Daily Oral HIV Pre-exposure Prophylaxis Among Young Men Who Have Sex With Men in the United States: Cost-saving at Generic Drug Price.

BACKGROUND: Adherence and retention concerns raise questions about the effectiveness and cost-effectiveness of oral HIV pre-exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). METHODS: Using an adolescent-focused simulation model, we compared annual HIV screening alone with tenofovir disoproxil fumarate/emtricitabine-based oral PrEP with every 3-month HIV screening in YMSM (aged 15-24) at increased risk of HIV. Data derived from published sources included: age-stratified HIV incidence/100 person-years (PY) on- or off-PrEP (0.6-10.1 or 0.4-6.4), PrEP retention at 6 years (28%), transmissions by HIV RNA level (0.0-78.4/100PY) and annual costs of antiretroviral therapy ($32 000-69 000), HIV care ($3100-34 600), and PrEP program/generic drug ($900/360). Outcomes included transmissions (percent of cohort infected), quality-adjusted life-years (QALYs), costs ($), and incremental cost-effectiveness ratios ($/QALY). We explored the sensitivity of findings to variation in HIV incidence and drug prices. RESULTS: Compared with annual screening alone, PrEP would increase QALYs (9.58 to 9.67), reduce new infections (37% to 30%), and decrease costs (by $5000) over 10 years. PrEP would remain cost-saving for HIV incidence off-PrEP ≥5.1/100PY or annual PrEP price ≤$1200. Over a lifetime horizon, PrEP would be cost-saving for HIV incidence off-PrEP ≥1.0/100PY, across all retention assumptions examined. PrEP would not be cost-effective at HIV incidence ≤0.1/100PY, regardless of drug price, due to programmatic costs. CONCLUSIONS: In US YMSM at increased risk of HIV, generic oral PrEP and every-3-month screening would be cost-saving compared with annual screening alone, even with high discontinuation and low adherence, over a range of HIV incidences.

Prevalence of Self-reported Neurologic and Ocular Symptoms in Early Syphilis Cases.

BACKGROUND: Neurosyphilis, a complication of syphilis, can occur at any stage of infection. Measuring the prevalence of neurosyphilis is challenging, and there are limited data on the prevalence of neurologic or ocular symptoms among patients with syphilis. We sought to describe the prevalence of neurologic and/or ocular symptoms among early syphilis (ES) cases and the clinical management of symptomatic cases enrolled in the STD Surveillance Network (SSuN) Neuro/Ocular Syphilis Surveillance project. METHODS: Persons diagnosed with ES were selected for interviews based on current health department protocols in 5 participating SSuN jurisdictions from November 2016 through October 2017. All interviewed ES cases were screened for self-reported neurologic and/or ocular symptoms. Additional clinical information on diagnostic testing and treatment for cases concerning for neurosyphilis/ocular syphilis was obtained from providers. RESULTS: Among 9123 patients with ES who were interviewed, 151 (1.7%; 95% confidence interval [CI], 1.4%-1.9%) reported ≥ 1 neurologic or ocular symptom. Of the 53 (35%) who underwent lumbar puncture, 22 (42%) had documented abnormal cerebrospinal fluid, of which 21 (95%) were treated for neurosyphilis/ocular syphilis. Among the remaining 98 symptomatic patients with no documented lumbar puncture (65%), 12 (12%) were treated for and/or clinically diagnosed with neurosyphilis/ocular syphilis. CONCLUSIONS: We observed a low prevalence of self-reported neurologic and/or ocular symptoms in interviewed ES cases. Approximately one-third of ES cases who self-reported symptoms underwent further recommended diagnostic evaluation. Understanding barriers to appropriate clinical evaluation is important to ensuring appropriate management of patients with possible neurologic and/or ocular manifestations of syphilis.

Cost-effectiveness of Frequent HIV Screening Among High-risk Young Men Who Have Sex With Men in the United States.

