Patterns in Tobacco, E-Cigarette, and Cannabis Advertising Exposure Among California Adolescents and Associations With Future Use Expectations.

BACKGROUND: Exposure to tobacco, e-cigarette, or cannabis marketing is associated with adolescent use. Few studies have examined advertising exposure prevalence and patterns across these products concurrently. METHODS: This study assessed past 30-day recalled exposure to promotional messages about tobacco, e-cigarettes ("vapes" on the survey), and cannabis ("marijuana") from various sources among California adolescents (ages 12-17) in the 2022 Teens, Nicotine, and Tobacco Online Survey (N = 2530). Principal components analysis (PCA) was conducted to examine the underlying structure and patterns in advertising exposure sources. Multivariable logistic regression was used to evaluate associations between any advertising exposure and future use expectations (a susceptibility measure) in one year and at age 25 among current never-users. RESULTS: Overall, 65.9% of participants recently noticed at least one tobacco (52.5%), vape (51.5%), or marijuana (45.6%) advertisement. Gas stations or convenience stores were the most common source for tobacco or vape ads; billboards were for marijuana ads. In PCA, advertising exposure patterns correlated with advertising source, not the type of product. Exposures from tobacco-specific sources and nearer point of sale were associated with current use, older age, LGBTQ + identity, and sensation seeking. Among never-users, advertising exposure was associated with one-year and age-25 use expectations for cigarettes (one-year expectations adjusted odds ratio: 1.7; 95% CI: 1.1, 2.5), vapes (2.3; 1.5, 3.5), and marijuana (2.1; 1.5, 3.0). CONCLUSION: California adolescents' exposure to tobacco, e-cigarette, and cannabis marketing is common, follows similar patterns, and is associated with use susceptibility. Comprehensive restrictions on marketing accessible to adolescents could help prevent youth use.

"I think we can do without [tobacco]": support for policies to end the tobacco epidemic among California adolescents.

INTRODUCTION: The tobacco endgame, policies aiming to end the commercial tobacco epidemic, requires sustained public support, including among youth. We assessed endgame support among California (USA) adolescents, including their reasons and associated participant and policy-specific factors. METHODS: Teens, Nicotine and Tobacco Project online surveys (n=4827) and focus groups were conducted in 2021 and 2022 among California residents aged 12-17 years. Cross-sectional survey participants were asked their agreement level with eight policy statements related to tobacco and/or cannabis sales restrictions, use in public places and use in multiunit housing. Ordered logistic regression modelled level of agreement according to respondent characteristics, behaviours and statement content. Qualitative data were collected through focus groups (n=51 participants), which were analysed to provide insight into support for different policies. RESULTS: Most survey participants agreed or strongly agreed with tobacco product sales restrictions (72%-75%, depending on the policy), bans on use in public spaces (76%-82%) and smoke-free (79%) and vape-free (74%) apartment buildings. Support was stronger among younger, female, Asian and tobacco non-using participants and for policies directed at 'tobacco' (vs 'vapes' or cannabis), at flavoured tobacco (compared with all tobacco), and when statements featured 'should end' (vs 'not allowed'). Focus group participants who were supportive viewed policies as protecting children from harmful products, while those less supportive cited concerns about limiting adults' freedoms and unintended consequences. CONCLUSIONS: Most participants supported strong tobacco control policies. Public communication that promotes broader endgame benefits besides protecting youth and accelerates industry denormalisation may counter youth concerns and further bolster their support.

Asian Americans' and Pacific Islanders' preferences in recruitment strategies and messaging for participation in the CARE registry: A discrete choice experiment.

