In this Policy Forum, Anna Grimsrud and colleagues discuss the future of HIV testing in eastern and southern Africa, using insights gleaned from a 2021 expert consultation.

BACKGROUND: Clinical scores to determine early (6-month) antiretroviral therapy (ART) mortality risk have not been developed for sub-Saharan Africa (SSA), home to 70% of people living with HIV. In the absence of validated scores, WHO eligibility criteria (EC) for ART care intensification are CD4 < 200/μL or WHO stage III/IV. METHODS: We used Botswana XPRES trial data for adult ART enrollees to develop CD4-independent and CD4-dependent multivariable prognostic models for 6-month mortality. Scores were derived by rescaling coefficients. Scores were developed using the first 50% of XPRES ART enrollees, and their accuracy validated internally and externally using South African TB Fast Track (TBFT) trial data. Predictive accuracy was compared between scores and WHO EC. RESULTS: Among 5553 XPRES enrollees, 2838 were included in the derivation dataset; 68% were female and 83 (3%) died by 6 months. Among 1077 TBFT ART enrollees, 55% were female and 6% died by 6 months. Factors predictive of 6-month mortality in the derivation dataset at p < 0.01 and selected for the CD4-independent score included male gender (2 points), ≥ 1 WHO tuberculosis symptom (2 points), WHO stage III/IV (2 points), severe anemia (hemoglobin < 8 g/dL) (3 points), and temperature > 37.5 °C (2 points). The same variables plus CD4 < 200/μL (1 point) were included in the CD4-dependent score. Among XPRES enrollees, a CD4-independent score of ≥ 4 would provide 86% sensitivity and 66% specificity, whereas WHO EC would provide 83% sensitivity and 58% specificity. If WHO stage alone was used, sensitivity was 48% and specificity 89%. Among TBFT enrollees, the CD4-independent score of ≥ 4 would provide 95% sensitivity and 27% specificity, whereas WHO EC would provide 100% sensitivity but 0% specificity. Accuracy was similar between CD4-independent and CD4-dependent scores. Categorizing CD4-independent scores into low (< 4), moderate (4-6), and high risk (≥ 7) gave 6-month mortality of 1%, 4%, and 17% for XPRES and 1%, 5%, and 30% for TBFT enrollees. CONCLUSIONS: Sensitivity of the CD4-independent score was nearly twice that of WHO stage in predicting 6-month mortality and could be used in settings lacking CD4 testing to inform ART care intensification. The CD4-dependent score improved specificity versus WHO EC. Both scores should be considered for scale-up in SSA.

BACKGROUND: Cryptococcal meningitis is a leading cause of death amongst people living with HIV. However, routine cryptococcal antigen (CrAg) screening was not in the national guidelines in Eswatini. OBJECTIVES: A cross-sectional study was conducted between August 2014 and March 2015 to examine CrAg prevalence at Mbabane Government Hospital in Eswatini. METHODS: We collected urine and whole blood from antiretroviral-therapy-naïve patients with HIV and a cluster of differentiation 4 (CD4) counts < 200 cells/mm(3) for plasma and urine CrAg lateral flow assay (LFA) screening at the national HIV reference laboratory. Two CD4 cut-off points were used to estimate CrAg prevalence: CD4 < 100 and < 200 cells/mm(3). Sensitivity and specificity of urine CrAg LFA was compared to plasma CrAg LFA. RESULTS: Plasma CrAg prevalence was 4% (8/182, 95% confidence interval [CI]: 2-8) amongst patients with CD4 counts of < 200 cells/mm(3), and 8% (8/102, 95% CI: 3-15) amongst patients with CD4 counts of < 100 cells/mm(3). Urine CrAg LFA had a sensitivity of 100% (95% CI: 59-100) and a specificity of 80% (95% CI: 72-86) compared with plasma CrAg LFA tests for patients with CD4 < 200 cells/mm(3). Forty-three per cent of 99 patients with CD4 < 100 were at World Health Organization clinical stages I or II. CONCLUSION: The prevalence of CrAg in Eswatini was higher than the current global estimate of 6% amongst HIV-positive people with CD4 < 100 cell/mm(3), indicating the importance of initiating a national screening programme. Mechanisms for CrAg testing, training, reporting, and drug and commodity supply issues are important considerations before national implementation.

