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Peng Li,1,2 Lei Gao,1– 3 Chenlu Gao,1,2 Robert A Parker,4– 6 Ingrid T Katz,5,7,8 Monty A Montano,5,9 Kun Hu1,2 1Medical Biodynamics Program, Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 2Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA; 3Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 4Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA; 5Harvard Medical School, Boston, MA, USA; 6Center for AIDS Research, Harvard University, Boston, MA, USA; 7Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 8Harvard Global Health Institute, Cambridge, MA, USA; 9Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USACorrespondence: Peng Li, Email pli9@bwh.harvard.eduPurpose: We investigated whether daytime sleep behaviors (DSBs) such as frequent daytime sleepiness or napping are associated with worse cognitive performance, and whether HIV infection moderates this relationship.Methods: Among 502,507 participants in the UK Biobank study, we identified 562 people living with HIV infection (PLWH; Mage= 50.51± 7.81; 25.09% female; 78.83% white) and extracted 562 uninfected controls who matched on age, sex, ethnic background, social-economic status, and comorbidities. DSB burden was assessed based on answers to two questions on DSBs. Participants who answered “sometimes” or “often/usually” to one of them were considered to have poor DSB burden, or otherwise were considered not having any. A composite cognition score was computed by averaging the available standardized individual test results from four neurocognitive tests: ie, a reaction time test for information processing speed, a pairs matching test for visual episodic memory, a fluid intelligence test for reasoning, and a prospective memory test. Mixed-effects models with adjustment for the variables used in extracting matched uninfected controls were performed to test the hypotheses.Results: Having poor DSB burden was associated with a 0.15 – standard deviation (SD) decrease in cognitive performance (p = 0.006). People living with HIV infection (PLWH) also performed worse on the cognitive tasks than uninfected controls, with an effect size similar to that of having poor DSB burden (p = 0.003). HIV infection significantly modified the negative association between DSB burden and cognition (p for interaction: 0.008). Specifically, the association between DSB burden and cognition was not statistically significant in uninfected controls, whereas PLWH who reported having poor DSB burden had a 0.28 – SD decrease in cognitive performance compared to PLWH who did not.Conclusion: HIV infection significantly increased the adverse association between DSBs and cognitive performance. Further studies are needed to investigate the potential mechanisms that underlie this interaction effect and whether poor DSBs and worse cognitive performance are causally linked.Keywords: aging, cognition, daytime napping, daytime sleepiness, risk factors, sleep

Few studies have focused on understanding pre-exposure prophylaxis (PrEP) non-initiation among young, high-risk women in sub-Saharan Africa. This study aimed to qualitatively explore why young women in Kenya at high-risk for HIV chose not to enroll in a PrEP adherence trial. We performed 40 semi-structured interviews with young high-risk women assessing concerns about PrEP and/or study participation. We also assessed community-level factors influencing decision-making around PrEP through 10 focus groups involving peers, young men, caregivers, and community leaders. Our qualitative data reflect the complexity of navigating barriers preventing PrEP initiation in settings where taking PrEP may be perceived as immoral behavior. Framed within the context of risk perception, the decision to start PrEP may run counter to the potential risk of losing support from one's community. Our findings suggest that approaches addressing social norms, while de-medicalizing HIV prevention services, are needed to further increase PrEP uptake among young Kenyan women.

Background: Adoption of “Treat All” policies has increased antiretroviral therapy (ART) initiation in sub-Saharan Africa; however, unexplained early losses continue to occur. More information is needed to understand why treatment discontinuation continues at this vulnerable stage in care. Methods: The Monitoring Early Treatment Adherence Study involved a prospective observational cohort of individuals initiating ART at early-stage versus late-stage disease in South Africa and Uganda. Surveys and HIV-1 RNA levels were performed at baseline, 6, and 12 months, with adherence monitored electronically. This analysis included nonpregnant participants in the first 6 months of follow-up; demographic and clinical factors were compared across groups with χ2, univariable, and multivariable models. Results: Of 669 eligible participants, 91 (14%) showed early gaps of ≥30 days in ART use (22% in South Africa and 6% in Uganda) with the median time to gap of 77 days (interquartile range: 43–101) and 87 days (74, 105), respectively. Although 71 (78%) ultimately resumed care, having an early gap was still significantly associated with detectable viremia at 6 months (P ≤ 0.01). Multivariable modeling, restricted to South Africa, found secondary education and higher physical health score protected against early gaps [adjusted odds ratio (aOR) 0.4, 95% confidence interval (CI): 0.2 to 0.8 and (aOR 0.93, 95% CI: 0.9 to 1.0), respectively]. Participants reporting clinics as “too far” had double the odds of early gaps (aOR 2.2: 95% CI: 1.2 to 4.1). Discussion: Early gaps in ART persist, resulting in higher odds of detectable viremia, particularly in South Africa. Interventions targeting health management and access to care are critical to reducing early gaps.

Global scale-up of HIV pre-exposure prophylaxis (PrEP) includes services to HIV-negative people in partnerships with people living with HIV (serodifferent couples). Data are needed on HIV outcomes, including uptake and adherence to PrEP and antiretroviral treatment (ART), to describe the impact of integrating PrEP into an existing HIV program.Using a stepped-wedge cluster randomized trial design, we launched PrEP delivery for HIV-negative members of serodifferent couples in Uganda by integrating PrEP into existing ART programs for people living with HIV. The program provided PrEP training for ART providers, ongoing technical assistance, and a provisional supply chain mechanism for PrEP medication. Primary data on PrEP initiation, PrEP refills, ART initiation, and HIV viremia at 6 months (measured at 42-270 days) were collected through data abstraction of medical records from HIV-serodifferent couples sequentially enrolling at the ART clinics. Modified Poisson regression models, controlling for time and cluster, compared viral suppression (1000 copies/ml) before and after launch of the PrEP program. This trial was registered at ClinicalTrials.gov, NCT03586128.From June 1, 2018-December 15, 2020, 1,381 HIV-serodifferent couples were enrolled across 12 ART clinics in Kampala and Wakiso, Uganda, including 730 enrolled before and 651 after the launch of PrEP delivery. During the baseline period, 99.4% of partners living with HIV initiated ART and 85.0% were virally suppressed at 6 months. Among HIV-negative partners enrolled after PrEP launched, 81.0% (527/651) initiated PrEP within 90 days of enrolling; among these 527, 11.2% sought a refill 6 months later. In our powered intent-to-treat analysis, 82.1% and 76.7% of partners living with HIV were virally suppressed, respectively, which was not a statistically significant difference (RR=0.94, 95% CI: 0.82-1.07) and was stable across sensitivity analyses.Integration of PrEP into ART clinics reached a high proportion of people in HIV-serodifferent relationships and did not improve the already high frequency of HIV viral suppression among partners living with HIV.National Institute of Mental Health (R01MH110296).