BACKGROUND: Of new HIV infections in the US, 20% occur among young men who have sex with men (YMSM, ages 13-24), but >50% of YMSM with HIV are unaware of their status. Using Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) data, we projected the clinical benefit and cost-effectiveness of frequent HIV screening among high-risk YMSM from age 15. METHODS: Using a mathematical simulation, we examined 3 screening strategies: Yearly, 6-monthly, and 3-monthly, each in addition to the Status quo (SQ, 0.7-10.3% screened/year, stratified by age). We used published data (YMSM-specific when available) including: HIV incidences (0.91-6.41/100PY); screen acceptance (80%), linkage-to-care/antiretroviral therapy (ART) initiation (76%), HIV transmission (0.3-86.1/100PY, by HIV RNA), monthly ART costs ($2290-$3780), and HIV per-screen costs ($38). Projected outcomes included CD4 count at diagnosis, primary HIV transmissions from ages 15-30, quality-adjusted life expectancy, costs, and incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year saved [QALY]; threshold ≤$100 000/QALY). RESULTS: Compared to SQ, all strategies increased projected CD4 at diagnosis (296 to 477-515 cells/µL) and quality-adjusted life expectancy from age 15 (44.4 to 48.3-48.7 years) among YMSM acquiring HIV. Compared to SQ, all strategies increased discounted lifetime cost for the entire population ($170 800 to $178 100-$185 000/person). Screening 3-monthly was cost-effective (ICER: $4500/QALY) compared to SQ and reduced primary transmissions through age 30 by 40%. Results were most sensitive to transmission rates; excluding the impact of transmissions, screening Yearly was ≤$100 000/QALY (ICER: $70 900/QALY). CONCLUSIONS: For high-risk YMSM in the US, HIV screening 3-monthly compared to less frequent screening will improve clinical outcomes and be cost-effective.

High Prevalence of Anal High-Grade Squamous Intraepithelial Lesions, and Prevention Through Human Papillomavirus Vaccination, in Young Men Who Have Sex With Men Living With Human Immunodeficiency Virus.

BACKGROUND: Men who have sex with men (MSM) are at high risk for human papillomavirus (HPV)-related anal cancer. Little is known about the prevalence of low-grade squamous intraepithelial lesions (LSILs) and the anal cancer precursor, high-grade squamous intraepithelial lesions (HSILs), among young MSM with HIV (MSMLWH). HPV vaccination is recommended in this group, but its safety, immunogenicity, and protection against vaccine-type HPV infection and associated LSILs/HSILs have not been studied. METHODS: Two hundred and sixty MSMLWH aged 18-26 years were screened at 17 US sites for a clinical trial of the quadrivalent (HPV6,11,16,18) HPV (qHPV) vaccine. Those without HSILs were vaccinated at 0, 2, and 6 months. Cytology, high-resolution anoscopy with biopsies of lesions, serology, and HPV testing of the mouth/penis/scrotum/anus/perianus were performed at screening/month 0 and months 7, 12, and 24. RESULTS: Among 260 MSMLWH screened, the most common reason for exclusion was detection of HSILs in 88/260 (34%). 144 MSMLWH were enrolled. 47% of enrollees were previously exposed to HPV16. No incident qHPV type-associated anal LSILs/HSILs were detected among men naive to that type, compared with 11.1, 2.2, 4.5, and 2.8 cases/100 person-years for HPV6,11,16,18-associated LSILs/HSILs, respectively, among those previously exposed to that type. qHPV was immunogenic and safe with no vaccine-associated serious adverse events. CONCLUSIONS: 18-26-year-old MSMLWH naive to qHPV vaccine types were protected against incident qHPV type-associated LSILs/HSILs. Given their high prevalence of HSILs, there is an urgent need to vaccinate young MSMLWH before exposure to vaccine HPV types, before initiating sexual activity, and to perform catch-up vaccination.

