Military HIV Natural History Study Research Articles

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.

Refractive surgery in the HIV-positive U.S. Military Natural History Study Cohort: complications and risk factors

This study sought to assess the frequency of refractive surgery complications in HIV+ individuals and related risk factors. Multiple centers in the United States. Prospective observational cohort study. The U.S. Military HIV Natural History Study is aprospective observational cohort study of HIV+service membersand beneficiaries. Participants were selected who hadCurrent Procedural Terminology codes for laser insitu keratomileusis (LASIK), photorefractive keratectomy (PRK), and other refractive surgeries. The frequency of complications was determined using International Classification of Diseases-9 codes. Covariates included age, sex, antiretroviral therapy, time since HIV diagnosis, history of AIDS, and CD4 (T lymphocytes) count and viral load. Statistical analysis was completed using univariate(χ2 and Wilcoxon-Mann-Whitney tests) and multivariate analyses. Seventy-nine of 2073 participants had refractive surgery. Fifty-three patients underwent PRK, 23 LASIK, 2 radial keratotomy (RK), and 1 astigmatic correction. Complications occurred in 6(7.6%) of 79 participants, including 5 patients who underwent PRK and 1 after RK, occurring between 8 and 217days after surgery. Five ulcers and 1 unspecified keratitis were noted. In the univariate analysis, type of surgery (P=.02) and history of AIDS (P=.02) were risk factors for complications. In logistic regression analysis, no variables were found to be risk factors for complications. Complications were infrequent among HIV+ participants after refractive surgery. Point estimates suggest that PRK might have more complications than LASIK and that advanced HIV, reflected by previous AIDS, might be associated with an increased risk for complications. Further study will be required to confirm these findings.

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.

Age, Race, and At-Risk Drinking in an HIV-infected U.S. Military Cohort.

There is a high prevalence of at-risk drinking in the U.S. military. Among HIV-infected individuals, alcohol abuse confers additional risk for adverse health outcomes. In the military, however, the characteristics of HIV-infected individuals who engage in high-risk drinking are not well defined. The purpose of this study was to assess risk factors associated with at-risk drinking in an HIV-positive longitudinal cohort of DoD beneficiaries. Annual prevalence of at-risk drinking was calculated for members of the U.S. Military HIV Natural History Study who initiated highly active antiretroviral therapy (HAART) during or after January 2006 through May 2014; each participant completed at least one self-reported alcohol survey within a year of HAART initiation. Univariate and multivariable logistic regression was used to analyze factors associated with at-risk drinking. Sixty-six percent of subjects (495/752) reported at-risk drinking on at least one survey after HAART initiation. At-risk drinkers were more likely to be Active Duty compared to Retired (OR 0.65 95% CI [0.46, 0.92]). In multivariate models, Caucasian race (OR 3.30 95% CI [2.31, 4.71]); Hispanic/other race (OR 2.17 95% CI [1.51, 3.14]) and younger age (OR 0.61 per 10 years older, [95%CI 0.49, 0.75]) were significantly associated with at-risk drinking. Single relationship status (OR 1.51 95% CI [1.08, 2.13]) was also associated with at-risk drinking. Consistent with general alcohol consumption patterns in the military, we found a high prevalence of at-risk drinking among individuals with HIV infection, which was associated most closely with young, non-African Americans. Targeting interventions toward this group will be important to reduce at-risk drinking and its potential for HIV-related complications.

