Synthesis and biological studies of 2-aminothiophene derivatives as positive allosteric modulators of glucagon-like peptide 1 receptor.

As a step toward the development of novel small-molecule positive allosteric modulators (PAMs) of glucagon-like peptide 1 receptor (GLP-1R) for the treatment of type 2 diabetes, obesity, and heart diseases, we discovered a novel 2-amino-thiophene (2-AT) based lead compound bearing an ethyl 3-carboxylate appendage. In this work, we report the syntheses and biological studies of more than forty 2-AT analogs, that have revealed a 2-aminothiophene-3-arylketone analogue 7 (MW 299) showing approximately a 2-fold increase in insulin secretion at 5 µM when combined with the GLP-1 peptide at 10 nM. In vivo studies using CD1 mice at a dose of 10 mg/kg, clearly demonstrated that the blood plasma glucose level was lowered by 50% after 60 min. Co-treatment of 7 with sitagliptin, an inhibitor of GLP-1 degrading enzyme Dipeptidyl Peptidase IV, further confirmed 7 to be an effective PAM of GLP-1R. The small molecular weight and demonstrated allosteric modulating properties of these compound series, show the potential of these scaffolds for future drug development.

Depression, Alcohol Use, and Sexual Behaviors by HIV Infection Stage and Diagnosis Timing Among STI Clinic Patients in Lilongwe, Malawi.

Understanding depression, alcohol use, and sexual behaviors according to HIV infection stage and diagnosis timing is important for HIV prevention efforts. We enrolled persons with recent infection and diagnosis (i.e., acute HIV infection (AHI) (n = 92) persons newly diagnosed seropositive (n = 360)) and persons previously diagnosed with HIV (n = 190) into a randomized controlled trial in Lilongwe, Malawi (N = 641) and estimated the prevalence of probable depression (Patient Health Questionnaire-9 ≥ 5), hazardous alcohol use (Alcohol Use Disorder Identification Test-C: men ≥ 4; women ≥ 3), and sexual behaviors (transactional sex, condomless sex). Compared with previously diagnosed participants, participants newly seropositive and those with AHI reported a higher proportion of probable depression (7%, 27%, 38%; AHI/Previous: Table Probability: 0.02, p < 0.01; AHI/New: Table Probability: <0.01, p < 0.01), hazardous alcohol use (8%, 18%, 29%; AHI/Previous and AHI/New: Table Probability: <0.01, p < 0.01), and transactional sex (5%, 14%, 20%; AHI/Previous: Table Probability: <0.01, p < 0.01; AHI/New: Table Probability: 0.06, p = 0.24), respectively. HIV prevention services addressing mental health and alcohol misuse may be particularly beneficial for persons with recent HIV infection and or diagnosis.

Predictors of Plasmodium falciparum Infection in the First Trimester Among Nulliparous Women From Kenya, Zambia, and the Democratic Republic of the Congo.

BACKGROUND: Malaria can have deleterious effects early in pregnancy, during placentation. However, malaria testing and treatment are rarely initiated until the second trimester, leaving pregnancies unprotected in the first trimester. To inform potential early intervention approaches, we sought to identify clinical and demographic predictors of first-trimester malaria. METHODS: We prospectively recruited women from sites in the Democratic Republic of the Congo (DRC), Kenya, and Zambia who participated in the ASPIRIN (Aspirin Supplementation for Pregnancy Indicated risk Reduction In Nulliparas) trial. Nulliparous women were tested for first-trimester Plasmodium falciparum infection by quantitative polymerase chain reaction. We evaluated predictors using descriptive statistics. RESULTS: First-trimester malaria prevalence among 1513 nulliparous pregnant women was 6.3% (95% confidence interval [CI], 3.7%-8.8%] in the Zambian site, 37.8% (95% CI, 34.2%-41.5%) in the Kenyan site, and 62.9% (95% CI, 58.6%-67.2%) in the DRC site. First-trimester malaria was associated with shorter height and younger age in Kenyan women in site-stratified analyses, and with lower educational attainment in analyses combining all 3 sites. No other predictors were identified. CONCLUSIONS: First-trimester malaria prevalence varied by study site in sub-Saharan Africa. The absence of consistent predictors suggests that routine parasite screening in early pregnancy may be needed to mitigate first-trimester malaria in high-prevalence settings.