Tuberculosis (TB) is the leading cause of death among people living with human immunodeficiency virus (PLHIV), and sub-Saharan Africa has a particularly heavy burden of HIV-associated TB. Although effective TB preventive treatment (TPT) has been available for decades and shorter regimens are newly available in some settings, TPT coverage among PLHIV is suboptimal, leading to preventable illness and death. In 2018, the United Nations High-Level Meeting on Ending Tuberculosis called for ambitious new targets for TPT coverage among PLHIV and many countries in sub-Saharan Africa have redoubled their efforts to take TPT to scale. Importantly, however, this push to expand TPT among PLHIV is taking place in the context of a changing HIV treatment delivery landscape. Countries in sub-Saharan Africa are at the forefront of innovative changes in HIV program design, including a shift towards less-intensive differentiated service delivery (DSD) models for stable patients doing well on antiretroviral therapy. Understanding the opportunities and challenges that DSD presents for TB diagnosis, prevention and linkage to care among PLHIV will be critical to success.

Nathan Ford and co-authors discuss global priorities in the provision of HIV prevention and treatment services.

INTRODUCTION: The unexpected identification of a neural tube defect (NTD) safety signal with preconception dolutegravir (DTG) exposure in the Botswana Tsepamo birth outcomes study brought into sharp focus the need for reliable data on use of new antiretrovirals in pregnancy, improved pharmacovigilance systems to evaluate safety of new drugs being introduced into populations including women of reproductive potential, and balanced risk-benefit messaging when a safety signal is identified. DISCUSSION: The Tsepamo study NTD safety signal and accompanying regulatory responses led to uncertainty about the most appropriate approach to DTG use among women of reproductive potential, affecting global DTG roll-out plans, and limiting DTG use in adolescent girls and women. It also revealed a tension between a public health approach to antiretroviral treatment (ART) and individual choice, and highlighted difficulties interpreting and messaging an unexpected safety signal with uncertainty about risk. This difficulty was compounded by the lack of high-quality data on pregnancy outcomes from women receiving ART outside the Tsepamo surveillance sites and countries other than Botswana, resulting in a prolonged period of uncertainty while data on additional exposures are evaluated to refute or confirm the initial safety signal. We discuss principles for evaluating and introducing new drugs in the general population that would ensure collection of appropriate data to inform drug safety in adolescent girls and women of reproductive potential and minimize confusion about drug use in this population when a safety signal is identified. CONCLUSIONS: The response to a signal suggesting a possible safety risk for a drug used in pregnancy or among women who may become pregnant needs to be rapid and comprehensive. It requires the existence of appropriately designed surveillance systems with broad population coverage; data analyses that examine risk-benefit trade-offs in a variety of contexts; guidance to transform this risk-benefit balance into effective and agreed-upon policy; involvement of the affected community and other key stakeholders; and a communication plan for all levels of knowledge and complexity. Implementation of this proposed framework for responding to safety signals is needed to ensure that any drug used in pregnancy can be rapidly and appropriately evaluated should a serious safety alert arise.

INTRODUCTION: The World Health Organization's (WHO) recommendation of "Treat All" has accelerated the call for differentiated antiretroviral therapy (ART) delivery, a method of care that efficiently uses limited resources to increase access to HIV treatment. WHO has further recommended that stable individuals on ART receive refills every 3 to 6 months and attend clinical visits every 3 to 6 months. However, there is not yet consensus on how to ensure that the quality of services is maintained as countries strive to meet these standards. This commentary responds to this gap by defining a pragmatic approach to the monitoring and evaluation (M&E) of the scale up of differentiated ART delivery for global and national stakeholders. DISCUSSION: Programme managers need to demonstrate that the scale up of differentiated ART delivery is achieving the desired effectiveness and efficiency outcomes to justify continued support by national and global stakeholders. To achieve this goal, the two existing global WHO HIV treatment indicators of ART retention and viral suppression should be augmented with two broad aggregate measures. The addition of indicators measuring the frequency of (1) clinical and (2) refill visits by PLHIV per year will allow evaluation of the pace of scale up while monitoring its overall effect on the quality and efficiency of services. The combination of these four routinely collected aggregate indicators will also facilitate the comparison of outcomes among facilities, regions or countries implementing different models of ART delivery. Enhanced monitoring or additional assessments will be required to answer other critical questions on the process of implementation, acceptability, effectiveness and efficiency. CONCLUSIONS: These proposed outcomes are useful markers for the effectiveness and efficiency of the health system's attempts to deliver quality treatment to those who need it-and still reserve as much of the available resource pool as possible for other key elements of the HIV response.

Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count <200 cells/muL) among persons starting antiretroviral therapy (ART) is important to understand ART program outcomes, inform HIV prevention strategy, and forecast need for adjunctive therapies.*,dagger, section sign To assess trends in prevalence of advanced disease at ART initiation in 10 high-burden countries during 2004-2015, records of 694,138 ART enrollees aged ≥15 years from 797 ART facilities were analyzed. Availability of national electronic medical record systems allowed up-to-date evaluation of trends in Haiti (2004-2015), Mozambique (2004-2014), and Namibia (2004-2012), where prevalence of advanced disease at ART initiation declined from 75% to 34% (p<0.001), 73% to 37% (p<0.001), and 80% to 41% (p<0.001), respectively. Significant declines in prevalence of advanced disease during 2004-2011 were observed in Nigeria, Swaziland, Uganda, Vietnam, and Zimbabwe. The encouraging declines in prevalence of advanced disease at ART enrollment are likely due to scale-up of testing and treatment services and ART-eligibility guidelines encouraging earlier ART initiation. However, in 2015, approximately a third of new ART patients still initiated ART with advanced HIV disease. To reduce prevalence of advanced disease at ART initiation, adoption of World Health Organization (WHO)-recommended "treat-all" guidelines and strategies to facilitate earlier HIV testing and treatment are needed to reduce HIV-related mortality and HIV incidence.

The recently updated World Health Organization (WHO) consolidated guidelines on the use of antiretroviral therapy (ART) recommending to “treat all” mark a paradigm shift in the delivery of HIV treatment: from who is eligible and when to start ART, to how to provide client-centred and high-quality care to all people living with HIV (PLHIV). As part of this shift, the new guidance includes service delivery recommendations based on a “differentiated care framework” [1]. Yet, despite the increased global attention paid to differentiated care [2–4], the concept is not well defined. | There is broad agreement that a “one-size-fits-all” model of HIV services will not succeed in providing sustainable access to ART and support services for the 37 million PLHIV today. Instead, health systems will need to both accelerate ART initiation and support retention and viral suppression, which requires adapting HIV services to specific client populations and contexts [5]. Past discussions have looked at differentiated care through a health system's lens – focusing on what aspects of care are needed, how often they are needed, where care should be delivered and who will provide it [6]. An approach to HIV testing, care and treatment that distinguishes client groups according to broad definitions, however, is more likely to succeed.

Objective To determine whether reduced growth velocity (GV) in extremely low birth weight infants is preceded by elevated inflammatory cytokines. Study Design GV was determined at 36 weeks' postmenstrual age (PMA) in 768 infants 401 to 1,000 g birth weight (BW). Association between blood cytokines measured through day of life 21 and GV was explored using linear regression models that adjusted for late-onset sepsis (LOS), BW, small for gestational age (SGA), gender, race, energy intake, and center. Results Serum interleukin-6 (IL-6) was increased at days 14 and 21 in LOS infants. LOS was associated with reduced energy intake and GV for weight (weight-GV) at 36 weeks' PMA. Linear regression analysis controlling for LOS and energy intake showed significant relationships between increased IL-6 at days 14 and 21 with reduced weight-GV at 36 weeks' PMA (p < 0.0001). The relationship between day 21 IL-6 and weight-GV was not associated with LOS (p = 0.12) when controlling for BW and energy intake. Both BW (p = 0.02) and energy intake (p = 0.003) influenced the relationship between day 14 IL-6 and weight-GV. Conclusion IL-6 elevation during the first month of life is associated with lower weight-GV at 36 weeks' PMA and may have a direct effect upon energy balance and postnatal growth.