602. Factors Associated With Erectile Dysfunction Diagnosis in HIV-Infected Individuals: A Case–Control Study

BackgroundHIV-infected men have increased incidence of erectile dysfunction (ED) compared with men without HIV infection. Risk factors for ED among HIV-positive individuals have not been widely described.MethodsA retrospective cohort study was completed evaluating participants in the US Military HIV Natural History Study, a cohort of HIV-infected active duty members and beneficiaries. Men with a diagnosis of ED after HIV diagnosis were included (n = 488). Cohort controls (n = 976) without ED diagnosis were matched 2:1 by age at HIV diagnosis. Multivariate logistic regression model was used to identify risk factors for ED.ResultsAt HIV diagnosis, the median CD4 count was similar for cases (523 cells/μL, IQR 396–675) and controls (508 cells/μL, IQR 366–673; P = 0.310) and the overall median age was 32 years. At ED diagnosis, cases had a median age of 43 years (IQR 37.0–49.0) and 445 (92.3%) were on antiretroviral therapy (ART). The median time from HIV diagnosis to ART start was longer for cases (5.0 years, IQR 2.0–9.0) compared with controls (3.0 years, IQR 1.0–6.0; P < 0.001). Cases had a higher proportion of the following diagnoses compared with controls (P < 0.001 for all): depression (33.4% vs. 21.7%), hypertension (37.9% vs. 20.4%), hyperlipidemia (54.3% vs. 32.4%), tobacco use (31.1% vs. 23.1%), sleep apnea (14.8% vs. 4.2%) and diabetes/cardiovascular disease (CVD)(10.5% vs. 4.7%). Multivariate logistic regression model is reported below (table).Logistic Regression Model to Predict ED Characteristic Odds Ratio 95% CI P-value Sleep apnea2.621.69–4.05<0.001Time from HIV diagnosis to ART start > mean2.071.58–2.71<0.001African-American race1.760.90–3.420.096Diabetes/cardiovascular disease1.611.01–2.580.048Tobacco use1.420.99–2.040.057Hypertension1.361.02–1.820.034Hyperlipidemia1.260.96–1.640.092Depression1.240.94–1.630.130CD4 count <200 cells/μL at HIV diagnosis0.630.32–1.250.184Prior protease inhibitor use0.430.31–0.60<0.001ConclusionDelay in ART initiation as well as risk factors for and presence of CVD were associated with ED in HIV-infected persons. Mitigating risk factors and optimizing comorbidities is important to improve sexual health and reduce ED in HIV-infected persons.Disclosures All authors: No reported disclosures.

601. Prescription Drug Misuse in an HIV-Infected US Military Cohort

BackgroundsPrescription drug misuse (PDM) has markedly increased over the last decade and is a significant contributor to the national opioid epidemic. HIV+ individuals are particularly vulnerable to PDM as they experience high levels of chronic pain, anxiety and depression. We examined the prevalence of PDM and associated risk factors among HIV-infected subjects in our cohort.MethodsThe US Military HIV Natural History Study (NHS) is comprised of HIV+ active duty, retired military personnel and dependents. Since 2014, participants have completed a computerized behavioral survey regarding patterns of drug use and sexual behavior. We specifically queried topics including use of narcotics, benzodiazepines or stimulants without a prescription or use of medications not as prescribed. Logistic regression was used to compare those reporting and not reporting a lifetime history of PDM. Analyses used anonymous data.ResultsAmong 1,558 respondents, 292 (18.7%) reported a history of PDM. The median age of individuals reporting history of PDM was 45 years (interquartile range [IQR] 31–53) compared with individuals without PDM (41 years; IQR 29–35; P = 0.049); the groups did not differ by race, CD4 count or viral load. The prevalence of lifetime PDM was highest among dependent individuals (31.8%), compared with retired (20.6%) or active-duty personnel (15.9%; P = 0.003 for comparison). After adjusting for age and duty status, military officers were significantly less likely to report PDM than enlisted personnel (OR 0.51; IQR 0.31–0.85). Those with a history of PDM were more likely to consume ≥3 alcoholic drinks/day (OR 1.9; IQR 1.4–2.5). In a sub-analysis of active-duty personnel only (median age 30 years), individuals reporting a history of PDM had fewer years since HIV diagnosis (median 2.9 years vs. 3.9 years, P = 0.019).ConclusionWe found prevalent PDM among HIV-infected military personnel and beneficiaries, and PDM was associated with at-risk drinking. This is the first estimate of PDM among HIV+ active-duty personnel, and longitudinal studies in similar cohorts will be useful in further characterizing the epidemiology of PDM. The higher prevalence among recently diagnosed active-duty personnel may suggest an increasing scope of PDM in this group, and interventions to decrease PDM are urgently needed.Disclosures All authors: No reported disclosures.

