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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.

Purpose of ReviewDespite the significant progress in the HIV response, gaps remain in ensuring engagement in care to support life-long medication adherence and viral suppression. This review sought to describe the different points in the HIV care cascade where people living with HIV were not engaging and highlight promising interventions.Recent FindingsThere are opportunities to improve engagement both between testing and treatment and to support re-engagement in care for those in a treatment interruption. The gap between testing and treatment includes people who know their HIV status and people who do not know their status. People in a treatment interruption include those who interrupt immediately following initiation, early on in their treatment (first 6 months) and late (after 6 months or more on ART). For each of these groups, specific interventions are required to support improved engagement.SummaryThere are diverse needs and specific populations of people living with HIV who are not engaged in care, and differentiated service delivery interventions are required to meet their needs and expectations. For the HIV response to realise the 2030 targets, engagement will need to be supported by quality care and patient choice combined with empowered patients who are treatment literate and have been supported to improve self-management.

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.

Some people with HIV (PWH) test positive multiple times without initiating antiretroviral therapy (ART). We surveyed 496 ART-eligible PWH following routine HIV testing at three clinics in Soweto and Gugulethu, South Africa in 2014-2015. Among repeat positive testers (RPTs) in this cohort, we compared rates of treatment initiation by prior treatment eligibility and assessed psychosocial predictors of treatment initiation in logistic regression models. RPTs represented 33.8% of PWH in this cohort. Less than half of those who reported eligibility for ART on prior testing started treatment upon retesting, in contrast to two thirds of RPTs who were previously ineligible for treatment who started treatment once they learned of their eligibility. Those who reported coping through substance use were more likely to decline treatment versus those not using substances. PWH who test repeatedly represent a vulnerable population at risk for ART non-initiation who may benefit from interventions addressing individualized coping strategies.

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

From Vaccine Nationalism to Vaccine Equity To help meet the global need for Covid vaccination, the United States could create a program that integrates global health needs into ongoing funding prio...

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.

Background Human Papillomavirus (HPV) vaccination among adolescents is an important strategy to prevent cervical and other cancers in adulthood. However, uptake remains far below the Healthy People 2020 targets for the US. Given the barriers to population-level vaccination policies and challenges to incorporating additional action items during clinical visits, we sought to explore alternative delivery mechanisms, specifically delivery of the vaccine in community settings. Methods We conducted six focus groups (three with adolescents aged 11–14 who had not received the HPV vaccine and three with caregivers of adolescents meeting those criteria) from Black, Latino, and Brazilian communities in Massachusetts. We utilized a framework analysis approach that involved a multi-stage coding process employing both prefigured and emergent codes. Initial interpretations were refined through consultation with an advisory board. Results Adolescents and caregivers expressed a range of concerns about the HPV vaccine and also described interest in learning more about the vaccine, emphasizing the importance of a relationship with a trusted provider as a facilitator of vaccine acceptance. Regarding community-based delivery of the vaccine, reactions were mainly negative. However, adolescents and caregivers noted that receiving information in community settings that could seed a conversation with a trusted provider would be welcome. Interestingly, the notion of a trusted provider seemed to extend broadly to practitioners linked to the trusted main provider. Conclusions The study highlights an opportunity for increasing HPV vaccination among some racial and ethnic minority populations by leveraging trusted community organizations to provide information and seed conversations with a potentially broad group of trusted providers. A task-shifting approach, or reliance on staff with fewer formal credentials, may offer opportunities to support vaccination in resource-constrained settings.

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.

As Martin Luther King Jr said, “In the end, we will remember not the words of our enemies but the silence of our friends”

Transforming Global Health with AI Artificial intelligence could revolutionize health and health care in low- and middle-income countries by addressing the large knowledge and judgment gaps that ma...

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.

