Characterizing Indicators of Engagement in HIV-Associated Healthcare and Clinical Outcomes among People with HIV and Mpox in Washington, DC: A Nested Case-Control Study of the DC Cohort.

The high proportion of people with HIV (PWH) in the 2022-2023 mpox outbreak has raised questions surrounding the association between HIV and mpox. The objectives of this study were to evaluate the association between engagement in HIV-associated healthcare and mpox diagnosis, as well as to characterize cases of mpox among PWH. The DC Cohort is a longitudinal cohort of PWH in Washington, DC. We conducted a 5:1 (controls:cases) nested case-cohort study on male participants, matching age and care site. Cases were participants with an identified mpox diagnosis. Conditional logistic regression was used to assess the impact of indicators of engagement in HIV-associated healthcare on mpox diagnosis. We identified 70 cases of mpox in DC Cohort participants randomly matched to 323 controls, for a total of 393 participants included in the analysis. Study participants were primarily non-Hispanic Black (72.3%) with a median age of 41 (IQR: 36, 50). There was no association between engagement in care and mpox diagnosis; however, low CD4 was associated with increased odds of mpox diagnosis (aOR: 4.60 (95% CI: 1.23, 17.11)). Among a cohort of PWH, engagement in care was not associated with mpox diagnosis, suggesting that the overrepresentation of PWH among mpox cases is not due to surveillance bias.

HIV treatment with dolutegravir and doravirine: rationale for selection and clinical outcomes in a highly treatment experienced population.

Dolutegravir and doravirine are individually safe and effective antiretroviral therapy (ART) components, but their combined use has not been studied in clinical trials and is not recommended in HIV treatment guidelines. We noted persons with HIV (PWH) receiving dolutegravir with doravirine at our Washington, DC, infectious disease clinic and undertook a service evaluation to understand why providers selected this ART, whether HIV virologic suppression was achieved and identify adverse effects of concomitant use. Case registry and prescriptions data identified 21 PWH receiving concomitant dolutegravir and doravirine with mean follow-up 576.1 days (range 413-751); frequent reasons for switching were multiple ART resistance (57.1%), proton pump inhibitor usage (28.6%) and renal failure (28.6%), with 52.4% switched from protease inhibitor or cobicistat-boosted regimens. Dolutegravir with doravirine alone was prescribed for 60%, and additional ART in 40%. During 12 months follow-up mean CD4 was 585.9 (baseline 570.7) with undetectable viral load in 77.8% (baseline 66.7%). No discontinuations for drug-related adverse events or virologic failure occurred. Dolutegravir with doravirine was well tolerated in small numbers of highly treatment experienced PWH at our clinic, achieving virologic suppression in most. Establishing the efficacy and safety of dolutegravir with doravirine for HIV treatment in randomized trials remains important.

Diabetes mellitus control in a large cohort of people with HIV in care-Washington, D.C.

With more effective antiretroviral therapy (ART), people with HIV (PWH) are living longer and have more chronic diseases, including diabetes mellitus (DM). The prevalence of DM has been estimated in PWH previously, however there is less research regarding DM control. Our objectives were to determine the prevalence of DM and DM control and determine factors associated with DM control in a large urban cohort of PWH in care. We examined DC Cohort participants aged ≥18 years old to determine DM prevalence and to assess DM control (HbA1c measurement <7.0%). Demographic, clinical, and HIV-related factors associated with DM control were identified using multivariate logistic regression. The cohort of 5876 participants was predominantly male (71.3%), Non-Hispanic Black (78.1%) and had a median age of 52.0 years. DM prevalence was 17.4% (1023/5876). Among participants with recent HbA1c data available (39.9%) the proportion with DM control was 60.0% (245/408). In multivariate analysis, higher BMI (aOR: 0.47; 95% CI 0.28, 0.79) and use of non-insulin DM medication (aOR 0.43, 95% CI 0.25, 0.73) or insulin (aOR 0.010, 95% CI 0.04,0.24) compared to no medication use. Our findings suggest that individuals on medication for their DM likely need enhanced support to reach their treatment goals.

Pharmacologic Treatment of Psychiatric Disorders and Time With Unsuppressed HIV Viral Load in a Clinical HIV Cohort.