Lower health-related quality of life predicts all-cause hospitalization among HIV-infected individuals

BackgroundHealth-related quality of life (HRQOL) is a patient-centered outcome measure used in assessing the individual’s overall functional health status but studies looking at HRQOL as a predictive tool are few. This work examines whether summary scores of HRQOL are predictive of all-cause hospitalization in the US Military HIV Natural History Study (NHS) cohort.MethodsThe Short Form 36 (SF-36) was administered between 2006 and 2010 to 1711 NHS cohort members whose hospitalization records we had also obtained. Physical component summary scores (PCSS) and mental component summary scores (MCSS) were computed based on standard algorithms. Terciles of PCSS and MCSS were generated with the upper terciles (higher HRQOL) as referent groups. Proportional hazards multivariate regression models were used to estimate the hazard of hospitalization for PCSS and MCSS separately (models 1 and 2, respectively) and combined (model 3).ResultsThe hazard ratios (HR) of hospitalization were respectively 2.12 times (95% CI: 1.59–2.84) and 1.59 times (95% CI: 1.19–2.14) higher for the lower and middle terciles compared to the upper PCSS tercile. The HR of hospitalization was 1.33 times (95% CI: 1.02–1.73) higher for the lower compared to the upper MCSS tercile. Other predictors of hospitalization were CD4 count < 200 cells/mm3 (HR = 2.84, 95% CI: 1.96, 4.12), CD4 count 200–349 cells/mm3 (HR = 1.67, 95% CI: 1.24, 2.26), CD4 count 350–499 cells/mm3 (HR = 1.41, 95% CI: 1.09, 1.83), plasma viral load > 50 copies/mL (HR = 1.82, 95% CI: 1.46, 2.26), and yearly increment in duration of HIV infection (HR = 0.94, 95% CI: 0.93, 0.96) (model 3).ConclusionAfter controlling for factors associated with hospitalization among those with HIV, both PCSS and MCSS were predictive of all-cause hospitalization in the NHS cohort. HRQOL assessment using the SF-36 may be useful in stratifying hospitalization risk among HIV-infected populations.

Brief Report: Racial Comparison of D-Dimer Levels in US Male Military Personnel Before and After HIV Infection and Viral Suppression.

D-dimer blood levels in persons with HIV infection are associated with risk of serious non-AIDS conditions and death. Black race has been correlated with higher D-dimer levels in several studies. We examined the effects of race and HIV on D-dimer over time and the impact of viral load suppression by longitudinally comparing changes in levels among healthy young adult male African Americans and whites before HIV seroconversion and before and after initiation of antiretroviral therapy (ART). We analyzed D-dimer levels and clinical and laboratory data of 192 participants enrolled in the US Military HIV Natural History Study, a 30-year cohort of military personnel infected with HIV. D-dimer levels were measured on stored sera from each participant at 3 time points: (1) before HIV seroconversion (Pre-SC), (2) ≥6 months after HIV seroconversion but before ART initiation (Post-SC), and (3) ≥6 months after ART with documented viral suppression (Post-ART). Levels were compared at each time point using nonparametric and logistic regression analysis. Compared with whites (n = 106), African Americans (n = 86) had higher D-dimer levels post-SC (P = 0.007), but in the same individuals, pre-SC baseline and post-ART levels were similar (P = 0.40 and P = 0.99, respectively). There were no racial differences in CD4 cell counts, HIV RNA viral load, time from estimated seroconversion to ART initiation, and duration on ART. Observed longitudinally, racial differences in D-dimer levels were seen only during HIV viremia. Higher levels of D-dimer commonly observed in African Americans are likely due to factors in addition to race.

Regimen Switching After Initial Haart By Race in a Military Cohort

Background: Prior studies have suggested that HAART switching may vary by ethnicity, but these associations may be confounded by socioeconomic differences between ethnic groups. Utilizing the U.S. military healthcare system, which minimizes many socioeconomic confounders, we analyzed whether HAART switching varies by race/ethnicity. Methods: HAART-naïve participants in the U.S. Military HIV Natural History Study who initiated HAART between 1996-2012 and had at least 12-months of follow-up were assessed for factors associated with HAART regimen change (e.g. NNRTI to PI) within one year of initiation. Multiple logistic regression was used to compare those who switched versus those who did not switch regimens. Results: 2457 participants were evaluated; 91.4% male, 42.3% Caucasian, 42.8% African-American, and 9% Hispanic. In a multivariate analysis, African-Americans had lower odds (OR 0.76, 95% CI 0.65, 0.98) while Hispanics had no significant difference with respect to HAART switching compared to Caucasians; however, Other race was noted to have higher odds (OR 1.77, 95% CI 1.11, 2.83). Additional significantly associated factors included CD4 &lt;200 cells/uL at HAART initiation, higher viral load, prior ARV use, and history of depression. Conclusion: In this cohort with open access to healthcare, African-American and Hispanic races were not associated with increased odds of switching HAART regimen at 12 months, but Other race was. The lack of association between race/ethnicity and regimen change suggest that associations previously demonstrated in the literature may be due to socioeconomic or other confounders which are minimized in the military setting.