Household Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 in the United States: Living Density, Viral Load, and Disproportionate Impact on Communities of Color.

BACKGROUND: Households are hot spots for severe acute respiratory syndrome coronavirus 2 transmission. METHODS: This prospective study enrolled 100 coronavirus disease 2019 (COVID-19) cases and 208 of their household members in North Carolina though October 2020, including 44% who identified as Hispanic or non-White. Households were enrolled a median of 6 days from symptom onset in the index case. Incident secondary cases within the household were detected using quantitative polymerase chain reaction of weekly nasal swabs (days 7, 14, 21) or by seroconversion at day 28. RESULTS: Excluding 73 household contacts who were PCR-positive at baseline, the secondary attack rate (SAR) among household contacts was 32% (33 of 103; 95% confidence interval [CI], 22%-44%). The majority of cases occurred by day 7, with later cases confirmed as household-acquired by viral sequencing. Infected persons in the same household had similar nasopharyngeal viral loads (intraclass correlation coefficient = 0.45; 95% CI, .23-.62). Households with secondary transmission had index cases with a median viral load that was 1.4 log10 higher than those without transmission (P = .03), as well as higher living density (more than 3 persons occupying fewer than 6 rooms; odds ratio, 3.3; 95% CI, 1.02-10.9). Minority households were more likely to experience high living density and had a higher risk of incident infection than did White households (SAR, 51% vs 19%; P = .01). CONCLUSIONS: Household crowding in the context of high-inoculum infections may amplify the spread of COVID-19, potentially contributing to disproportionate impact on communities of color.

SARS-CoV-2 Mitigation Strategies, Testing, and Cases at 254 Jails in the US Southeast, October 2020 to May 2021.

Objectives. To characterize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mitigation strategies, testing, and cases across county jails in the Southeastern United States, examining variability by jail characteristics. Methods. We administered a 1-time telephone survey to personnel of 254 jails in Alabama, Georgia, North Carolina, and South Carolina between October 2020 and May 2021. Results. Some SARS-CoV-2 mitigation strategies (e.g., screening at intake, isolation and masking for symptomatic persons) were commonly reported (≥ 75% of jails). Other measures, such as masking regardless of symptoms (52%) and screening at release (26%), were less common and varied by jail state or population size. Overall, 41% of jails reported no SARS-CoV-2 testing in the past 30 days. Jails with testing (59%) tested a median of 6 per 100 incarcerated persons; of those jails, one third reported 1 or more cases of positive tests. Although most jails detected no cases, in the 20% of all jails with 1 or more case in the past 30 days, 1 in 5 tests was positive. Conclusions. There was low testing coverage and variable implementation of SARS-CoV-2 mitigation strategies in Southeastern US jails during the first year of the COVID-19 pandemic. (Am J Public Health. 2022;112(11):1589-1598. https://doi.org/10.2105/AJPH.2022.307012).

The Effect of PrEP Use Disclosure on Adherence in a Cohort of Adolescent Girls and Young Women in South Africa.

Effective strategies to support PrEP adherence among adolescent girls and young women (AGYW) are needed. We examined PrEP use disclosure and its effect on adherence among 200 AGYW ages 16-25 initiating PrEP in South Africa to help inform these  strategies. We estimated the relative prevalence of high adherence (intracellular tenofovir-diphosphate concentration ≥ 700 fmol/punch) 3- and 6-months after PrEP initiation among those who disclosed vs. did not disclose their PrEP use, both overall and by age. Most AGYW disclosed to a parent (58%), partner (58%), or friend (81%) by month 6. We did not observe a strong effect of disclosure on adherence overall; however, among younger AGYW (≤ 18 years), those who disclosed to a parent were 6.8 times as likely to have high adherence at month 6 than those who did not (95% CI 1.02, 45.56). More work is needed to understand parents' roles as allies and identify ways peers and partners can motivate PrEP use for AGYW.