An Automated Syphilis Serology Record Search and Review Algorithm to Prioritize Investigations by Health Departments.

BACKGROUND: Reactive syphilis serologies are investigated by health departments to determine if they represent new infection, reinfection, or treatment failure. Serologies prioritized for investigation based on nontreponemal test titer and age (using a "reactor grid") undergo manual record search and review. We developed a computerized algorithm that automates the record search and review. METHODS: We developed and tested the algorithm using a Florida Department of Health data set containing serologies reported January 2016 to December 2018 and previous records linked to each individual. The algorithm was based on the syphilis case definition, which requires (except primary cases with signs and symptoms) (1) a positive treponemal test result and a newly positive nontreponemal test result or (2) a 4-fold increase in nontreponemal test titer. Two additional steps were added to avoid missing cases. New York City Department of Health and Mental Hygiene validated this algorithm. RESULTS: The algorithm closed more investigations (49.9%) than the reactor grid (27.0%). The algorithm opened 99.4% of the individuals investigated and labeled as cases by the health department; it missed 75 cases. Many investigations opened by the algorithm were closed by the reactor grid; we could not assess how many would have been cases. In New York City, the algorithm closed 70.9% of investigations, likely because more individuals had previous test in the database (88.2%) compared with Florida (56.5%). CONCLUSIONS: The automated algorithm successfully searched and reviewed records to help identify cases of syphilis. We estimate the algorithm would have saved Florida 590 workdays for 3 years.

Changes in Bone Mass After Discontinuation of Preexposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine in Young Men Who Have Sex With Men: Extension Phase Results of Adolescent Trials Network Protocols 110 and 113.

Human immunodeficiency virus-seronegative men aged 15-22 years who lost bone mineral density (BMD) during tenofovir disoproxil fumarate/emtricitabine preexposure prophylaxis (PrEP) showed BMD recovery 48 weeks following PrEP discontinuation. Lumbar spine and whole body BMD z-scores remained below baseline 48 weeks off PrEP in participants aged 15-19 years. Clinical Trials Registration. NCT01772823 (ATN 110) and NCT01769456 (ATN 113).

Pressure promoted low-temperature melting of metal-organic frameworks.

Metal-organic frameworks (MOFs) are microporous materials with huge potential for chemical processes. Structural collapse at high pressure, and transitions to liquid states at high temperature, have recently been observed in the zeolitic imidazolate framework (ZIF) family of MOFs. Here, we show that simultaneous high-pressure and high-temperature conditions result in complex behaviour in ZIF-62 and ZIF-4, with distinct high- and low-density amorphous phases occurring over different regions of the pressure-temperature phase diagram. In situ powder X-ray diffraction, Raman spectroscopy and optical microscopy reveal that the stability of the liquid MOF state expands substantially towards lower temperatures at intermediate, industrially achievable pressures and first-principles molecular dynamics show that softening of the framework coordination with pressure makes melting thermodynamically easier. Furthermore, the MOF glass formed by melt quenching the high-temperature liquid possesses permanent, accessible porosity. Our results thus imply a route to the synthesis of functional MOF glasses at low temperatures, avoiding decomposition on heating at ambient pressure.

Prior incarceration associated with missed HIV care visits among young people living with HIV in the US.

Maintenance in HIV care is important to achieve optimal personal health and HIV viral load suppression for young people living with HIV (PLWH). We assessed the relationship between incarceration and missed visits in a longitudinal data cohort of PLWH (n = 910), ages 12-24, from 14 adolescent trial network sites across the US. The time from study entry to missed visits was modeled using Cox proportional hazards models. The cohort was mostly male (78%) and African American (75%) with a median age of 22. Prior incarceration had been experienced by 39% of the cohort, with a median number of times incarcerated of 2 (IQR: 1-3). The crude and adjusted hazard ratios for missed HIV care visits comparing those with incarceration histories to those without were 1.27 (95% CI: 1.06, 1.54) and 1.53 (95% CI: 1.26, 1.86). Among those returning to care, HIV viral loads were more likely to be unsuppressed among those with incarceration history compared to those without (RR: 1.28, 95% CI: 0.95, 1.74). This association was attenuated to the null after adjustment for suppression of viral load prior to the missed visit. Young PLWH with incarceration histories are at higher risk of missing HIV care visits.