In India, many people living with HIV (PLHIV) do not successfully initiate antiretroviral therapy (ART) after diagnosis. We conducted a clinic-based qualitative study at the Y.R. Gaitonde Centre for AIDS Research in Chennai, Tamil Nadu to explore factors that influence ART non-initiation. We interviewed 22 men and 15 women; median age was 42 (IQR, 36–48) and median CD4+ was 395 (IQR, 227–601). Participants were distrustful of HIV care freely available at nearby government facilities. Faced with the perceived need to access the private sector and therefore pay for medications and transportation costs, non-initiators with high CD4+ counts often decided to postpone ART until they experienced symptoms whereas non-initiators with low CD4+ counts often started ART but defaulted quickly after experiencing financial stressors or side effects. Improving perceptions of quality of care in the public sector, encouraging safe serostatus disclosure to facilitate stronger social support, and alleviating economic hardship may be important in encouraging ART initiation in India.

PrEParing to End the HIV Epidemic A new California law will allow pharmacists to furnish a 30-to-60-day supply of preexposure prophylaxis for HIV without a prescription from a physician. Though the...

Chronic inflammation predicts complications in persons with human immunodeficiency virus infection. We compared D-dimer, soluble CD14, and interleukin 6 levels before and 12 months after antiretroviral therapy (ART) initiation, among individuals starting ART during earlier-stage (CD4 T-cell count >350/µL) or late-stage disease (CD4 T-cell count .05), owing to loss from observation and greater declines in biomarkers in late-stage initiators (P < .001). Earlier initiation of ART is associated with decreased inflammation, but levels seem to converge between earlier and later initiators surviving to 12 months.

BackgroundSouth Africa has the highest number of people living with HIV (PLWH) and one of the largest antiretroviral therapy (ART) programs globally. High rates of substance use comorbidity exist, including speculation of recreational ART use (i.e., mixing ART with other illicit drugs). Recreational ART use may affect viral load among PLWH due to ART nonadherence and/or viral resistance; however, prior quantitative research has not examined rates of recreational ART use, nor associations with HIV treatment outcomes longitudinally.MethodsData were drawn from a prospective, observational cohort study (n = 500) of ART-eligible adults recruited from two HIV voluntary counseling and testing centers in Cape Town, and Johannesburg, South Africa. Multiple logistic regression models assessed recreational ART use as a predictor of ART initiation over six months and viral load suppression over nine months, above and beyond other substance use (binge drinking and illicit drug use).ResultsApproximately 5% (n = 24) reported recreational ART use, which was less frequent in Cape Town compared to Johannesburg (AOR = 0.025; 95%CI: 0.003-0.19; p

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We conducted a novel pilot randomized controlled trial of the Treatment Ambassador Program (TAP), an 8-session, peer-based, behavioral intervention for people with HIV (PWH) in South Africa not on antiretroviral therapy (ART). PWH (43 intervention, 41 controls) completed baseline, three- and six-month assessments. TAP was highly feasible (90% completion), with peer counselors demonstrating good intervention fidelity. Post-intervention interviews showed high acceptability of TAP and counselors, who supported autonomy, assisted with clinical navigation, and provided psychosocial support. Intention-to-treat analyses indicated increased ART initiation by three months in the intervention vs. control arm (12.2% [5/41] vs. 2.3% [1/43], Fisher exact p-value = 0.105; Cohen’s h = 0.41). Among those previously on ART (off for >6 months), 33.3% initiated ART by three months in the intervention vs. 14.3% in the control arm (Cohen’s h = 0.45). Results suggest that TAP was highly acceptable and feasible among PWH not on ART.

Differentiated models of service delivery (DSD models) for HIV treatment in sub-Saharan Africa were conceived as a way to manage rapidly expanding populations of experienced patients who are clinically “stable” on antiretroviral therapy (ART). Entry requirements for most models include at least six months on treatment and a suppressed viral load. These models thus systematically exclude newly-initiated patients, who instead experience the conventional model of care, which requires frequent, multiple clinic visits that impose costs on both providers and patients. In this open letter, we argue that the conventional model of care for the first six months on ART is no longer adequate. The highest rates of treatment discontinuation are in the first six-month period after treatment initiation. Newly initiating patients are generally healthier than in the past, with higher CD4 counts, and antiretroviral medications are better tolerated, with fewer side effects and substitutions, making extra clinic visits unnecessary. Improvements in the treatment initiation process, such as same-day initiation, have not been followed by innovations in the early treatment period. Finally, the advent of COVID-19 has made it riskier to require multiple clinic visits. Research to develop differentiated models of care for the first six-month period is needed. Priorities include estimating the minimum number and type of provider interactions and ART education needed, optimizing the timing of a patient’s first viral load test, determining when lay providers can replace clinicians, ensuring that patients have sufficient but not burdensome access to support, and identifying ways to establish a habit of lifelong adherence.