Modelling the impact of a sex work crackdown on syphilis transmission among female sex workers and their clients in South China.

OBJECTIVE: To estimate the potential effects of an intense sex work crackdown on syphilis transmission in Guangdong Province, China. METHODS: We developed a deterministic compartmental model of syphilis transmission among female sex workers (FSW) and their male clients in Guangdong Province, China. We based model assumptions on census data and scientific literature, and we fitted the model to sentinel surveillance estimates of syphilis prevalence (positive results in both treponemal and non-treponemal tests) among FSW between 2009 and 2013. We estimated the impact of an intense sex work crackdown in 2014 by comparing the number of new syphilis infections between 2014 and 2020 in crackdown versus basecase (no crackdown) scenarios. In modelling scenarios, we examined main crackdown mechanisms of impact, including changed number of FSW engaging in sex work, reduction of weekly transactions, condom usage rate and syphilis diagnosis rate. RESULTS: In the basecase, predicted syphilis prevalence in FSW decreased from 2% in 2014 to 0.4% in 2020. In crackdown scenarios, syphilis incidence was predicted to transiently decrease and then to rebound relative to basecase levels a few years later. Shorter crackdowns led to higher, faster rebounds. CONCLUSIONS: Short-term intense crackdowns may exacerbate syphilis transmission among FSW and further marginalise an already vulnerable group. This study provides a quantitative, infection-related basis for changing sex work policies to reduce harms.

Syndromes Associated with Sexually Transmitted Infections in Lilongwe, Malawi: Burden and Trends, 2006 to 2015.

ABSTRACT: Monitoring the burden of and trends in sexually transmitted infection syndromes is useful in informing syndromic management guidelines. Among sexually transmitted infection clinic patients in Lilongwe, Malawi, between 2006 and 2015, genital discharge, lower abdominal pain, and genital ulcer syndromes were common. Prevalence of most syndromes remained stable during the 10-year period.

Estimating the Effect of Depression on HIV Transmission Risk Behaviors Among People Who Inject Drugs in Vietnam: A Causal Approach.

The burden of depression and HIV is high among people who inject drugs (PWID), yet the effect of depression on transmission risk behaviors is not well understood in this population. Using causal inference methods, we analyzed data from 455 PWID living with HIV in Vietnam 2009-2013. Study visits every 6 months over 2 years measured depressive symptoms in the past week and injecting and sexual behaviors in the prior 3 months. Severe depressive symptoms (vs. mild/no symptoms) increased injection equipment sharing (risk difference [RD] = 3.9 percentage points, 95% CI -1.7, 9.6) but not condomless sex (RD = -1.8, 95% CI -6.4, 2.8) as reported 6 months later. The cross-sectional association with injection equipment sharing at the same visit (RD = 6.2, 95% CI 1.4, 11.0) was stronger than the longitudinal effect. Interventions on depression among PWID may decrease sharing of injection equipment and the corresponding risk of HIV transmission.Clinical trial registration ClinicalTrials.gov NCT01689545.

Modeling Adherence Interventions Among Youth with HIV in the United States: Clinical and Economic Projections.

The Adolescent Medicine Trials Network for HIV/AIDS Interventions is evaluating treatment adherence interventions (AI) to improve virologic suppression (VS) among youth with HIV (YWH). Using a microsimulation model, we compared two strategies: standard-of-care (SOC) and a hypothetical 12-month AI that increased cohort-level VS in YWH in care by an absolute ten percentage points and cost $100/month/person. Projected outcomes included primary HIV transmissions, deaths and life-expectancy, lifetime HIV-related costs, and incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year [QALY]). Compared to SOC, AI would reduce HIV transmissions by 15% and deaths by 12% at 12 months. AI would improve discounted life expectancy/person by 8 months at an added lifetime cost/person of $5,300, resulting in an ICER of $7,900/QALY. AI would be cost-effective at $2,000/month/person or with efficacies as low as a 1 percentage point increase in VS. YWH-targeted adherence interventions with even modest efficacy could improve life expectancy, prevent onward HIV transmissions, and be cost-effective.