INTRODUCTION: This discrete choice experiment (DCE) identified Asian American and Pacific Islander (AAPI) adults' preferences for recruitment strategies/messaging to enroll in the Collaborative Approach for AAPI Research and Education (CARE) registry for dementia-related research. METHODS: DCE recruitment strategy/messaging options were developed in English, Chinese, Korean, and Vietnamese. AAPI participants 50 years and older selected (1) who, (2) what, and (3) how they would prefer hearing about CARE. Analyses utilized conditional logistic regression. RESULTS: Participants self-identified as Asian Indian, Chinese, Filipino, Japanese, Korean, Samoan, or Vietnamese (N = 356). Overall, they preferred learning about CARE from the healthcare community (vs. community champions and faith-based organizations), joining CARE to advance research (vs. personal experiences), and hearing about CARE through social media/instant messaging (vs. flyer or workshop/seminar). Preferences varied by age, ethnic identity, and survey completion language. DISCUSSION: DCE findings may inform tailoring recruitment strategies/messaging to engage diverse AAPI in an aging-focused research registry.

Flavors increase adolescents' willingness to try nicotine and cannabis vape products.

BACKGROUND: Certain product characteristics, such as flavor, may increase adolescents' willingness to try vaped nicotine and cannabis (marijuana) products. METHODS: A discrete choice experiment embedded within the 2021-2022 California Teens Nicotine and Tobacco Project Online Survey was administered to a non-probability sample of N = 2342 adolescents ages 12-17. Participants were sequentially presented four randomly-generated pairs of hypothetical vape products that varied in device type (disposable, refillable), content (nicotine, marijuana, "just vapor"), and flavor (seven options) and asked which of these (or neither) they would be more willing to try if a best friend offered. Conditional logistic regression quantified associations between product characteristics and participants' selections, including interactions by past 30-day use of e-cigarettes, marijuana, or both. RESULTS: Candy/dessert, fruit, and fruit-ice combination flavors were all associated with greater willingness to try a vape product (versus tobacco flavor) among participants not using e-cigarettes or marijuana, those using only e-cigarettes, and those co-using e-cigarettes and marijuana. Among participants only using marijuana, the most preferred flavors were no flavor, candy/dessert, and icy/frost/menthol. Among participants not using e-cigarettes or marijuana, model-predicted willingness to try a displayed vape product was greater when products were sweet or fruit flavored than tobacco or unflavored, regardless of whether displayed options contained nicotine (fruit/sweet: 21 %, tobacco/unflavored: 4 %), marijuana (fruit/sweet: 18 %, tobacco/unflavored: 6 %), or "just vapor" (fruit/sweet: 29 %, tobacco/unflavored: 16 %). CONCLUSIONS: In this online non-probability sample, flavors in nicotine and cannabis vape products increased adolescents' willingness to try them. Comprehensive bans on flavored vapes would likely reduce adolescent use.

MRI-Based Prostate-Specific Antigen Density Predicts Gleason Score Upgrade in an Active Surveillance Cohort.

OBJECTIVE. Elevated prostate-specific antigen density (PSAD) based on transrectal ultrasound (TRUS) measurements has been shown to be strongly associated with clinically significant disease and to predict progression on active surveillance (AS) for men with disease that is at a low stage or grade. We hypothesized that elevated MRI PSAD is similarly associated with increased risk of progression on subsequent biopsy. MATERIALS AND METHODS. In this retrospective study, men with Gleason score of 3+3 on diagnostic TRUS-guided biopsy who were managed with AS, had undergone MRI, and had at least one additional biopsy were included. MRI PSAD was calculated using prostate volume on MRI and prostate-specific antigen level temporally closest to the MRI. Multivariable logistics regression models were used to evaluate the association between MRI PSAD and predictors of upgrade on serial biopsy. RESULTS. A total of 166 patients were identified, of whom 74 (44.6%) were upgraded to a Gleason score of 7 or higher on subsequent biopsy. Lesions with Prostate Imaging Reporting and Data System (PI-RADS) scores of 4 and 5 more commonly had MRI PSAD of 0.15 ng/mL2 or higher (51.93% vs 22.22%, p = 0.01) than lesions with PI-RADS scores of 1-3. Median MRI PSAD was significantly higher in the upgraded group compared with the group that was not upgraded (0.15 ng/mL2 vs 0.11 ng/mL2, p = 0.01). MRI PSAD was significantly associated with increased odds of upgrading on subsequent biopsy (log transformation; odds ratio, 1.9 [95% CI, 1.2-2.8]; p = 0.01) after adjusting for age and length of follow-up. CONCLUSION. MRI PSAD was significantly associated with Gleason score upgrading on subsequent biopsy for men initially diagnosed with Gleason 3+3 disease. Although this result is intuitive, to our knowledge it has not been previously shown. As MRI utilization increases, MRI PSAD can aid in risk stratification for men managed with AS.