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BACKGROUND: HIV-related stigma among people living with HIV (PLHIV) is associated with worse health outcomes. We used longitudinal data from a multi-site cohort in South Africa to assess changes over time in stigma after HIV diagnosis and determine whether antiretroviral therapy (ART) initiation is associated with stigma reduction. METHODS: We administered the Internalized AIDS-Related Stigma Scale (IARSS, a six-item dichotomous scale questionnaire) at baseline, three months, and six months to newly diagnosed ART-eligible participants between 2014–2015. A confirmatory factor analysis indicated that the IARSS contained a four-item internalized stigma factor (α=0.80) and a two-item disclosure concerns factor (α=0.75). We fitted multiple logistic regression models specifying internalized stigma/disclosure concerns at six months as the outcome and ART initiation as the predictor of interest. RESULTS: Of the 500 participants (187 men and 313 women) enrolled, 308 (62%) initiated ART. Internalized stigma declined among people entering care (mean score, 1.0 to 0.7, p

The UNAIDS 90-90-90 treatment targets aim to dramatically increase the number of people who initiate antiretroviral therapy (ART) by 2020. Greater understanding of barriers to ART initiation in high prevalence countries like South Africa is critical. Qualitative semi-structured interviews were conducted with 30 participants in Gugulethu Township, South Africa, including 10 healthcare providers and 20 people living with HIV (PLWH) who did not initiate ART. Interviews explored barriers to ART initiation and acceptability of theory-based intervention strategies to optimize ART initiation. An inductive content analytic approach was applied to the data. Consistent with the Theory of Triadic Influence, barriers to ART initiation were identified at the individual, social, and structural levels. Results suggested high acceptability for intervention strategies involving trained HIV-positive peers among South African PLWH and healthcare providers. Research is needed to evaluate their feasibility and efficacy in high HIV prevalence countries.

Purpose To determine the prevalence of screening, cervical dysplasia, and malignancy on the basis of histologic diagnoses from colposcopy and large loop excision of the transformation zone among women living with HIV (WLWH) who attended an urban antiretroviral treatment (ART) clinic in KwaZulu-Natal, South Africa. Materials and Methods We performed a retrospective cohort study to examine a random sample of 462 WLWH during a 5-year period from 2004 to 2009. Women on ART for < 3 months were excluded. Data were abstracted from electronic records and paper charts to assess rates of cervical abnormalities detected on Pap smears as well as time to colposcopy. Results During the study period, 432 women (93.5%) had at least one evaluable Papanicolau test. At baseline, 237 women (54.9%) had an abnormal Papanicolau test, and of these patients, 181 (76.3%) had a Papanicolau test that qualified for further colposcopic evaluation. In addition, 115 women (63.5%) received colposcopy within a median of 39 days from referral. This yielded 74 evaluable histologic samples (64.3%), of which 21.6%, 27.0%, 27.0%, and 1.4% had cervical intraepithelial neoplasia (CIN) 1, CIN2, CIN3, and invasive cervical cancer, respectively. Conclusion In a large sample of WLWH who received ART in KwaZulu-Natal, South Africa, where Papanicolau test coverage and rates of referral for colposcopy and large loop excision of the transformation zone were high, > 75% of women with evaluable histologic samples had evidence of cervical dysplasia or malignancy. These findings underscore the importance of routine cervical screening upon entry into HIV care to optimize survival.

Beyond Burnout High burnout rates among physicians are taking a high financial and human toll. Burnout can undermine a physician’s sense of purpose and altruism and lead to substance use, depression, and suicidality. Some medical organizations are starting to tackle the challenge.

OBJECTIVE: Failure to initiate antiretroviral therapy (ART) and achieve virologic suppression are significant barriers to the United Nations 90–90–90 goals. Identifying resilience resources, or modifiable strength-based factors, among people living with HIV is critical for successful HIV treatment and prevention. DESIGN: Prospective cohort study. METHODS: From July 2014 to July 2015, 500 adults presenting for voluntary counseling and HIV testing who were diagnosed with HIV and were ART-eligible in South Africa (Soweto and Gugulethu) were enrolled and surveyed. Logistic regression models assessed resilience-related predictors of ART initiation within 6 months of voluntary counseling and HIV testing for HIV, and HIV-1 plasma RNA suppression within 9 months, adjusting for sociodemographic factors. RESULTS: Within 6 months, 62% initiated ART, and within 9 months, 25% had evidence of an undetectable HIV-1 plasma RNA (

Alcohol and other drug use is prevalent among peri-urban, South African adolescents. We identified correlates of alcohol and other drug use by gender among adolescents (age = 16–18 years; N = 822) in peri-urban Johannesburg. Interviewer-administered surveys assessed sexual activity, alcohol and other drug use, and relevant psychosocial factors. In separate logistic regression models of alcohol and other drug use stratified by gender, violence exposure and sexual activity were associated with alcohol use for both males and females. For females only, depressive symptoms were associated with drug use. For males only, being older and sexually active were associated with drug use. Substance use interventions for South African adolescents should consider psychological health, sexual health, and tailoring by gender.

Introduction The success of universal antiretroviral therapy (ART) access and aspirations for an AIDS‐free generation depend on high adherence in individuals initiating ART during early‐stage HIV infection; however, adherence may be difficult in the absence of illness and associated support. Methods From March 2015 to October 2017, we prospectively observed three groups initiating ART in routine care in Uganda and South Africa: men and non‐pregnant women with early‐stage HIV infection (CD4 > 350 cells/μL), pregnant women with early‐stage HIV infection and men and non‐pregnant women with late‐stage HIV infection (CD4 0.72). In South Africa, median adherence was higher in early/non‐pregnant versus early/pregnant or late/non‐pregnant participants (76%, 37%, 52%; p

This randomized clinical trial compares the effect of immediate antiretroviral therapy (ART) vs referral to the nearest health facility on linkage to care and viral suppression among ART-native adults in rural Lesotho who home-tested positive for HIV.