Racial disparities and factors associated with prescription for smoking cessation medications among smokers receiving routine clinical care for HIV.

Factors associated with prescription of smoking cessation medication (SCM), including the impact of race, have not been well described among a large population of people living with HIV (PLWH) engaged in routine clinical care. Our study investigated whether there are racial differences between African-American and White PLWH regarding SCM prescription and sought to identify other factors associated with these prescriptions at a large HIV clinic in the Southeastern United States. Among 1899 smokers, 38.8% of those prescribed SCMs were African-American and 61.2% were White. Factors associated with lower odds of SCM prescription included African-American race (AOR, 0.63 [95% CI: 0.47, 0.84]) or transferring care from another HIV provider during the study period (AOR, 0.63 [95% CI: 0.43, 0.91]). Whereas major depression (AOR, 1.54 [95% CI: 1.10, 2.15]), anxiety symptoms (AOR, 1.43 [95% CI: 1.05, 1.94]), and heavy smoking (>20 cigarettes/day) (OR, 3.50 [95% CI: 2.11, 5.98]) were associated with increased likelihood of SCM prescription. There were racial disparities in the prescription of SCM in African Americans with HIV. These findings underscore the need to increase pharmacotherapy use among African Americans to improve smoking cessation outcomes across racial groups among PLWH.

Inducing Social Self-Sorting in Organic Cages To Tune The Shape of The Internal Cavity.

Many interesting target guest molecules have low symmetry, yet most methods for synthesising hosts result in highly symmetrical capsules. Methods of generating lower symmetry pores are thus required to maximise the binding affinity in host-guest complexes. Herein, we use mixtures of tetraaldehyde building blocks with cyclohexanediamine to access low-symmetry imine cages. Whether a low-energy cage is isolated can be correctly predicted from the thermodynamic preference observed in computational models. The stability of the observed structures depends on the geometrical match of the aldehyde building blocks. One bent aldehyde stands out as unable to assemble into high-symmetry cages-and the same aldehyde generates low-symmetry socially self-sorted cages when combined with a linear aldehyde. We exploit this finding to synthesise a family of low-symmetry cages containing heteroatoms, illustrating that pores of varying geometries and surface chemistries may be reliably accessed through computational prediction and self-sorting.

Rich Polymorphism of a Metal-Organic Framework in Pressure-Temperature Space.

We present an in situ powder X-ray diffraction study on the phase stability and polymorphism of the metal-organic framework ZIF-4, Zn(imidazolate)2, at simultaneous high pressure and high temperature, up to 8 GPa and 600 °C. The resulting pressure-temperature phase diagram reveals four, previously unknown, high-pressure-high-temperature ZIF phases. The crystal structures of two new phases-ZIF-4-cp-II and ZIF-hPT-II-were solved by powder diffraction methods. The total energy of ZIF-4-cp-II was evaluated using density functional theory calculations and was found to lie in between that of ZIF-4 and the most thermodynamically stable polymorph, ZIF- zni. ZIF-hPT-II was found to possess a doubly interpenetrated diamondoid topology and is isostructural with previously reported Cd(Imidazolate)2 and Hg(Imidazolate)2 phases. This phase exhibited extreme resistance to both temperature and pressure. The other two new phases could be assigned with a unit cell and space group, although their structures remain unknown. The pressure-temperature phase diagram of ZIF-4 is strikingly complicated when compared with that of the previously investigated, closely related ZIF-62 and demonstrates the ability to traverse complex energy landscapes of metal-organic systems using the combined application of pressure and temperature.