Automating the Capture of Structured Pathology Data for Prostate Cancer Clinical Care and Research.

PURPOSE: Cancer pathology findings are critical for many aspects of care but are often locked away as unstructured free text. Our objective was to develop a natural language processing (NLP) system to extract prostate pathology details from postoperative pathology reports and a parallel structured data entry process for use by urologists during routine documentation care and compare accuracy when compared with manual abstraction and concordance between NLP and clinician-entered approaches. MATERIALS AND METHODS: From February 2016, clinicians used note templates with custom structured data elements (SDEs) during routine clinical care for men with prostate cancer. We also developed an NLP algorithm to parse radical prostatectomy pathology reports and extract structured data. We compared accuracy of clinician-entered SDEs and NLP-parsed data to manual abstraction as a gold standard and compared concordance (Cohen's κ) between approaches assuming no gold standard. RESULTS: There were 523 patients with NLP-extracted data, 319 with SDE data, and 555 with manually abstracted data. For Gleason scores, NLP and clinician SDE accuracy was 95.6% and 95.8%, respectively, compared with manual abstraction, with concordance of 0.93 (95% CI, 0.89 to 0.98). For margin status, extracapsular extension, and seminal vesicle invasion, stage, and lymph node status, NLP accuracy was 94.8% to 100%, SDE accuracy was 87.7% to 100%, and concordance between NLP and SDE ranged from 0.92 to 1.0. CONCLUSION: We show that a real-world deployment of an NLP algorithm to extract pathology data and structured data entry by clinicians during routine clinical care in a busy clinical practice can generate accurate data when compared with manual abstraction for some, but not all, components of a prostate pathology report.

Feasibility, Acceptability, and Behavioral Outcomes from a Technology-enhanced Behavioral Change Intervention (Prostate 8): A Pilot Randomized Controlled Trial in Men with Prostate Cancer.

BACKGROUND: Increasing evidence suggests that lifestyle factors may decrease the risk of prostate cancer progression. Lifestyle guidelines and tools may support lifestyle modification after diagnosis. OBJECTIVE: To determine the feasibility and acceptability of a digital lifestyle intervention among men with prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: A 12-wk pilot randomized controlled trial among 76 men with clinical stage T1-T3a prostate cancer. Eligibility included Internet access, no contraindications to aerobic exercise, and engaging in four or fewer of eight targeted behaviors at baseline. INTERVENTION: Website, Fitbit One, and text messaging to facilitate adoption of eight behaviors: vigorous activity, smoking cessation, and six diet improvements. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Our primary outcomes were feasibility and acceptability based on recruitment and user data, and surveys, respectively. Secondarily, we evaluated the change in eight lifestyle behaviors, and also objective physical activity. Each factor was assigned one point, for an overall "P8 score" (range 0-8). Analysis of covariance (ANCOVA) was conducted. Exploratory outcomes included quality of life, anthropometrics, and circulating biomarkers after 12wk, and behaviors after 1yr. RESULTS AND LIMITATIONS: At baseline, men in both arms met a median of three targeted behaviors. Sixty-four men (n=32 per arm) completed the study; 88% completed 12-wk assessments (intervention, 94%; control, 82%). Intervention participants wore their Fitbits a median of 82d (interquartile range [IQR]: 72-83), replied to a median of 71% of text messages (IQR: 57-89%), and visited the website a median of 3d (IQR: 2-5) over 12wk. Median (IQR) absolute changes in the P8 score from baseline to 12wk were 2 (1, 3) for the intervention and 0 (-1, 1) for the control arm. The estimated mean score of the intervention arm was 1.5 (95% confidence interval: 0.7, 2.3) higher than that of the control arm at 12wk (ANCOVA p<0.001). Changes were driven by diet rather than exercise. Limitations include self-reported diet and exercise data. CONCLUSIONS: Overall, in this novel pilot trial, the intervention was feasible and acceptable to men with prostate cancer. Next steps include improving the intervention to better meet individuals' needs and focusing on increasing physical activity in men not meeting nationally recommended physical activity levels. PATIENT SUMMARY: Tailored print materials combined with technology integration, including the use of a website, text messaging, and physical activity trackers, helped men with prostate cancer adopt healthy lifestyle habits, in particular recommended dietary changes, in the Prostate 8 pilot trial.