Objectives To assess the relationship between CD4 count at presentation and ART uptake and assess predictors of timely treatment initiation in rural KwaZulu‐Natal, South Africa. Methods We used Kaplan‐Meier and Cox proportional hazards models to assess the association between first CD4 count and time from first CD4 to ART initiation among all adults presenting to the Hlabisa HIV Treatment and Care Programme between August 2011 and December 2012 with treatment‐eligible CD4 counts (≤ 350 cells/mm3). For a subset of healthier patients (200 < CD4 ≤ 350 cells) residing within the population surveillance of the Africa Health Research Institute, we assessed sociodemographic, economic and geographic predictors hypothesised to influence ART uptake. Results A total of 4739 patients presented for care with eligible CD4 counts. The proportion initiating ART within six months of diagnosis was 67% (95% CI 63, 71) in patients with CD4 ≤ 50, 59% (0.55, 0.63) in patients with CD4 151–200 and 48% (95% CI 44, 51) in patients with CD4 301–350. The hazard of starting ART fell by 17% (95% CI 14, 20) for every 100‐cell increase in baseline CD4 count. Among healthier patients under demographic surveillance (n = 193), observable sociodemographic, economic and geographic predictors did not add discriminatory power beyond CD4 count, age and sex to identify patients at high risk of non‐initiation. Conclusions Individuals presenting for HIV care at higher CD4 counts were less likely to initiate ART than patients presenting at low CD4 counts. Overall, ART uptake was low. Under new guidelines that establish ART eligibility regardless of CD4 count, patients with high CD4 counts may require additional interventions to encourage treatment initiation.

Background Many people living with HIV (PLWH) who are eligible for antiretroviral therapy (ART) do not initiate treatment, leading to excess morbidity, mortality, and viral transmission. As countries move to treat all PLWH at diagnosis, it is critical to understand reasons for non-initiation. Methods We conducted a systematic review of the qualitative literature on reasons for ART non-initiation in low- and middle-income countries. We screened 1376 titles, 680 abstracts, and 154 full-text reports of English-language qualitative studies published January 2000–April 2017; 20 met criteria for inclusion. Our analysis involved three steps. First, we used a “thematic synthesis” approach, identifying supply-side (facility) and demand-side (patient) factors commonly cited across different studies and organizing these factors into themes. Second, we conducted a theoretical mapping exercise, developing an explanatory model for patients’ decision-making process to start (or not to start) ART, based on inductive analysis of evidence reviewed. Third, we used this explanatory model to identify opportunities to intervene to increase ART uptake. Results Demand-side factors implicated in decisions not to start ART included feeling healthy, low social support, gender norms, HIV stigma, and difficulties translating intentions into actions. Supply-side factors included high care-seeking costs, concerns about confidentiality, low-quality health services, recommended lifestyle changes, and incomplete knowledge of treatment benefits. Developing an explanatory model, which we labeled the Transdisciplinary Model of Health Decision-Making, we posited that contextual factors determine the costs and benefits of ART; patients perceive this context (through cognitive and emotional appraisals) and form an intention whether or not to start; and these intentions may (or may not) be translated into actions. Interventions can target each of these three stages. Conclusions Reasons for not starting ART included consistent themes across studies. Future interventions could: (1) provide information on the large health and prevention benefits of ART and the low side effects of current regimens; (2) reduce stigma at the patient and community levels and increase confidentiality where stigma persists; (3) remove lifestyle requirements and support patients in integrating ART into their lives; and (4) alleviate economic burdens of ART. Interventions addressing reasons for non-initiation will be critical to the success of HIV “treat all” strategies.

President Trump’s proposal to cut the NIH budget has far-reaching implications for public and global health, research and drug development, and America’s economic growth. It also threatens young scientists who are academia and industry’s future leaders.

Cervical cancer is the second leading cause of cancer deaths among women worldwide. The objective of this study was to describe the most common oncogenic mutations in cervical cancers and to explore genomic differences between the 2 most common histologic subtypes: adenocarcinoma and squamous cell carcinoma.A high-throughput genotyping platform, termed Oncomap, was used to interrogate 80 cervical tumors for 1250 known mutations in 139 cancer genes. Samples were analyzed using a mass spectrometry-based genotyping platform and were validated using orthogonal chemistry. Epidermal growth factor receptor (EGFR) mutations were further validated by massive parallel sequencing. Human papilloma virus (HPV) genotyping also was performed.Validated mutations were detected in 48 of 80 tumors (60%) examined. The highest mutation rates were in the genes phosphatidylinositol 3-kinase, catalytic subunit α (PIK3CA) (31.3%); Kirsten rat sarcoma viral oncogene homolog (KRAS) (8.8%); and EGFR (3.8%). PIK3CA mutation rates did not differ significantly between adenocarcinomas and squamous cell carcinomas (25% vs 37.5%, respectively; P = .33). In contrast, KRAS mutations were identified only in adenocarcinomas (17.5% vs 0%; P = .01), and a novel EGFR mutation was detected only in squamous cell carcinomas (0% vs 7.5%; P = .24). There were no associations between HPV-16 or HPV-18 and somatic mutations or overall survival. In adjusted analyses, PIK3CA mutations were associated with shorter survival (67.1 months vs 90.3 months; hazard ratio, 9.1; 95% confidence interval, 2.8-29.5 months; P.001).Cervical cancers harbor high rates of potentially targetable oncogenic mutations. In addition, cervical squamous cell carcinoma and adenocarcinoma have distinct molecular profiles, suggesting that clinical outcomes may be improved with the use of more tailored treatment strategies, including PI3K and MEK inhibitors.

Leadership positions in global health are greatly skewed toward men; the imbalance is more pronounced in low- and middle-income countries (LMICs). The under-representation of women in leadership is a threat to gender equality, and also impacts the improvement of women's health outcomes globally. In this perspectives piece, we assert that the promotion and retention of women in global health leadership has a ripple effect that can achieve improvement in global health outcomes. We present pragmatic, actionable solutions to promote and retain female global health leaders in this field.Les positions de dirigeant dans la santé du monde sont largement orientées vers les hommes et ce déséquilibre est encore plus prononcé dans les pays à revenu faible et moyen. La sous-représentation des femmes en termes de dirigeant menace l'égalité des genres et a également un impact sur l'amélioration de l'état de santé des femmes dans le monde. Dans cette perspective, nous affirmons que la promotion et la rétention des femmes au sein du leadership de la santé dans le monde a un effet d'entraînement qui peut aboutir à une amélioration de l'état de santé dans le monde. Nous présentons des solutions pragmatiques et réalisables pour promouvoir et retenir des leaders féminins en matière de santé dans le monde.Los puestos directivos en materia de salud mundial se asignan de manera desproporcionada a los hombres; este desequilibrio es aun más notorio en los países de ingresos bajos y medianos. La subrepresentación de las mujeres en los cargos de responsabilidad pone en peligro la equidad entre los hombres y las mujeres y tiene además repercusiones en los resultados de salud de las mujeres en el mundo. En el presente artículo de opinión, se sostiene que promover a las mujeres a las funciones directivas relacionadas con la salud mundial y facilitar su permanencia en ellas genera una reacción en cadena que puede dar lugar a mejores resultados de salud a escala mundial. Se proponen soluciones viables y prácticas encaminadas a estimular la presencia de las mujeres en los cargos de responsabilidad en materia de salud mundial y a respaldar su permanencia en esta actividad.

