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[Display omitted] • A series of 2-aminothiophene derivatives was designed and synthesized. • These derivatives were evaluated for their positive allosteric modulating effect on GLP1R. • Compound 7 significantly lowered blood plasma glucose level through In vivo studies using CD1 mice at a dose of 10 mg/kg. • Compound 7 is a promising lead compound for treating obesity and type 2 diabetes. 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. [ABSTRACT FROM AUTHOR]

The lack of standardized criteria for measuring therapeutic response is a major obstacle to the development of new therapeutic agents for chronic graft-versus-host disease (cGVHD). National Institutes of Health (NIH) consensus criteria for evaluating therapeutic response were published in 2006. We report the results of 4 consecutive pilot trials evaluating the feasibility and estimating the interrater reliability and minimum detectable change of these response criteria. Hematology-oncology clinicians with limited experience in applying the NIH cGVHD response criteria (n = 34) participated in a 2.5-hour training session on response evaluation in cGVHD. Feasibility and interrater reliability between subspecialty cGVHD experts and this panel of clinician raters were examined in a sample of 25 children and adults with cGVHD. The minimum detectable change was calculated using the standard error of measurement. Clinicians’ impressions of the brief training session, the photo atlas, and the response criteria documentation tools were generally favorable. Performing and documenting the full set of response evaluations required a median of 21 minutes (range: 12-60 minutes) per rater. The Schirmer tear test required the greatest time of any single test (median: 9 minutes). Overall, interrater agreement for skin and oral manifestations was modest; however, in the third and fourth trials, the agreement between clinicians and experts for all dimensions except movable sclerosis approached satisfactory values. In the final 2 trials, the threshold for defining change exceeding measurement error was 19% to 22% body surface area (BSA) for erythema, 18% to 26% BSA for movable sclerosis, 17% to 21% BSA for nonmovable sclerosis, and 2.1 to 2.6 points on the 15-point NIH Oral cGHVD scale. Agreement between clinician-expert pairs was moderate to substantial for the measures of functional capacity and for the gastrointestinal and global cGVHD rating scales. These results suggest that the NIH response criteria are feasible for use, and these reliability estimates are encouraging, because they were observed following a single 2.5-hour training session given at multiple transplant centers, with no opportunity for iterative training and calibration. Research is needed to evaluate inter- and intrarater reliability in larger samples, and to evaluate these response criteria as predictors of outcomes in clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: HIV diagnosis is the necessary first step towards HIV care initiation, yet many persons living with HIV (PLWH) remain undiagnosed. Employing multiple HIV testing strategies in tandem could increase HIV detection and promote linkage to care. We aimed to assess an intervention to improve HIV detection within socio‐sexual networks of PLWH in two sexually transmitted infections (STI) clinics in Lilongwe, Malawi. Methods: We conducted a randomized controlled trial to evaluate an intervention combining acute HIV infection (AHI) screening, contract partner notification and social contact referral versus the Malawian standard of care: serial rapid serological HIV tests and passive partner referral. Enrolment occurred between 2015 and 2019. HIV‐seropositive persons (two positive rapid tests) were randomized to the trial arms and HIV‐seronegative (one negative rapid test) and ‐serodiscordant (one positive test followed by a negative confirmatory test) persons were screened for AHI with HIV RNA testing. Those found to have AHI were offered enrolment into the intervention arm. Our primary outcome of interest was the number of new HIV diagnoses made per index participant within participants' sexual and social networks. We also calculated total persons, sexual partners and PLWH (including those previously diagnosed) referred per index participant. Results: A total of 1230 HIV‐seropositive persons were randomized to the control arm, and 561 to the intervention arm. Another 12,713 HIV‐seronegative or ‐serodiscordant persons underwent AHI screening, resulting in 136 AHI cases, of whom 94 enrolled into the intervention arm. The intervention increased the number of new HIV diagnoses made per index participant versus the control (ratio: 1.9; 95% confidence interval (CI): 1.2 to 3.1). The intervention also increased the numbers of persons (ratio: 2.5; 95% CI: 2.0 to 3.2), sexual partners (ratio: 1.7; 95% CI: 1.4 to 2.0) and PLWH (ratio: 2.3; 95% CI: 1.7 to 3.2) referred per index participant. Conclusions: Combining three distinct HIV testing and referral strategies increased the detection of previously undiagnosed HIV infections within the socio‐sexual networks of PLWH seeking STI care. Combination HIV detection strategies that leverage AHI screening and socio‐sexual contact networks offer a novel and efficacious approach to increasing HIV status awareness. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: HIV diagnosis, the first step in HIV care and treatment engagement, may be inhibited by substance use among female sex workers (FSW). We assessed the relationship between alcohol and cannabis use and lack of HIV infection awareness among HIV-infected FSW in Lilongwe, Malawi.Methods: From July to September, 2014, 200 FSW aged ≥18 years were enrolled using venue-based sampling to examine substance use, HIV testing history, and serostatus ascertained by HIV rapid test. We used Poisson regression with robust variance estimates to estimate the associations of alcohol and cannabis use and lack of HIV infection awareness.Results: Of the 138 HIV-infected FSW, 20% were unaware of their HIV infection, with 70% not testing within 6 months prior. According to the Alcohol Use Disorder Identification Tests (AUDIT), 55% of FSW unaware of their HIV infection reported hazardous, harmful, or dependent alcohol consumption. We observed a dose-response relationship between alcohol use and lack of HIV infection awareness, with alcohol dependency significantly associated with lack of HIV infection awareness (adjusted prevalence ratio: 3.0, 95% CI: 1.3, 6.8). Current cannabis use was uncommon (26%) among unaware HIV-infected FSW and weakly associated with lack of HIV infection awareness adjusted prevalence ratio: 1.1, 95% CI: 0.5, 2.5).Conclusion: Increased levels of alcohol use is associated with lack of HIV infection awareness among HIV-infected FSW in Malawi. Frequent, consistent HIV testing integrated with alcohol reduction strategies could improve the health and infection awareness of substance-using FSW. [ABSTRACT FROM AUTHOR]