Gonorrhea (GC) and Chlamydia (CT) Infection in a Large, Well-Characterized Military Cohort: Prevalence, Incidence, Site of Infection, and Patient Characteristics

BackgroundIn the US military, routine extra-genital (EG) GC/CT testing in persons living with HIV was implemented in 2012. This study examines the prevalence/incidence and risk factors associated with genital (GU) and EG GC/CT infections in the US Military HIV Natural History Study (NHS), a cohort of HIV-infected Department of Defense beneficiaries.MethodsSince 2012, willing NHS subjects have undergone nucleic acid-based tests (NAAT) to identify anorectal (AR)/ pharyngeal (PH) GC/CT infections. Incident cases had a positive test following an initial negative test. Risk factors for incident GC/CT infections were assessed with a multivariate Cox proportional hazards model.ResultsA total of 405 GC and 457 CT infections were observed among 1998 subjects (median age 28.7 years, 94% male, 44.1% African-American [AA]); 21% of GC and 18% of CT cases were re-infections. The incidence of AR GC, PH GC, and AR CT increased over time (P = 0.02, P = 0.03 and P = 0.02, respectively). Incident GC infections were associated with younger age [HR 0.61 per 5 year increase (0.57–0.66)], AA ethnicity [HR 1.46 (1.06–2.00)], higher viral load [HR 1.63 per log increase (1.47–1.80)] and a prior history of syphilis [HR 2.20 (1.62–2.99)]. Incident CT infections were associated with younger age [HR 0.7 per 5 year increase (0.66–0.74)], male gender [HR 5.82 (1.86–18.20)], higher viral load [HR 1.61 for each log increase (1.47–1.76)], lower CD4 count [HR 0.86 per 200 cell increase (0.79–0.95)], prior GC [HR 1.55 (1.15–2.08)] and prior syphilis [HR 2.16 (1.67–2.79)].ConclusionIncident AR GC and CT infections are increasing in the NHS and approximately 20% of infections were repeat infections. The increased incidence is attributable at-least in part to the increased uptake of EG testing. Our study highlights the importance of prevention in positive programs to reduce the risk of HIV transmission. Table. Incidence rate per 100 person-years (95% confidence interval) by site GC CTYearARaPHaGUARaPHGU20121.3 (0.7–2.3)1.9 (1.1–2.9)2 (1.2–3)2.7 (1.8–4)1 (0.5–1.9)4.4 (3.2–5.9)20131.8 (1.1–2.6)2 (1.3–2.8)1 (0.6–1.7)2.5 (1.8–3.5)0.5 (0.2–1)2.2 (1.5–3.1)20141.2 (0.7–1.9)1.3 (0.7–2)1.2 (0.7–1.9)2.4 (1.7–3.4)0.4 (0.2–1)1.5 (0.9–2.2)20152.1 (1.4–3.1)2.3 (1.6–3.2)1.1 (0.6–1.8)3.1 (2.3–4.3)0.8 (0.4–1.5)1.8 (1.1–2.6)20162 (1.3–3)2.4 (1.6–3.4)1.1 (0.6–1.8)3.8 (2.7–5)0.8 (0.4–1.5)1.5 (0.9–2.4) aSignificant change over time.Disclosures All authors: No reported disclosures.