Association between a 17-gene genomic prostate score and multi-parametric prostate MRI in men with low and intermediate risk prostate cancer (PCa).

BACKGROUND: We aimed to directly compare results from multi-parametric prostate MRI (mpMRI) and a biopsy-based 17-gene RT-PCR assay providing a Genomic Prostate Score (GPS) among individuals who were candidates for active surveillance with low and intermediate risk prostate cancer (PCa). PATIENTS AND METHODS: We evaluated the association between GPS results (scale 0-100) and endorectal mpMRI findings in men with clinically localized PCa. MR studies were reviewed to a five-tier scale of increasing suspicion of malignancy. Mean apparent diffusion coefficient (ADC) was calculated from a single dominant lesion. Mean rank of the GPS (0-100) among MRI strata was compared with the Kruskal-Wallis test and Dunn's multiple comparison test. Spearman's correlation was performed to examine the association between mean ADC and scaled GPS. RESULTS: Of 186 patients who received GPS testing, 100 were identified who received mpMRI. Mean GPS results differed between mpMRI categories (p = 0.001); however a broad range was observed in all mpMRI categories. Among men with biopsy Gleason pattern 3+3, mean GPS results were not significantly different among MRI groups (p = 0.179), but GPS differences were seen among MRI categories for patients with pattern 3+4 (p = 0.010). Mean ADC was weakly associated with GPS (σ = -0.151). Stromal response (p = 0.015) and cellular organization (p = 0.045) gene group scores differed significantly by MRI findings, but no differences were seen among androgen signaling or proliferation genes. CONCLUSIONS: Although a statistically significant association was observed between GPS results and MRI scores, a wide range of GPS values were observed across imaging categories suggesting that mpMRI and genomic profiling may offer non- overlapping clinical insights.

Validity of the Cancer of the Prostate Risk Assessment Score Derived From Targeted Biopsy: Modeling Evidence From Ultrasound Lesion-Directed Biopsy.

OBJECTIVE: Our aim was to evaluate the impact of direct, ultrasound lesion-targeted prostate biopsy, alone or in combination with systematic sampling, on prostate cancer risk prediction. MATERIALS AND METHODS: We reviewed biopsy findings for men with known or clinical suspicion of prostate cancer undergoing direct, ultrasound-targeted biopsy of radiographic lesions with concomitant systematic extended peripheral zone biopsy. We examined the resulting tumor volume estimates, Gleason grade, and Cancer of the Prostate Risk Assessment score generated from each strategy. Resulting multivariate clinical models of adverse surgical pathology-defined as high grade (Gleason pattern, ≥ 4+3) or non-organ-confined disease (≥ pT3a) were compared by the area under the Receiver Operating Characteristic curve. RESULTS: A total of 352 patients received ultrasound-targeted biopsy. At diagnosis, the mean age was 63 years, median prostate-specific antigen, 5.7 ng/mL (interquartile range, 4.3-8.2), and median 15 cores (interquartile range, 12-18). The addition of targeted cores to systematic biopsy resulted in reclassification of 52 patients (14.7%) based on Gleason score, 45 (12.8%) by percentage of cores involved > 33%, and 51 (14.5%) by single core positivity > 50%; Cancer of the Prostate Risk Assessment risk category increased in 44 (12.5%). In multivariable logistic regression models of 196 men treated with prostatectomy, the area under the Receiver Operating Characteristic curve for the prediction of adverse pathology generated from targeted (0.754), systematic (0.753), and combined approaches (0.763) were not significantly different (P = .831). CONCLUSIONS: The validity of clinical risk prediction assessed with a multi-variable instrument was maintained in the setting of lesion-targeted biopsy.

