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7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK, Introduction Current UK guidelines recommend initiation of HAART in all patients with a CD4 count of According to the European consensus, late presentation for care refers to persons presenting with [...]

Background: Extreme weather events pose a risk to health and disproportionately affect vulnerable groups, such as people living with HIV. We aimed to investigate the effects of extreme weather events on HIV testing uptake, HIV treatment and care, and HIV transmission., Methods: For this systematic review, we searched PubMed, Web of Science, and PsycINFO for peer-reviewed studies published between database inception and Aug 31, 2023. Eligible studies were English-language qualitative, quantitative observational (retrospective, prospective, cross-sectional, longitudinal, case-control, and cohort), and mixed-method studies, and randomised controlled trials related to HIV and extreme weather events. We excluded reviews, mathematical models, and case reports. After exporting the search results, two authors independently screened the titles and abstracts of identified articles, reviewing the full text of those that met the inclusion criteria. We used systems thinking to develop a framework linking extreme weather events and HIV and summarised the results using thematic narrative synthesis., Findings: Of the 6126 studies identified by the search, 27 met the inclusion criteria and were eligible for analysis, of which 19 were quantitative, six were qualitative, and two were mixed-method studies. We identified five main themes linking extreme weather events to HIV: economic and livelihood conditions (12 studies), psychosocial factors (19 studies), infrastructure damage and operational challenges (17 studies), migration and displacement (ten studies), and associated medical conditions and health-care needs (12 studies). We showed how these themes interact in complex ways, resulting in a reduction in uptake of HIV testing, interruption of HIV care and subsequent disease progression, altered risk behaviours, and an increased prevalence of HIV., Interpretation: Extreme weather events are associated with disruptions to HIV services. Owing to the design of the included studies, we could not establish a causal relationship between extreme weather events and HIV incidence, highlighting a research gap. Appropriate adaptations and mitigation policies that protect the health and wellbeing of people living with HIV during and after extreme weather events are warranted. Such actions will be crucial to achieving the UNAIDS goal of ending HIV as a public health threat by 2030., Funding: None., Competing Interests: Declaration of interests CCI received grant funding (paid to his institution) for investigator-sponsored research from Gilead Sciences and support from the International Vaccine Institute to attend the Indo-Pacific Climate Resilience Forum. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose of Review: Extreme weather events (EWEs) pose a challenge to achieving UNAIDS goal of eliminating HIV as a public health threat by 2030. This review summarizes recent findings describing the disruption of HIV services by EWEs and discusses strategies for a resilient HIV care programme in resource-limited settings., Recent Findings: EWEs impact each component of the continuum of care - HIV testing, linkage to treatment, viral suppression and other HIV prevention services. EWEs disrupt healthcare provision either through impacting the ability of the healthcare system to deliver care because of infrastructure damage and increased workload or by limiting people's ability to seek healthcare because of access challenges and forced displacements. This culminates in disengagement from care, poor treatment adherence and increase in HIV disease progression with more vulnerable groups such as women and young people being more adversely impacted., Summary: Most people affected by or at risk of HIV reside in resource-poor settings which are the region with the least capacity to adapt to climate change. Few recent studies with very limited geographical coverage show that EWEs affect the delivery of HIV care in this setting. Climate adaptation and mitigation policies are required to protect health in resource-limited settings., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This analysis investigates the relationship between drought and antiretroviral treatment (ART) adherence and retention in HIV care in the Hlabisa sub-district, KwaZulu-Natal, South Africa. Data on drought and ART adherence and retention were collated for the study period 2010-2019. Drought was quantified using the 3-month Standard Precipitation Evapotranspiration Index (SPEI) and Standard Precipitation Index (SPI) from station data. Adherence, proxied by the Medication Possession Ratio (MPR), and retention data were obtained from the public ART programme database. MPR and retention were calculated from individuals aged 15-59 years who initiated ART between January 2010 and December 2018 and visited clinic through February 2019. Between 01 January 2010 and 31 December 2018, 40,714 individuals started ART in the sub-district and made 1,022,760 ART visits. The SPI showed that 2014-2016 were dry years, with partial recovery after 2016 in the wet years. In the period from 2010 to 2012, mean 6-month MPR increased from 0.85 in July 2010 to a high of 0.92 in December 2012. MPR then decreased steadily through 2013 and 2014 to 0.78 by December 2014. The mean proportion retained in care 6 months after starting ART showed similar trends to MPR, increasing from 86.9% in July 2010 to 91.4% in December 2012. Retention then decreased through 2013, with evidence of a pronounced drop in January 2014 when the odds of retention decreased by 30% (OR = 0.70, CI = 0.53-0.92, P = 0.01) relative to the end of 2013. Adherence and retention in care decreased during the drought years., (© 2023. The Author(s).)