OBJECTIVE: Early initiation of antiretroviral treatment (ART) at CD4 cell count ≥500 cells per microliter reduces morbidity and mortality in HIV-infected adults. We determined the proportion of HIV-infected people with high viral load (VL) for whom transmission prevention would be an additional benefit of early treatment. DESIGN: A randomly selected subset of a nationally representative sample of HIV-infected adults in Swaziland in 2012. METHODS: Eight to 12 months after a national survey to determine adult HIV prevalence, 1067 of 5802 individuals identified as HIV-infected were asked to participate in a follow-up cross-sectional assessment. CD4 cell enumeration, VL measurements, and ART status were obtained to estimate the proportion of currently untreated adults and of the entire HIV-infected population with high VL (≥1000 copies/mL) whose treatment under a test-and-treat or VL threshold eligibility strategy would reduce HIV transmission. RESULTS: Of the 927 (87% of 1067) participants enrolled, 466 (50%) reported no ART use. Among them, 424 (91%) had VL ≥1000 copies per milliliter; of these, 148 (35%) were eligible for ART at the then existing CD4 count threshold of <350 cells per microliter; an additional 107 (25%) were eligible with expanded CD4 criterion of <500 cells per microliter; and 169 (40%) remained ART ineligible. Thus, 36% of the 466 currently untreated and 18% of the total 927 had high VL yet remained ART ineligible under a CD4 criterion of <500 cells per microliter. CONCLUSIONS: A test-and-treat or VL threshold for treatment eligibility is necessary to maximize the HIV transmission prevention benefits of ART.

To improve early enrollment in HIV care, the Swaziland Ministry of Health implemented new linkage procedures for persons HIV diagnosed during the Soka Uncobe male circumcision campaign (SOKA, 2011-2012) and the Swaziland HIV Incidence Measurement Survey (SHIMS, 2011). Abstraction of clinical records and telephone interviews of a retrospective cohort of HIV-diagnosed SOKA and SHIMS clients were conducted in 2013-2014 to evaluate compliance with new linkage procedures and enrollment in HIV care at 92 facilities throughout Swaziland. Of 1,105 clients evaluated, within 3, 12, and 24 months of diagnosis, an estimated 14.0%, 24.3%, and 37.0% enrolled in HIV care, respectively, after adjusting for lost to follow-up and non-response. Kaplan-Meier functions indicated lower enrollment probability among clients 14-24 (P = 0.0001) and 25-29 (P = 0.001) years of age compared with clients >35 years of age. At 69 facilities to which clients were referred for HIV care, compliance with new linkage procedures was low: referral forms were located for less than half (46.8%) of the clients, and few (9.6%) were recorded in the appointment register or called either before (0.3%) or after (4.9%) their appointment. Of over one thousand clients newly HIV diagnosed in Swaziland in 2011 and 2012, few received linkage services in accordance with national procedures and most had not enrolled in HIV care two years after their diagnosis. Our findings are a call to action to improve linkage services and early enrollment in HIV care in Swaziland.

BACKGROUND: In 2007, Swaziland initiated a hub-and-spoke model for decentralizing antiretroviral therapy (ART) access for HIV-infected children (<15 years old). Decentralization was facilitated through: (1) down-referral of stable children on ART from overburdened central facilities (hubs) to primary healthcare clinics (spokes), and (2) pediatric ART initiation at spokes (spoke-initiation). METHODS: We conducted a nationally representative retrospective cohort study among children starting ART during 2004-2010 to assess effect of down-referral and spoke-initiation on rates of loss to follow-up (LTFU), death, and attrition (death or LTFU). Twelve of 28 pediatric ART hubs were randomly selected using probability-proportional-to-size sampling. Seven selected facilities had initiated hub-and-spoke decentralization by study start; at these facilities, 901 of 1,893 hub-initiated and maintained (hub-maintained) children, and 495 of 1,105 down-referred or spoke-initiated children were randomly selected for record abstraction. At the five hub-only facilities, 612 of 1,987 children were randomly selected. Multivariable proportional hazards regression was used to estimate adjusted hazards ratios (AHR) for effect of down-referral (a time-varying covariate) and spoke-initiation on outcomes. RESULTS: Among 2,008 children at ART initiation, median age was 5.0 years, median CD4 percentage 12.0%, median CD4 count 358 cells/microL, and median weight-for-age z-score -1.91. Controlling for known confounders, down-referral was strongly protective against LTFU (AHR 0.40; 95% CI, 0.20-0.79) and attrition (AHR 0.46; 95% CI, 0.26-0.83) but not mortality. Compared with hub-only children or hub-maintained children, spoke-initiated children had similar outcomes. CONCLUSIONS: Decentralization of pediatric ART through down-referral and spoke-initiation within a hub-and-spoke system should be continued and might improve program outcomes.