RESUMEN: La Red de Ensayos Médicos sobre Adolescentes para Realizar Intervenciones sobre el VIH/SIDA está evaluando intervenciones de adherencia (IAs) al tratamiento para mejorar la supresión virológica (SV) entre los jóvenes con VIH (JCV). Usando un modelo de microsimulación, comparamos dos estrategias: cuidado convencional (CC) y una intervención de adherencia hipotética durando 12 meses que aumentaría la SV a nivel de cohorte entre JCV en tratamiento por 10 puntos de porcentuales y que costaría US$ 100/mes/persona. Resultados proyectados incluyeron transmisiones de VIH primarias, muertes y esperanza de vida, costos de por vida asociados con el VIH, y razones incrementales de costo-efectividad (RICEs, $/año de vida ajustado por la calidad [AVAC]). Comparado al CC, la IA reduciría transmisiones de VIH por 15% y muertes por 12% a los 12 meses. La IA mejoraría esperanza de vida descontada/persona por 8 meses a un costo de por vida adicional/persona de US$ 5.300, resultando en una RICE de US$ 7.900/AVAC. La IA sería costo-efectiva a un costo de US$ 2.000/mes/persona o si mejorara SV por al menos un punto porcentual. Intervenciones de adherencia dirigidas a jóvenes con una eficacia incluso modesta podrían mejorar esperanza de vida, prevenir transmisiones de VIH, y ser costo-efectivas.

Trajectories of fertility intentions among women living with HIV in South Africa.

Fertility intentions are thought to be dynamic among women of reproductive age, yet few studies have assessed fertility intentions over time among women with HIV. We examine temporal patterns of fertility intentions in women with HIV to assess the extent to which fertility intentions - and the corresponding need for safer conception and judicious antiretroviral therapy (ART) regimen selection - vary over time. 850 non-pregnant HIV-positive women aged 18-35 on or being initiated onto ART in Johannesburg, South Africa were enrolled into a prospective cohort study (2009-2010). Fertility intentions were assessed at enrollment and at 30-day intervals via an interviewer-administered questionnaire. We used group-based trajectory modelling to identify longitudinal patterns of fertility intentions over 12 months. We identified four patterns of fertility intentions, which we labelled "consistently low" (representing ∼60% of the population), "low and increasing" (∼23%), "high and increasing" (∼12%), and "high and decreasing" (∼5%). Our findings suggest that a single family-planning assessment at one time point is insufficient to fully identify and meet the reproductive needs of women with HIV. As HIV testing and treatment evolve in South Africa, routine screening for fertility intentions can offer important opportunities to optimize HIV treatment, prevention, and maternal and child health.

Network Interconnectivity and Community Detection in HIV/Syphilis Contact Networks Among Men Who Have Sex With Men.

BACKGROUND: Despite persistent HIV and syphilis epidemics among men who have sex with men (MSM), the relationship between HIV and syphilis contact networks has not been well characterized. We aimed to measure interconnectivity between HIV and syphilis contact networks among MSM and identify network communities with heightened interconnectivity of the syphilis network with the HIV network. METHODS: Using contact-tracing data, we generated independent and combined HIV and syphilis networks for all MSM diagnosed with HIV or early syphilis, respectively, in North Carolina between 2015 and 2017. We treated the independent networks as layers and identified network communities, or groups of densely connected nodes, in the 2-layer network. We assessed interconnectivity by comparing the mean node degree among syphilis network members in the syphilis network alone versus the combined HIV/syphilis network, both overall and by network community. RESULTS: The syphilis network was interconnected with the HIV network, especially in network communities with younger median age, higher proportions of persons self-identifying as Black, non-Hispanic, and higher proportions of syphilis cases diagnosed at sexually transmitted disease clinics. CONCLUSIONS: Interconnected contact networks underlie HIV and syphilis epidemics among MSM, particularly among young, Black MSM. Intensified transmission prevention interventions within highly interconnected network communities may be particularly beneficial.