Climate change is directly and indirectly linked to human health, including through access to treatment and care. Our systematic review presents a systems understanding of the nexus between drought and antiretroviral therapy (ART) adherence in HIV-positive individuals in the African setting. Narrative synthesis of 111 studies retrieved from Web of Science, PubMed/MEDLINE, and PsycINFO suggests that livelihoods and economic conditions, comorbidities and ART regimens, human mobility, and psychobehavioural dispositions and support systems interact in complex ways in the drought-ART adherence nexus in Africa. Economic and livelihood-related challenges appear to impose the strongest impact on human interactions, actions, and systems that culminate in non-adherence. Indeed, the complex pathways identified by our systems approach emphasise the need for more integrated research approaches to understanding this phenomenon and developing interventions., Competing Interests: Declaration of interests CCI and DK received grant funding paid to their institution for this work from the Sussex Sustainability Research Programme (SSRP), University of Sussex. The SSRP grant provided salary support for KSO and SN and travel support for SA-K to visit the project sites. CCI received conference attendance support from Gilead Sciences unrelated to the submitted work. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

In 2015, South Africa experienced one of the worst (El Niño-induced) droughts in 35 years. This affected economic activities, individual and community livelihoods and wellbeing especially in rural communities in northern KwaZulu-Natal. Drought's direct and indirect impacts on public health require urgent institutional responses, especially in South Africa's stride to eliminate HIV as a public health threat by 2030 in line with the UNAIDS goals. This paper draws on qualitative data from interviews and policy documents to discuss how the devastating effect of the 2015 drought experience in the rural Hlabisa sub-district of uMkhanyakude, a high HIV prevalence area, imposes an imperative for more proactive institutional responses to drought and other climate-related events capable of derailing progress made in South Africa's HIV/AIDS response. We found that drought had a negative impact on individual and community livelihoods and made it more difficult for people living with HIV to consistently engage with care due to economic losses from deaths of livestock, crop failure, food insecurity, time spent in search of appropriate water sources and forced relocations. It also affected government institutions and their interventions. Interviewed participants' reflections on drought-related challenges, especially those related to institutional and coordination challenges, showed that although current policy frameworks are robust, their implementation has been stalled due to complex reporting systems, and inadequate interdepartmental collaboration and information sharing. We thus argue that to address the gaps in the institutional responses, there is a need for more inclusive systems of drought-relief implementation, in which government departments, especially at the provincial and district levels, work with national institutions to better share data/information about drought-risks in order to improve preparedness and implementation of effective mitigation measures.

Background: Currently recommended boosted protease-inhibitor (bPI) regimens may be associated with increased risk of cardiovascular or chronic kidney diseases; in addition, boosted regimens are particularly associated with drug-drug interactions. Since both cardiovascular and renal disease, and polypharmacy, are common in ageing people with HIV, there is a need for alternative efficacious regimens. bPI-based regimens are often the treatment of choice for individuals with pre-treatment or treatment-acquired resistance but it is plausible that carefully selected HIV-positive individuals with drug resistance, who are virologically suppressed on their current bPI regimen, could maintain virological efficacy when switched to bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) fixed dose combination (FDC)., Methods/design: A phase IV, investigator-initiated, multicentre, open label pilot, randomised two-arm study to assess the safety and efficacy of switching from bPI regimen to B/F/TAF single tablet regimen in integrase inhibitor-naïve, virologically suppressed adults with HIV-1 infection harbouring drug resistance mutations. Eligible individuals will either continue on their bPI regimen or switch to B/F/TAF FDC. After 24 weeks, all participants in the bPI arm will be switched to B/F/TAF and followed for a further 24 weeks and all participants will be followed for 48 weeks. The primary efficacy endpoint is the proportion of participants with HIV-1 RNA < 50 copies/mL at week 24 using pure virologic response whilst the secondary efficacy endpoint is the proportion of participants with HIV-1 RNA < 50 copies/mL at Week 48. Other secondary outcome measures include between arm comparisons of drug resistance at virological failure, safety and tolerability and patient-reported outcome measures., Discussion: We aim to provide preliminary evidence of the efficacy of switching to B/F/TAF in patients with virological suppression on a bPI-based regimen who harbour select drug resistance mutations., Trial Registration: ISRCTN 44453201 , registered 19 June 2019 and EudraCT 2018-004732-30.

