Clinical Predictors and Outcomes of Invasive Anal Cancer for People With Human Immunodeficiency Virus in an Inception Cohort.

BACKGROUND: Due to the heterogeneity of risk for invasive anal cancer (IAC) among people with human immunodeficiency virus (PWH), we investigated predictors of IAC and described outcomes among those with a cancer diagnosis. METHODS: Using a longitudinal inception cohort of anal cancer screening, we evaluated risk factors and outcome probabilities for incident IAC in Cox models. Screening included anal cytology and digital anorectal examination, and, if results of either were abnormal, high-resolution anoscopy. RESULTS: Between 30 November 2006 and 3 March 2021, a total of 8139 PWH received care at the University of California, San Diego, with 4105 individuals undergoing screening and subsequently followed up over a median of 5.5 years. Anal cancer developed in 33 of them. IAC was more likely to develop in patients with anal high-grade squamous intraepithelial lesions (aHSILs) on initial or subsequent follow-up cytology (hazard ratio, 4.54) and a nadir CD4 cell count ≤200/µL (2.99). The joint effect of aHSILs and nadir CD4 cell count ≤200/µL amplified the hazard of IAC by 9-fold compared with the absence of both. PWH with time-updated cytology aHSIL and CD4 cell counts ≤200/µL had 5- and 10-year probabilities of IAC of 3.40% and 4.27%, respectively. Twelve individuals with cancer died, 7 (21% of the total 33) due to cancer progression, and they had clinical stage IIIA or higher cancer at initial diagnosis. CONCLUSIONS: PWH with both aHSIL and a nadir CD4 cell count ≤200/µL have the highest risk of IAC. PWH who died due to IAC progression had clinical stage IIIA cancer or higher at diagnosis, highlighting the importance of early diagnosis through high-resolution anoscopic screening.

Whole Genomic Analysis Revealed High Genetic Diversity and Drug-Resistant Characteristics of Mycobacterium tuberculosis in Guangxi, China.

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a major public health issue in China. Nevertheless, the prevalence and drug resistance characteristics of isolates vary in different regions and provinces. In this study, we investigated the population structure, transmission dynamics and drug-resistant profiles of Mtb in Guangxi, located on the border of China. Methods: From February 2016 to April 2017, 462 clinical M. tuberculosis isolates were selected from 5 locations in Guangxi. Drug-susceptibility testing was performed using 6 common anti-tuberculosis drugs. The genotypic drug resistance and transmission dynamics were analyzed by the whole genome sequence. Results: Our data showed that the Mtb in Guangxi has high genetic diversity including Lineage 1 to Lineage 4, and mostly belong to Lineage 2 and Lineage 4. Novelty, 9.6% of Lineage 2 isolates were proto-Beijing genotype (L2.1), which is rare in China. About 12.6% of isolates were phylogenetically clustered and formed into 28 transmission clusters. We observed that the isolates with the high resistant rate of isoniazid (INH, 21.2%), followed by rifampicin (RIF, 13.2%), and 6.7%, 12.1%, 6.7% and 1.9% isolates were resistant to ethambutol (EMB), streptomycin (SM), ofloxacin (OFL) and kanamycin (KAN), respectively. Among these, 6.5% and 3.3% of isolates belong to MDR-TB and Pre-XDR, respectively, with a high drug-resistant burden. Genetic analysis identified the most frequently encountered mutations of INH, RIF, EMB, SM, OFL and KAN were katG_Ser315Thr (62.2%), rpoB_Ser450Leu (42.6%), embB_Met306Vol (45.2%), rpsL_Lys43Arg (53.6%), gyrA_Asp94Gly (29.0%) and rrs_A1401G (66.7%), respectively. Additionally, we discovered that isolates from border cities are more likely to be drug-resistant than isolates from non-border cities. Conclusion: Our findings provide a deep analysis of the genomic population characteristics and drug-resistant of M. tuberculosis in Guangxi, which could contribute to developing effective TB prevention and control strategies.

Effects of drug and hazardous alcohol use on having a detectable HIV viral load: An adherence mediation analysis.

