A telehealth-delivered intervention to extend the veteran HIV treatment cascade for cardiovascular disease prevention: V-EXTRA-CVD study protocol for a randomized controlled trial.

Background: Veterans living with HIV have up to twice the risk of atherosclerotic cardiovascular disease (ASCVD) compared to those without HIV.Objective: Our study seeks to test a non-physician led virtual self-management implementation strategy to reduce ASCVD risk among people living with HIV (PWH). We aim to conduct a randomized control trial among PWH (n = 300) with a diagnosis of hypertension (HTN) who are enrolled in Veterans Health Administration (VHA) clinics, on suppressive antiretroviral therapy (ART), randomized 1:1 to intervention vs. education control for a 12-month duration.Methods: Using human centered design approach, we have adapted a previous 5-component telehealth focused, non-physician led intervention to a Veteran population. The education control arm receives enhanced education in addition to usual care. The primary outcome is 6 mmHg reduction in systolic BP over 12-month in the intervention arm compared to the control arm. The secondary outcome is a 12-month difference in non-HDL cholesterol. While each component of our intervention has an evidence base, they have not been tested together in an HIV context.Conclusion: The proposed multicomponent intervention has the potential to improve cardiovascular outcomes in PWH using novel virtual care methods in a patient centered care approach.

Sexually Transmitted Infections in Older Adults: Increasing Tide and How to Stem It.

Sexually transmitted infections (STIs) have been increasing in older adults. Sexual health remains an important part of overall health care at any age. There are several barriers and facilitators to addressing sexual health in this population. Changes attributable to normal physiologic aging as well as sexual dysfunction can affect sexuality in older adults. When it comes to preventing STIs, combination prevention strategies remain applicable in older adults. Addressing sexual health using a tailored approach is critical to stem the tide of increasing STIs rates in older adults.

Sexually Transmitted Infection Testing in the National Veterans Health Administration Patient Cohort During the Coronavirus Disease 2019 Pandemic.

Background: We performed a retrospective study of chlamydia, gonorrhea, syphilis, and human immunodeficiency virus (HIV) testing in the Veterans Health Administration (VHA) during 2019-2021. Methods: We determined the annual number of chlamydia, gonorrhea, syphilis, and HIV tests from 2019 through 2021 using electronic health record data. We calculated rates by age, birth sex, race, census region, rurality, HIV status, and use of preexposure prophylaxis. Results: The VHA system experienced a 24% drop in chlamydia/gonorrhea testing, a 25% drop in syphilis testing, and a 29% drop in HIV testing in 2020 versus 2019. By the conclusion of 2021, testing rates had recovered to 90% of baseline for chlamydia/gonorrhea, 91% for syphilis, and 88% for HIV. Declines and subsequent improvements in sexually transmitted infection (STI) testing occurred unequally across age, sex, race, and geographic groups. Testing for all 4 STIs in 2021 remained below baseline in rural Veterans. Excluding those aged <25 years, women experienced a steeper decline and slower recovery in chlamydia/gonorrhea testing relative to men, but quicker recovery in HIV testing. Asian Americans and Hawaiian/Pacific Islanders had a steeper decline and a slower recovery in testing for chlamydia/gonorrhea. Black and White Veterans had slower recovery in HIV testing compared with other race groups. People living with HIV experienced a smaller drop in testing for syphilis compared with people without HIV, followed by a near-total recovery of testing by 2021. Conclusions: After dramatic reductions from 2019 to 2020, STI testing rates returned to near-baseline in 2021. Testing recovery lagged in rural, female, Asian American, Hawaiian/Pacific Islander, and Black Veterans.

Discussion and Initiation of HIV Pre-exposure Prophylaxis Were Rare Following Diagnoses of Sexually Transmitted Infections Among Veterans.