The Impact of Continuous Virologic Suppression on the Development of Non-AIDS Diagnoses

Background In the era of effective antiretroviral therapy (ART) non-AIDS diagnoses (NAD) have emerged as significant concerns. HIV viremia is an important driver of systemic inflammation that has been linked to the development of NAD. In this study, we examined the distribution of NAD in a group of early diagnosed and treated HIV-infected individuals with equal access to care to evaluate the effect of continuous virologic suppression (CS) on NAD.Methods The U.S. Military HIV Natural History Study (NHS) is a prospective cohort of HIV-infected DoD beneficiaries the majority of whom are dated seroconverters. Medical record review and structured interviews are utilized to capture NAD. We included subjects initiating ART after 1996 if they had ≥2 viral loads (VLs) measured while on ART. CS was defined as having all VLs <50 copies/mL. A Cox proportional hazard model was used to evaluate the association between CS and NAD.ResultsOf the 2,642 eligible participants (93% male, 43% African-American AA), median follow-up 6.5 (IQR 3.31–12) years, 985 (37.3%) subjects (94% male, 42% AA, median follow-up 3.74 years) met criteria for CS. The median time from HIV diagnosis to ART initiation was 1.34 (IQR 0.19–5.46) years, while the median seroconversion window was 1.31 (IQR 0.8–2.1) years. A total of 402 (15.2%) NAD were recorded and were recorded (table). Factors associated with NAD included older age at ART initiation (HR 1.6 per 10-year increase [95% CI 1.4–1.8]) and female gender (HR 1.6 [95% CI 1.0–2.7]), while a higher CD4 count was protective (HR 0.93 per 50 cell increase [95% CI 0.90–0.95]). CS status was not associated with NAD (HR 0.75 [95% CI 0.50–1.11]). Total (n = 2,642) CS (n = 985) NAD402 (15.2%)49 (5%)CancerAnal Cancer27 (1.0%)1 (0.1%)Prostate Cancer17 (0.6%)2 (0.2%)Cardiovascular DiseaseCAD w and w/o MI115 (4.4%)8 (0.8%)NephropathyAcute Renal Failure74 (2.8%)4 (0.4%)CKD - eGFR <30ml/minute52 (2.0%)4 (0.4%)LiverCirrhosis22 (0.8%)0 (0.0%)ConclusionIn the ART era, about 1 in 7 NHS subjects had a NAD. The numbers of NAD in the CS subjects were lower than the rest of the cohort. While not statistically significant, the hazard ratios trended towards demonstrating a benefit for continuous virologic suppression. This trend is consistent with previous reports that have demonstrated a benefit of immunologic reconstitution and virologic control on the incidence of NAD.Disclosures All authors: No reported disclosures.

High-risk Behavior Among U.S. Military HIV-Infected Active-Duty and Retired Personnel

BackgroundDespite a high incidence of sexually transmitted infections (STIs), sexual behavior among U.S. military personnel remains understudied. Since 2014, the U.S. Military HIV Natural History Study has administered a behavioral questionnaire to a cohort of HIV-infected active-duty (AD) and retired personnel (RP). We compared patterns of risk behavior between AD and RP.MethodsMale participants who completed a behavioral questionnaire (n = 1,465) were included in this study. Chi-square and stepwise logistic regression were used to compare AD with RP. Our model included all behavioral variables listed below with adjustment for age and race. We assumed a priori that duty status would be correlated with age and selected the former as our variable of interest, hypothesizing that AD would engage in a higher number of risk behaviors.ResultsSelected demographics and behavioral data are summarized below.AD (n = 731) %RP (n = 734) %Univariate Odds (95% CI)Multivariate Odds (95% CI)DemographicsMedian Age (IQR)30 (26,37)51 (46,57)Race--White32.745.0--Black46.143.6--Hispanic/Other21.211.4Behavioral DataConsumed > 6 drinks on a single occasion (past year)50.932.12.2 (1.7,2.8)Ever experienced injury from drinking84.572.92.0 (1.6,2.6)Ever used hard drugs7.317.60.4 (0.3,0.5)0.5 (0.3,0.9)High self-perceived risk for STI22.119.11.3 (1.0,1.6)> 2 new sexual partners in past three months22.614.51.7 (1.3,2.3)Ever had sex with woman65.982.80.4 (0.3,0.5)Ever had sex with man82.179.81.2 (0.9,1.5)Condomless anal intercourse in last 3 mos (casual partner)29.527.21.1 (0.8,1.5)Condomless anal intercourse in last 3 mos (anonymous partner)22.318.21.3 (0.9,1.8)AD had significantly (P < 0.01) higher rates of gonorrhea (6.4) and chlamydia (6.0) per 100 person-years (py) than RP (2.2 and 1.6, respectively); syphilis rates did not differ between the groups (AD 1.2/100 py; RP 1.3/100 py).Conclusion In contrast with our hypothesis, we found a high prevalence of sexual risk behavior among both AD and RP, and only lifetime use of hard drugs was independently associated with duty status. Despite high STI rates, ~20% in either group reported high self-perceived risk for STIs and/or recent condomless sex with an anonymous partner. Our findings demonstrate a need for intensive STI screening and counseling among HIV-infected military personnel in multiple career stages.Disclosures All authors: No reported disclosures.