Objectives: People living with HIV (PWH) with substance or alcohol use often have unsuppressed plasma HIV viral loads (pVL). The degree to which substance and alcohol use effects on HIV viral suppression are mediated through medication nonadherence is incompletely understood. Methods: We included PWH prescribed antiretroviral therapy and receiving care at an academic HIV clinic between 2014 and 2018 who completed both patient-reported outcomes (PRO) questionnaires and had subsequent pVL measurements. Measures included assessments of alcohol use (AUDIT-C), drug use (NIDA-ASSIST), and self-reported adherence measured using four different methods. Substances found in bivariate analysis to predict detectable pVL were modeled separately for mediation effects through adherence. We report natural direct (NDE) and indirect effect (NIE), marginal total effect (MTE), and percentage mediated. Results: Among 3125 PWH who met eligibility criteria, 25.8% reported hazardous alcohol use, 27.1% cannabis, 13.1% amphetamines, 1.9% inhalants, 5.3% cocaine, 4.5% sedative-hypnotics, 2.9% opioids, and 2.3% hallucinogens. Excellent adherence was reported by 58% of PWH, and 10% had detectable pVL. Except for sedatives, using other substances was significantly associated with worse adherence. Bivariate predictors of detectable pVL were [OR (95% CI)]: amphetamine use 2.4 (1.8-3.2) and opioid use 2.3 (1.3-4.0). The percent of marginal total effect mediated by nonadherence varied by substance: 36% for amphetamine use, 27% for opioid use, and 39% for polysubstance use. Conclusion: Use of amphetamines, opioids, and multiple substances predicted detectable pVL. Up to 40% of their effects were mediated by self-reported nonadherence. Confirmation using longitudinal measurement models will strengthen causal inference from this cross-sectional analysis.

Efficacy and Risk Factors of Interferon-Gamma Release Assays among HIV-Positive Individuals.

Latent tuberculosis is prevalent in HIV-infected people and has an impact on the progression of AIDS. The aim of this study is to match a more accurate IGRA method for the better detection of latent tuberculosis infection in HIV patients. All 2394 patients enrolled were tested using three IGRA methods. The positive rate consistency of pairwise comparison and risk factors were analyzed. Receiver operator characteristic (ROC) curve analysis was applied to evaluate the diagnostic value of T-SPOTTB. The positive rates of the three methods were statistically different (p < 0.001). The CD4+ T cell number statistically impacted the QuantiFERON and Wan Tai tests after the analysis with univariate logistic regression, while no statistical difference was observed in T-SPOT.TB. Additionally, there was a better sensitivity and specificity of T-SPOT.TB if the positive cut-off value of ESAT-6 and CFP-10 was 4.5 and 5.5, respectively. This study provides an insight into the IGRA methods and demonstrated that the positive response detected via QuantiFERON declined with decreased CD4+ T cells in the HIV-infected population; T-SPOT.TB functions independently of the CD4+ T cell level and Wan Tai was affected in some cases. This will be useful in the diagnosis of LTBI in the HIV-infected population, which will be a key step toward TB elimination in China.

Tuberculosis among Ambulatory People Living with HIV in Guangxi Province, China: A Longitudinal Study.

BACKGROUND: This study aims to determine the prevalence of TB among ambulatory people living with HIV in Guangxi Province, which experienced the biggest HIV epidemic in China. METHODS: We undertook a longitudinal study in five HIV/AIDS designated hospitals randomly selected from Guangxi Province; all newly diagnosed HIV/AIDS outpatients from 2019 to 2021 were screened for TB and interviewed with a questionnaire. RESULTS: A total of 4539 HIV/AIDS outpatients were enrolled, with 2886 (63.6%) men and 1653 (26.4%) women. The prevalence of TB/HIV coinfection was 0.8%, with a clear downward trend from 1.3% in 2019 to 0.4% in 2021 (p = 0.0011). The prevalence of LTBI was 24.3%, with no significant differences from 2019 to 2021. The percentages of AIDS, comorbidity, nine symptoms and abnormal chest X-ray of TB were higher than those of the other PLWH. CONCLUSION: The prevalence of TB among ambulatory people with HIV in Guangxi Province was 14 times higher than the general population, and the annual declined TB prevalence indicated the effectiveness of TB and HIV control and prevention over recent years. The findings proved that symptom screening was insufficient for TB diagnosis and highlighted the importance of systematic TB screening at every visit to a health facility.

Impact of switching to tenofovir alafenamide on weight gain as compared to maintaining a non-tenofovir alafenamide containing regimen.

