Anti-cytomegalovirus antibody levels stratify human immune profiles across the lifespan.

Human cytomegalovirus (hCMV) is a ubiquitous latent persistent herpesvirus infecting 60-90% of the population worldwide. hCMV carriage in immunocompetent people is asymptomatic; thus, hCMV can be considered a component of normative aging. However, hCMV powerfully modulates many features of the immune, and likely other, systems and organs. Questions remain as to how hCMV carriage affects the human host. We used anti-CMV antibody titers as a stratifying criterion to examine the impact of "intensity" of hCMV infection as a potential biomarker of aging, inflammation, and immune homeostasis in a cohort of 247 participants stratified into younger (21-40 years) and older (> 65 years of age) groups. We showed that anti-CMV antibody titers increased with age and directly correlated to increased levels of soluble tumor necrosis factor (sTNFR) I in younger but not older participants. CD8 + cell numbers were reduced in the older group due to the loss in CD8 + T naïve (Tn) cells. In CMV carriers and, in particular, in anti-CMV Ab-high participants, this loss was mitigated or reversed by an increase in the numbers of CD8 + T effector memory (Tem) and T effector memory reexpressing CD45RA (Temra) cells. Analysis of CD38, HLA-DR, and CD57 expression revealed subset (CD4 or CD8)-specific changes that correlated with anti-CMV Ab levels. In addition, anti-CMV Ab levels predicted anti-CMV CD8 T cell responsiveness to different CMV open reading frames (ORFs) selectively in older participants, which correlated to the transcriptional order of expression of specific CMV ORFs. Implications of these results for the potential predictive value of anti-CMV Ab titers during aging are discussed.

Antiretroviral Laboratory Monitoring and Implications for HIV Clinical Care in the Era of COVID-19 and Beyond.

In the era of COVID-19, providers are delaying laboratory testing in people with HIV (PWH). The purpose of this study was to examine the clinical significance of renal, liver, and lipid testing. We reviewed the charts of 261 PWH who initiated care at an academic HIV clinic between January 1, 2016 and December 21, 2018. Analysis included one-sided binomial exact tests and multiple linear, Poisson, and Beta regression models. The most common abnormality was a glomerular filtration rate (GFR) <60 mL/min (10%). Age <40 years [estimated relative rate (rr) 0.017, 95% confidence interval (CI) 0.207 to 0.494], cobicistat (rr 0.284, 95% CI 0.128 to 0.63), and tenofovir alafenamide (rr 0.295 95% CI 0.151 to 0.573) were associated with a decreased risk of GFR <60 mL/min. An increased AST and ALT ≥2 × upper limit of normal (ULN) was found in 5% and 3%, respectively. Hepatitis C and use of darunavir and lopinavir were associated with increased AST or ALT. When a GFR was <60 mL/min or an AST or ALT was ≥2 × ULN, no action was taken in 53% of cases. In 18% of cases the only intervention was repeat testing. The most common interventions after lipid results were calculation of a 10-year cardiovascular risk score (31%) and addition of a statin (18%). Taking action after lipid results was strongly associated with age ≥40 (rr 7.37, 95% CI 3.0 to 18.3). Young PWH without hepatitis C rarely have renal, liver, or lipid test results that alter clinical care. Decreased testing should be considered.

PrEP Knowledge and Attitudes Among Adults Attending Public Health Clinics in Southern Arizona.

HIV pre-exposure prophylaxis (PrEP) is underutilized among Hispanics, women, and low-income individuals. To better understand PrEP barriers in this population, questionnaires were administered to 500 patients attending public health clinics in southern Arizona which provide family planning and sexually transmitted infections care. Sixty-three percent believed that they had no risk of HIV infection. When asked "Before today, did you know that there was a pill that can prevent HIV infection?" 80% of persons answered no. Among women, 88% answered no to this question. As expected, individuals with a higher perceived HIV risk (OR 1.76) or one HIV risk factor (OR 5.85) had a higher probability of knowledge. Among survey participants 87% would take a daily pill, 91% would visit a health-care provider every 3 months, and 92% would have laboratory testing every 3 months. Fifty-four percent would not be afraid or embarrassed if friends or family knew they were taking PrEP. Seventy-two percent would take PrEP despite temporary nausea. Sixty-two percent would pay ≥ $40 every 3 months for PrEP. Lack of knowledge, rather than patient attitudes, is the more important barrier to wider utilization of PrEP among individuals, especially women, attending public health clinics in Southern Arizona. Future efforts need to focus on education and access to PrEP in underserved populations including women and Hispanics.