The article explores the role of parents in the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) during pregnancy and breastfeeding. It explains the high risk of acquiring HIV in women in sub-Saharan Africa during pregnancy and breastfeeding. The use of a couples-based approach to HIV prevention is suggested. The impact of an HIV infection on a woman's survival and quality of life is discussed.

Purpose: Chronic graft-versus-host disease (cGVHD) is a significant cause of mortality and morbidity after allogeneic hematopoietic cell transplant and is associated with a wide range of distressing symptoms. A pediatric measure of cGVHD-related symptoms is needed to advance clinical research. Our aim was to elicit descriptions of the cGVHD symptom experience directly from children and to compare the specific language used by children to describe their symptoms and the comprehension of symptom concepts across the developmental spectrum. Methods: We used qualitative methods to identify the phrases, terms, and constructs that children (ages 5-8 [ n = 8], 9-12 [ n = 8], and 13-17 [ n = 8]) with cGVHD employ when describing their symptoms. The symptom experience of each participant was determined through individual interviews with each participant and parent (5-7 year olds were interviewed together with a parent). Medical practitioners with experience in evaluating cGVHD performed clinical assessments of each participant. Results: Pediatric transplant survivors and their parents identified a wide range of bothersome cGVHD symptoms, and common concepts and terminologies to describe these experiences emerged. Overall concordance between patient and parent reports was moderate (70-75 %). No consistent pattern of child under- or over-reporting in comparison to the parent report was observed. Conclusion: These study results identify concepts and vocabulary to inform item generation for a new pediatric self-report measure of cGVHD symptoms for use in clinical research. The findings also confirm the prevalence and nature of symptom distress in pediatric patients with cGVHD and support implementation of systematic approaches to symptom assessment and intervention in routine clinical practice. [ABSTRACT FROM AUTHOR]

The high burden of syphilis in China presents a unique opportunity to examine temporal trends. This study used wavelet transformation and Fourier analysis to assess the presence of temporal oscillations in the incidence of syphilis among adults, gonorrhea, and congenital syphilis over 11 years in China's largest province. This study found a significant annual oscillation trend in the incidence of adult syphilis, consistent with a peak during July–September, which was 4-fold higher than the trough, which occurred during January–March. A similar but dampened trend was observed in the incidence of gonorrhea, and no trend was observed for the incidence of congenital syphilis. Further research on the temporal oscillation of the incidence of syphilis is needed. [ABSTRACT FROM PUBLISHER]

The article offers the insights of Kimberly Powers and colleagues on the role of acute infection in HIV transmission. It says that Powers and colleagues concluded that anti-retroviral treatment (ART) will not interrupt transmission unless it can be allowed during the acute stage of infection. Moreover, the data submitted by the colleagues suggests that acute phase may have a role in the epidemic and the effect of ART is positive in the prevention of the infection.