Quantified Clinical Risk Change as an End Point During Prostate Cancer Active Surveillance.

For men with low-stage prostate cancer (PCa) managed with active surveillance (AS), clinical thresholds for intervention have not been definitively established. We aimed to evaluate whether the magnitude of quantitative risk change may serve as a refined end point. We identified 735 men managed with AS at our institution who received a minimum of two biopsies and who were followed for a median of 52 mo. We described the relative changes in the Cancer of the Prostate Risk Assessment (CAPRA) score from diagnosis to last follow-up and evaluated the proportion of patients experiencing changes in constituent clinical variables. Among patients treated with radical prostatectomy (RP), the association between change in CAPRA score and the occurrence of adverse pathology (pT3a or higher and/or primary Gleason pattern ≥4) was assessed using logistic regression models. Among patients ultimately treated with RP (n=196), unit increases in CAPRA score from diagnosis were associated with the occurrence of adverse pathology (odds ratio: 1.60; 95% confidence interval, 1.25-2.04; p<0.01). On this basis, disease reclassification should be regarded from the vantage of multiple parameters. PATIENT SUMMARY: In this study of men with favorable-risk prostate cancer on active surveillance, we evaluated the change in risk status from initial diagnosis to last biopsy using a readily tabulated clinical instrument. Unit change in the Cancer of the Prostate Risk Assessment (CAPRA) score was associated with increasing risk of adverse pathologic findings at delayed prostatectomy. This framework may be useful to stratify men based on the degree of clinical change from baseline over time.

Response to Transdermal Selegiline Smoking Cessation Therapy and Markers in the 15q24 Chromosomal Region.

INTRODUCTION: Current treatments for smoking cessation have limited efficacy. A potential pharmaceutical treatment for smoking cessation is selegiline, a selective and irreversible monoamine oxidase B inhibitor. A few clinical trials have been carried out using selegiline but the results have been mixed. We sought to determine if genetic markers in cholinergic loci in the 15q24 chromosomal region predict response to smoking cessation therapy with selegiline. METHODS: We performed an 8-week double-blind, placebo-controlled clinical trial of the selegiline transdermal system in heavy smokers, with follow-up at weeks 25 and 52. Eight single nucleotide polymorphisms (SNPs) in the 15q24 region, which contains the genes for the nicotinic acetylcholine receptor subunits CHRNA5, CHRNA3, and CHRNB4, were investigated for association with treatment response. RESULTS: The CHRNB4 promoter SNP rs3813567 was associated with both point prevalence abstinence and post-quit craving. Carriers of the minor C allele treated with selegiline showed lower rates of abstinence and higher levels of craving than selegiline-treated non-carriers, indicating that the rs3813567 C allele adversely affects abstinence in selegiline-treated smokers. This effect was not present among placebo-treated smokers. Selegiline-treated smokers with the CHRNA5 rs680244 GG genotype had lower post-quit craving, and unlike placebo-treated GG-carrying smokers, did not experience a post-quit increase in depressive symptoms. CONCLUSIONS: Variants in genes encoding cholinergic receptors affect abstinence, craving and mood in selegiline-treated smokers. Selegiline primarily affects dopamine levels in the brain, but cholinergic input affects nicotine-induced dopaminergic activity. These markers may have value in identifying those likely to respond to selegiline for smoking cessation.