ABSTRACT: Evaluate the impact of switching to an anti-retroviral regimen containing tenofovir alafenamide (TAF) on weight and the development of metabolic complications compared to remaining on a non-TAF containing regimen.Single-center retrospective case-control study.We evaluated people living with human immunodeficiency virus (PLWH) who were on an anti-retroviral regimen not containing TAF and were switched to a regimen containing TAF between January 1, 2016 and September 30, 2018. The control group included PLWH on a TAF free regimen throughout the study period. The primary outcome was change in weight from baseline to 12 months postswitch. Secondary outcomes included percent change in weight, change in body mass index (BMI), change in BMI class, and new diagnoses of diabetes, hypertension, and hyperlipidemia (HLD) during the study period.PLWH switched to TAF (n = 446) demonstrated significantly greater mean increase in weight compared to the control group (n = 162) (1.97 vs 0.88 kg, P = .01), however the effect was only seen in those switched from tenofovir disoproxil fumarate. Those that switched to TAF also had a significantly higher percent increase in weight, increase in BMI, and BMI class. We observed a higher rate of new diagnosis of HLD in the control group compared to the TAF switch group during the study period.PLWH switched to TAF had greater increases in weight after 1 year as compared to those continuing on a TAF free regimen. However, this did not translate to higher rates of obesity related illnesses such as diabetes, hypertension, and HLD during the follow up period.

Screening for Sexually Transmitted Infections During Hepatitis C Treatment to Predict Reinfection Among People With HIV.

BACKGROUND: Little is known about the risk of hepatitis C virus (HCV) reinfection among people with HIV (PWH) in the direct-acting antiviral (DAA) era. We evaluate HCV reinfection rates in the DAA era and characterize presustained virologic response (SVR) behavioral risk factors associated with reinfection among PWH at the University of California, San Diego (UCSD). METHODS: Observational longitudinal cohort of PWH treated with DAAs between 2014 and July 2019 who achieved SVR and had at least 1 subsequent HCV viral load measurement. HCV reinfection was defined as new HCV viremia after SVR. We examined whether screening for sexually transmitted infections (STIs) and substance use during the pre-SVR period could identify patients at greater risk for reinfection using exact Poisson regression to compare reinfection incidence rates between those with and without pre-SVR STIs and positive urine drug screens. RESULTS: Eight out of 200 PWH were reinfected with HCV a median ~26 weeks after SVR over 328.1 person-years of follow-up (PYFU), for an incidence rate of 2.44/100 PYFU. The observed HCV reinfection rate was highest among men who have sex with men who inject drugs (MSM IDU; 4.63/100 PFYU) and those aged 30-39 years (6.80/100 PYFU). Having a positive gonorrhea/chlamydia test during the pre-SVR period was a predictor of HCV reinfection. CONCLUSIONS: The HCV reinfection rate in the DAA era is similar to the rate observed in the interferon era in San Diego in PWH. STI screening during HCV treatment may help determine those at higher risk for HCV reinfection.

The role of barriers to care on the propensity for hepatitis C virus nonreferral among people living with HIV.

: Twenty-five percent of HIV/hepatitis C virus (HCV) coinfected patients were not referred for HCV treatment despite unrestricted access in California to direct-acting antivirals (DAA) in 2018. Having unstable housing and ongoing drug use directly affected HCV treatment nonreferral. However, psychiatric history and alcohol use impacted HCV treatment nonreferral through the mediation of not being engaged in HIV care. Achieving HCV elimination requires DAA treatment outside conventional health settings, including substance rehabilitation centers, mental health crisis houses, and homeless shelters.

Infectivity of Mycobacterium tuberculosis Genotypes and Outcome of Contact Investigation in Classroom in Guangxi, China.