Equitable access to antiretroviral therapy (ART) for men and women with human immunodeficiency virus (HIV) infection is a principle endorsed by most countries and funding bodies, including the U.S. President's Emergency Plan for AIDS (acquired immunodeficiency syndrome) Relief (PEPFAR) (1). To evaluate gender equity in ART access among adults (defined for this report as persons aged ≥15 years), 765,087 adult ART patient medical records from 12 countries in five geographic regions* were analyzed to estimate the ratio of women to men among new ART enrollees for each calendar year during 2002-2013. This annual ratio was compared with estimates from the Joint United Nations Programme on HIV/AIDS (UNAIDS)(dagger) of the ratio of HIV-infected adult women to men in the general population. In all 10 African countries and Haiti, the most recent estimates of the ratio of adult women to men among new ART enrollees significantly exceeded the UNAIDS estimates for the female-to-male ratio among HIV-infected adults by 23%-83%. In six African countries and Haiti, the ratio of women to men among new adult ART enrollees increased more sharply over time than the estimated UNAIDS female-to-male ratio among adults with HIV in the general population. Increased ART coverage among men is needed to decrease their morbidity and mortality and to reduce HIV incidence among their sexual partners. Reaching more men with HIV testing and linkage-to-care services and adoption of test-and-treat ART eligibility guidelines (i.e., regular testing of adults, and offering treatment to all infected persons with ART, regardless of CD4 cell test results) could reduce gender inequity in ART coverage.

BACKGROUND: Gaps in the HIV care continuum contribute to suboptimal individual health outcomes and increased risk of HIV transmission at the population level. Implementation science studies are needed to evaluate clinic-based interventions aimed at improving retention of patients across the continuum. METHODS/DESIGN: Link4Health uses an unblended cluster site-randomized design to evaluate the effectiveness of a combination intervention strategy (CIS) as compared to standard of care on linkage to and retention in care among HIV-diagnosed adults in Swaziland. The CIS intervention targets a multiplicity of structural, behavioral, and biomedical barriers through five interventions: (1) point-of-care CD4 testing at time of HIV testing, (2) accelerated antiretroviral therapy (ART) initiation for eligible patients, (3) mobile phone appointment reminders, (4) care and prevention packages, and (5) non-cash financial incentives for linkage and retention. The unit of randomization is a network of HIV clinics inclusive of a secondary facility coupled with an affiliated primary facility. Ten study units were randomized based on implementing partner, geographic location, and historic volume of HIV patients. Target enrollment was 2200 individuals, each to be followed for 12 months. Eligibility criteria includes HIV-positive test, age >18 years, willing to receive HIV care at a clinic in the study unit and consent to study procedures. Exclusion criteria included previous HIV care in the past 6 months, planning to leave the community, and current pregnancy. The primary study outcome is linkage within 1 month and retention at 12 months after testing HIV positive. Secondary outcomes include viral load suppression at 12 months, time to ART eligibility and initiation, participant acceptability, and cost-effectiveness. The trial status is that study enrollment is complete and follow-up procedures are ongoing. DISCUSSION: Link4Health evaluates a novel and pragmatic combination intervention strategy to improve linkage to and retention in care among adults with HIV in Swaziland. If the strategy is found to be effective, this study has the potential to inform HIV service delivery in resource-limited settings. TRIAL REGISTRATION: Clinicaltrials.gov NCT01904994.