BACKGROUND: Healthcare encounters for the diagnosis and treatment of sexually transmitted infections (STIs) are common and represent an opportunity to discuss and initiate HIV pre-exposure prophylaxis (PrEP). Little is known about how frequently PrEP is discussed and initiated in association with encounters for STIs. DESIGN: Retrospective cohort and nested case-control study, matched by STI date, in national Veterans Health Administration (VHA) facilities  from January 2013 to December 2018. PARTICIPANTS: Veterans with a first STI diagnosis (i.e., early syphilis, gonorrhea, or chlamydia) based on ICD codes, excluding those with prior HIV diagnosis, prior PrEP use, or STI diagnosed on screening during a visit to initiate PrEP. MAIN MEASURES: Frequency of PrEP initiation within 90 days of healthcare encounter for STIs. In the case-control study, we performed a structured chart review from the initial STI-related clinical encounter and quantified frequency of PrEP discussions among matched patients who did and did not initiate PrEP in the following 90 days. KEY RESULTS: We identified 23,312 patients with a first STI, of whom 90 (0.4%) started PrEP within 90 days. PrEP initiation was associated with urban residence (OR = 5.0, 95% CI 1.8-13.5), White compared to Black race (OR = 1.7, 95% CI 1.0-2.7), and syphilis diagnosis (OR = 5.7, 95% CI 3.7-8.6). Chart review revealed that discussion of PrEP was rare among people with STIs who did not subsequently start PrEP (1.1%, 95% CI 0.1-4.0). PrEP initiation was associated with documentation of sexual history (80.0% of initiators vs. 51.0% of non-initiators, p < 0.01) and discussion of PrEP (52.2% vs. 1.1%, p < 0.01) during the initial STI diagnosis encounter. CONCLUSIONS: Discussion and initiation of PrEP were rare following healthcare encounters for STIs. Interventions are needed to improve low rates of sexual history-taking and discussion of PrEP during healthcare encounters for STIs.

Differences in Syphilis Incidence Using a Laboratory Algorithm in People With and Without HIV in an 11-Year Nationwide Cohort Study.

BACKGROUND: To measure the incidence of syphilis diagnoses among people with HIV vs those without HIV in a national multiyear retrospective cohort. METHODS: Treponemal and nontreponemal tests, HIV status, and demographic data were identified among all individuals receiving Veterans Health Administration (VHA) care between January 1, 2009, and December 31, 2019. Syphilis testing rates and incident syphilis diagnoses as defined by a laboratory algorithm were stratified by HIV status. RESULTS: Syphilis was diagnosed in 1.2% (n = 2283) of 194 322 tested individuals in VHA care in 2019. Among individuals with HIV tested for syphilis, 6.1% met criteria for syphilis compared with 0.7% without HIV. Syphilis incidence in 2019 was 35/100 000, a 17% increase from 2009 (30/100 000). In 2019, syphilis incidence was 3381 per 100 000 persons among individuals with HIV and 19 per 100 000 in those without HIV. CONCLUSIONS: Using a laboratory-based diagnostic algorithm, a 178-fold difference in syphilis incidence was observed between individuals with and without HIV in 2019. US syphilis incidence data that incorporate HIV status are needed. Interventions to monitor and prevent sexually transmitted infections should address the role of HIV status.

Testing Practices and Incidence of Chlamydial and Gonococcal Infection in the Veterans Health Administration, 2009-2019.

BACKGROUND: Chlamydia trachomatis and Neisseria gonorrhoeae cases reached a record high in the United States in 2018. Although active-duty military service members have high rates of chlamydia and gonorrhea infection, trends in chlamydia and gonorrhea in the Veterans Health Administration (VHA) system have not been previously described, including among patients living with human immunodeficiency virus (HIV) and young women. METHODS: We identified all veterans in VHA care from 2009 through 2019. Tests and cases of chlamydia and gonorrhea were defined based on laboratory results in the electronic health record. Chlamydia and gonorrhea incidence rates were calculated each year by demographic group and HIV status. RESULTS: In 2019, testing for chlamydia and gonorrhea occurred in 2.3% of patients, 22.6% of women aged 18-24 years, and 34.1% of persons living with HIV. The 2019 incidence of chlamydia and gonorrhea was 100.8 and 56.3 cases per 100 000 VHA users, an increase of 267% and 294%, respectively, since 2009. Veterans aged ≤34 years accounted for 9.5% of the VHA population but 66.9% of chlamydia and 42.9% of gonorrhea cases. Chlamydia and gonorrhea incidence rates in persons living with HIV were 1432 and 1687 per 100 000, respectively. CONCLUSIONS: The incidence of chlamydia and gonorrhea rose dramatically from 2009 to 2019. Among tested persons, those living with HIV had a 15.2-fold higher unadjusted incidence of chlamydia and 34.9-fold higher unadjusted incidence of gonorrhea compared with those not living with HIV. VHA-wide adherence to chlamydia and gonorrhea testing in high-risk groups merits improvement.