OBJECTIVE: To evaluate the infectivity of Mycobacterium tuberculosis (M.tb) genotypes of index cases in the classroom of adolescent schools in Guangxi, China. METHODS: Adolescent school tuberculosis (TB) contact investigations were conducted for all reported index TB cases from November 2016 to December 2017 in Guangxi, China. Genotypes of index cases and contact cases were identified by 15-loci mycobacterial interspersed repetitive units-variable number tandem repeat and spoligotyping. Outcome variable was 5 levels' order of tuberculin skin test (TST) results to new active TB [0-5 mm, 6-9 mm, 10-14 mm, ≥ 15 mm (without TB), and ≥15 mm (with TB)]. Multivariate ordered logistic regression analysis was performed to evaluate the independent effect of genotypes of index case on contact screening outcome. RESULTS: Beijing genotype occurred more commonly in female index patients. One genotypic cluster of two index cases and one cluster of two contact cases were detected. The association between infectivity of Beijing genotype of index cases and outcome of contact investigation was statistically significant in univariate analysis but no so after adjustment for characteristics of contacts and sex of index cases (P value=0.057). Female index cases increased the chance for TB infection/being active TB among contacts (ordinal odds ratio = 1.39, 95% confidence interval: 1.21, 1.60). Contacts who studied in the middle school, who with non-Han ethnicity and who without BCG scar had increased risk for TB infection/being active TB. CONCLUSION: There was not enough evidence from our data to support that Beijing strains were more infective than non-Beijing strains in TB transmission in school setting.

Tuberculosis Transmission in Households and Classrooms of Adolescent Cases Compared to the Community in China.

The aim of this paper is to evaluate the link between the history of exposure to tuberculosis (TB) in the household and diagnosed TB cases at school, and to compare the detection rate of active TB among household contacts and classroom contacts of adolescent TB cases with the rates among contacts of healthy controls. From November 2016 to December 2017, a prospective matched case-control study was conducted using passively identified index adolescent student cases from the TB surveillance system and healthy controls (matched by county, school type, sex, age and ethnicity). Contacts in households and classrooms of index cases and of controls were investigated. Matched tabulation of 117 case-control pairs revealed exposure to TB in the household as a strong risk factor (odds ratio (OR) = 21.0, 95% confidence interval (CI): 3.4, 868.6). Forty-five (case detection rate 0.69%) and two (case detection rate 0.03%) new active TB cases were detected among 6512 and 6480 classroom contacts of the index cases and controls, respectively. Having an index case in the classroom significantly increased the risk of classmates contracting active TB (OR = 22.5, 95% CI: 5.9, 191.4). Our findings suggested that previous exposure to TB in the household could lead a child to catch TB at school, then spread TB to classmates.

Assessing baseline religious practices and beliefs to predict adherence to highly active antiretroviral therapy among HIV-infected persons.

The efficacy of highly active antiretroviral therapy (HAART) is dependent upon moderately high levels of adherence; however, predicting adherence before HAART initiation can be difficult. We conducted a prospective, longitudinal study among 350 HIV-infected adults attending a HIV clinic in San Diego, CA (USA) from January 2010 to December 2011 to examine both established and novel predictors of adherence, including religious practices and beliefs. Statistically significant (p < .05) variables identified in bivariate analyses were included in multivariate analyses predicting ≥90% adherence. Higher annual household income (p = .004) and religious affiliation (p = .031) were predictive of greater adherence. Participants who said their beliefs gave meaning to their lives, made them feel they had a connection with a higher being, were influential during their recovery, and helped them feel connected to humanity were more likely to be ≥90% adherent (p < .015). Conversely, participants who believed God created all things in the universe; that God will not turn his back on them; and those who regularly attended religious services, participated in religious rituals, and prayed and meditated to get in touch with God were less likely to be ≥90% adherent (p ≤ .025). Results indicate that a patient's religious beliefs and practices may predict medication adherence. Interventions should be designed to emphasize the use of positive religious coping strategies and address the adverse implications of religious fatalism.

Retention: building a patient-centered medical home in HIV primary care through PUFF (Patients Unable to Follow-up Found).

Here, we describe our patient-centered medical home (PCMH) quality improvement retention project conducted by a Health Resources and Services Administration (HRSA) Ryan White-funded Primary Care HIV clinic. The single urban academic clinic serving 2,776 active HIV positive patients identified 25.8% (716/2,776) patients who had not been retained in care within the prior six months during two separate six-month interval analyses. Multiple modalities including a retention specialist, a secure clinic phone message line, algorithms, flyers, brochures, database, and staff education were built to facilitate re-engagement. The project located 87.7% (628/716) patients who had not been retained. The retention specialist was directly responsible for the return of 16.2% (116/716) patients. Results from the project demonstrated that a formalized approach is a necessary component to effective retention efforts. We believe that this work will provide a strategic framework for the development of randomized control trials to formally evaluate an HIV retention intervention.

Characterizing HIV transmission networks across the United States.