This investigation explores Ebola conspiracy beliefs, a form of medical mistrust, and their potential impact on health behavior. Results of an online survey in the United States in December 2014 demonstrated that 16 percent of 202 participants held conspiracy beliefs. Participants who were less knowledgeable about Ebola, more mistrustful of medical organizations, and more xenophobic more strongly endorsed conspiracy beliefs. Participants who more strongly endorsed conspiracy beliefs reported that they would be less likely to seek care for Ebola and were less supportive of quarantining people returning from West Africa. Results suggest that medical mistrust may influence health behaviors during infectious disease outbreaks.

Background Despite recommendations that 11–12-year-olds receive the full three-shot Human papillomavirus (HPV) vaccine series, national HPV immunization coverage rates remain low. Disparities exist, with Blacks and Latinos being less likely than Whites to complete the series. We aimed to identify and compare barriers to HPV immunization perceived by healthcare providers, Black and Latino adolescents, and their caregivers to inform a clinic-based intervention to improve immunization rates. Methods We conducted semi-structured interviews between March and July 2014 with Black and Latino adolescents (n = 24), their caregivers (n = 24), and nurses (n = 18), and 2 focus groups with 18 physicians recruited from two pediatric primary care clinics. Qualitative protocol topics included: general perceptions and attitudes towards vaccines; HPV knowledge; and perceived individual and systems-level barriers affecting vaccine initiation and completion. Results Themes were identified and organized by individual and systems-level barriers to HPV immunization. Adolescents and their caregivers, particularly Blacks, expressed concerns about HPV being an untested, “newer” vaccine. All families felt they needed more information on HPV and found it difficult to return for multiple visits to complete the vaccine series. Providers focused on challenges related to administering multiple vaccines simultaneously, and perceptions of parental reluctance to discuss sexually transmitted infections. Conclusions Optimizing HPV immunization rates may benefit from a multi-pronged approach to holistically address provider, structural, and individual barriers to care. Further research should examine strategies for providing multiple modalities of support for providers, including a routinized system of vaccine promotion and delivery, and for addressing families’ concerns about vaccine safety and efficacy.

With more than half of new infections occurring among youth, HIV/AIDS remains a major contributor to morbidity and mortality in Uganda. Semi-structured interviews were performed with 48 adolescents and 15 adult key informants in a rural Ugandan community to identify influences on adolescent sexual decision-making. Inductive data analytic methods revealed five thematic influences: (1) social pressure, (2) decline of the Senga (a familial figure who traditionally taught female adolescents about how to run a household), (3) cultural barriers to condom use, (4) knowledge of HIV transmission and modes of prevention, and (5) a moral injunction against sex before marriage. Influences were classified as HIV/AIDS risk and protective factors and organized to form an explanatory framework of adolescent sexual risk-taking. Risk factors pull youth toward risky behavior, while protective factors push them away. Predominance of risk over protective influences explains persistent sexual risk-taking by Ugandan youth. HIV prevention programs designed for Ugandan adolescents should take competing factors and sociocultural and economic influences into account.

OBJECTIVE: To determine rates and predictors of treatment refusal in newly identified HIV-infected individuals in Soweto South Africa. DESIGN: It is designed as a cross-sectional study. METHODS: We analyzed data from adult clients (>18 years) presenting for voluntary counseling and testing (VCT) at the Zazi Testing Center Perinatal HIV Research Unit to determine rates of antiretroviral therapy (ART) refusal among treatment-eligible HIV-infected individuals (CD4(+) cell count < 200 cells/mul or WHO stage 4). Multiple logistic regression models were used to investigate factors associated with refusal. RESULTS: From December 2008 to December 2009 7287 adult clients were HIV tested after counseling. Two thousand five hundred and sixty-two (35%) were HIV-infected of whom 743 (29%) were eligible for immediate ART. One hundred and forty-eight (20%) refused referral to initiate ART most of whom (92%) continued to refuse after 2 months of counseling. The leading reason for ART refusal was given as feeling healthy (37%) despite clients having a median CD4(+) cell count of 110 cells/mul and triple the rate of active tuberculosis as seen in nonrefusers. In adjusted models single clients [adjusted odds ratio (AOR) 1.80 95% confidence interval (CI) 1.06-3.06] and those with active tuberculosis (AOR 3.50 95% CI 1.55-6.61) were more likely to refuse ART. CONCLUSION: Nearly one in five treatment-eligible HIV-infected individuals in Soweto refused to initiate ART after VCT putting them at higher risk for early mortality. Feeling healthy was given as the most common reason to refuse ART despite a suppressed CD4(+) count and comorbidities such as tuberculosis. These findings highlight the urgent need for research to inform interventions targeting ART refusers.