Frequency and Characteristics of Biological False-Positive Test Results for Syphilis Reported in Florida and New York City, USA, 2013 to 2017.

Discordant syphilis test results, with a reactive nontreponemal test and nonreactive treponemal test are usually considered biological false-positive test results (BFPs), which can be attributed to other conditions. Syphilis surveillance laws mandate laboratory reporting of reactive syphilis tests, which include many BFPs. We describe the frequency of BFPs, titer distributions, and titer increases from reported test results in Florida and New York City (NYC). Reactive nontreponemal tests for individuals with at least one nonreactive treponemal test and no reactive treponemal test were extracted from sexually transmitted disease (STD) surveillance systems in Florida and NYC from 2013 to 2017. Characteristics of individuals with BFPs were analyzed after selecting the observation with the highest titer from each individual. We next considered all results from individuals to characterize persons who had a 4-fold titer increase between successive nontreponemal tests. Among 526,540 reactive nontreponemal tests, there were 57,580 BFPs (11%) from 39,920 individuals. Over 90% (n = 52,330) of BFPs were low titer (≤1:4), but 654 (1%) were high-titer BFPs (≥1:32). Very high-titer (≥1:128) BFPs were more common among individuals over 60 years of age (odds ratio [OR], 2.68; 95% confidence interval [CI], 1.22 to 5.91). A 4-fold increase in titer was observed among 1,863 (14%) individuals with more than one reported BFP. Most BFPs detected by surveillance were low titer, but some were high titer and some had a 4-fold increase in titer. Review of patient histories might identify underlying conditions contributing to these high and rising titers.

Using an Email Alert to Improve Identification of Pregnancy Status for Women With Syphilis-Florida, 2017-2018.

BACKGROUND: Congenital syphilis can be prevented if syphilis is treated early in pregnancy. Identifying women with syphilis who are pregnant facilitates prioritization for follow-up. In 2016, Florida reported 1062 female syphilis cases, aged 15 to 44 years, and 160 (15%) cases were missing pregnancy status. The Florida Department of Health developed a system-generated weekly email notification sent to local program staff for all female syphilis investigations with unknown pregnancy status. We describe the outcome of these efforts to reduce unknown pregnancy status among women with syphilis. METHODS: Review of the frequency and outcomes (reduction in investigations flagged and change in pregnancy status variable) of the first email notification (October 2, 2017) were compared with subsequent notifications through June 25, 2018. In addition, we reviewed pregnancy status of reported female syphilis cases (age, 15-44 years) from 2013 to 2018. RESULTS: The first email notification listed 76 investigations with unknown pregnancy status. This number decreased to 40 in 1 week and to 22 by 1 month. The decreased volume continued through June 2018 (n = 13). Of the original 76 investigations, 3 women were pregnant, and 38 (50%) were determined to meet the syphilis case definition (including 1 who was pregnant). In 2017, pregnancy ascertainment for female syphilis cases reached 98%. CONCLUSIONS: Focused efforts using email notification to obtain pregnancy status improved ascertainment in large sexually transmitted disease (STD) programs with minimal effort. Most but not all women with unknown pregnancy status were identified as not pregnant.

Predictors of smoking cessation among people living with HIV receiving routine clinical care.