Factors associated with high cardiovascular risk in a primarily African American, urban HIV-infected population.

OBJECTIVE: To determine factors associated with increased risk of developing cardiovascular disease in a high-risk patient population. DESIGN: Cross-sectional analysis of a retrospective cohort study. METHODS: One-hundred patients at an inner city HIV clinic in 2008 were reviewed. The atherosclerotic vascular disease risk score was calculated using the Pooled Cohort Equation. Chi-square test was performed to identify associations of potential risk factors with elevated atherosclerotic vascular disease risk. RESULTS: Eighty-one participants were included in the final analysis. In total, 95.1% were African American, and 38.3% were women. The median atherosclerotic vascular disease risk score was 8.8% and 8.1% in 2008 and 2012, respectively. The medical co-morbidities associated with increased atherosclerotic vascular disease risk were hepatitis C infection (X2 = 3.93; p value = 0.048), elevated triglycerides levels (X2 = 4.0; p value = 0.046), and low albumin (X2 = 4.65; p value = 0.031). There were a higher number of women with known atherosclerotic vascular disease despite lower median atherosclerotic vascular disease risk score compared to men. CONCLUSION: An elevated risk of developing cardiovascular disease persists in high-risk demographic groups of the HIV epidemic even in the current HIV era. There is an unexplained gender disparity and some non-traditional risk factors not accounted for in the Pooled Cohort Equation may be contributing to the excess cardiovascular disease risk observed among HIV-infected patients.

Colonoscopy Findings in HIV-Infected Men and Women from an Urban U.S. Cohort Compared with Non-HIV-Infected Men and Women.

INTRODUCTION: As HIV-infected patients live longer, non-AIDS-defining cancers are now a major cause of morbidity and mortality. The purpose of this study was to compare the prevalence, type, and location of colorectal neoplastic lesions found on colonoscopy in HIV-infected patients from an urban U.S. cohort with non-HIV-infected patients. METHODS: We collected clinical data and colonoscopy findings on 263 HIV-infected patients matched with 657 non-HIV-infected patients on age, race, and sex. Frequency distributions and descriptive statistics were used to characterize the study population. The primary exposure was HIV infection, and the primary outcome was any adenoma or adenocarcinoma. Logistic regression models were used to estimate odds ratios with 95% confidence intervals (CIs). RESULTS: Participants were primarily African American and 40% were women. HIV-infected patients were less likely to have any neoplastic lesions (21.3% vs. 27.7%, p < .05), adenoma (20.5% vs. 27.1%, p = .04), tubular adenomas >10 mm (0.4% vs. 2.9%, p = .02), and serrated adenomas (0.0% vs.2.6%, p = <.01). There was a nonsignificant increased prevalence of adenocarcinoma in HIV-infected individuals compared with non-HIV-infected individuals (1.5% vs. 0.8%, p = .29). The lower prevalence of any adenoma remained after controlling for age, sex, smoking status, body-mass index, and diabetes mellitus [adjusted odds ratio (aOR), 0.61; 95% CI, 0.43-0.88]. HIV-infected patients had a lower prevalence of colorectal neoplastic lesions, including high-risk adenomas, than non-HIV-infected patients. CONCLUSIONS: Our findings suggest that HIV infection in a primarily African American population is associated with a lower prevalence of colorectal adenomas, but not adenocarcinoma, found by colonoscopy.

Cancer Knowledge and Opportunities for Education Among HIV-Infected Patients in an Urban Academic Medical Center.