BACKGROUND: Clinically, human immunodeficiency virus type 1 (HIV-1) pol sequences are used to evaluate for drug resistance. These data can also be used to evaluate transmission networks and help describe factors associated with transmission risk. METHODS: HIV-1 pol sequences from participants at 5 sites in the CFAR Network of Integrated Clinical Systems (CNICS) cohort from 2000-2009 were analyzed for genetic relatedness. Only the first available sequence per participant was included. Inferred transmission networks ("clusters") were defined as ≥2 sequences with ≤1.5% genetic distance. Clusters including ≥3 patients ("networks") were evaluated for clinical and demographic associations. RESULTS: Of 3697 sequences, 24% fell into inferred clusters: 155 clusters of 2 individuals ("dyads"), 54 clusters that included 3-14 individuals ("networks"), and 1 large cluster that included 336 individuals across all study sites. In multivariable analyses, factors associated with being in a cluster included not using antiretroviral (ARV) drugs at time of sampling (P < .001), sequence collected after 2004 (P < .001), CD4 cell count >350 cells/mL (P < .01), and viral load 10,000-100,000 copies/mL (P < .001) or >100,000 copies/mL (P < .001). In networks, women were more likely to cluster with other women (P < .001), and African Americans with other African Americans (P < .001). CONCLUSIONS: Molecular epidemiology can be applied to study HIV transmission networks in geographically and demographically diverse cohorts. Clustering was associated with lack of ARV use and higher viral load, implying transmission may be interrupted by earlier diagnosis and treatment. Observed female and African American networks reinforce the importance of diagnosis and prevention efforts targeted by sex and race.

Tuberculosis due to Mycobacterium bovis in patients coinfected with human immunodeficiency virus.

We reviewed 86 cases of human immunodeficiency virus and tuberculosis coinfection; 34.9% were caused by Mycobacterium bovis. Patients with M. bovis infection were more likely to have advanced immunosuppression (CD4 T cell counts ≤200 cells/µL). Hispanic ethnicity, male sex, and abdominal disease were strongly associated with M. bovis disease.

Factors associated with higher levels of injury severity in occupants of motor vehicles that were severely damaged in traffic crashes in Kentucky, 2000-2001.

OBJECTIVES: The majority of motor vehicle occupants who were killed or hospitalized in crashes in Kentucky in 2000-2001 occupied vehicles that were severely damaged in the crash. Even so, overall only a small percentage of all severely damaged vehicle occupants were killed or hospitalized. The purpose was to identify occupant, vehicle, crash, and roadway/environmental factors that were associated with increased risk of severe injury in crashes where the occupant's vehicle was severely damaged. METHODS: This study probabilistically linked Kentucky's statewide motor vehicle crash and inpatient hospital discharge data files for 2000 and 2001, and selected cases representing occupants of vehicles that were reported by police as having either "severe" or "very severe" damage. For occupants who were identified through data linkage as having been hospitalized, the Injury Severity Score (ISS) was calculated using ICDMAP-90 software, and the scores were stratified into the following categories: critical (>24), severe (15-24), moderate (9-14), and mild (<9). We then created an outcome variable, injury severity level, with five levels: killed; hospitalized with at least moderate injuries (ISS = critical, severe, or moderate); hospitalized with mild injuries (ISS = mild); injured according to the police report but not hospitalized; and no apparent injury according to the police report. We performed a stepwise, ordinal logistic regression of injury severity, using independent variables identified from the existing crash literature. RESULTS: Occupant risk factors for higher levels of injury severity selected by the regression were age (risk increased with age, other factors being equal), female gender, restraint non-use, ejection from the vehicle, and driver impairment (by alcohol and/or drugs). Crash risk factors included head-on collision, collision with a fixed object, vehicle rollover, and vehicle fire. Roadway/environmental factors were federal- or state-maintained roadway and posted speed limit 89 kph (55 mph) or greater. CONCLUSIONS: Many of the identified risk factors are explicitly or implicitly mentioned in the strategic plans of key organizations involved in highway safety and injury prevention in Kentucky. Our analysis provides additional evidence of their importance, and confirms that their mitigation will reduce injury severity in crashes involving severe vehicle damage. Additionally, older occupants and female occupants showed increased risks of serious injury, but to our knowledge these factors are not currently addressed in any state plans. An opportunity exists to clarify the nature of these risks through further studies, which might lead to the identification of countermeasures specific to these populations.