People living with HIV (PLWH) have a higher prevalence of smoking and are less likely to quit smoking than the general population. Few studies involving a large sample of PLWH receiving routine care have evaluated factors associated with smoking cessation. This retrospective longitudinal cohort study evaluated factors associated with smoking cessation among PLWH from 2007 to 2018. Of 1,714 PLWH smokers included in the study, 27.6% reported quitting smoking. Suppressed plasma HIV-1 RNA (<200 copies/ml) was significantly associated with an increased likelihood of smoking cessation (HRadjusted = 1.27, 95% CI [1.03, 1.58]); whereas age/10 year increments (HRadjusted = 0.12, 95% CI [0.04, 0.38]), greater length of care at the HIV clinic (HRadjusted = 0.97, 95% CI [0.94, 0.99]), lack of insurance (HRadjusted = 0.77, 95% CI [0.61, 0.99]) or having public insurance (HRadjusted = 0.74, 95% CI [0.55, 0.97)]), current substance use (HRadjusted = 0.66, 95% CI [0.43, 0.97]) and risk of developing alcohol use disorder (HRadjusted = 0.60, 95% CI [0.43, 0.84]) were associated with a reduced likelihood of quitting smoking. These findings underscore the importance of early smoking cessation intervention among PLWH. In addition, targeted smoking cessation intervention strategies are needed for groups at risk for being less likely to quit, including older patients, and those with alcohol and substance use disorders.

High-Pressure Study of the Elpasolite Perovskite La2NiMnO6.

Here we report a high-pressure investigation into the structural and magnetic properties of the double perovskite La2NiMnO6 using neutron scattering over a temperature range of 4.2-300 K at ambient pressure and over a temperature range of 120-1177 K up to a maximum pressure of 6.6 GPa. X-ray diffraction was also used up to a maximum pressure of 64 GPa, over a temperature range of 300-720 K. The sample was found to exist in a mixed rhombohedral/monoclinic symmetry at ambient conditions, the balance of which was found to be strongly temperature- and pressure-dependent. Alternating current magnetometry and X-ray absorption near-edge structure measurements were made at ambient pressure to characterize the sample, suggesting that the transition-metal sites exist in a mixed Ni3+/Mn3+ and Ni2+/Mn4+ state at ambient temperature and pressure. Analysis of the magnetic properties of the sample shows that the Curie temperature can be enhanced by ∼12 K with 2 GPa applied pressure, but it is highly stable at pressures beyond this. We report a pressure-volume-temperature equation of state for this material over this combined temperature and pressure range, with an ambient temperature bulk modulus of ∼179(8) GPa. The previously reported transition from monoclinic to rhombohedral symmetry upon heating to 700 K is seen to be encouraged with applied pressure, transforming fully by ∼1.5 GPa. Raman spectroscopy data were collected up to ∼8 GPa and show no clear changes or discontinuities over the reported phase transition to rhombohedral symmetry or any indication of further changes over the range considered. The ambient-pressure Grüneisen parameter γth was determined to be γth = 2.6 with a Debye temperature of 677 K. The individual modal parameters γj at ambient temperature were also determined from the high-pressure Raman data.

Mental health disorders and alcohol use are associated with increased likelihood of smoking relapse among people living with HIV attending routine clinical care.

BACKGROUND: People living with HIV (PLWH) have a high level of interest in quitting smoking, but only a small proportion have sustainable abstinence 6 months after cessation. Few investigations have focused on relapse to smoking among PLWH. In this investigation, we evaluated the prevalence of relapse after smoking cessation and the characteristics associated with smoking relapse using a retrospective, longitudinal cohort of PLWH during an eight-year observation. METHODS: All patients aged ≥19 years that reported current smoking during the study period and then reported not smoking on a subsequent tobacco use questionnaire (quitters) were eligible for the study. In addition, patients required at least one subsequent follow-up visit after quitting where smoking status was again reported to allow for assessment of relapse. A Cox proportional hazard model was fit to evaluate factors associated with smoking relapse in PLWH attending routine clinical care. RESULTS: Of the 473 patients who quit smoking in the study, 51% relapsed. In multivariable analysis, factors significantly associated with a higher likelihood of relapse were anxiety symptoms (HR = 1.55, 95% CI [1.11, 2.17]) and at-risk alcohol use (HR = 1.74, 95% CI [1.06, 2.85]), whereas antiretroviral therapy (ART) adherence (HR = 0.65, 95% CI [0.49, 0.99]) and longer time in care (HR = 0.94, 95% CI [0.91, 0.98]) were associated with a reduced likelihood of relapse after cessation. CONCLUSION: Our study underscores the high prevalence of smoking relapse that exists among PLWH after they quit smoking. Successful engagement in mental health care may enhance efforts to reduce relapse in the underserved populations of PLWH.

