajectories. Overall, participants with clinically diagnosed depression were less likely to report often using condoms with new sexual partners in the past 3 months than those who have never been diagnosed with depression (OR 0.15, 95% CI 0.49–2.53). Participants with ROD (OR 0.52, 95% CI 0.28–0.97) and HD (OR 0.48, 95% CI 0.24–0.96) trajectories were less likely to report often using condoms with new sexual partners in the past 3 months than those with LD trajectories. Moreover, those with either ROD (OR 2.13, 95% CI 1.19–3.80) or HD (OR 2.74, 95% CI 1.43–5.24) trajectories were more likely to have had sex with ≥2 new sexual partners in the last 3 months than those with LD trajectories. Continued efforts targeting HIV-infected persons with mental health disorders are warranted to reduce sexual risk behaviors.

Persistent Low-level Viremia While on Antiretroviral Therapy Is an Independent Risk Factor for Virologic Failure.

Whether persistent low-level viremia (pLLV) predicts virologic failure (VF) is unclear. We used data from the US Military HIV Natural History Study (NHS), to examine the association of pLLV and VF. NHS subjects who initiated combination antiretroviral therapy (ART) after 1996 were included if they had 2 or more VLs measured with a lower limit of detection of ≤50 copies/mL. VF was defined as a confirmed VL ≥200 copies/mL or any VL >1000 copies/mL. Participants were categorized into mutually exclusive virologic categories: intermittent LLV (iLLV) (VL of 50-199 copies/mL on <25% of measurements), pLLV (VL of 50-199 copies/mL on ≥25% of measurements), high-level viremia (hLV) (VL of 200-1000 copies/mL), and continuous suppression (all VL <50 copies/mL). Cox proportional hazards models were used to evaluate the association between VF and LLV; hazard ratios and 95% confidence interval (CI) are presented. Two thousand six subjects (median age 29.2 years, 93% male, 41% black) were included; 383 subjects (19%) experienced VF. After adjusting for demographics, VL, CD4 counts, ART regimen, prior use of mono or dual antiretrovirals, and time to ART start, pLLV (3.46 [2.42-4.93]), and hLV (2.29 [1.78-2.96]) were associated with VF. Other factors associated with VF include black ethnicity (1.33 [1.06-1.68]) and antiretroviral use prior to ART (1.79 [1.34-2.38]). Older age at ART initiation (0.71 [0.61-0.82]) and non-nucleoside reverse transcriptase inhibitor (0.68 [0.51-0.90]) or integrase strand transfer inhibitor use (0.26 [0.13-0.53]) were protective. Our data add to the body of evidence that suggests persistent LLV is associated with deleterious virologic consequences.