Substance use and depression are prevalent in sexual and gender minorities (SGM), but evidence about their impacts on HIV pre-exposure prophylaxis (PrEP) use is mixed. We assessed these impacts in a US-based cohort of 3,330 young SGM who tested negative for HIV and completed baseline and semiannual assessments on substance use (cocaine, methamphetamine, or heroin), depression, and PrEP use and adherence. We estimated prevalence differences (PDs) to compare baseline and 12-month PrEP use and adherence between participants with and without substance use and depression, separately and jointly. At baseline, 8% of participants reported substance use and depression, 7% reported substance use only, 38% reported depression only, and 47% reported neither. PrEP use was reported by 22%, with 78% reporting prior-day adherence. Compared to participants without depression or substance use, participants with substance use alone were more likely to report PrEP use at baseline (PD = 18.9; 95% CI: 7.6, 30.2) and 12 months (PD = 15.9, 95% CI: 5.1, 26.7), without adherence differences. Depression alone was associated with lower baseline PrEP use (PD=-3.6, 95% CI: -6.7, -0.4) and adherence (PD=-10.0, 95% CI: -18.4, -1.6), but associations attenuated over 12 months. Those with both substance use and depression (vs. neither) reported higher baseline PrEP use (PD = 6.5, 95% CI: -0.6, 13.5) and lower adherence (PD=-12.9, 95% CI: -26.2, 0.5), with associations weakening over 12 months. Substance use and depression had opposing relationships with PrEP use and adherence. In addition to its mental health benefits, depression treatment may improve PrEP uptake and adherence in young SGM., Competing Interests: Declarations. Prior Presentation: Portions of this study were presented at the International Workshop on HIV and Hepatitis Observational Databases (Athens, Greece) in March 2023 as a poster presentation with interim findings. Conflict of Interest: None declared., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The prevention and control of infectious disease outbreaks in carceral settings face unique challenges. Transmission modeling is a powerful tool for understanding and addressing these challenges, but reviews of modeling work in this context pre-date the proliferation of outbreaks in jails and prisons during the SARS-CoV-2 pandemic. We conducted a systematic review of studies using transmission models of respiratory infections in carceral settings before and during the pandemic., Methods: We searched PubMed, Embase, Scopus, CINAHL, and PsycInfo to identify studies published between 1970 and 2024 that modeled transmission of respiratory infectious diseases in carceral settings. We extracted information on the diseases, populations, and settings modeled; approaches used for parameterizing models and simulating transmission; outcomes of interest and techniques for model calibration, validation, and sensitivity analyses; and types, impacts, and ethical aspects of modeled interventions., Results: Forty-six studies met eligibility criteria, with transmission dynamics of tuberculosis modeled in 24 (52 %), SARS-CoV-2 in 20 (43 %), influenza in one (2 %), and varicella-zoster virus in one (2 %). Carceral facilities in the United States were the most common focus (15, 33 %), followed by Brazil (8, 17 %). Most studies (36, 80 %) used compartmental models (vs. individual- or agent-based). Tuberculosis studies typically modeled transmission within a single facility, while most SARS-CoV-2 studies simulated transmission in multiple places, including between carceral and community settings. Half of studies fit models to epidemiological data; three validated model predictions. Models were used to estimate past or potential future intervention impacts in 32 (70 %) studies, forecast the status quo (without changing conditions) in six (13 %), and examine only theoretical aspects of transmission in eight (17 %). Interventions commonly involved testing and treatment, quarantine and isolation, and/or facility ventilation. Modeled interventions substantially reduced transmission, but some were not well-defined or did not consider ethical issues., Conclusion: The pandemic prompted urgent attention to transmission dynamics in jails and prisons, but there has been little modeling of respiratory infections other than SARS-CoV-2 and tuberculosis. Increased attention to calibration, validation, and the practical and ethical aspects of intervention implementation could improve translation of model estimates into tangible benefits for the highly vulnerable populations in carceral settings., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors report financial support was provided by the National Institutes of Health. There are no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Abstract: This study quantitatively examined factors related to young men who have sex with men (YMSM)'s decisions to use pre-exposure prophylaxis (PrEP) by their history of PrEP use and qualitatively elicited their perspectives on PrEP options. Higher proportions of YMSM who had never used (vs. ever used) PrEP considered the following factors as important in their decisions to use PrEP: (a) Returning to PrEP follow-up visits ( p = .02), (b) having to talk about sex/PrEP with providers ( p = .013), (c) people assuming they are infected with HIV ( p = .021), (d) family finding out about their PrEP use ( p = .001), and (e) friends finding out about their PrEP use ( p = .008). Through inductive content analysis, qualitative data showed that a higher proportion of YMSM who had never used PrEP (vs. ever used) expressed concerns about HIV stigma from nonaffirming health care providers and the potential risk of inadvertently revealing their LGBTQ+ identity to others, which were described as potential barriers to PrEP use. Overall, our findings suggest that future interventions may consider tailoring PrEP messaging to YMSM's history of PrEP use, which may ultimately increase PrEP uptake and adherence., (Copyright © 2024 Association of Nurses in AIDS Care.)