Calculated Globulin Adds Predictive Value to Hepatitis B Vaccine Response in HIV-infected Persons Independently of HIV Viral load and CD4 Cell Count

BackgroundResponse rates to hepatitis B (HBV) virus vaccine are low compared with the general population. Recent data suggest baseline total IgG levels add predictive value for vaccine failure. We retrospectively analyzed the relationship of calculated globulin (CG) levels with HBV vaccine response in participants in the U.S. Military HIV Natural History Study (NHS).MethodsNHS is a longitudinal observational cohort of DoD active duty and beneficiaries with HIV infection, enrolling since 1986. Inclusion criteria was: (1) no current or past HBV or hepatitis C infection (2) HBV vaccination after positive HIV date, (3) available post-vaccination follow-up serum HBV surface antibody (HBsAb) test, (4) CD4 cell count, HIV RNA viral load (VL), and protein levels within 90 days prior to the last vaccine dose. Using a standard approach, CG levels were derived by subtracting the albumin level from total protein. Variables were analyzed using univariate and multivariate logistic regression model.ResultsData from 674 eligible participants were analyzed. Subjects were 87% male, 44% Caucasian, 41% African-American. At time of last vaccine dose, median values were age, 34 yrs; CD4 cells/uL, 515; nadir CD4 cells/ul, 318. 51% were receiving ART and VL was <400 copies/ml in 51%. Overall, HBV vaccine response rate was 54%. Among CG quartiles, HBV vaccine response was 70%, 60%, 40% and 44% from lowest to highest quartile respectively (P < 0.001). In the multivariate analysis, CD4 cell count, VL and CG were independently associated with vaccine response (Table).ConclusionCG levels at time of last dose independently predicted successful HBV vaccine response in HIV-infected persons. These data suggest B-cell dysfunction, characterized by higher CG levels, may be clinically significant regardless of VL and CD4 cell count.Univariate Analysis*Multivariate Analysis*Age per decade1.21 (1.04–1.43)0.94 (0.77–1.13)Female gender1.44 (0.91–2.27)1.38 (0.81–2.33)Non-white race1.11 (0.81–1.51)1.21 (0.83–1.76)>3 vaccine doses1.71 (1.26–2.37)1.09 (0.79–1.59)CD4 cell at last vaccine dose (per 100 cells)1.22 (1.14–1.31)1.13 (1.04–1.22)VL per log 100.68 (0.60–0.77)0.77 (0.65–0.97)CG above median (3.3 g/dl)0.39 (0.29–0.53)0.66 (0.44–0.97)Disclosures All authors: No reported disclosures.

Incidence of Herpes Zoster in a Large Cohort of Persons Living with HIV

Herpes Zoster (HZ) incidence has decreased over 40% in the United States but remains elevated in persons living with HIV (PLWH). HZ vaccine is not routinely recommended for PLWH and provider-prescribing patterns vary greatly. Updated incidence information in this population is needed to guide vaccine strategies. Using data from the US military HIV Natural History Study (NHS), we evaluated the incidence and risk factors for HZ in the modern ART era. NHS subjects undergo bi-annual visits with laboratory testing, examinations, and records reviewed for clinical diagnosis, including HZ. Analysis was restricted to subjects contributing to follow-up after 2001. Risk factors for HZ (demographic and HIV-specific) were assessed with a multivariate Cox proportional hazards model. Of the 2954 subjects meeting inclusion criteria, 237 (8%) were diagnosed with HZ. At HZ diagnosis, the median age, CD4 count, and viral load were 38.6 years [IQR-30.8, 45.8], 461 cells/uL [IQR-333, 638] and 1900 copies/mL [IQR-50, 19580] respectively. The incidence of HZ was highest prior to 1996 at 3.24 cases/100 person-years (PY) of follow-up (2.96–3.54) and declined significantly over time with 1.9 (1.6–2.3), 1.4 (1.2–1.8), 1.4 (1.1–1.7), and 0.9 (0.7–1.2) cases/100 PY recorded in 1996–2000, 2001–2005, 2006–2010, and 2011–2016, respectively. In the multivariate model, longer time from HIV diagnosis to ART initiation was associated with HZ. ART use, higher CD4 count, recent year of HIV diagnosis, and older age were protective (Table 1). HZ remains a common diagnosis in the ART era. NHS subjects with HZ were in the fourth and fifth decades of their life and had preserved CD4 counts highlighting the need for HZ vaccine safety and efficacy studies to help guide provider practice. Delays in ART initiation were associated with HZ emphasizing the need for compliance with current ART guidelines. Table 1. Table 1. All authors: No reported disclosures.