Introduction Cross‐sectional evidence suggests that internalized HIV stigma is associated with lower likelihoods of antiretroviral therapy (ART) initiation and HIV‐1 RNA suppression among people living with HIV (PLWH). This study examined these associations with longitudinal data spanning the first nine months following HIV diagnosis and explored whether avoidant coping mediates these associations. Methods Longitudinal data were collected from 398 South African PLWH recruited from testing centres in 2014 to 2015. Self‐report data, including internalized stigma and avoidant coping (denying and distracting oneself from stressors), were collected one week and three months following HIV diagnosis. ART initiation at six months and HIV‐1 RNA at nine months were extracted from the South Africa National Health Laboratory Service database. Two path analyses were estimated, one testing associations between internalized stigma, avoidant coping and ART initiation, and the other testing associations between internalized stigma, avoidant coping and HIV‐1 RNA suppression. Results Participants were 36 years old, on average, and 63% identified as female, 18% as Zulu and 65% as Xhosa. The two path models fit the data well (ART initiation outcome: X 2(7) = 8.14, p = 0.32; root mean square error of approximation (RMSEA) = 0.02; comparative fit index (CFI) = 0.92; HIV‐1 RNA suppression outcome: X 2(7) = 6.58, p = 0.47; RMSEA = 0.00; CFI = 1.00). In both models, internalized stigma one week after diagnosis was associated with avoidant coping at three months, controlling for avoidant coping at one week. In turn, avoidant coping at three months was associated with lower likelihood of ART initiation at six months in the first model and lower likelihood of HIV‐1 RNA suppression at nine months in the second model. Significant indirect effects were observed between internalized stigma with ART non‐initiation and unsuppressed HIV‐1 RNA via the mediator of avoidant coping. Conclusions Internalized stigma experienced soon after HIV diagnosis predicted lower likelihood of ART initiation and HIV‐1 RNA suppression over the first year following HIV diagnosis. Avoidant coping played a role in these associations, suggesting that PLWH who internalize stigma engage in greater avoidant coping, which in turn worsens medication‐ and health‐related outcomes. Interventions are needed to address internalized stigma and avoidant coping soon after HIV diagnosis to enhance treatment efforts during the first year after HIV diagnosis.

BACKGROUND Detectable HIV-1 RNA at delivery is the strongest predictor of mother-to-child transmission. The risk factors for detectable HIV, including type of regimen, are unknown. We evaluated factors, including highly active antiretroviral (HAART) regimen, associated with detectable HIV-1 RNA at delivery in the Women and Infants Transmission Study (WITS). METHODS Data from 630 HIV-1-infected women who enrolled from 1998 to 2005 and received HAART during pregnancy were analyzed. Multivariable analyses examined associations between regimens, demographic factors, and detectable HIV-1 RNA (>400 copies/milliliter) at delivery. RESULTS Overall, 32% of the women in the cohort had detectable HIV-1 RNA at delivery. Among the subset of 364 HAART-experienced women, a lower CD4 cell count at enrollment [adjusted odds ratio (AOR) = 1.20 per 100 cells/microL, confidence interval (CI) 1.04 to 1.37] and higher HIV-1 RNA at enrollment (AOR = 1.52 per log10 copies/milliliter, CI 1.32 to 1.75) were significantly associated with detectable HIV-1 RNA levels at delivery. For the 266 HAART-naive women, both lower CD4 cell count at enrollment (AOR = 1.24 per 100 cells/microL, CI 1.05 to 1.48) and higher HIV-1 RNA at enrollment (AOR = 1.35 per log10 copies/milliliter, CI 1.12 to 1.63) were associated with detectable HIV-1 RNA at delivery. In addition, age at delivery (AOR = 0.92 per 10 years older, CI 0.86 to 0.99) and maternal illicit drug use (AOR = 3.15, CI 1.34 to 7.41) were significantly associated with detectable HIV-1 RNA at delivery among HAART-naive women. Type of HAART regimen was not significant in either group. CONCLUSIONS Lack of viral suppression at delivery was common in the WITS cohort, but differences by antiretroviral regimen were not identified. Despite a transmission rate below 1% in the last 5 years of the WITS cohort, improved measures to maximize HIV-1 RNA suppression at term among high-risk women are warranted.

Drs. Ingrid Katz and Alexi Wright report that, in a radical departure from earlier strategies, public health officials are now arguing that circumcision of men should be a key weapon in the fight against infection with HIV in Africa. Skeptics argue that efforts to “scale-up” circumcision programs on the continent that has the fewest physicians per capita may draw funds away from other necessary public health programs.