Roadblocks to PrEP: What Medical Records Reveal About Access to HIV Pre-exposure Prophylaxis.

BACKGROUND: Pre-exposure prophylaxis (PrEP) has been shown to be efficacious in preventing HIV; however, its uptake remains modest. Given that there are fewer cost barriers to receiving PrEP within VHA than via commercial insurance, VHA represents an ideal setting in which to study other barriers that may impact patients seeking PrEP. OBJECTIVE: We sought to understand potential barriers to obtaining PrEP within the Veterans Health Administration (VHA) through examination of documentation in electronic medical records. DESIGN: Retrospective structured chart review, including chart abstractions of notes, referrals, and communications; content analysis of charts from a subsample of patients receiving PrEP in VHA. PARTICIPANTS: One hundred sixty-one patients prescribed PrEP at 90 sites varying in PrEP prescribing rates. APPROACH: We extracted descriptive information and conducted a qualitative analysis of all PrEP-relevant free-text notes including who initiated the PrEP conversation (patient vs. provider), time interval between request and prescription, reasons for denying PrEP, and patient responses to barriers. KEY RESULTS: Patients initiated 94% of PrEP conversations and 35% of patients experienced delays receiving PrEP ranging from six weeks to 16 months. Over 70% of cases evidenced barriers to access. Barriers included provider knowledge gaps about PrEP, provider knowledge gaps about VHA systems related to PrEP, confusion or disagreement over clinic purview for PrEP, and provider attitudes or stigma associated with patients seeking PrEP. CONCLUSIONS: Although PrEP is recommended for HIV prevention in high-risk persons, many PrEP-eligible individuals faced barriers to obtaining a prescription. Current practices place substantial responsibility on patients to request and advocate for this service, in contrast to many other preventive services. Understanding the prevalence and content of PrEP knowledge gaps and attitudinal barriers can inform organizational interventions to increase PrEP access and decrease HIV transmission.

Brief Report: Incidence of HIV in a Nationwide Cohort Receiving Pre-exposure Prophylaxis for HIV Prevention.

BACKGROUND: Cases of HIV, while infrequent, have been reported during tenofovir disoproxil fumarate/emtricitabine use as pre-exposure prophylaxis (PrEP). We describe the incidence of HIV and patterns of PrEP use within the Veterans Health Administration (VHA). METHODS: We conducted a retrospective cohort study among persons initiating PrEP in the VHA between July 2012 and April 2016 using national VHA data. We defined time on PrEP and time at risk of HIV exposure as the total time from the first PrEP fill to exhaustion of supply of the final PrEP prescription. We identified incident cases of HIV infection after PrEP initiation based on laboratory data. Medication adherence measures and days without pills were calculated using pharmacy fill data. We used a chart review to determine patient-reported PrEP use around the time of diagnosis. RESULTS: We identified 825 unique patients initiating PrEP; they were 97% men and 67% white, with a mean age of 41 years. Six HIV infections were observed during the study period, yielding an HIV incidence of 0.8 (Poisson exact 95% confidence interval: 0.3 to 1.8) cases per 100 person-years. Two cases occurred during active PrEP use by self-report and perfect adherence based on fill data. Both were infected with viruses containing the M184V mutation. Four additional cases were diagnosed after self-reported discontinuation. CONCLUSIONS: HIV infection was rare in a nationwide cohort of PrEP users. Although most of the infections occurred during inconsistent PrEP use, infections during periods of high measured adherence were also observed. These findings highlight the importance of PrEP persistence during periods of risk.

Health Care Facility Characteristics are Associated with Variation in Human Immunodeficiency Virus Pre-exposure Prophylaxis Initiation in Veteran's Health Administration.