HIV-infected patients frequently present with advanced stage cancer. It is possible that late stage presentation may be related to lack of cancer knowledge and/or barriers to care. Questionnaires were administered to 285 adult HIV-infected patients to evaluate knowledge of cancer risk factors and symptoms and barriers to care between 2011 and 2012. Differences in mean and percent scores by group were assessed using a t test for independent samples and chi-square analysis, respectively. Respondents were predominantly male (64%), African-American (86%), and low income (60% < $10,000/year). Thirty-four (12%) had been diagnosed with cancer, and 169 (59%) had a family history of cancer. The mean knowledge score was 17.5 out of 24 questions (73%). Mean scores were not significantly different by sex, age, race, or income. Respondents with a college education scored significantly higher than those with less than a high school education (p < 0.01). In unadjusted analysis, a higher proportion of patients with a personal/family history of cancer (74%) scored in the highest quartile (>70% correct) compared to those without any personal history of cancer (62%) (p = 0.03). There was a higher level of cancer knowledge in this population compared to studies that have evaluated the HIV-uninfected population. Nevertheless, there were knowledge deficits, suggesting the need for further education about cancer to improve earlier detection rates and, ultimately, outcomes.

High cancer-related mortality in an urban, predominantly African-American, HIV-infected population.

OBJECTIVE: To determine mortality associated with a new cancer diagnosis in an urban, predominantly African-American, HIV-infected population. DESIGN: Retrospective cohort study. METHODS: All HIV-infected patients diagnosed with cancer between 1 January 2000 and 30 June 2010 were reviewed. Mortality was examined using Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: There were 470 cases of cancer among 447 patients. Patients were predominantly African-American (85%) and male (79%). Non-AIDS-defining cancers (NADCs, 69%) were more common than AIDS-defining cancers (ADCs, 31%). Cumulative cancer incidence increased significantly over the study period. The majority (55.9%) was taking antiretroviral therapy (ART) at cancer diagnosis or started afterward (26.9%); 17.2% never received ART. Stage 3 or 4 cancer was diagnosed in 67%. There were 226 deaths during 1096 person years of follow-up, yielding an overall mortality rate of 206 per 1000 person years. The cumulative mortality rate at 30 days, 1 year, and 2 years was 6.5, 32.2, and 41.4%, respectively. Mortality was similar between patients on ART whether they started before or after the cancer diagnosis but was higher in patients who never received ART. In patients with a known cause of death, 68% were related to progression of the underlying cancer. CONCLUSION: In a large cohort of urban, predominantly African-American patients with HIV and cancer, many patients presented with late-stage cancer. There was substantial 30-day and 2-year mortality, although ART had a significant mortality benefit. Deaths were most often caused by progression of cancer and not from another HIV-related or AIDS-related event.

Successful treatment with atazanavir and lopinavir/ritonavir combination therapy in protease inhibitor-susceptible and protease inhibitor-resistant HIV-infected patients.

The combination of atazanavir (ATV) plus lopinavir/ritonavir (LPV/r) has been used in practice. However, clinical data supporting its use are limited. The objective of this study was to evaluate the efficacy and tolerability of regimens with ATV + LPV/r in protease inhibitor (PI)-susceptible and PI-resistant patients. A retrospective review of 2703 charts was performed to identify all patients who received ATV + LPV/r. From June 2003 to January 2005, 33 patients received ATV + LPV/r with nucleoside reverse transcriptase inhibitors (NRTIs) for 3 months or more. Virologic success (HIV-RNA < 400 copies per milliliter) was achieved in 30 patients (91%) in a median of 10 weeks (range, 2-68). Nineteen of the 23 patients (83%) who had ultrasensitive viral load (VL) assays were nondetectable. Among patients with 6 or more protease resistance (PR) mutations (PI-resistant), 11 of 14 (79%) achieved virologic success. Eleven of those received phenotypic testing (10 Virtual Phenotype, VircoLab, Baltimore, MD). Despite predicted phenotypic resistance to ATV (6 patients) and LPV/r (7 patients), virologic success was achieved in 4 of 6 (67%) and 4 of 7 (57%), respectively. The 3 PI-resistant patients who were virologic failures had extensive prior LPV/r use, 8-11 PR mutations, and predicted phenotypic resistance to LPV/r, but 2 of 3 had CD4 increases with ATV + LPV/r. Overall, 28 patients (85%) continue to tolerate ATV + LPV/r for a median of 32 weeks follow-up (range, 12-76). Combination ATV + LPV/r with NRTIs appears safe, tolerable, and efficacious in PI-resistant patients (>/=6 PR mutations) and predicted phenotypic resistance to ATV and LPV/r. Further studies of ATV + LPV/r in HIV-treatment are warranted.