OBJECTIVE: To evaluate associations of mood, anxiety, stress-/trauma-related, and psychotic disorders, both treated and untreated, with duration of unsuppressed HIV viral load (VL) among persons living with HIV (PLWH). SETTING: The DC Cohort, an observational clinical cohort of PLWH followed from 2011 to 2018 at 14 sites in Washington, DC. METHODS: Among PLWH ≥18 years old who received primary care at their HIV clinic, we determined in a time-updated manner whether participants had diagnoses and pharmacologic prescriptions for mood, anxiety, stress-/trauma-related, and/or psychotic disorders. Associations between psychiatric disorders/treatments and the proportion of subsequent days with VL ≥200 copies/mL were assessed using multivariable Poisson regression with generalized estimating equations. RESULTS: Among 5904 participants (median age 51; 70% men; 82% Black), 45% had ≥1 psychiatric disorder, including 38% with mood disorders (50% treated), 18% with anxiety or stress-/trauma-related disorders (64% treated), and 4% with psychotic disorders (52% treated). Untreated major depressive disorder (adjusted rate ratio = 1.17; 95% confidence interval: 1.00 to 1.37), untreated other/unspecified depressive disorder (1.23; 1.01 to 1.49), untreated bipolar disorder (1.39; 1.15 to 1.69), and treated bipolar disorder (1.25; 1.02 to 1.53) (vs. no mood disorder) predicted more time with VL ≥200 copies/mL. Treated anxiety disorders (vs. no anxiety disorder) predicted less time (0.78; 0.62 to 0.99). Associations were weaker and nonsignificant for treated depressive disorders (vs. no mood disorder) and untreated anxiety disorders (vs. no anxiety disorder). CONCLUSIONS: PLWH with depressive and bipolar disorders, particularly when untreated, spent more time with unsuppressed VL than PLWH without a mood disorder. Treatment of mood disorders may be important for promoting sustained viral suppression.

Quality of life of persons living with HIV and congruence with surrogate decision-makers.

PURPOSE: Physicians and caregivers rate patient quality of life (QOL) lower than patients rate their own QOL. This study investigated discrepancies between self-assessments of patient QOL by adults with HIV and their surrogate decision-makers. METHODS: We collected baseline data from 223 adult dyads in the FAmily-CEntered (FACE) Advance Care Planning (ACP) clinical trial, consisting of HIV positive patients and their chosen surrogates. Participants independently completed the Medical Outcome Study-HIV Survey (MOS-HIV) and the Palliative care Outcome Scale (POS). We used Wilcoxon Signed-Rank Test to assess differences in overall patient-surrogate means. We used Prevalence Adjusted Bias Adjusted Kappa (PABAK) statistics to assess dyadic agreement, with surrogate HIV status and cohabitation status as grouping variables. RESULTS: Patients were 56.1% male, 86.1% Black/African-American, aged 22-77 (mean = 50.83, SD = ± 12.33). Surrogates were 43.8% male, 84.1% Black/African-American, aged 18-82 (mean = 49.73, SD = ± 14.22). 46.2% of surrogates lived with the patient. 64.6% of surrogates reported negative HIV status. Surrogates were more likely to state patients were ill, p = 0.032. Among patient-surrogate dyads, most QOL assessments showed poor (0.00-0.39) or fair (0.40-0.59) agreement and agreement tended to be even poorer among patient-surrogate dyads where the surrogate had a shared HIV diagnosis. CONCLUSIONS: QOL discrepancies are said to arise from healthy surrogates overestimating the effects of chronic illness. In this novel assessment, many surrogates had a shared HIV diagnosis, without increased agreement. These findings highlight the challenge of accurately assessing patient QOL by surrogates, even when there is a shared HIV diagnosis. Improved communication is needed between patients and surrogates about the patients' representation of illness. National Clinical Trial Number: NCT01775436.

Sexually Transmitted Infections Among HIV-Infected Individuals in the District of Columbia and Estimated HIV Transmission Risk: Data From the DC Cohort.