This retrospective observational review documents the efforts of the Swaziland National Tuberculosis (TB) Control Programme between 2004 and 2014. The objective is to describe the disparity between actual declines in case notification and increases in estimated incidence. The review of policies and practices shows the most influential factors associated with the decrease in TB case notification to be an increase in access to antiretroviral therapy for co-infected TB patients, the general success of TB and human immunodeficiency virus service integration in the country and improvements in implementation of all components of directly observed treatment, active case finding, and rapid diagnosis using new technologies.

BACKGROUND: In 2007, Swaziland initiated a hub-and-spoke model for decentralizing antiretroviral therapy (ART) access. Decentralization was facilitated through (1) down-referral of stable ART patients from overburdened central facilities (hubs) to primary health care clinics (spokes) and (2) ART initiation at spokes (spoke initiation). METHODS: We conducted a nationally representative retrospective cohort study among adult ART enrollees during 2004-2010 to assess the effect of down-referral and spoke-initiation on rates of loss to follow-up (LTFU), death, and attrition (death or LTFU). Sixteen of 31 hubs were randomly selected using probability-proportional-to-size sampling. Seven selected facilities had initiated the hub-and-spoke model by study start. At these facilities, 1149 of 24,782 hub-initiated and maintained and 878 of 7722 down-referred or spoke-initiated patient records were randomly selected and analyzed. At the 9 hub-only facilities, 483 of 6638 records were randomly selected and analyzed. Multivariable proportional hazards regression was used to assess effect of down-referral (a time-varying covariate) and spoke-initiation on outcomes. RESULTS: At ART initiation, median age was 35, 65% were female, and median CD4 count was 147 cells per microliter. Controlling for known confounders, down-referral was strongly protective against LTFU [adjusted hazard ratio (AHR) 0.38; 95% confidence interval (CI): 0.29 to 0.50] and attrition (AHR = 0.50; 95% CI: 0.34 to 0.76) but not mortality. Compared with hub-initiated and maintained patients, spoke-initiated patients had lower LTFU (AHR 0.59; 95% CI: 0.45 to 0.77) and attrition rates (AHR 0.60; 95% CI: 0.47 to 0.77), but not mortality. CONCLUSIONS: Down-referral and spoke-initiation within a hub-and-spoke ART decentralization model were protective against LTFU and overall attrition and could facilitate future ART program expansion.

Although scale-up of antiretroviral therapy (ART) since 2005 has contributed to declines of about 30% in the global annual number of human immunodeficiency (HIV)-related deaths and declines in global HIV incidence, estimated annual HIV-related deaths among adolescents have increased by about 50% and estimated adolescent HIV incidence has been relatively stable. In 2012, an estimated 2,500 (40%) of all 6,300 daily new HIV infections occurred among persons aged 15-24 years. Difficulty enrolling adolescents and young adults in ART and high rates of loss to follow-up (LTFU) after ART initiation might be contributing to mortality and HIV incidence in this age group, but data are limited. To evaluate age-related ART retention challenges, data from retrospective cohort studies conducted in seven African countries among 16,421 patients, aged ≥15 years at enrollment, who initiated ART during 2004-2012 were analyzed. ART enrollment and outcome data were compared among three groups defined by age at enrollment: adolescents and young adults (aged 15-24 years), middle-aged adults (aged 25-49 years), and older adults (aged ≥50 years). Enrollees aged 15-24 years were predominantly female (81%-92%), commonly pregnant (3%-32% of females), unmarried (54%-73%), and, in four countries with employment data, unemployed (53%-86%). In comparison, older adults were more likely to be male (p<0.001), employed (p<0.001), and married, (p<0.05 in five countries). Compared with older adults, adolescents and young adults had higher LTFU rates in all seven countries, reaching statistical significance in three countries in crude and multivariable analyses. Evidence-based interventions to reduce LTFU for adolescent and young adult ART enrollees could help reduce mortality and HIV incidence in this age group.