D-Dimer Levels before HIV Seroconversion Remain Elevated Even after Viral Suppression and Are Associated with an Increased Risk of Non-AIDS Events.

The mechanism underlying the excess risk of non-AIDS diseases among HIV infected people is unclear. HIV associated inflammation/hypercoagulability likely plays a role. While antiretroviral therapy (ART) may return this process to pre-HIV levels, this has not been directly demonstrated. We analyzed data/specimens on 249 HIV+ participants from the US Military HIV Natural History Study, a prospective, multicenter observational cohort of >5600 active duty military personnel and beneficiaries living with HIV. We used stored blood specimens to measure D-dimer and Interleukin-6 (IL-6) at three time points: pre-HIV seroconversion, ≥6 months post-HIV seroconversion but prior to ART initiation, and ≥6 months post-ART with documented HIV viral suppression on two successive evaluations. We evaluated the changes in biomarker levels between time points, and the association between these biomarker changes and future non-AIDS events. During a median follow-up of 3.7 years, there were 28 incident non-AIDS diseases. At ART initiation, the median CD4 count was 361cells/mm3; median duration of documented HIV infection 392 days; median time on ART was 354 days. Adjusted mean percent increase in D-dimer levels from pre-seroconversion to post-ART was 75.1% (95% confidence interval 24.6–148.0, p = 0.002). This increase in D-dimer was associated with a significant 22% increase risk of future non-AIDS events (p = 0.03). Changes in IL-6 levels across time points were small and not associated with future non-AIDS events. In conclusion, ART initiation and HIV viral suppression does not eliminate HIV associated elevation in D-dimer levels. This residual pathology is associated with an increased risk of future non-AIDS diseases.

Factors associated with HIV viral load "blips" and the relationship between self-reported adherence and efavirenz blood levels on blip occurrence: a case-control study.

BackgroundThe uncertain etiology of HIV viral load (VL) blips may lead to increased use of clinical resources. We evaluated the association of self-reported adherence (SRA) and antiretroviral (ART) drug levels on blip occurrence in US Military HIV Natural History Study (NHS) participants who initiated the single-tablet regimen efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF).MethodsART-naïve NHS participants started on EFV/FTC/TDF between 2006 and 2013 who achieved VL suppression (<50 copies/mL) within 12 months and had available SRA and stored plasma samples were included. Participants with viral blips were compared with those who maintained VL suppression without blips. Untimed EFV plasma levels were evaluated on consecutive blip and non-blip dates by high performance liquid chromatography, with a level ≥1 mcg/mL considered therapeutic. SRA was categorized as ≥85 or <85 %. Descriptive statistics were performed for baseline characteristics and univariate and multivariate Cox proportional hazard models were used to assess the relationship between covariates and blip occurrence.ResultsA total of 772 individuals met inclusion criteria, including 99 (13 %) blip and 673 (87 %) control participants. African-American was the predominant ethnicity and the mean age was 29 years for both groups. SRA ≥ 85 % was associated with therapeutic EFV levels at both blip and non-blip time points (P = 0.0026); however no association was observed between blips and SRA or EFV levels among cases. On univariate analysis of cases versus controls, blips were associated with higher mean pre-treatment VL (HR 1.45, 95 % CI 1.11–1.89) and pre-treatment CD4 count <350 cells/µL (68.1 vs 49.7 %). Multivariate analysis also showed that blips were associated with a higher mean VL (HR 1.42, 95 % CI 1.08–1.88; P = 0.0123) and lower CD4 count at ART initiation, with CD4 ≥500 cells/µL having a protective effect (HR 0.45, 95 % CI 0.22–0.95; P = 0.0365). No association was observed for demographic characteristics or SRA.ConclusionBlips are commonly encountered in the clinical management of HIV-infected patients. Although blip occurrence was not associated with SRA or EFV blood levels in our study, blips were associated with HIV-related factors of pre-ART high VL and low CD4 count. Additional studies are needed to determine the etiology of blips in HIV-infected patients.