The Global Burden of Disease study introduced mental disorders to the global health agenda more than two decades ago. Mental disorders are among the principal causes of disability burden in low-income and middle-income countries.1 Emphasising the value of treating mental disorders not only to relieve human suffering, but also to improve other health outcomes of interest (eg, HIV) or to enhance economic development has been partly effective in mobilising concern. Despite these efforts, resources to address this issue at a population level have yet to be organised on a large scale.2,3 The successful scale-up of HIV treatment through the US President's Emergency Plan for AIDS Relief (PEPFAR) has provided a prominent example of the population health possibilities that can be achieved in low-income and middle-income countries through coordinated efforts to deliver effective treatment at scale.4 Life expectancy gains for people with HIV have been great.5 The same cannot be said for people with mental disorders: even in Scandinavian countries with among the most equitably distributed health-care resources in the world, life expectancy of people with mental health problems lags by two decades.6 Unfortunately, a PEPFAR for mental disorders is nearly impossible to imagine at this time. The specialty is too fractured, political will non-existent, and stigma too great.3,7 In the meantime, the field continues to benefit from research on the development and testing of scalable, evidence-based treatments for common mental disorders that also improve other health outcomes of interest. In the setting of HIV, common mental disorders are of great public health importance: depression is highly prevalent in people with HIV,8 effective depression treatment improves HIV-related outcomes,9 and the stigma of HIV heavily compromises treatment adherence.10 In The Lancet HIV, Etheldreda Nakimuli-Mpungu and colleagues11 report the findings of a randomised trial showing that a group psychotherapy intervention improved depression symptom severity, role and social functioning, and self-esteem in people with HIV in northern Uganda. They used an active comparison group, the short-term treatment effects were large and similar to those estimated in previous studies, and the researchers handled loss to follow-up appropriately. Their study offers an excellent example of a carefully planned approach to intervention development informed by qualitative research, instrument validation, and pilot testing. The study also provides a starting point to explore several important questions. First, how can we provide scalable models of psychological treatments for common mental disorders in low-income and middle-income countries? Previous concerns have typically focused on limitations in human resources and the generalisability of treatments developed in high-income settings. However, human resource limitations can be overcome through task shifting (ie, to non-specialist health providers12) and task sharing (eg, through stepped or collaborative care13). Likewise, studies have shown that cultural adaptations of psychological treatments modify their implementation while preserving fidelity to the core content.14 The group psychotherapy intervention in the study by Nakimuli-Mpungu and colleagues11 was delivered by mental health professionals with diploma and degree-level education. We believe that research showing how to adapt the intervention for delivery at scale by trained laypeople would be of great public health significance.12 Second, how can we expand on these findings to assess its implications for other aspects of health and wellbeing? Effective depression treatment has been linked to improved HIV-related outcomes in studies done in high-income countries.9 We do not know whether a similar effect was noted in this sample,11 since these data are not reported. Future studies can extend the work of Nakimuli-Mpungu and colleagues by additionally studying HIV-related outcomes of interest, such as stigma, treatment adherence, virological suppression, and retention in care. By doing so they might help to build the evidence base for the integration of psychological interventions in the more established HIV treatment infrastructure. Lastly, Nakimuli-Mpungu and colleagues postulated that “when [group support psychotherapy] reduces depression symptoms, livelihood strategies will be enhanced thereby leading to acquisition of livelihood assets”.11 But which variable is the mediator, and which is the outcome? Could the income-generating skills taught through the intervention have improved livelihoods, thereby ameliorating depression symptom severity?15 The authors did not present data describing the extent to which the participants' income-generating activities were successful. We believe this represents an important area for future research. For people who are stigmatised and excluded, livelihood interventions can contribute powerfully to social reintegration and reversal of status loss.16 That this study raises more questions than it answers is appropriate for the somewhat nascent specialty of global mental health. More research like the study by Nakimuli-Mpungu and colleagues11 will help to spur an effective response to the nearly decade-old call for action issued in the 2007 Lancet Series on global mental health. Programmatic work to optimise scale-up of treatments for mental disorders in low-income and middle-income countries is, now more than ever, urgently needed to address one of the most neglected aspects of human health and wellbeing.

Drs. Alexi Wright and Ingrid Katz write that abortion supporters fear that Roe may soon be overturned. If that happens, states will have to choose whether to ban or protect abortion.

The FDA has been struggling for nearly two decades over the possible approval of a do-it-yourself home test for HIV. Drs. Alexi Wright and Ingrid Katz write that it finally looks possible.

Background. Both population- and individual-level benefits of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) are contingent on early diagnosis and initiation of therapy. We estimated trends in disease status at presentation to care and at ART initiation in sub-Saharan Africa. Methods. We searched PubMed for studies published January 2002–December 2013 that reported CD4 cell count at presentation or ART initiation among adults in sub-Saharan Africa. We abstracted study sample size, year(s), and mean CD4 count. A random-effects meta-regression model was used to obtain pooled estimates during each year of the observation period. Results. We identified 56 articles reporting CD4 count at presentation (N= 295455) and 71 articles reporting CD4 count at ART initiation (N = 549702). The mean estimated CD4 count in 2002 was 251 cells/µL at presentation and 152 cells/µL at ART initiation. During 2002–2013, neither CD4 count at presentation (β= 5.8 cells/year; 95% confidence interval [CI], −10.7 to 22.4 cells/year), nor CD4 count at ART initiation (β= −1.1 cells/year; 95% CI, −8.4 to 6.2 cells/year) increased significantly. Excluding studies of opportunistic infections or prevention of mother-to-child transmission did not alter our findings. Among studies conducted in South Africa (N= 14), CD4 count at presentation increased by 39.9 cells/year (95% CI, 9.2–70.2 cells/year; P=.02), but CD4 count at ART initiation did not change. Conclusions. CD4 counts at presentation to care and at ART initiation in sub-Saharan Africa have not increased over the past decade. Barriers to presentation, diagnosis, and linkage to HIV care remain major challenges that require attention to optimize population-level benefits of ART.

With the U.S. government halving the budget for the President's Emergency Plan for AIDS Relief in South Africa by 2017, the country is transitioning to full ownership of its HIV program. Will the move jeopardize the health of 1.7 million South Africans being treated for HIV?

OBJECTIVE: To evaluate the accuracy of the diagnosis of presumed ectopic pregnancy. METHODS: This was a retrospective cohort analysis at a tertiary care medical center. The patient population was composed of 1) clinically stable pregnant women with human chorionic gonadotropin (hCG) above 2000 mIU/mL and no evidence of an intrauterine pregnancy by ultrasound, or 2) women with an abnormal rise or fall of serial hCG below 2000 mIU/mL. Outcome was determined by pathologic evidence of chorionic villi in the endometrial curettings (or fallopian tube), or complete resolution of hCG. RESULTS: Overall, 38.4% (43/112) of the women were diagnosed with a miscarriage and 61.6% (69/112) were found to have an ectopic pregnancy. No significant difference was found in race, age, gravity, parity, hCG trends, or time to diagnosis between women with ectopic pregnancies and those with miscarriages. Patients were more likely to be diagnosed with an ectopic pregnancy if the initial hCG value was below the discriminatory zone (relative risk 2.44; 95% confidence interval 1.07, 5.52). Ultrasound correlated well with the final diagnosis (P = .001) but was not definitive. CONCLUSION: In an effort to save time, avoid dilation and curettage (D&C), and treat with methotrexate, the presence of an ectopic pregnancy is often presumed. The presumed diagnosis of ectopic pregnancy is inaccurate in almost 40% of cases. A D&C is necessary to differentiate an ectopic pregnancy from a miscarriage before a woman is presumptively treated with methotrexate.