Summary Background Health care for people living with HIV has improved substantially in the past two decades. Robust estimates of how these improvements have affected prognosis and life expectancy are of utmost importance to patients, clinicians, and health-care planners. We examined changes in 3 year survival and life expectancy of patients starting combination antiretroviral therapy (ART) between 1996 and 2013. Methods We analysed data from 18 European and North American HIV-1 cohorts. Patients (aged ≥16 years) were eligible for this analysis if they had started ART with three or more drugs between 1996 and 2010 and had at least 3 years of potential follow-up. We estimated adjusted (for age, sex, AIDS, risk group, CD4 cell count, and HIV-1 RNA at start of ART) all-cause and cause-specific mortality hazard ratios (HRs) for the first year after ART initiation and the second and third years after ART initiation in four calendar periods (1996–99, 2000–03 [comparator], 2004–07, 2008–10). We estimated life expectancy by calendar period of initiation of ART. Findings 88 504 patients were included in our analyses, of whom 2106 died during the first year of ART and 2302 died during the second or third year of ART. Patients starting ART in 2008–10 had lower all-cause mortality in the first year after ART initiation than did patients starting ART in 2000–03 (adjusted HR 0·71, 95% CI 0·61–0·83). All-cause mortality in the second and third years after initiation of ART was also lower in patients who started ART in 2008–10 than in those who started in 2000–03 (0·57, 0·49–0·67); this decrease was not fully explained by viral load and CD4 cell count at 1 year. Rates of non-AIDS deaths were lower in patients who started ART in 2008–10 (vs 2000–03) in the first year (0·48, 0·34–0·67) and second and third years (0·29, 0·21–0·40) after initiation of ART. Between 1996 and 2010, life expectancy in 20-year-old patients starting ART increased by about 9 years in women and 10 years in men. Interpretation Even in the late ART era, survival during the first 3 years of ART continues to improve, which probably reflects transition to less toxic antiretroviral drugs, improved adherence, prophylactic measures, and management of comorbidity. Prognostic models and life expectancy estimates should be updated to account for these improvements. Funding UK Medical Research Council, UK Department for International Development, EU EDCTP2 programme.

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.

BACKGROUND: The World Health Organization recommends initiating antiretroviral therapy (ART) regardless of CD4 count. We assessed the effect of ART eligibility on treatment uptake and simulated the impact of WHO's recommendations in South Africa. METHODS: We conducted an empirical analysis of cohort data using a regression discontinuity design, and then used this model for policy simulation. We enrolled all patients (n = 19,279) diagnosed with HIV between August 2011 and December 2013 in the Hlabisa HIV Treatment and Care Programme in rural South Africa. Patients were ART-eligible with CD4

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.

Context South Africa has the most HIV infections of any country in the world, yet little is known about the adolescent continuum of care from HIV diagnosis through viral suppression. Objective To determine the adolescent HIV continuum of care in South Africa. Data sources We searched PubMed, Google Scholar and online conference proceedings from International AIDS Society (IAS), International AIDS Conference (AIDS) and Conference on Retrovirology and Opportunistic Infections (CROI) from 1 January 2005 to 31 July 2015. Data extraction We selected published literature containing South African cohorts and epidemiological data reporting primary data for youth (15–24 years of age) at any stage of the HIV continuum of care (ie, diagnosis, treatment, retention, viral suppression). For the meta-analysis we used six sources for retention in care and nine for viral suppression. Results Among the estimated 867 283 HIV-infected youth from 15 to 24 years old in South Africa in 2013, 14% accessed antiretroviral therapy (ART). Of those on therapy, ∼83% were retained in care and 81% were virally suppressed. Overall, we estimate that 10% of HIV-infected youth in South Africa in 2013 were virally suppressed. Limitations This analysis relies on published data from large mostly urban South Africa cohorts limiting the generalisability to all adolescents. Conclusions Despite a large increase in ART programmes in South Africa that have relatively high retention rates and viral suppression rates among HIV-infected youth, only a small percentage are virally suppressed, largely due to low numbers of adolescents and young adults accessing ART.

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.

Recent recommendations by the World Health Organization support treatment for all people living with HIV (PLWH) globally to be initiated at the point of testing. While there has been marked success in efforts to identify and expand treatment for PLWH throughout sub-Saharan Africa, the goal of universal treatment may prove challenging to achieve. The pre-ART phase of the care cascade from HIV testing to HIV treatment initiation includes several social and structural barriers. One such barrier is antiretroviral therapy (ART) treatment refusal, a phenomenon in which HIV-infected individuals choose not to start treatment upon learning their ART eligibility. Our goal is to provide further understanding of why treatment-eligible adults may choose to present for HIV testing but not initiate ART when indicated. In this article, we will discuss factors driving pre-ART loss and present a framework for understanding the impact of decision-making on early losses in the care cascade, with a focus on ART refusal.

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.