Hospitalizations among HIV controllers and persons with medically controlled HIV in the U.S. Military HIV Natural History Study

IntroductionHIV controllers (HICs) experience relatively low-level viraemia and CD4 preservation without antiretroviral therapy (ART), but also immune activation that may predispose to adverse clinical events such as cardiovascular disease and hospitalization. The objective of this study was to characterize the rates and reasons for hospitalization among HICs and persons with medically controlled HIV.MethodsSubjects with consistently well-controlled HIV were identified in the U.S. Military HIV Natural History Study. ART prescription and HIV-1 RNA data were used to categorize subjects as HICs or medically controlled as defined by ≥3 HIV-1 RNA measurements ≤2000 or ≤400 copies/mL, respectively, representing the majority of measurements spanning ≥12 months. Hospitalizations were tallied and assigned diagnostic categories. All-cause hospitalization rates were compared between groups using negative binomial regression.Results and discussionOf 3106 subjects followed from 2000 to 2013, 221 were HICs, including 33 elite (1.1%) and 188 viraemic (6.0%) controllers, who contributed 882 person-years (PY) of observation time. An additional 870 subjects with medically controlled HIV contributed 4217 PY. Mean hospitalization rates were 9.4/100 PY among HICs and 8.8/100 PY among medically controlled subjects. Non-AIDS-defining infections were the most common reason for hospitalization (2.95/100 PY and 2.70/100 PY, respectively) and rates of cardiovascular hospitalization were similar in both groups (0.45/100 PY and 0.76/100 PY). There was no difference in hospitalization rate for HICs compared with subjects with medically controlled HIV (adjusted incidence rate ratio 1.15 [95% confidence interval 0.80 to 1.65]).ConclusionsAll-cause and cardiovascular hospitalization rates did not differ between HICs and persons with medically controlled HIV. Non-AIDS defining infections were common in this young, healthy, predominantly male cohort of military personnel and beneficiaries.

Impact of the highly active antiretroviral therapy era on the epidemiology of primary HIV-associated thrombocytopenia.

BackgroundPrimary HIV-associated thrombocytopenia (PHAT) typically improves with highly active antiretroviral therapy (HAART); however, cases continue to occur. Data comparing the epidemiology of PHAT between the pre-HAART and HAART eras are limited. We retrospectively examined the incidence of PHAT over 28 years in the US Military HIV Natural History Study (NHS) from 1986 to 2013.ResultsSubjects had a nadir platelet count <100 × 109/l with no other identifiable cause. Time periods were categorized as pre-HAART (1986–1995), early HAART (1996–2001), and later HAART (2002–2013). Incidence, demographic data, and CD4 count were compared across the three eras. A generalized estimating equations model was used to assess any association of platelet count and HIV viral load in cases diagnosed during the HAART eras. 218 participants met the case definition. 86.2 % of cases occurred prior to 2002. The incidence of PHAT per 1000 person-years of follow-up was 16.3, 4.6, and 1.9 during pre-HAART, early HAART and later HAART eras respectively. CD4 cell counts were significantly higher in the HAART eras at the time of thrombocytopenia (p < 0.001). Of patients diagnosed after 1996, 96.4 % were viremic within six months preceding the platelet nadir and over half were antiretroviral naïve. Viral load (per log10 copies/ml) inversely correlated with platelet count throughout the HAART eras (p < 0.0001).ConclusionsThe incidence of PHAT has markedly decreased in the HAART era. However, viremic individuals, including those with healthy CD4 cell counts, may be at risk. Achieving viral suppression as early as possible may decrease the incidence further.

Toxoplasma gondii seroprevalence: 30-year trend in an HIV-infected US military cohort

To determine if Toxoplasma gondii IgG antibody prevalence is declining in HIV-infected persons, we analyzed data (1984–2013) from the US Military HIV Natural History Study. We found that T. gondii seroprevalence at enrollment was associated with age and decreased significantly after 1995 (P=0.004), similar to the general US population.