Permanent ductal closure involves anatomic remodeling, in which transforming growth factor (TGF)-beta appears to play a role. Our objective was to evaluate the relationship, if any, between blood spot TGF-beta on day 3 and day 7 of life and patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. Prospective observational study involving ELBW infants (n = 968) in the National Institute of Child Health and Human Development Neonatal Research Network who had TGF-beta measured on filter paper spot blood samples using a Luminex assay. Infants with a PDA (n = 493) were significantly more immature, had lower birth weights, and had higher rates of respiratory distress syndrome than those without PDA (n = 475). TGF-beta on days 3 and 7 of life, respectively, were significantly lower among neonates with PDA (median 1,177 pg/ml [range 642-1,896]; median 1,386 pg/ml [range 868-1,913]) compared with others without PDA (median 1,334 pg/ml [range 760-2,064]; median 1,712 pg/ml [range 1,014-2,518 pg/ml]). The significant difference persisted when death or PDA was considered a composite outcome. TGF-beta levels were not significantly different among subgroups of infants with PDA who were not treated (n = 51) versus those who were treated medically (n = 283) or by surgical ligation (n = 159). TGF-beta was not a significant predictor of death or PDA (day 3 odds ratio [OR] 0.99, 95 % confidence interval [CI] 0.83-1.17; day 7 OR 0.88, 95 % CI 0.74-1.04) on adjusted analyses. Our results suggest that blood spot TGF-beta alone is unlikely to be a reliable biomarker of a clinically significant PDA or its responsiveness to treatment.

OBJECTIVE: To determine if selected pro-inflammatory and anti-inflammatory cytokines and/or mediators of inflammation reported to be related to the development of cerebral palsy (CP) predict neurodevelopmental outcome in extremely low birth weight infants. STUDY DESIGN: Infants with birth weights ≤1000 g (n = 1067) had blood samples collected at birth and on days 3 +/- 1, 7 +/- 1, 14 +/- 3, and 21 +/- 3 to examine the association between cytokines and neurodevelopmental outcomes. The analyses were focused on 5 cytokines (interleukin [IL] 1beta; IL-8; tumor necrosis factor-alpha; regulated upon activation, normal T-cell expressed, and secreted (RANTES); and IL-2) reported to be most predictive of CP in term and late preterm infants. RESULTS: IL-8 was higher on days 0-4 and subsequently in infants who developed CP compared with infants who did not develop CP in both unadjusted and adjusted analyses. Other cytokines (IL-12, IL-17, tumor necrosis factor-beta, soluble IL R alpha, macrophage inflammatory protein 1beta) were found to be altered on days 0-4 in infants who developed CP. CONCLUSIONS: CP in former preterm infants may, in part, have a late perinatal and/or early neonatal inflammatory origin.

The aim of the study was to assess the median time between HIV diagnosis and entry into primary HIV medical care in a large urban area and to assess the potential individual, diagnosing facility, and community level factors influencing entry into care. One thousand two hundred and sixty-six individuals diagnosed with HIV in Philadelphia between 1 July 2005 and 30 June 2006 were followed until entry into care through 15 June 2007. Time to entry into care was calculated as a survival time variable and was defined as the time in months between the date of HIV diagnosis and the date more than 3 weeks after diagnosis when a CD4 cell count or percentage and/or HIV viral load were obtained. The median time to entry into care for all individuals was 8 months, with a range of 1-26 months. Factors associated with delayed entry into care included age more than 40 years [hazard ratio (HR) = 0.85; 95% confidence interval (CI) = 0.75-0.97] and diagnosis as an inpatient in the hospital (HR = 0.37; 95% CI = 0.37-0.57). Factors associated with earlier entry into care included Hispanic ethnicity (HR = 1.39; 95% CI = 1.05-1.84), male sex with men as HIV transmission risk factor (HR = 1.27; 95% CI = 1.03-1.56), and residence in a census tract with a high poverty rate (HR = 1.68; 95% CI = 1.22-2.30). Individuals newly diagnosed with HIV in Philadelphia demonstrated marked delays in accessing care highlighting the tremendous need for interventions to improve overall linkage. These interventions should especially be targeted at those aged more than 40 years and those diagnosed in the hospital.