The Influence of Screening, Misclassification, and Reporting Biases on Reported Chlamydia Case Rates Among Young Women in the United States, 2000 Through 2017.

BACKGROUND: National chlamydia case rate trends are difficult to interpret because of biases from partial screening coverage, imperfect diagnostic tests, and underreporting. We examined the extent to which these time-varying biases could influence reported annual chlamydia case rates. METHODS: Annual reported case rates among women aged 15 through 24 years from 2000 through 2017 were obtained from the Centers for Disease Control and Prevention's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention AtlasPlus tool. Estimates of reporting completeness, diagnostic test sensitivity and specificity, and screening coverage were derived from literature review and expert opinion. We adjusted annual reported case rates for incomplete reporting, imperfect diagnostic tests, and partial screening coverage through a series of corrections, and calculated annual adjusted case rates of correctly diagnosed chlamydia. RESULTS: Adjusted chlamydia case rates among young women were higher than reported case rates throughout the study period. Reported case rates increased over the study period, but adjusted rates declined from 12,900 to 7900 cases per 100,000 person-years between 2000 and 2007. After 2007, adjusted case rates declined to 7500 cases per 100,000 person-years in 2017. Bias from partial screening coverage had a larger impact on case rate magnitude and trend shape than bias from imperfect diagnostic tests or underreporting. CONCLUSIONS: Reported chlamydia case rates may be substantially lower than true chlamydia case rates because of incomplete reporting, imperfect diagnostic tests, and partial screening coverage. Because the magnitude of these biases has declined over time, the differences between reported and adjusted case rates have narrowed, revealing a sharp decline in adjusted case rates even as reported case rates have risen. The decline in adjusted case rates suggests that the rise in reported case rates should not be interpreted strictly as increasing chlamydia incidence, as the observed rise can be explained by improvements in screening coverage, diagnostic tests, and reporting.

Fertility Intentions and Clinical Care Attendance Among Women Living with HIV in South Africa.

Poor HIV care retention impedes optimal treatment outcomes in persons living with HIV. Women trying to become pregnant may be motivated by periconception horizontal and vertical transmission concerns and thus more likely to attend HIV care visits than women not trying to conceive. We estimated the effect of fertility intentions on HIV care attendance over 12 months among non-pregnant, HIV-positive women aged 18-35 years who were on or initiating antiretroviral therapy in Johannesburg, South Africa. The percentage of women attending an HIV care visit decreased from 93.4% in the first quarter to 82.8% in the fourth quarter. Fertility intentions were not strongly associated with care attendance in this cohort of reproductive-aged women; however, attendance declined over time irrespective of childbearing plans. These findings suggest a need for reinforced efforts to support care engagement and risk reduction, including safer conception practices for women wishing to conceive.

Human Immunodeficiency Virus (HIV)-1 Transmission Among Persons With Acute HIV-1 Infection in Malawi: Demographic, Behavioral, and Phylogenetic Relationships.

BACKGROUND: Understanding sexual networks involving acute human immunodeficiency virus (HIV)-1 infections (AHI) may lead to prevention opportunities to mitigate high rates of onward transmission. We evaluated HIV-1 phylogenetic and behavioral characteristics among persons with AHI and their referred partners. METHODS: Between 2012 and 2014, 46 persons with AHI in Malawi participated in a combined behavioral and biomedical intervention. Participants referred sexual partners by passive referral. Demographics and sexual behaviors were collected through interviews and HIV-1 genetic relationships were assessed with phylogenetics. RESULTS: Among 45 AHI participants with HIV-1 sequences, none was phylogenetically-linked with another AHI index. There were 19 (42%) AHI participants who referred a single partner that returned for testing. Most partners (n = 17) were HIV-infected, with 15 (88%) presenting with an established infection. There were 14 index-partner pairs that had sequences available; 13 (93%) pairs were phylogenetically-linked dyads. The AHI index was female in 7/13 (54%) dyads. Age-disparate relationships among dyads were common (≥5-year age difference in 67% of dyads), including 3/6 dyads involving a male index and a younger woman. Index participants with a referred partner were more likely to report no casual partners and to be living with their current partner than participants not in dyads. CONCLUSIONS: Passive-partner referral successfully identified partners with genetically-similar HIV infections-the likely source of infection-but only 40% of index cases referred partners who presented for HIV-1 testing. Future work evaluating assisted partner notification may help reach susceptible partners or more people with untreated HIV-1 infections connected to acute transmission. CLINICAL TRIALS REGISTRATION: NCT01450189.