BACKGROUND: Washington, DC, has one of the highest rates of HIV infection in the United States. Sexual intercourse is the leading mode of HIV transmission, and sexually transmitted infections (STIs) are a risk factor for HIV acquisition and transmission. METHODS: We evaluated the incidence and demographic factors associated with chlamydia, gonorrhea, and syphilis among HIV-infected persons enrolled at 13 DC Cohort sites from 2011 to 2015. Using Poisson regression, we assessed covariates of risk for incident STIs. We also examined HIV viral loads (VLs) at the time of STI diagnosis as a proxy for HIV transmission risk. RESULTS: Six point seven percent (451/6672) developed an incident STI during a median follow-up of 32.5 months (4% chlamydia, 3% gonorrhea, 2% syphilis); 30% of participants had 2 or more STI episodes. The incidence rate of any STIs was 3.8 cases per 100 person-years (95% confidence interval [CI], 3.5-4.1); age 18-34 years, 10.8 (95% CI, 9.7-12.0); transgender women, 9.9 (95% CI, 6.9-14.0); Hispanics, 9.2 (95% CI, 7.2-11.8); and men who have sex with men (MSM), 7.7 (95% CI, 7.1-8.4). Multivariate Poisson regression showed younger age, Hispanic ethnicity, MSM risk, and higher nadir CD4 counts to be strongly associated with STIs. Among those with an STI, 41.8% had a detectable VL within 1 month of STI diagnosis, and 14.6% had a VL ≥1500 copies/mL. CONCLUSIONS: STIs are highly prevalent among HIV-infected persons receiving care in DC. HIV transmission risk is considerable at the time of STI diagnosis. Interventions toward risk reduction, antiretroviral therapy adherence, and HIV virologic suppression are critical at the time of STI evaluation.

Impact of Larger Sputum Volume on Xpert® MTB/RIF Assay Detection of Mycobacterium tuberculosis in Smear-Negative Individuals with Suspected Tuberculosis.

As a strategy to improve the sensitivity of nucleic acid-based testing in acid-fast bacilli (AFB) negative samples, larger volumes of sputum (5-10 mL) were tested with Xpert® MTB/RIF from 176 individuals with smear-negative sputum undergoing tuberculosis evaluation. Despite larger volumes, this strategy had a suboptimal sensitivity of 50% (4/8).

Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons.

OBJECTIVE: Compare the effectiveness, tolerability, and safety of 3 months of weekly rifapentine and isoniazid under direct observation (3HP) versus 9 months of daily isoniazid (9H) in HIV-infected persons. DESIGN: Prospective, randomized, and open-label noninferiority trial. SETTING: The United States , Brazil, Spain, Peru, Canada, and Hong Kong. PARTICIPANTS: HIV-infected persons who were tuberculin skin test positive or close contacts of tuberculosis cases. INTERVENTION: 3HP versus 9H. MAIN OUTCOME MEASURES: The effectiveness endpoint was tuberculosis; the noninferiority margin was 0.75%. The tolerability endpoint was treatment completion; the safety endpoint was drug discontinuation because of adverse drug reaction. RESULTS: Median baseline CD4 cell counts were 495 (IQR 389-675) and 538 (IQR 418-729) cells/µl in the 3HP and 9H arms, respectively (P = 0.09). In the modified intention-to-treat analysis, there were two tuberculosis cases among 206 persons [517 person-years (p-y) of follow-up] in the 3HP arm (0.39 per 100 p-y) and six tuberculosis cases among 193 persons (481 p-y of follow-up) in the 9H arm (1.25 per 100 p-y). Cumulative tuberculosis rates were 1.01 versus 3.50% in the 3HP and 9H arms, respectively (rate difference: -2.49%; upper bound of the 95% confidence interval of the difference: 0.60%). Treatment completion was higher with 3HP (89%) than 9H (64%) (P < 0.001), and drug discontinuation because of an adverse drug reaction was similar (3 vs. 4%; P = 0.79) in 3HP and 9H, respectively. CONCLUSION: Among HIV-infected persons with median CD4 cell count of approximately 500 cells/µl, 3HP was as effective and safe for treatment of latent Mycobacterium tuberculosis infection as 9H, and better tolerated.

Evaluation of Xpert MTB/RIF Versus AFB Smear and Culture to Identify Pulmonary Tuberculosis in Patients With Suspected Tuberculosis From Low and Higher Prevalence Settings.