The association between diet and physical activity on insulin resistance in the Women's Interagency HIV Study.

OBJECTIVES: To evaluate the association of diet and physical activity with insulin resistance (IR) in HIV-infected and HIV-uninfected women. METHODS: Cross-sectional analyses of summary dietary measures and physical activity intensity scores obtained from women enrolled in the San Francisco (n = 113) and Chicago (n = 65) Women's Interagency HIV Study (WIHS) sites. IR was estimated using the homeostasis model assessment (HOMA-IR). Stepwise regression models assessed the association of diet and physical activity with HOMA-IR after adjustment for demographic, behavioral, and clinical factors. RESULTS: Compared with HIV-uninfected women, HIV-infected women were older and more likely to have health insurance. In multivariable analysis including all women, being from San Francisco ( P = 0.005), having a higher mean body mass index (BMI, P < 0.001), and having a higher percent kilocalories from sweets (P = 0.025) were associated with greater HOMA-IR; heavy intensity physical activity (P = 0.006) and annual household income more than $36,000 ( P = 0.02) was associated with a lower HOMA-IR. In analysis limited to HIV-infected women, having a higher body mass index (P < 0.001) and a history of protease inhibitor use (P = 0.002) were significantly associated with higher HOMA-IR; heavy intensity activity (P = 0.06) was marginally associated with lower HOMA-IR and being menopausal (P = 0.05) was marginally associated with higher HOMA-IR. CONCLUSIONS: Among urban women with or at risk for HIV-infection, heavy intensity physical activity was associated with lower HOMA-IR, whereas higher percent kilocalories from sweets were associated with higher HOMA-IR. Given the overall health benefits of physical activity and a diet low on sugar, these behaviors should be encouraged whenever possible.

Atazanavir concentration in hair is the strongest predictor of outcomes on antiretroviral therapy.

BACKGROUND: Adequate exposure to antiretrovirals is important to maintain durable responses, but methods to assess exposure (eg, querying adherence and single plasma drug level measurements) are limited. Hair concentrations of antiretrovirals can integrate adherence and pharmacokinetics into a single assay. METHODS: Small hair samples were collected from participants in the Women's Interagency HIV Study (WIHS), a large cohort of human immunodeficiency virus (HIV)-infected (and at-risk noninfected) women. From 2003 through 2008, we analyzed atazanavir hair concentrations longitudinally for women reporting receipt of atazanavir-based therapy. Multivariate random effects logistic regression models for repeated measures were used to estimate the association of hair drug levels with the primary outcome of virologic suppression (HIV RNA level, <80 copies/mL). RESULTS: 424 WIHS participants (51% African-American, 31% Hispanic) contributed 1443 person-visits to the analysis. After adjusting for age, race, treatment experience, pretreatment viral load, CD4 count and AIDS status, and self-reported adherence, hair levels were the strongest predictor of suppression. Categorized hair antiretroviral levels revealed a monotonic relationship to suppression; women with atazanavir levels in the highest quintile had odds ratios (ORs) of 59.8 (95% confidence ratio, 29.0-123.2) for virologic suppression. Hair atazanavir concentrations were even more strongly associated with resuppression of viral loads in subgroups in which there had been previous lapses in adherence (OR, 210.2 [95% CI, 46.0-961.1]), low hair levels (OR, 132.8 [95% CI, 26.5-666.0]), or detectable viremia (OR, 400.7 [95% CI, 52.3-3069.7]). CONCLUSIONS: Antiretroviral hair levels surpassed any other predictor of virologic outcomes to HIV treatment in a large cohort. Low antiretroviral exposure in hair may trigger interventions prior to failure or herald virologic failure in settings where measurement of viral loads is unavailable. Monitoring hair antiretroviral concentrations may be useful for prolonging regimen durability.

Retention and attendance of women enrolled in a large prospective study of HIV-1 in the United States.