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Understanding heterogeneity across patients in effectiveness of network-based HIV testing interventions may optimize testing and contact tracing strategies, expediting linkage to therapy or prevention for contacts of persons with HIV (PWH)., Setting: We analyzed data from a randomized controlled trial of a combination intervention comprising acute HIV testing, contract partner notification (cPN), and social contact referral conducted among PWH at 2 STI clinics in Lilongwe, Malawi, between 2015 and 2019., Methods: We used binomial regression to estimate the effect of the combination intervention vs. passive PN (pPN) on having any (1) contact, (2) newly HIV-diagnosed contact, and (3) HIV-negative contact present to the clinic, overall and by referring participant characteristics. We repeated analyses comparing cPN alone with pPN., Results: The combination intervention effect on having any presenting contact was greater among referring women than men [prevalence difference (PD): 0.17 vs. 0.10] and among previously vs. newly HIV-diagnosed referring persons (PD: 0.20 vs. 0.11). Differences by sex and HIV diagnosis status were similar in cPN vs. pPN analyses. There were no notable differences in the intervention effect on newly HIV-diagnosed referrals by referring participant characteristics. Intervention impact on having HIV-negative presenting contacts was greater among younger vs. older referring persons and among those with >1 vs. ≤1 recent sex partner. Effect differences by age were similar for cPN vs. pPN., Conclusion: Our intervention package may be particularly efficacious in eliciting referrals from women and previously diagnosed persons. When the combination intervention is infeasible, cPN alone may be beneficial for these populations., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: On-demand dosing of preexposure prophylaxis (PrEP) requires accurate prediction of sex; however, prediction abilities among young men who have sex with men (YMSM) have not been characterized., Setting: A nationally recruited prospective cohort of YMSM ages 16-24 years., Methods: We followed 120 YMSM for 8 weeks using digital daily surveys (DDSs) to measure engagement in and prediction of anal sex over 24 hours, along with condom use and other encounter-level circumstances. Our main outcome, an "unpredicted spontaneous encounter," was defined as an anal sex encounter that occurred without sufficient prior knowledge to (hypothetically) enable protective on-demand PrEP use according to dosing guidelines. We operationalized this outcome as an anal sex encounter for which a participant indicated: (1) on the prior day's DDS that there was a low likelihood of sex occurring in the subsequent 24 hours (unpredicted) and (2) on the current day's DDS that he knew ≤2 hours in advance that the encounter would occur (spontaneous)., Results: Approximately one-third of all anal sex encounters during the study period were unpredicted and spontaneous and would not have been protected (hypothetically) by on-demand dosing. More than two-thirds of participants experienced such an encounter and almost three-quarters of all acts were condomless., Conclusions: On-demand PrEP to prevent HIV acquisition may be challenging for many YMSM. Clinical and public health approaches that account for patients' predictive abilities alongside their dosing preferences may help to optimize selection of and adherence to PrEP dosing strategies., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Despite widespread success in reducing vertical HIV transmission, most antenatal care (ANC) programmes in eastern and southern Africa have not emphasized primary prevention of maternal HIV acquisition during pregnancy and lactation/breastfeeding. We hypothesized that combination HIV prevention interventions initiated alongside ANC could substantially reduce maternal HIV incidence., Methods: We constructed a multi-state model describing male-to-female HIV transmission in steady heterosexual partnerships during pregnancy and lactation/breastfeeding, with initial conditions based on population distribution estimates for Malawi and Zambia in 2020. We modelled individual and joint increases in three HIV prevention strategies at or soon after ANC initiation: (1) HIV testing of male partners, resulting in HIV diagnosis and less condomless sex among those with previously undiagnosed HIV; (2) initiation (or re-initiation) of suppressive antiretroviral therapy (ART) for male partners with diagnosed but unsuppressed HIV; and (3) adherent pre-exposure prophylaxis (PrEP) for HIV-negative female ANC patients with HIV-diagnosed or unknown-status male partners. We estimated the percentage of within-couple, male-to-female HIV transmissions that could be averted during pregnancy and lactation/breastfeeding with these strategies, relative to base-case conditions in which 45% of undiagnosed male partners become newly HIV diagnosed via testing, 75% of male partners with diagnosed but unsuppressed HIV initiate/re-initiate ART and 0% of female ANC patients start PrEP., Results: Increasing uptake of any single strategy by 20 percentage points above base-case levels averted 10%-11% of maternal HIV acquisitions during pregnancy and lactation/breastfeeding in the model. Joint uptake increases of 20 percentage points in two interventions averted an estimated 19%-23% of transmissions, and with a 20-percentage-point increase in uptake of all three interventions, 29% were averted. Strategies achieving 95% male testing, 90% male ART initiation/re-initiation and 40% female PrEP use reduced incident infections by 45%., Conclusions: Combination HIV prevention strategies provided alongside ANC and sustained through the post-partum period could substantially reduce maternal HIV incidence during pregnancy and lactation/breastfeeding in eastern and southern Africa., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Objective: To estimate the effect of intimate partner violence (IPV) on oral pre-exposure prophylaxis (PrEP) adherence among adolescent girls and young women (AGYW)., Design: We conducted a secondary analysis of data from HIV Prevention Trials Network 082 (HPTN 082), a multisite prospective study designed to assess oral PrEP adherence among AGYW in southern Africa., Methods: We estimated the relative prevalence of high PrEP adherence 3 and 6 months after initiation among AGYW 16-25 years who reported a history of any IPV in the past year at enrollment versus AGYW who did not, both overall and by age. High adherence was defined as an intracellular tenofovir-diphosphate concentration at least 700 fmol/punch or more dried blood spots., Results: Among 409 PrEP-initiating AGYW, half (49%) reported experiencing any IPV by a current/recent partner in the year prior to enrollment. Overall, a similar proportion of AGYW who reported IPV had high PrEP adherence at months 3 and 6 as AGYW who did not report IPV. There was, however, evidence of effect modification by age at month 3: among AGYW less than 21 years old, those who reported IPV were less than half as likely to have high adherence [adjusted PR (aPR) = 0.43, 95% confidence interval (CI) 0.22-0.86]; among AGYW aged 21 years or older, those who reported IPV were more than twice as likely to have high adherence (aPR = 2.21, 95% CI 1.34-3.66). At month 6, effect estimates within each age stratum were consistent in direction to those at month 3., Conclusion: IPV events may either impede or motivate PrEP adherence among African AGYW, with age appearing to be an important consideration for IPV-related adherence interventions., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Teachers are central to school-associated transmission networks, but little is known about their behavioral patterns during the COVID-19 pandemic., Methods: We conducted a cross-sectional survey of 700 North Carolina public school teachers in 4 districts open to in-person learning in November-December 2020 (pre-COVID-19 vaccines). We assessed indoor and outdoor time spent, numbers of people encountered at <6 feet ("close contacts"), and mask use by teachers and those around them at specific locations on the most recent weekday and weekend day., Results: Nearly all respondents reported indoor time at home (98%) and school (94%) on the most recent weekday, while 62% reported indoor time at stores, 18% at someone else's home, and 17% at bars/restaurants. Responses were similar for the most recent weekend day, excepting school (where 5% reported indoor time). Most teachers (>94%) reported wearing masks inside school, stores, and salons; intermediate percentages (∼50%-85%) inside places of worship, bars/restaurants, and recreational settings; and few (<25%) in their or others' homes. Approximately half reported daily close contact with students., Conclusions: As schools reopened in the COVID-19 pandemic, potential transmission opportunities arose through close contacts within and outside of school, along with suboptimal mask use by teachers and/or those around them. Our granular estimates underscore the importance of multilayered mitigation strategies and can inform interventions and mathematical models addressing school-associated transmission., (Copyright © 2022 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