To quantify health care facility-level variation in pre-exposure prophylaxis (PrEP) use in the Veteran's Health Administration (VHA); to identify facility characteristics associated with PrEP use. Retrospective analysis of the health care facility-level rate of PrEP initiation in VHA through June 30, 2017. Standardized PrEP initiation rates were used to rank facilities. Characteristics of facilities, prescribers, and PrEP recipients were examined within quartiles. Multiple linear regression was used to identify associations between facility characteristics and PrEP use. We identified 1600 PrEP recipients. Mean PrEP initiation rate was 20.0/100,000 (SD 22.8), ranging from 3.0/100,000 (SD 2.0) in the lowest quartile to 48.1/100,000 (SD 29.1) in the highest. PrEP prescribing was positively associated with proportions of urban dwellers and individuals < 45, tertiary care status, and location. Variability in PrEP uptake across a national health care system highlights opportunities to expand access in non-tertiary care facilities and underserved areas.

Gaps in Preexposure Prophylaxis Uptake for HIV Prevention in the Veterans Health Administration.

OBJECTIVES: To report demographics, regional variations, and indications for preexposure prophylaxis (PrEP) use for HIV prevention in the Veterans Health Administration (VHA). METHODS: We identified persons initiating tenofovir/emtricitabine for the PrEP indication in the United States between July 2012 and April 2016 in a VHA national database. We stratified PrEP use by provider type and VHA region. We calculated PrEP initiation rate for each region with VHA population data. RESULTS: Of the 825 persons who initiated PrEP during the observation period, 67% were White and 76% were men who have sex with men. People who inject drugs and transgender persons represented less than 1% each of the cohort. The majority of PrEP initiations were clustered in 3 states, leading with California (28%) followed by Florida (9%) and Texas (8%). The Southeast had one of the lowest PrEP rates at 10 PrEP initiations per 100 000 persons in care. Infectious disease specialists issued more than two thirds of index PrEP prescriptions. CONCLUSIONS: Uptake of PrEP in the VHA is uneven along geographic and risk categories. Understanding the reasons behind these gaps will be key in expanding the use of this important prevention tool.

Medication Adherence in a Nationwide Cohort of Veterans Initiating Pre-exposure Prophylaxis (PrEP) to Prevent HIV Infection.

BACKGROUND: Current guidelines for pre-exposure prophylaxis (PrEP) to prevent HIV infection call for long-term, daily use of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). Little is known about long-term adherence with TDF/FTC prescribed for PrEP in routine clinical practice. SETTING: Veterans Health Administration (VHA) clinics. METHODS: We used VHA data to create a nationwide cohort of Veterans initiating PrEP between July 1, 2012, and June 30, 2016. We examined pharmacy refill data to estimate adherence based on the proportion of days covered (PDC) by TDF/FTC in the first year and used logistic regression to identify patient characteristics associated with high adherence (ie, PDC >0.8). We also quantified how often Veterans discontinued PrEP in the first year, based on a gap of 120 days or more in medication possession. RESULTS: Among 1086 individuals initiating PrEP, the median PDC for TDF/FTC in the first year was 0.74 (interquartile range 0.40-0.92). In multivariable analysis, high adherence was associated with older age (odds ratio 1.97; 1.41-2.74 for age 50-64 compared with <35), white compared with black race (odds ratio 2.12; 1.53-2.93), and male sex (odds ratio 3.39; 1.37-8.42). Forty-four percent discontinued PrEP in the first year. CONCLUSIONS: First-year adherence with TDF/FTC was overall high in a nationwide cohort of PrEP users. Differences in adherence by age, race, and sex suggest potential for disparities in PrEP effectiveness in routine clinical practice.

Accessibility and Uptake of Pre-Exposure Prophylaxis for HIV Prevention in the Veterans Health Administration.

To increase access, the National PrEP Working Group is expanding outreach outside of primary care and among nonspecialists, ensuring uniformly high-quality care and targeting high-risk populations.

Human Immunodeficiency Virus and Aging in the Era of Effective Antiretroviral Therapy.