Comparison of Measures of Adherence to Human Immunodeficiency Virus Preexposure Prophylaxis Among Adolescent and Young Men Who Have Sex With Men in the United States.

Background: Young men-who-have-sex-with-men (MSM) are disproportionately impacted by human immunodeficiency virus (HIV). Preexposure prophylaxis (PrEP) could reduce HIV acquisition among youth, but suboptimal adherence threatens effectiveness. Optimal metrics of PrEP adherence among adolescents have remain undefined. Methods: The Adolescent Trials Network 110/113 studies provided daily oral PrEP with tenofovir (TFV) disoproxil fumarate/emtricitabine over 48 weeks to a diverse population of MSM (aged 15-22 years). Self-reported adherence was assessed and PrEP drug concentrations measured from hair and dried blood spot (DBS) samples; 23% of participants received Wisepill electronic monitoring devices. The average number of PrEP doses per week taken was estimated, and concordance between measures assessed. Results: Among 243 participants, hair samples were collected at 1186/1238 (96%) person-visits. The concordance of TFV levels in hair and TFV-diphosphate in DBS around thresholds consistent with taking ≥4 and 7 PrEP doses/week was high (76% and 80%). Hair and DBS concentrations correlated poorly with self-report and Wisepill metrics. Through week 12, 40%-60% of participants (by hair and DBS), ≤31% (Wisepill), and >85% (self-report) were estimated to have taken ≥4 PrEP doses/week (a threshold associated with protection among MSM). For all measures except self-report, adherence declined over time, with half of participants taking <2 doses/week by week 48. Conclusions: Among youth on PrEP, adherence waned over time. Self-report overestimated adherence, and use of Wisepill was limited. Hair collection was highly acceptable and provided similar interpretations to DBS. Incorporation of either metric in future PrEP studies among youth could identify suboptimal adherence and trigger interventions.

Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults With Human Immunodeficiency Virus Infection Being Treated With Tenofovir Disoproxil Fumarate: A Randomized, Placebo-Controlled Trial.

Background: Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized that vitamin D3 (VITD3) would increase BMD in youth receiving TDF. Methods: This was a randomized, double-blind, placebo-controlled trial of directly observed VITD3 vs placebo every 4 weeks for 48 weeks in youth aged 16-24 years with HIV, RNA load <200 copies/mL, taking TDF-containing combination antiretroviral therapy (TDF-cART) for ≥180 days. Participants (N = 214) received a daily multivitamin containing VITD3 400 IU and calcium 162 mg, plus monthly randomized VITD3 50000 IU (n = 109) or placebo (n = 105). Outcome was change from baseline to week 48 in lumbar spine BMD (LSBMD). Data presented are median (Q1, Q3). Results: Participants were aged 22.0 (21.0, 23.0) years, 84% were male, and 74% were black/African American. At baseline, 62% had 25-hydroxy vitamin D (25-OHD) <20 ng/mL. Multivitamin adherence was 49% (29%, 69%), and VITD3/placebo adherence 100% (100%, 100%). Vitamin D intake was 2020 (1914, 2168) and 284 (179, 394) IU/day, and serum 25-OHD concentration was 36.9 (30.5, 42.4) and 20.6 (14.4, 25.8) ng/mL at 48 weeks in VITD3 and placebo groups, respectively (P < .001). From baseline to week 48, LSBMD increased by 1.15% (-0.75% to 2.74%) in the VITD3 group (n = 99; P < .001) and 0.09% (-1.49% to 2.61%) in the placebo group (n = 89; P = .25), without between-group difference (P = .12). VITD3 group changes occurred with baseline 25-OHD <20 ng/mL (1.17% [-.82% to 2.90%]; P = .004) and ≥20 ng/mL (0.93% [-.26% to 2.15%]; P = .033). Conclusions: For youth taking TDF-cART, LSBMD increased through 48 weeks with VITD3 plus multivitamin, but not with placebo plus multivitamin, independent of baseline vitamin D status. Clinical Trials Registration: NCT01751646.