OBJECTIVE: The objective was to assess study retention and attendance for two recruitment waves of participants in the Women's Interagency HIV Study (WIHS). METHODS: The WIHS, a prospective study at six clinical centers in the United States, has experienced two phases of participant recruitment. In phase one, women were screened and enrolled at the same time, and in phase two, women were screened and enrolled at separate visits. Compliance with study follow-up was evaluated by examining semiannual study retention and visit attendance. RESULTS: After 10 study visits, the retention rate in the original recruits (enrolled in 1994-1995) was 83% for the HIV-infected women and 69% for the HIV-uninfected women compared with 86% and 86%, respectively, in the new recruits (enrolled in 2001-2002). In logistic regression analysis of the HIV-infected women, factors associated with early (visits 2 and 3) nonattendance were temporary housing, moderate alcohol consumption, use of crack/cocaine/heroin, having a primary care provider, WIHS site of enrollment, lower CD4 cell count, and higher viral load. Among HIV-uninfected women, the factors associated with early nonattendance were recruitment into the original cohort, household income >or=$12,000 per year, temporary housing, unemployment, use of crack/cocaine/heroin, and WIHS site of enrollment. Factors associated with nonattendance at later visits (7-10) among HIV-infected participants were younger age, white race, not having a primary care provider, not having health insurance, WIHS site of enrollment, higher viral load, and nonattendance at a previous visit. In HIV-uninfected participants, younger age, white race, WIHS site of enrollment, and nonattendance at a previous visit were significantly associated with nonattendance at later visits. CONCLUSIONS: Preventing early loss to follow-up resulted in better study retention early, but late loss to follow-up may require different retention strategies.

Protease inhibitor levels in hair strongly predict virologic response to treatment.

OBJECTIVE: Antiretroviral (ARV) therapies fail when behavioral or biologic factors lead to inadequate medication exposure. The currently available methods to assess ARV exposure are limited. Levels of ARVs in hair reflect plasma concentrations over weeks to months, and may provide a novel method for predicting therapeutic responses. DESIGN/METHODS: The Women's Interagency HIV Study, a prospective cohort of HIV-infected women, provided the basis for developing and assessing methods to measure commonly prescribed protease inhibitors (lopinavir/ritonavir and atazanavir) in small hair samples. We examined the association between hair protease inhibitor levels and initial virologic responses to therapy in multivariate logistic regression models. RESULTS: ARV concentrations in hair were strongly and independently associated with treatment response for 224 women starting a new protease inhibitor-based regimen. For participants initiating lopinavir/ritonavir, the odds ratio (OR) for virologic suppression was 39.8 [95% confidence interval (CI) = 2.8-564] for those with lopinavir hair levels in the top tertile (>1.9 ng/mg) compared to the bottom (3.4 ng/mg) compared to the lowest (

Growth hormone enhances thymic function in HIV-1-infected adults.

Growth hormone (GH) is an underappreciated but important regulator of T cell development that can reverse age-related declines in thymopoiesis in rodents. Here, we report findings of a prospective randomized study examining the effects of GH on the immune system of HIV-1-infected adults. GH treatment was associated with increased thymic mass. In addition, GH treatment enhanced thymic output, as measured by both the frequency of T cell receptor rearrangement excision circles in circulating T cells and the numbers of circulating naive and total CD4(+) T cells. These findings provide compelling evidence that GH induces de novo T cell production and may, accordingly, facilitate CD4(+) T cell recovery in HIV-1-infected adults. Further, these randomized, prospective data have shown that thymic involution can be pharmacologically reversed in humans, suggesting that immune-based therapies could be used to enhance thymopoiesis in immunodeficient individuals.

Herpes simplex virus infection in women in the WIHS: epidemiology and effect of antiretroviral therapy on clinical manifestations.