Age of menopause and menopausal symptoms in HIV-infected women.

The objective of this study was to examine the median age of menopause, factors associated with postmenopausal status, and the prevalence of menopausal symptoms in HIV-infected women. We surveyed 120 HIV-infected women between 40 and 57 years old who attended an inner city infectious diseases clinic. Ninety-five percent of the women surveyed were African American and almost half of the women (44%) had used methadone, heroin, cocaine, marijuana, or a combination of these drugs within the past 6 months. Eighty-seven percent had smoked cigarettes at least some time during their life and 45% drank alcohol between the ages of 40 and 49 years old. Thirty women were postmenopausal (having no menstrual periods in the previous 12 consecutive months), 31 were perimenopausal (having 1-11 periods within the previous 12 months), and 59 were premenopausal (having 12 or more periods within the previous 12 months). The median age of menopause was 50 years old (95% confidence interval = 49, 53). In a multivariate model, methadone use within the past 6 months was associated with postmenopausal status. We did not find an association between postmenopausal status and body mass index, number of pregnancies, CD4 cell counts, HIV viral load, individual and grouped antiretroviral therapies, cigarette smoking, and current or past oral contraceptive use. In multivariate analysis, postmenopausal status was associated with hot flashes and cocaine use was associated with vaginal dryness.

Impaired oxygen on-kinetics in persons with human immunodeficiency virus are not due to highly active antiretroviral therapy.

OBJECTIVE: To determine the effects of human immunodeficiency virus (HIV) and highly active antiretroviral therapy (HAART) on oxygen on-kinetics in HIV-positive persons. DESIGN: Quasi-experimental cross-sectional. SETTING: Infectious disease clinic and exercise laboratory. PARTICIPANTS: Referred participants (N=39) included 13 HIV-positive participants taking HAART, 13 HIV-positive participants not taking HAART, and 13 noninfected controls. INTERVENTIONS: Participants performed 1 submaximal exercise treadmill test below the ventilatory threshold, 1 above the ventilatory threshold, and 1 maximal treadmill exercise test to exhaustion. MAIN OUTCOME MEASURES: Change in oxygen consumption (Delta.VO2) and oxidative response index (Delta.VO2/mean response time). RESULTS: Delta.VO2 was significantly lower in both HIV-positive participants taking (946.5+/-68.1mL) and not taking (871.6+/-119.6mL) HAART than in controls (1265.3+/-99.8mL) during submaximal exercise above the ventilatory threshold. The oxidative response index was also significantly lower (P<.05) in HIV-positive participants both taking (15.0+/-1.3mL/s) and not taking (15.1+/-1.7mL/s) HAART than in controls (20.8+/-2.1mL/s) during exercise above the ventilatory threshold. CONCLUSION: Oxygen on-kinetics during submaximal exercise above the ventilatory threshold was impaired in HIV-positive participants compared with a control group, and it appeared that the attenuated oxygen on-kinetic response was primarily caused by HIV infection rather than HAART.

Decreased peak arteriovenous oxygen difference during treadmill exercise testing in individuals infected with the human immunodeficiency virus.