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., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2021. The Author(s).)

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.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Little is known about temporal patterns of physical intimate partner violence (PIPV) among South African adolescent girls. We sought to identify and describe PIPV risk trajectories and related correlates in this population., Methods: Our analytical cohort came from the HPTN 068 Cash Transfer Trial in Mpumalanga Province, South Africa. Cohort members were eighth and ninth graders (median age 14 years) who enrolled in 2011 and had three to four annual, self-reported PIPV measurements. We used group-based trajectory models to identify groups of girls with similar longitudinal patterns of PIPV risk over 4 years and potential correlates of group membership., Results: We identified two trajectory groups (n = 907): a higher-risk group (~52.8% of the cohort) with predicted PIPV probabilities of 13.5%-41.1% over time and a lower-risk group (~47.2% of the cohort) with predicted probabilities of 2.3%-10.3%. Baseline correlates of higher-risk group membership were ever having had sex (adjusted odds ratio [aOR]: 4.42, 95% confidence interval [CI]: 1.56-12.57), borrowing money (aOR: 1.95, 95% CI: 1.01-3.79), and older age (aOR per 1-year increase: 1.39, 95% CI: 1.11-1.73), while being in the 068 intervention arm (aOR: .29, 95% CI: .17-.51) and supporting more gender-equitable norms (aOR per 1-unit score increase: .89, 95% CI: .81-.97) were inversely associated., Conclusions: A high proportion of adolescent girls experience sustained PIPV risk in rural South Africa, suggesting a need for interventions in late primary school that encourage gender-equitable norms, healthy relationships, and safe ways to earn income during adolescence., (Copyright © 2020 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: The Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 and other cross-sectional metrics can lead to potentially counterintuitive conclusions when used to evaluate health systems' performance. This study demonstrates how time and population dynamics impact UNAIDS 90-90-90 metrics in comparison with a longitudinal analogue., Design: A simplified simulation representing a hypothetical population was used to estimate and compare inference from UNAIDS 90-90-90 metrics and longitudinal metrics based on Kaplan-Meier-estimated 2-year probability of transition between stages., Methods: We simulated a large cohort over 15 years. Everyone started out at risk for HIV, and then transitioned through the HIV care continuum based on fixed daily probabilities of acquiring HIV, learning status, entering care, initiating antiretroviral therapy (ART), and becoming virally suppressed, or dying. We varied the probability of ART initiation over three five-year periods (low, high, and low). We repeated the simulation with an increased probability of death., Results: The cross-sectional probability of being on ART among persons who were diagnosed responded relatively slowly to changes in the rate of ART initiation. Increases in ART initiation rates caused apparent declines in the cross-sectional probability of being virally suppressed among persons who had initiated ART, despite no changes in the rate of viral suppression. In some cases, higher mortality resulted in the cross-sectional metrics implying improved healthcare system performance. The longitudinal continuum was robust to these issues., Conclusion: The UNAIDS 90-90-90 care continuum may lead to incorrect inference when used to evaluate health systems performance. We recommend that evaluation of HIV care delivery include longitudinal care continuum metrics wherever possible.