Background South Africa has undergone multiple expansions in antiretroviral therapy (ART) eligibility from an initial CD4+ threshold of ≤200 cells/μl to providing ART for all people living with HIV (PLWH) as of September 2016. We evaluated the association of programmatic changes in ART eligibility with loss from care, both prior to ART initiation and within the first 16 weeks of starting treatment, during a period of programmatic expansion to ART treatment at CD4+ ≤ 350 cells/μl. Methods and findings We performed a retrospective cohort study of 4,025 treatment-eligible, non-pregnant PLWH accessing care in a community health center in Gugulethu Township affiliated with the Desmond Tutu HIV Centre in Cape Town. The median age of participants was 34 years (IQR 28–41 years), almost 62% were female, and the median CD4+ count was 173 cells/μl (IQR 92–254 cells/μl). Participants were stratified into 2 cohorts: an early cohort, enrolled into care at the health center from 1 January 2009 to 31 August 2011, when guidelines mandated that ART initiation required CD4+ ≤ 200 cells/μl, pregnancy, advanced clinical symptoms (World Health Organization [WHO] stage 4), or comorbidity (active tuberculosis); and a later cohort, enrolled into care from 1 September 2011 to 31 December 2013, when the treatment threshold had been expanded to CD4+ ≤ 350 cells/μl. Demographic and clinical factors were compared before and after the policy change using chi-squared tests to identify potentially confounding covariates, and logistic regression models were used to estimate the risk of pre-treatment (pre-ART) loss from care and early loss within the first 16 weeks on treatment, adjusting for age, baseline CD4+, and WHO stage. Compared with participants in the later cohort, participants in the earlier cohort had significantly more advanced disease: median CD4+ 146 cells/μl versus 214 cells/μl (p < 0.001), 61.1% WHO stage 3/4 disease versus 42.8% (p < 0.001), and pre-ART mortality of 34.2% versus 16.7% (p < 0.001). In total, 385 ART-eligible PLWH (9.6%) failed to initiate ART, of whom 25.7% died before ever starting treatment. Of the 3,640 people who started treatment, 58 (1.6%) died within the first 16 weeks in care, and an additional 644 (17.7%) were lost from care within 16 weeks of starting ART. PLWH who did start treatment in the later cohort were significantly more likely to discontinue care in, In a retrospective cohort study, Ingrid Katz and colleagues report on the continuity of care for people with HIV in Gugulethu Township, South Africa, Author summary Why was this study done? Global HIV treatment initiatives have focused on increasing access to antiretroviral therapy, with the goal of creating an “AIDS-free generation.” In line with guidelines put forth by the World Health Organization, the focus is on starting newly diagnosed people on immediate treatment and maintaining long-term retention in care. There is growing evidence, however, that treatment availability alone is insufficient to stop the spread of the disease. In countries where HIV is hyperendemic such as South Africa, it remains unclear if expanding treatment eligibility to all individuals living with HIV will have an impact on patients’ engagement in care and early retention on treatment. We performed this study in a large, urban community HIV treatment site in Cape Town to understand the association of South Africa’s expanding treatment program with pre-treatment loss from care and early loss from care during treatment. What did the researchers do and find? We performed a retrospective study of 2 cohorts (which included over 4,000 treatment-eligible people living with HIV in total) who entered care at a community health center in Cape Town: an early cohort, enrolled into care from January 2009 to August 2011, when guidelines mandated that ART initiation required a CD4+ cell count of ≤200 cells/μl, pregnancy, advanced clinical symptoms (World Health Organization stage 4), or comorbidity (active tuberculosis), and a later cohort, enrolled September 2011 to December 2013, when the treatment threshold had been expanded to CD4+ ≤ 350 cells/μl. We determined the risk of pre-treatment and early losses (

Media reports have described recreational use of HIV antiretroviral medication in South Africa, but little has been written about this phenomenon in the scientific literature. We present original, qualitative data from eight semi-structured interviews that characterize recreational antiretroviral use in Soweto, South Africa. Participants reported that antiretrovirals, likely efavirenz, are crushed, mixed with illicit drugs (in a mixture known as whoonga), and smoked. They described medications being stolen from patients and expressed concern that antiretroviral abuse jeopardized the safety of both patients and users. Further studies are needed to understand the prevalence, patterns, and consequences of antiretroviral abuse and diversion.

In 2003, WHO published their fi rst HIV treatment guidelines recommending initiation of antiretroviral therapy (ART) for patients with CD4 counts of 200 cells per μL or less. Because few aff ordable options existed in sub-Saharan Africa at the time, this recommendation seemed ambitious. An indication that worldwide HIV control eff orts have improved in the interim is that the question has shifted from whether anyone can start therapy in the region to whether everyone should. The current focus for WHO and treatment programme planners is whether the threshold of a CD4 count lower than 500 cells per μL should be replaced with a plan to abolish thresholds altogether. Active debate continues as to whether off ering treatment to all people living with HIV worldwide is appropriate and feasible. 1,2

Owing to escalating violence against aid workers, the Medecins sans Frontieres pulled out of Iraq and Afghanistan. In both regions, write Drs. Ingrid Katz and Alexi Wright, aid workers fear being kidnapped or murdered, but they also face the threat of being coopted by the coalition forces.

More Americans are choosing hospice for end-of-life care, but ironically, hospice patients increasingly are forced to give up effective palliative treatments along with aggressive medical intervention. Drs. Alexi Wright and Ingrid Katz discuss open-access care, which allows patients to add hospice care to their current medical treatment.

In 2005, China ratified the WHO Framework Convention on Tobacco Control. Drs. Alexi Wright and Ingrid Katz write that as international pressure to cut tobacco use mounts, the Chinese government struggles to balance advancing the country's economy with maintaining the health of its society and garnering global support. Dr. Steven Schroeder, director of the Smoking Cessation Leadership Center at the University of California, San Francisco, discusses the history of research on smoking-related illness and the state of tobacco control in the United States and the developing world.

Millions of women have already been exposed to HPV. Drs. Ingrid Katz and Alexi Wright discuss cervical-cancer screening and the worry that the HPV vaccine could have a negative effect on Pap-smear screening.

Drs. Alexi Wright and Ingrid Katz describe a small revolution in patient safety that is taking place in the basement of their hospital. Bar coding is the latest technology designed to improve patient safety at a time when hospitals are under increased scrutiny for medical errors.