OBJECTIVE: To determine if arteriovenous oxygen difference was lower in asymptomatic individuals with human immunodeficiency virus (HIV) infection than in sedentary but otherwise healthy controls. DESIGN: Quasi-experimental cross-sectional. SETTING: Clinical exercise laboratory. PARTICIPANTS: Fifteen subjects (10 men, 5 women) with HIV and 15 healthy gender- and activity level-matched controls (total N=30). INTERVENTION: Participants performed an incremental maximal exercise treadmill test to exhaustion. Electrocardiogram, metabolic, and noninvasive cardiac output measurements were evaluated at rest and throughout the tests. Data were analyzed by using analysis of covariance. MAIN OUTCOME MEASURES: Peak oxygen consumption (Vo(2)), cardiac output, stroke volume, and arteriovenous oxygen difference. The arteriovenous oxygen difference was determined indirectly using the Fick equation. RESULTS: Peak VO(2) was significantly lower (P<.0005) in participants with HIV (24.6+/-1.2mL.kg(-1).min(-1)) compared with controls (32.0+/-1.2mL.kg(-1).min(-1)). There were no significant intergroup differences in cardiac output or stroke volume at peak exercise. Peak arteriovenous oxygen difference was significantly lower (P<.04) in those infected with HIV (10.8+/-0.5 volume %) than in controls (12.4+/-0.5 volume %). CONCLUSION: The observed deficit in aerobic capacity in the participants with HIV appeared to be the result of a peripheral tissue oxygen extraction or utilization limitation. In addition to deconditioning, potential mechanisms for this significant attenuation may include HIV infection and inflammation, highly active antiretroviral therapy medication regimens, or a combination of these factors.

A comparison of Qt and a-vO2 in individuals with HIV taking and not taking HAART.

PURPOSE: The aim of this study was to determine whether highly active antiretroviral therapy (HAART), rather than the direct effect of HIV infection, limits peripheral muscle oxygen extraction-utilization (a-vO(2)) in individuals infected with the human immunodeficiency virus (HIV). METHODS: Fifteen subjects (6 female and 9 male) with HIV taking HAART, 15 subjects infected with HIV not taking HAART, and 15 healthy gender and activity level matched non-HIV infected controls (N = 45) performed an maximal treadmill exercise test to exhaustion. Noninvasive cardiac output Qt was measured at each stage and at peak exercise using the indirect Fick method based on the exponential rise carbon dioxide rebreathing method. Intergroup comparisons were adjusted for interactions of peak oxygen consumption ([V02), body surface area, and [V02]t using ANCOVA. RESULTS: Peak a-vO(2) was significantly lower (P < 0.05) in subjects with HIV taking HAART (10.0 +/- 0.5 vol%) compared with subjects with HIV not taking HAART (11.7 +/- 0.5 vol%) and noninfected controls (12.7 +/- 0.5 vol%). In subjects with HIV taking HAART, peak heart rate (HR) (170.5 +/- 3.9 bpm) was lower than (P < 0.05) and stroke volume (Vs) (123.0 +/- 3.9 mL x beat-1) at peak exercise was higher (P < 0.05) than subjects with HIV not taking HAART (179.9 +/- 3.5 bpm) (106.6 +/- 3.9 mL x beat-1) and noninfected controls (185.4 +/- 3.8 bpm) (100.6 +/- 4.0 mL.beat-1) upon ANCOVA. There were no significant differences in peak [VO2]t between groups. CONCLUSION: Peak a-vO(2) was diminished in subjects infected with HIV taking HAART compared with HIV-infected subjects not taking HAART and noninfected controls matched for age, gender, and physical activity level. Findings of the current study implicated HAART as a primary contributor to decreased muscle oxygen extraction-utilization in individuals infected with HIV.

Mycobacterium avium complex-associated cholecystitis in an HIV-infected woman.

Mycobacterium avium complex (MAC) is commonly associated with fever, fatigue, nausea, diarrhea, and cytopenias related to invasion of the intestine and bone marrow. Infection and clinical disease has been reported in other organs as well. We report the first case of cholecystitis associated with MAC infection of the gallbladder.

Vertigo and abacavir.

Vertigo can cause significant morbidity and make a person unable to perform activities of daily life. A human immunodeficiency virus (HIV)-infected patient experienced vertigo while taking abacavir that resolved immediately on cessation of therapy. The mechanism by which abacavir appeared to be associated with vertigo in this patient is unknown.