Persons living with HIV (PLWH) have accentuated risks for age-associated comorbidities. Compared to the general population, PLWH have a 2-fold higher risk of cardiovascular disease, a 3-fold increased risk of fracture, and a risk of kidney disease that is comparable to that in diabetes. Some comorbidities may present at younger ages than among the general population, suggesting the possibility of accelerated aging with HIV infection.

Preexisting Immunity, Not Frailty Phenotype, Predicts Influenza Postvaccination Titers among Older Veterans.

Both preexisting immunity to influenza and age have been shown to be correlates of influenza vaccine responses. Frailty, an indicator of functional impairment in older adults, was also shown in one study to predict lower influenza vaccine responses among nonveterans. In the current study, we aimed to determine the associations between frailty, preexisting immunity, and immune responses to influenza vaccine among older veterans. We studied 117 subjects (age range, 62 to 95 years [median age, 81 years]), divided into three cohorts based on the Fried frailty test, i.e., nonfrail (NF) (n = 23 [median age, 68 years]), prefrail (n = 50 [median age, 80 years]), and frail (n = 44 [median age, 82 years]), during the 2010-2011 and 2011-2012 influenza seasons. Subjects received the seasonal trivalent inactivated influenza vaccine, and baseline and postvaccination samples were obtained. Anti-influenza humoral immunity, as measured by hemagglutination inhibition (HI) and microneutralization assays, was measured for influenza B, A(H1N1)pdm09, and A(H3N2) viruses. Postvaccination titers were not different between frail and NF subjects overall in this older subset of veterans. However, preexisting HI titers were strongly correlated with postvaccination titers among all functional status groups. When microneutralization titers were compared, the association between preexisting immunity and vaccine responses varied by frailty status, with the strongest correlation being observed for the NF group. In conclusion, preexisting immunity rather than frailty appeared to predict postvaccination titers in this older veteran cohort.

Ertapenem-Induced Hallucinations and Delirium in an Elderly Patient.

OBJECTIVE: To report a case of ertapenem-induced hallucinations and delirium in an elderly, morbidly obese patient. SETTING/PRACTICE DESCRIPTION: A 71-year-old male was receiving intravenous antibiotics at an outside nursing facility through our Outpatient Parenteral Antimicrobial Therapy (OPAT) program, which has enrolled more than 800 patients since 2009. He was admitted to our medical center, a 673-bed tertiary health care facility, which provides care to more than 100,000 veterans in Northeast Ohio. MAIN OUTCOME/RESULTS: Our patient was admitted with an acute heart failure exacerbation after being discharged four weeks prior with a plan to complete six weeks of intravenous daptomycin 1 g daily and ertapenem 1 g daily for a left-calcaneal diabetic foot osteomyelitis. On initial exam, in addition to volume overload, he was noted to have fluctuating orientation, hallucinations, and suicidal ideations, which were all a significant change from his baseline mentation. A physical, laboratory, and radiologic workup revealed no conclusive etiology for his symptoms, at which point drug-induced toxicity was suspected. Upon discontinuation of ertapenem, the patient rapidly improved over the next 72 hours, including return to baseline mentation and absence of any suicidal thoughts. Use of the Naranjo probability scale indicated a probable relationship between ertapenem and the adverse effects experienced by our patient. CONCLUSION: This case report and literature review demonstrates the potential severity of non-seizure-related neurotoxicity associated with ertapenem. As this toxicity can be life-threatening if unrecognized, it is crucial that clinicians across all practice settings be proactive in detecting and preventing it.

Herpes Zoster Vaccination: Controversies and Common Clinical Questions.

Herpes zoster, clinically referred to as shingles, is an acute, cutaneous viral infection caused by reactivation of the varicella zoster virus, the same virus that causes chickenpox. The incidence of herpes zoster and its complications increase with decline in cell-mediated immunity, including age-associated decline. The most effective management strategy for herpes zoster is prevention of the disease through vaccination in those who are most vulnerable. Despite the demonstrated efficacy in reducing the incidence and severity of herpes zoster, the uptake of vaccine remains low. Here, we will discuss the controversies that surround the live herpes zoster vaccine and address the common clinical questions that arise. We will also discuss the new adjuvanted herpes zoster vaccine currently under investigation.