Depression, ART Adherence, and Receipt of Case Management Services by Adults with HIV in North Carolina, Medical Monitoring Project, 2009-2013.

Depression among persons with HIV is associated with antiretroviral therapy (ART) interruption and discontinuation, virological failure, and poor clinical and survival outcomes. Case management services can address needs for emotional counseling and other supportive services to facilitate HIV care engagement. Using 2009-2013 North Carolina Medical Monitoring Project data from 910 persons engaged in HIV care, we estimated associations of case management utilization with "probable current depression" and with 100% ART dose adherence. After weighting, 53.2% of patients reported receiving case management, 21.7% reported depression, and 87.0% reported ART adherence. Depression prevalence was higher among those reporting case management (24.9%) than among other patients (17.6%) (p < 0.01). Case management was associated with depression among patients living above the poverty level [adjusted prevalence ratio (aPR), 2.05; 95% confidence interval (CI) 1.25-3.36], and not among other patients (aPR, 1.01; 95% CI 0.72-1.43). Receipt of case management was not associated with ART adherence (aPR, 1.00; 95% CI 0.95-1.05). Our analysis indicates a need for more effective depression treatment, even among persons receiving case management services. Self-reported ART adherence was high overall, though lower among persons experiencing depression (unadjusted prevalence ratio, 0.92; 95% CI 0.86-0.99). Optimal HIV clinical and prevention outcomes require addressing psychological wellbeing, monitoring of ART adherence, and effective case management services.

Antiretroviral Adherence Following Prison Release in a Randomized Trial of the imPACT Intervention to Maintain Suppression of HIV Viremia.

Many people living with HIV (PLWH) pass through correctional facilities each year, a large proportion of whom do not maintain viral suppression following release. We examined the effects of imPACT, an intervention designed to promote post-release viral suppression, on antiretroviral therapy (ART) adherence. PLWH awaiting release from prisons in two southern states were randomized to imPACT (consisting of motivational interviewing, care linkage coordination, and text message medication reminders) versus standard care (SC). ART adherence, measured by unannounced monthly telephone pill counts, was compared between study arms over 6 months post-release. Of 381 participants eligible for post-release follow-up, 302 (79%) completed ≥ 1 of 6 possible pill counts (median: 4; IQR 1-6). Average adherence over follow-up was 80.3% (95% CI 77.5, 83.1) and 81.0% (78.3, 83.6) of expected doses taken in the imPACT and SC arms, respectively. There was no difference between arms when accounting for missing data using multiple imputation (mean difference = - 0.2 percentage points [- 3.7, 3.3]), controlling for study site and week of follow-up. Of the 936 (40.9%) pill counts that were missed, 212 (22.7%) were due to re-incarceration. Those who missed pill counts for any reason were more likely to be unsuppressed, suggesting that they had lower adherence. However, missingness was balanced between arms. Among PLWH released from prison, ART adherence averaged > 80% in both study arms over 6 months-a level higher than seen with most other chronic diseases. However, missing data may have led to an overestimate of adherence. Factors independent of the intervention influence ART adherence in this population and should be identified to inform future targeted interventions.

Repeat Human Immunodeficiency Virus Testing by Transmission Risk Group and Rurality of Residence in North Carolina.