BACKGROUND: The Xpert MTB/RIF (Xpert) assay is a rapid nucleic acid amplification test widely used in settings of high tuberculosis prevalence to detect tuberculosis as well asrpoBmutations associated with rifampin resistance. Data are needed on the diagnostic performance of Xpert in lower-prevalence settings to inform appropriate use for both tuberculosis detection and the need for respiratory isolation. METHODS: Xpert was compared to 2 sputum samples, each evaluated with acid-fast bacilli (AFB) smear and mycobacterial culture using liquid and solid culture media, from participants with suspected pulmonary tuberculosis from the United States, Brazil, and South Africa. RESULTS: Of 992 participants enrolled with evaluable results, 22% had culture-confirmed tuberculosis. In 638 (64%) US participants, 1 Xpert result demonstrated sensitivity of 85.2% (96.7% in participants with AFB smear-positive [AFB(+)] sputum, 59.3% with AFB smear-negative [AFB(-)] sputum), specificity of 99.2%, negative predictive value (NPV) of 97.6%, and positive predictive value of 94.9%. Results did not differ between higher- and low-prevalence settings. A second Xpert assay increased overall sensitivity to 91.1% (100% if AFB(+), 71.4% if AFB(-)), with specificity of 98.9%. In US participants, a single negative Xpert result predicted the absence of AFB(+)/culture-positive tuberculosis with an NPV of 99.7%; NPV of 2 Xpert assays was 100%, suggesting a role in removing patients from airborne infection isolation. Xpert detected tuberculosis DNA and mutations associated with rifampin resistance in 5 of 7 participants with rifampin-resistant, culture-positive tuberculosis. Specificity for rifampin resistance was 99.5% and NPV was 98.9%. CONCLUSIONS: In the United States, Xpert testing performed comparably to 2 higher-tuberculosis-prevalence settings. These data support the use of Xpert in the initial evaluation of tuberculosis suspects and in algorithms assessing need for respiratory isolation.

Tuberculosis reactivation in hepatocellular carcinoma: association with transarterial chemoembolization.

Transarterial chemoembolization (TACE) is an important therapeutic option for patients with hepatocellular carcinoma (HCC). We discuss five patients with HCC and tuberculosis (TB) reactivation following TACE. Screening patients for latent TB infection at diagnosis of cirrhosis or HCC should be considered because of the immunosuppression inherent in both the diseases and their treatments.

True durability: HIV virologic suppression in an urban clinic and implications for timing of intensive adherence efforts and viral load monitoring.

Although the majority of HIV-infected patients who begin potent antiretroviral therapy should expect long-term virologic suppression, the realities in practice are less certain. Durability of viral suppression was examined to define the best timing of targeted adherence strategies and intensive viral load monitoring in an urban clinic population with multiple challenges to ART adherence. We examined the risk of viral rebound for patients who achieved two consecutive viral loads lower than the lower limit of quantification (LLOQ) within 390 days. For 791 patients with two viral loads below the LLOQ, viral rebound >LLOQ from the first viral load was 36.9 % (95 % CI 32.2-41.6) in the first year, 26.9 % (95 % CI 21.7-32.1) in the year following one year of viral suppression, and 24.6 % (95 % CI 18.4-30.9) in the year following 2 years of viral suppression. However, for patients with CD4 ≥300 cells/µl who had 3-6 years of virologic suppression, the risk of viral rebound was very low. At the population level, the risk of viral rebound in a complex urban clinic population is surprisingly high even out to 3 years. Intensified monitoring and adherence efforts should target this high risk period. Thereafter, confidence in truly durable virologic suppression is improved.

Progress realized: trends in HIV-1 viral load and CD4 cell count in a tertiary-care center from 1999 through 2011.

BACKGROUND: HIV-1 RNA and CD4 cell counts are important parameters for HIV care. The objective of this study was to assess the overall trends in HIV-1 viral load and CD4 cell counts within our clinic. METHODS: Patients with at least one of each test performed by the Infectious Diseases Laboratory from 1999 through 2011 were included in this analysis. By adapting a novel statistical model, log(10) HIV-1 RNA means were estimated by month, and log(10)-transformed HIV-1 RNA means were estimated by calendar year. Geometric means were calculated for CD4 cell counts by month and calendar year. Log(10) HIV-1 RNA and CD4 cell count monthly means were also examined with polynomial regression. RESULTS: There were 1,814 individuals with approximately 25,000 paired tests over the 13-year observation period. Based on each patient's final value of the year, the percentage of patients with viral loads below the lower limit of quantitation rose from 29% in 1999 to 72% in 2011, while the percentage with CD4 counts <200 cells/µL fell from 31% to 11%. On average annually, the mean HIV-1 RNA decreased by 86 copies/mL and the mean CD4 counts increased by 16 cells/µL. For the monthly means, the correlations (R(2)) from second-order polynomial regressions were 0.944 for log(10) HIV-1 RNA and 0.840 for CD4 cell counts. CONCLUSIONS: Marked improvements in HIV-1 RNA suppression and CD4 cell counts were achieved in a large inner-city population from 1999 through 2011. This success demonstrates that sustained viral control with improved immunologic status can be a realistic goal for most individuals in clinical care.