CD4+ T cell polyfunctional profile in HIV-TB coinfection are similar between individuals with latent and active TB infection.

CD4+ T cell counts of HIV-infected individuals with pulmonary TB (PTB) are higher than with other opportunistic infections suggesting that progression to PTB is not merely due to T cell depletion but also dysfunction. There are limited data examining T cell functional signatures in human HIV-TB co-infection particularly in PTB which accounts for about 80% of active TB disease overall. We examined a cohort of HIV-infected anti-retroviral naïve individuals in Kampala, Uganda, a TB endemic area using multiparametric flow cytometry analysis to determine IFN-γ, IL-2, IL-17, and TNF-α production in CD4+ memory T cell subsets. The cytokine frequency and polyfunctionality profile of Mycobacterium tuberculosis (MTB)-specific CD4+ T cells in HIV-infected persons with latent TB infection (LTBI) or PTB is comparable. This similarity suggests that LTBI may represent a smoldering state of persistent MTB replication rather than dormant infection. This may be a contributory mechanism to the significantly increased risk of progression to PTB in this population.

Age-related differences in polyfunctional T cell responses.

BACKGROUND: A reduced number of naïve T cells along with an accumulation of differentiated cell types in aging have been described but little is known about the polyfunctionality of the T cell responses. In this study we compared the individual and polyfunctional expression of IFN-γ, MIP-1α, TNF-α, perforin, and IL-2 by T cell subsets, including the newly described stem cell like memory T cells (TSCM), in response to stimulation with superantigen staphylococcal enterotoxin B (SEB) in older (median age 80, n = 23) versus younger (median age 27; n = 23) adults. RESULTS: Older age was associated with a markedly lower frequency of CD8+ naïve T cells (11% vs. 47%; p < 0.0001) and an expansion in memory T cell subsets including central memory (p < 0.05), effector memory and effector T cells (p < 0.001 for both). There was also a decline in CD4+ naïve T cells in older subjects (33% vs. 45%; p = 0.02). There were no differences in frequencies or polyfunctional profiles of TSCM between groups. CD8+ naïve cells in the older group had increased expression of all functional parameters measured compared to the younger subjects and exhibited greater polyfunctionality (p = 0.04). CD4+ naïve T cells in the older group also showed greater polyfunctionality with a TNF-α and IL-2 predominance (p = 0.005). CD8+ effector memory and effector T cells exhibited increased polyfunctionality in the older group compared with younger (p = 0.01 and p = 0.003). CONCLUSIONS: These data suggest that aging does not have a negative effect on polyfunctionality and therefore this is likely not a major contributor to the immunesenescence described with aging.

Older age is associated with peripheral blood expansion of naïve B cells in HIV-infected subjects on antiretroviral therapy.

Older HIV infected subjects were previously found to have significant B cell expansion during initial antiretroviral therapy in a prospective age-differentiated cohort of older and younger (≥45 vs. ≤30 years) HIV-infected subjects initiating antiretroviral therapy (ART) through the AIDS Clinical Trials Group. Here to further describe this expansion, using a subset of subjects from the same cohort, we characterized B cell phenotypes at baseline and after 192 weeks of ART in both older and younger HIV-infected groups and compared them to uninfected age-matched controls. We also examined whether phenotypes at baseline associated with response to tetanus and hepatitis A vaccine at 12 weeks. Forty six subjects were analyzed in the HIV infected group (21 older, 25 younger) and 30 in the control group (15 per age group). We observed naïve B cells to normalize in younger subjects after 192 weeks of ART, while in older subjects naïve B cells increased to greater levels than those of controls (p = 0.045). Absolute resting memory (RM) cell count was significantly lower in the older HIV infected group at baseline compared to controls and numbers normalized after 192 weeks of ART (p<0.001). Baseline RM cell count positively correlated with week 12 increase in antibody to tetanus vaccine among both younger and older HIV-infected subjects combined (p = 0.01), but not in controls. The age-associated naïve B cell expansion is a novel finding and we discuss several possible explanations for this observation. Relationship between RM cells at baseline and tetanus responses may lead to insights about the effects of HIV infection on B cell memory function and vaccine responses.