A cross-sectional study examining associations between substance use frequency, problematic use and STIs among youth living with HIV.

OBJECTIVES: This study sought to examine the prevalence of STIs and whether substance use frequency and/or problematic use-specifically alcohol, marijuana and other drugs-was associated with having an STI diagnosis among youth living with HIV (YLWH) METHODS: A sample of 823 YLWH were recruited at 14 adolescent HIV clinics through the Adolescent Medicine Trials Network for HIV Interventions. Study staff abstracted STI data from medical records for up to 26 weeks prior to participants' completing a cross-sectional survey including the ASSIST (Alcohol, Smoking and Substance Involvement Screening Test), which measures substance use frequency and consequences. RESULTS: Almost one-third of youth had been diagnosed with an STI (30.5%) at the time of their baseline assessment. In multivariable analyses, those who engaged in weekly or greater marijuana use (adjusted OR (AOR)=10.66, 95% CI: 4.39 to 25.87, P<0.001) had an increased odds of being diagnosed with an STI. Additionally, youth who met alcohol use criteria for moderate (AOR=5.23, 95% CI: 2.50 to 10.93, P<0.001) and high risk (AOR=6.53, 95% CI: 1.20 to 35.68, P<0.05) alcohol use had an increased odds of being diagnosed with an STI compared with low-risk alcohol users. CONCLUSIONS: Study findings underscore the need to investigate the role of greater frequency of marijuana use and problematic alcohol use in STI incidence among YLWH. Given the associations between both substance use frequency and problematic use in STI diagnoses among YLWH seen in HIV care settings, clinicians should use validated substance use screening tools which capture both frequencies and consequences in order to identify YLWH who may need further evaluation and treatment.

Going Off Grid: Modeling an Automated Record Search to Process Electronically Reported Reactive Nontreponemal Syphilis Tests.

BACKGROUND: Before searching prior records, sexually transmitted disease programs use syphilis reactor grids to exclude some reactive nontreponemal test results (RNTs) based on patient age, gender, and test titer. We propose a new algorithm that starts with comparing RNTs to previous syphilis nontreponemal tests and current treponemal test results. METHODS: Deduplicated RNTs from Florida's surveillance system (2006-2015) were extracted and stratified on morbidity. An algorithm was developed to triage RNTs. Sensitivity and specificity of the algorithm and the current reactor grid were estimated using reported syphilis cases. A random sample of cases missed by the proposed algorithm, stratified by stage of disease, was reviewed to verify case classification. RESULTS: Reported RNTs increased 58% from 2006 (n = 34,808) to 2015 (n = 55,001) (total = 372,902). The current reactor grid removed 91,518 (24.5%) RNTs and missed 1149 potential cases. Strictly following the reactor grid would result in a sensitivity of 97.4% and a specificity of 27.5%. The proposed algorithm would remove 242,078 (64.9%) RNTs and miss 2768 potential cases. This results in a slightly lower sensitivity of 93.8%, but nearly triples the specificity, 72.9%. A review of a random sample of the 2768 cases estimated that 72.7% would not have met the syphilis surveillance case definition, resulting in an adjusted sensitivity of 98.4%. CONCLUSIONS: In Florida, an algorithm that starts by searching previous syphilis test results vastly improved specificity and slightly improved sensitivity compared with the current reactor grid. Implementing an automated algorithm could increase case ascertainment efficiency and further prioritize likely cases for investigation.