Is frequent CD4+ T-lymphocyte count monitoring necessary for persons with counts >=300 cells/µL and HIV-1 suppression?

Among patients infected with human immunodeficiency virus (HIV), those with HIV-1 RNA <200 copies/mL and CD4 counts ≥300 cells/µL had a 97.1% probability of maintaining durable CD4 ≥200 cells/µL for 4 years. When non-HIV causes of CD4 lymphopenia were excluded, the probability rose to 99.2%. Our data support less frequent CD4 monitoring during viral suppression.

Present and past influences on current smoking among HIV-positive male veterans.

INTRODUCTION: Cigarette smoking has become an important influence of morbidity and mortality for HIV-positive individuals in the era of highly active antiretroviral therapy. Although smoking is common among military personnel and veterans, the lasting impact of military service on smoking at a later stage of life has not been examined. The current study investigated present and past influences on current smoking among HIV-positive male veterans. METHODS: Participants were 200 HIV-positive men served by the Veterans Affairs Medical Center. A survey was administered via audio-enhanced computer-assisted self-interview, and additional information was extracted from the computerized patient record system. RESULTS: Logistic regression was performed to test hypotheses concerning the participants' current situations as well as characteristics of their past military service. Having smokers in one's environment, being more depressed, and having used alcohol or drugs were associated with having smoked in the previous 30 days, whereas stronger endorsement of attitudes stating adverse effects of smoking was linked to lower likelihood of smoking. Neither having been in a military conflict nor the length of the military service was significantly related to current smoking. CONCLUSIONS: Remote experiences in the military did not have a sustained effect on smoking behavior years later. Implications of this study for the development of smoking cessation programs targeting HIV-positive veterans include the importance of altering attitudes about tobacco, treating underlying depression, addressing social influence, decreasing substance use, and increasing awareness of the heightened vulnerability to a variety of negative consequences of smoking among infected individuals.

Clinical evaluation of the nelfinavir-rifabutin interaction in patients with tuberculosis and human immunodeficiency virus infection.

STUDY OBJECTIVE: To characterize the bidirectional interaction between twice-daily nelfinavir and twice-weekly rifabutin and isoniazid in patients with tuberculosis and human immunodeficiency virus (HIV) infection. DESIGN: Prospective cohort study. SETTING: Three clinical research centers. PATIENTS: Seven patients with HIV-related tuberculosis. INTERVENTION: Rifabutin 300 mg and isoniazid 15 mg/kg (maximum dose 900 mg) twice/week were administered for at least 2 weeks during the continuation phase of tuberculosis treatment. Antiretroviral therapy with nelfinavir 1250 mg twice/day and two nucleoside reverse transcriptase inhibitors was then added. MEASUREMENTS AND MAIN RESULTS: Patients underwent blood sampling for pharmacokinetic analysis during the continuation phase of tuberculosis therapy and after a median of 21 days after the addition of antiretroviral treatment. When rifabutin was coadministered with nelfinavir, its area under the concentration-time curve from 0-21 hours (AUC(0-21)) increased 22% (geometric mean 5.01 microg.hr/ml [90% confidence interval (CI) 3.25-7.71] with nelfinavir vs 4.10 microg.hr/ml [90% CI 3.18-5.27] without nelfinavir; geometric mean ratio 1.22 [90% CI 0.78-1.92]). Also, the AUC(0-21) for the active metabolite, desacetylrifabutin, increased significantly (geometric mean ratio 3.46, 90% CI 1.84-6.47, p=0.009). In the presence of rifabutin, the pharmacokinetic parameters of nelfinavir and its principal metabolite M8 were similar to those of patients not taking rifabutin. No drug interaction between nelfinavir and isoniazid was detected. CONCLUSIONS: Coadministration of rifabutin and isoniazid without dosage adjustment during twice-weekly tuberculosis therapy with nelfinavir-based antiretroviral therapy resulted in rifabutin exposures within the acceptable ranges for safety and efficacy. Therefore, this combination is an appropriate option for the simultaneous treatment of tuberculosis and HIV infection when tuberculosis therapy is given twice weekly.