BACKGROUND: Understanding of repeat human immunodeficiency virus (HIV) testing (RHT) is limited and the impact of rural residence as a potential barrier to RHT is unknown. Rural populations are of particular interest in the Southeastern United States because of their disproportionate HIV burden. METHODS: We used HIV surveillance data from publicly funded HIV testing sites in North Carolina to assess repeat testing by transmission risk group and residential rurality in a retrospective cohort study. Linear binomial regression models were used to estimate adjusted, 1-year cumulative incidences and cumulative incidence differences comparing RHT within transmission risk populations by level of rurality. RESULTS: In our total study population of 600,613 persons, 19,275 (3.2%) and 9567 (1.6%) self-identified as men who have sex with men (MSM) and persons who inject drugs (PWID), respectively. A small minority, 13,723 (2.3%) resided in rural ZIP codes. Men who have sex with men were most likely to repeat test (unadjusted, 1-year cumulative incidence after an initial negative test, 16.4%) compared with PWID (13.2%) and persons who did not identify as either MSM or PWID (13.6%). The greatest effect of rurality was within PWID; the adjusted, 1-year cumulative incidence of RHT was 6.4 (95% confidence interval, 1.4-11.4) percentage points higher among metropolitan versus rural PWID. CONCLUSIONS: One-year cumulative incidence of RHT was low among all clients of publicly funded HIV testing sites in North Carolina, including MSM and PWID for whom annual testing is recommended. Our findings suggest a need for public health efforts to increase access to and support for RHT, particularly among rural PWID.

Chlamydia Prevalence Trends Among Women and Men Entering the National Job Training Program From 1990 Through 2012.

BACKGROUND: Evaluating chlamydia prevalence trends from sentinel surveillance is important for understanding population disease burden over time. However, prevalence trend estimates from surveillance data may be misleading if they do not account for changes in risk profiles of individuals who are screened (case mix) and changing performance of the screening tests used. METHODS: We analyzed chlamydia screening data from a sentinel surveillance population of 389,555 young women (1990-2012) and 303,699 young men (2003-2012) entering the US National Job Training Program. This period follows the introduction of national chlamydia screening programs designed to prevent transmission and reduce population disease burden. After ruling out bias due to case mix, we used an expectation-maximization-based maximum likelihood approach to account for measurement error from changing screening tests, and generated minimally biased long-term chlamydia prevalence trend estimates among youth and young adults in this sentinel surveillance population. RESULTS: Adjusted chlamydia prevalence among women was high throughout the study period, but fell from 20% in 1990 to 12% in 2003, and remained between 12% and 14% through 2012. Adjusted prevalence among men was steady throughout the study period at approximately 7%. For both women and men, adjusted prevalence was highest among Black and American Indian youth and young adults, and in the Southern and Midwestern regions of the United States throughout the study period. CONCLUSIONS: Our minimally biased trend estimates provide support for an initial decrease in chlamydia prevalence among women soon after the introduction of national chlamydia screening programs. Constant chlamydia prevalence in more recent years suggests that screening may not be sufficient to further reduce chlamydia prevalence among high-risk youth and young adults.

Sustained Sexual Behavior Change After Acute HIV Diagnosis in Malawi.

BACKGROUND: Identification of acute HIV infection (AHI) allows for important opportunities for HIV prevention through behavior change and biomedical intervention. Here, we evaluate changes in sexual risk behaviors among persons with AHI enrolled in a combined behavioral and biomedical intervention designed to reduce onward transmission of HIV. METHODS: Participants were randomized to standard HIV counseling, a multisession behavioral intervention, or a multisession behavioral intervention plus antiretrovirals. Sexual behaviors were assessed periodically over 1 year. RESULTS: Four weeks after diagnosis, the predicted probability of reporting multiple sexual partners decreased from 24% to 9%, and the probability of reporting unprotected sex decreased from 71% to 27%. These declines in sexual risk behaviors were sustained over follow-up irrespective of study arm. CONCLUSIONS: Diagnosis of AHI alone may be sufficient to achieve immediate and sustained behavior change during this highly infectious period.