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.

Objectives: A previous meta-analysis reported high HIV incidence among pregnant and breast-feeding women in sub-Saharan Africa (SSA), but limited evidence of elevated risk of HIV acquisition during pregnancy or breast-feeding when compared with nonpregnant periods. The rapidly evolving HIV prevention and treatment landscape since publication of this review may have important implications for maternal HIV incidence., Design: Systematic review and meta-analysis., Methods: We searched four databases and abstracts from relevant conferences through 1 December 2018, for literature on maternal HIV incidence in SSA. We used random-effects meta-analysis to summarize incidence rates and ratios, and to estimate 95% prediction intervals. We evaluated potential sources of heterogeneity with random-effects meta-regression., Results: Thirty-seven publications contributed 100 758 person-years of follow-up. The estimated average HIV incidence rate among pregnant and breast-feeding women was 3.6 per 100 person-years (95% prediction interval: 1.2--11.1), while the estimated average associations between pregnancy and risk of HIV acquisition, and breast-feeding and risk of HIV acquisition, were close to the null. Wide 95% prediction intervals around summary estimates highlighted the variability of HIV incidence across populations of pregnant and breast-feeding women in SSA. Average HIV incidence appeared associated with age, partner HIV status, and calendar time. Average incidence was highest among studies conducted pre-2010 (4.1/100 person-years, 95% prediction interval: 1.1--12.2) and lowest among studies conducted post-2014 (2.1/100 person-years, 95% prediction interval: 0.7--6.5)., Conclusion: Substantial HIV incidence among pregnant and breast-feeding women in SSA, even in the current era of combination HIV prevention and treatment, underscores the need for prevention tailored to high-risk pregnant and breast-feeding women.

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.

Background: Sexual partners are the primary source of incident HIV infection among adolescent girls and young women (AGYW) in sub-Saharan Africa. Identifying partner types at greatest risk of HIV transmission could guide the design of tailored HIV prevention interventions., Methods: We conducted a secondary analysis of data from AGYW (aged 13-23 years) enrolled in a randomized controlled trial of cash transfers for HIV prevention in South Africa. Annually, AGYW reported behavioral and demographic characteristics of their 3 most recent sexual partners, categorized each partner using prespecified labels, and received HIV testing. We used latent class analysis (LCA) to identify partner types from reported characteristics, and generalized estimating equations to estimate the relationship between both LCA-identified and prespecified partner types and incident HIV infection., Results: Across 2140 AGYW visits, 1034 AGYW made 2968 partner reports and 63 AGYW acquired HIV infection. We identified 5 LCA partner types, which we named monogamous HIV-negative peer partner; one-time protected in-school peer partner; out-of-school older partner; anonymous out-of-school peer partner; and cohabiting with children in-school peer partner. Compared to AGYW with only monogamous HIV-negative peer partners, AGYW with out-of-school older partners had 2.56 times the annual risk of HIV infection (95% confidence interval: 1.23 to 5.33), whereas AGYW with anonymous out-of-school peer partners had 1.72 times the risk (95% confidence interval: 0.82 to 3.59). Prespecified partner types were not associated with incident HIV., Conclusion: By identifying meaningful combinations of partner characteristics and predicting the corresponding risk of HIV acquisition among AGYW, LCA-identified partner types may provide new insights for the design of tailored HIV prevention interventions.

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.