OBJECTIVE: To determine the prevalence of infection with herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) among women with and at high risk for HIV infection, and to evaluate the effect of HAART on the recurrence of genital lesions. METHODS: We evaluated the epidemiology and clinical manifestations associated with HSV-1 and HSV-2 among 1796 HIV-infected and 476 HIV-uninfected women enrolled in a multisite cohort study. Serum antibodies to HSV-1 and HSV-2 at baseline and self-reported history of genital herpes, reports of recent genital sores and presence of genital ulcers on examination, and use of HAART regimen at each study visit were analyzed. RESULTS: Reactivity to HSV-1 only and HSV-2 only was detected in 18% and 20% of HIV-infected, and in 28% and 18% of HIV-uninfected participants respectively; 58% of HIV-infected women and 45% of HIV-uninfected women were seropositive for both HSV types. Reactivity to HSV-2 was associated with increasing age, more male sexual partners, earlier sexual debut, African-American race, Latina ethnicity, less education and lower income. HIV-uninfected women reported significantly fewer genital sores than HIV-infected women who had used HAART for at least 1 year and had optimal CD4 cell gain and viral suppression (adjusted odds ratio (OR), 0.19; 95% confidence interval (CI), 0.13-0.28). CONCLUSION: Use of HAART and subsequent immune recovery does not completely eliminate the effect of HIV infection on genital lesions among women with concurrent HSV-2 infection.

Eligibility criteria for HIV clinical trials and generalizability of results: the gap between published reports and study protocols.

OBJECTIVE: Applicability of randomized controlled clinical trial (RCT) results to 'real world' situations is dependent on the comparability of trial participants to general patient populations. A full disclosure of criteria employed for trial enrollment is necessary for clinicians to assess generalizability. We sought to assess both the impact on generalizability and the disclosure rate of enrollment criteria for 32 major HIV RCTs in the AIDS Clinical Trial Group (ACTG) and Community Programs for Clinical Research on AIDS (CPCRA) trial networks. DESIGN AND METHODS: Eligibility criteria were compared in complete protocols to criteria listed in publications from these 32 NIH-funded HIV RCTs. We then applied these criteria to the Women's Interagency HIV Study (WIHS), the largest cohort study of HIV-infected women in the US. RESULTS: When applied to WIHS, eligibility criteria from protocols excluded 0-67.6% (median 42%) of WIHS participants (50.6% excluded from ACTG trials). Eligibility criteria in publications excluded 0-62% (median 19.6%) of WIHS (21.2% excluded from ACTG trials). The number of women in WIHS seemingly ineligible for trial participation per enrollment criteria listed in publications averaged only 60% of those actually excluded based on the protocols. CONCLUSIONS: We found that HIV RCT eligibility criteria excluded a large proportion of a representative cohort of HIV-infected women from trial participation. Furthermore, trial publications are not fully reflective of protocols in terms of disclosing eligibility criteria. Standardization and full disclosure of trial methodology will allow clinicians and researchers to more fully assess the generalizability of findings to their patient populations.

The effect of highly active antiretroviral therapy on dermatologic disease in a longitudinal study of HIV type 1-infected women.

The effect of highly active antiretroviral therapy (HAART) on skin diseases was evaluated in 878 human immunodeficiency virus type 1 (HIV-1)-infected women in the Women's Interagency HIV Study, a multicenter prospective study. HIV-1-infected women receiving HAART were less likely to have eczema, folliculitis, tinea pedis, and xerosis than were women who had not initiated HAART, independent of CD4+ cell count. Participants who had a prior history of a nadir CD4+ cell count of <200 cells/microL and recent CD4+ cell counts of 200-349 cells/microL were more likely to have eczema and xerosis than were women with a nadir CD4+ cell count of >200 cells/microL and recent CD4+ cell counts of >349 cells/microL. An HIV-1 RNA load of >100,000 copies/mL was associated with increased prevalence of herpes zoster infection (odds ratio, 6.10; 95% confidence interval, 2.00-18.65). History of injection drug use was associated with a higher prevalence of onychomycosis, tinea pedis, and xerosis. Molluscum contagiosum was more prevalent among younger women.