Background: Previous studies in human immunodeficiency virus (HIV)-positive individuals on thymidine analogue backbone antiretroviral therapy (ART) with either nevirapine or efavirenz have suggested poorer virological outcomes in the presence of pretreatment drug resistance (PDR). We assessed the impact of PDR on virological suppression (VS; <50 copies/mL) in individuals prescribed primarily tenofovir/emtricitabine/efavirenz in rural KwaZulu-Natal within a treatment-as-prevention trial., Methods: Among 1557 HIV-positive individuals who reported no prior ART at study entry and provided plasma samples, 1328 individuals with entry viral load (VL) >1000 copies/mL had next-generation sequencing (NGS) of the HIV pol gene with MiSeq technology. Results were obtained for 1148 individuals, and the presence of PDR was assessed at 5% and 20% detection thresholds. Virological outcome was assessed using Cox regression in 837 of 920 ART initiators with at least 1 follow-up VL after ART initiation., Results: PDR prevalence was 9.5% (109/1148) and 12.8% (147/1148) at 20% and 5% thresholds, respectively. After a median of 1.36 years (interquartile range, 0.91-2.13), mostly on fixed-dose combination tenofovir/emtricitabine/efavirenz, presence of both nonnucleoside reverse transcriptase inhibitor (NNRTI)/nucleoside reverse transcriptase inhibitor PDR vs no PDR was associated with longer time to VS (adjusted hazard ratio [aHR], 0.32; 95% confidence interval [CI], 0.12-0.86), while there was no difference between those with only NNRTI PDR vs no PDR (aHR, 1.05; 95% CI, 0.82-1.34) at the 5% threshold. Similar differences were observed for mutations detected at the 20% threshold, although without statistical significance., Conclusions: NGS uncovered a high prevalence of PDR among participants enrolled in trial clinics in rural KwaZulu-Natal. Dual-class PDR to a mainly tenofovir/emtricitabine/efavirenz regimen was associated with poorer VS. However, there was no impact of NNRTI PDR alone., Clinical Trials Tegistration: NCT01509508; South African National Clinical Trials Register: DOH-27-0512-3974., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objectives: The WHO recently recommended the use of a new first-line ART containing dolutegravir. We investigated the efficacy of NRTI backbones (tenofovir or abacavir with a cytosine analogue) in low- and middle-income countries where there is significant prior exposure to antiretrovirals and drug resistance to NRTIs., Methods: Within the treatment-as-prevention study in South Africa, we selected participants with available next-generation sequencing (NGS) data for the HIV-1 pol gene at trial entry; they were either ART initiators (n = 1193) or already established on ART (n = 94). NGS of the HIV-1 pol gene was carried out using MiSeq technology; reverse transcriptase drug resistance mutations (DRMs) were detected at 5% (DRM5%) and 20% (DRM20%) for all 1287 participants. Genotypic susceptibility was assessed using the Stanford HIVDB resistance interpretation algorithm., Results: NRTI DRM20% and DRM5% were detected among 5/1193 (0.4%) and 9/1193 (0.8%) of ART initiators, respectively. There was tenofovir exposure in 73/94 (77.7%) of those established on ART, with full susceptibility to abacavir in 57/94 (60.6%) and 56/94 (59.6%) for DRM20% and DRM5%, respectively, while 67/94 (71.3%) and 64/94 (68.1%) were fully susceptible to tenofovir, respectively. The differences between tenofovir and abacavir were not statistically significant at the 20% or 5% variant level (P = 0.16 and 0.29, respectively). NGS detection of variants at the 5% level increased detection of K65R in both naive and treated groups. One of 607 integrase sequences carried a DRM20% (Q148R)., Conclusions: Dolutegravir with a cytosine analogue plus tenofovir or abacavir appears to have similar efficacy in South Africans naive to ART. NGS should be considered in HIV drug resistance surveillance.