Background: Prediction of HIV transmission cluster growth may help guide public health action. We developed a predictive model for cluster growth in North Carolina (NC) using routine HIV surveillance data., Methods: We identified putative transmission clusters with ≥2 members through pairwise genetic distances ≤1.5% from HIV-1 pol sequences sampled November 2010-December 2017 in NC. Clusters established by a baseline of January 2015 with any sequences sampled within 2 years before baseline were assessed for growth (new diagnoses) over 18 months. We developed a predictive model for cluster growth incorporating demographic, clinical, temporal, and contact tracing characteristics of baseline cluster members. We internally and temporally externally validated the final model in the periods January 2015-June 2016 and July 2016-December 2017., Results: Cluster growth was predicted by larger baseline cluster size, shorter time between diagnosis and HIV care entry, younger age, shorter time since the most recent HIV diagnosis, higher proportion with no named contacts, and higher proportion with HIV viremia. The model showed areas under the receiver-operating characteristic curves of 0.82 and 0.83 in the internal and temporal external validation samples., Conclusions: The predictive model developed and validated here is a novel means of identifying HIV transmission clusters that may benefit from targeted HIV control resources.

Depressive symptoms vary in severity and chronicity. We used group-based trajectory models to describe trajectories of depressive symptoms (measured using the Patient Health Questionnaire-9) and predictors of trajectory group membership among 1493 HIV-infected men (84%) and 292 HIV-infected women (16%). At baseline, 29% of women and 26% of men had depressive symptoms. Over a median of 30 months of follow-up, we identified four depressive symptom trajectories for women (labeled "low" [experienced by 56% of women], "mild/moderate" [24%], "improving" [14%], and "severe" [6%]) and five for men ("low" [61%], "mild/moderate" [14%], "rebounding" [5%], "improving" [13%], and "severe" [7%]). Baseline antidepressant prescription, panic symptoms, and prior mental health diagnoses were associated with more severe or dynamic depressive symptom trajectories. Nearly a quarter of participants experienced some depressive symptoms, highlighting the need for improved depression management. Addressing more severe or dynamic depressive symptom trajectories may require interventions that additionally address mental health comorbidities.

Objective: Symptoms of acute retroviral syndrome (ARS) may be used to identify patients with acute HIV-1 infection who seek care. ARS symptoms in African adults differ by region. We assessed whether reporting of ARS was associated with HIV-1 subtype in a multicentre African cohort study representing countries with predominant HIV-1 subtypes A, C, and D., Methods: ARS symptoms were assessed in adults enrolling within 6 weeks after the estimated date of infection in an acute and early HIV-1 infection cohort study. HIV-1 subtype was determined by POL genotyping. We used log-binomial regression to compare ARS symptom prevalence among those with subtype A vs. C or D, adjusting for sex, time since enrolment, and enrolment viral load., Results: Among 183 volunteers ascertained within 6 weeks after estimated date of infection, 77 (42.0%) had subtype A, 83 (45.4%) subtype C, and 23 (12.6%) subtype D infection. Individuals with subtype A were 1.40 (95% confidence interval: 1.17, 1.68) times as likely as individuals with subtypes C or D to report any ARS symptoms; each individual symptom other than rash was also more prevalent in subtype A than in subtype C or D, with prevalence ratios ranging from 1.94 (1.40, 2.70) for headache to 4.92 (2.24, 10.78) for lymphadenopathy., Conclusion: Individuals with subtype A were significantly more likely than individuals with subtypes C or D to report any ARS symptoms. HIV-1 subtypes may help explain differences in ARS that have been observed across regions in Africa, and may impact the yield of symptom-based screening strategies for acute HIV infection detection.

The structure of the sexual network of a population plays an essential role in the transmission of HIV. Concurrent partnerships, i.e. partnerships that overlap in time, are important in determining this network structure. Men and women may differ in their concurrent behavior, e.g. in the case of polygyny where women are monogamous while men may have concurrent partnerships. Polygyny has been shown empirically to be negatively associated with HIV prevalence, but the epidemiological impacts of other forms of gender-asymmetric concurrency have not been formally explored. Here we investigate how gender asymmetry in concurrency, including polygyny, can affect the disease dynamics. We use a model for a dynamic network where individuals may have concurrent partners. The maximum possible number of simultaneous partnerships can differ for men and women, e.g. in the case of polygyny. We control for mean partnership duration, mean lifetime number of partners, mean degree, and sexually active lifespan. We assess the effects of gender asymmetry in concurrency on two epidemic phase quantities (R 0 and the contribution of the acute HIV stage to R 0 ) and on the endemic HIV prevalence. We find that gender asymmetry in concurrent partnerships is associated with lower levels of all three epidemiological quantities, especially in the polygynous case. This effect on disease transmission can be attributed to changes in network structure, where increasing asymmetry leads to decreasing network connectivity., (Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Long-term HIV care and treatment engagement is required for maximal clinical and prevention benefits, but longitudinal care patterns are poorly understood. We used the last 10 years' worth of HIV surveillance data from North Carolina to describe longitudinal HIV care trajectories from diagnosis., Methods: We conducted a retrospective, population-based cohort study of all persons newly diagnosed with HIV in North Carolina between March 31, 2006 and March 31, 2015 (N = 16,207). We defined HIV care attendance in each 3-month and 6-month interval after diagnosis as the presence of viral load and/or CD4 records (care visit proxies) in the interval. We used group-based trajectory modeling to identify common care trajectories and baseline predictors thereof., Results: A predicted 26% of newly HIV-diagnosed persons showed consistently high care attendance over time; ∼16% exhibited steadily declining attendance; ∼26% showed consistently low attendance; ∼17% had initially weak attendance with an increase starting ∼1.5 year later; and ∼15% showed initially weak attendance with an increase starting ∼3 years later. Older age at diagnosis was protective against all suboptimal trajectories (with the "consistently high" pattern as referent), and being a man who has sex with men was protective against 3 of the 4 suboptimal patterns., Conclusions: As measured by surveillance-based laboratory proxies, most newly HIV-diagnosed persons exhibited suboptimal care trajectories, but there was wide variation in the particular pathways followed. The insights provided by this analytical approach can help to inform the design of epidemic models and tailored interventions, with the ultimate goal of improving HIV care engagement and transmission prevention., Competing Interests: We have no conflicts of interest to declare.

The HIV cascade--often referred to as "the HIV continuum"--provides a valuable framework for population-level representations of engagement with the HIV healthcare system. The importance and appeal of this framework are evidenced by a large body of scientific literature, as well as by the adoption of cascade-related indicators by medical and public health organizations worldwide. Despite its centrality in the fields of HIV treatment and prevention, however, the traditional cascade provides limited description of the processes affecting the numbers it represents. Representations that describe these processes and capture the dynamic nature of HIV-infected persons' pathways through the healthcare system are essential for monitoring and predicting intervention effects and epidemic trends. We propose here a complementary schema--termed the "HIV States and Transitions" framework--designed to maintain key strengths of the traditional cascade while addressing key limitations and more fully describing the dynamic aspects of HIV testing, care, and treatment at the population level.

Objectives: To estimate the effect of receiving HIV-positive test results on intentions to have future children and on contraceptive use and to assess the association between pregnancy intentions and pregnancy incidence among HIV-positive women in Malawi., Methods: Women of unknown HIV status completed a questionnaire about pregnancy intentions and contraceptive use and then received HIV voluntary counseling and testing (VCT). Women who were HIV-positive and not pregnant were enrolled and followed for 1 year while receiving HIV care and access to family planning (FP) services., Results: Before receiving their HIV test results, 33% of women reported a desire to have future children; this declined to 15% 1 week later (P < 0.0001) and remained constant throughout follow-up. Contraceptive use increased from 38% before HIV testing to 52% 1 week later (P < 0.0001) and then decreased to 46% by 12 months. The pregnancy incidence among women not reporting a desire to have future children after VCT was less than half of the incidence among women reporting this desire., Conclusions: With knowledge of their HIV-positive status, women were less likely to desire future pregnancies. Pregnancy incidence was lower among women not desiring future children. Integration of VCT, FP, and HIV care could prevent mother-to-child HIV transmission.

Pegylated interferon (PEG-IFN) has become standard therapy for hepatitis C virus (HCV) infection. We evaluated whether PEG-IFN pharmacodynamics and pharmacokinetics account for differences in treatment outcome and whether these parameters might be predictors of therapeutic outcome. Twenty-four IFN-naïve, HCV/human immunodeficiency virus-coinfected patients received PEG-IFN alpha-2b (1.5 microg/kg) once weekly plus daily ribavirin (1000 or 1200 mg) for up to 48 weeks. HCV RNA and PEG-IFN alpha concentrations were obtained from samples collected frequently after the first 3 PEG-IFN doses. We modeled HCV kinetics incorporating pharmacokinetic and pharmacodynamic parameters. Although PEG-IFN concentrations and pharmacokinetic parameters were similar in sustained virological responders (SVRs) and nonresponders (NRs), the PEG-IFN alpha-2b concentration that decreases HCV production by 50% (EC50) was lower in SVRs compared with NRs (0.04 vs. 0.45 microg/L [P = .014]). Additionally, the median therapeutic quotient (i.e., the ratio between average PEG-IFN concentration and EC50 [C/EC50]), and the PEG-IFN concentration at day 7 divided by EC50 (C(7)/EC50) were significantly increased in SVRs compared with NRs after the first (10.1 vs. 1.0 [P = .012], 2.8 vs. 0.3 [P = .007], respectively) and second (14.0 vs. 1.1 [P = .016], 5.4 vs. 0.4 [P = .02], respectively) PEG-IFN doses. All 3 parameters may be used to identify NRs. In conclusion, PEG-IFN concentrations and pharmacokinetic parameters do not differ between SVRs and NRs. In contrast, pharmacodynamic measurements-namely EC50, the therapeutic quotient, and C(7)/EC50--are different in coinfected SVRs and NRs. These parameters might be useful predictors of treatment outcome during the first month of therapy.