Background: Universal antiretroviral therapy (ART), as per the 2015 WHO recommendations, might reduce population HIV incidence. We investigated the effect of universal test and treat on HIV acquisition at population level in a high prevalence rural region of South Africa., Methods: We did a phase 4, open-label, cluster randomised trial of 22 communities in rural KwaZulu-Natal, South Africa. We included individuals residing in the communities who were aged 16 years or older. The clusters were composed of aggregated local areas (neighbourhoods) that had been identified in a previous study in the Hlabisa subdistrict. The study statisticians randomly assigned clusters (1:1) with MapInfo Pro (version 11.0) to either the control or intervention communities, stratified on the basis of antenatal HIV prevalence. We offered residents repeated rapid HIV testing during home-based visits every 6 months for about 4 years in four clusters, 3 years in six clusters, and 2 years in 12 clusters (58 cluster-years) and referred HIV-positive participants to trial clinics for ART (fixed-dose combination of tenofovir, emtricitabine, and efavirenz) regardless of CD4 cell count (intervention) or according to national guidelines (initially ≤350 cells per μL and <500 cells per μL from January, 2015; control). Participants and investigators were not masked to treatment allocation. We used dried blood spots once every 6 months provided by participants who were HIV negative at baseline to estimate the primary outcome of HIV incidence with cluster-adjusted Poisson generalised estimated equations in the intention-to-treat population after 58 cluster-years of follow-up. This study is registered with ClinicalTrials.gov, number NCT01509508, and the South African National Clinical Trials Register, number DOH-27-0512-3974., Findings: Between March 9, 2012, and June 30, 2016, we contacted 26 518 (93%) of 28 419 eligible individuals. Of 17 808 (67%) individuals with a first negative dried blood spot test, 14 223 (80%) had subsequent dried blood spot tests, of whom 503 seroconverted after follow-up of 22 891 person-years. Estimated HIV incidence was 2·11 per 100 person-years (95% CI 1·84-2·39) in the intervention group and 2·27 per 100 person-years (2·00-2·54) in the control group (adjusted hazard ratio 1·01, 95% CI 0·87-1·17; p=0·89). We documented one case of suicidal attempt in a woman following HIV seroconversion. 128 patients on ART had 189 life-threatening or grade 4 clinical events: 69 (4%) of 1652 in the control group and 59 (4%) of 1367 in the intervention group (p=0·83)., Interpretation: The absence of a lowering of HIV incidence in universal test and treat clusters most likely resulted from poor linkage to care. Policy change to HIV universal test and treat without innovation to improve health access is unlikely to reduce HIV incidence., Funding: ANRS, GiZ, and 3ie., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Antiretroviral therapy (ART) was highly efficacious in preventing human immunodeficiency virus (HIV) transmission in stable serodiscordant couples in the HPTN-052 study, a resource-intensive randomized controlled trial with near-perfect ART adherence and mutual HIV status disclosure among all participating couples. However, minimal evidence exists of the effectiveness of ART in preventing HIV acquisition in stable serodiscordant couples in "real-life" population-based settings in hyperendemic communities of sub-Saharan Africa, where health systems are typically resource-poor and overburdened, adherence to ART is often low, and partners commonly do not disclose their HIV status to each other., Methods: Data arose from a population-based open cohort in KwaZulu-Natal, South Africa. A total of 17 016 HIV-uninfected individuals present between January 2005 and December 2013 were included. Interval-censored time-updated proportional hazards regression was used to assess how the ART status affected HIV transmission risk in stable serodiscordant relationships., Results: We observed 1619 HIV seroconversions in 17 016 individuals, over 60 349 person-years follow-up time. During the follow-up period, 1846 individuals had an HIV-uninfected and 196 had an HIV-infected stable partner HIV incidence was 3.8/100 person-years (PY) among individuals with an HIV-infected partner (95% confidence interval [CI], 2.3-5.6), 1.4/100 PY (.4-3.5) among those with HIV-infected partners receiving ART, and 5.6/100 PY (3.5-8.4) among those with HIV-infected partners not receiving ART. Use of ART was associated with a 77% decrease in HIV acquisition risk among serodiscordant couples (adjusted hazard ratio, 0.23; 95% CI, .07-.80)., Conclusions: ART initiation was associated with a very large reduction in HIV acquisition in serodiscordant couples in rural KwaZulu-Natal. However, this "real-life" effect was substantially lower than the effect observed in the HPTN-052 trial. To eliminate HIV transmission in serodiscordant couples, additional prevention interventions are probably needed., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: The 2015 WHO recommendation of antiretroviral therapy (ART) for all immediately following HIV diagnosis is partially based on the anticipated impact on HIV incidence in the surrounding population. We investigated this approach in a cluster-randomised trial in a high HIV prevalence setting in rural KwaZulu-Natal. We present findings from the first phase of the trial and report on uptake of home-based HIV testing, linkage to care, uptake of ART, and community attitudes about ART., Methods and Findings: Between 9 March 2012 and 22 May 2014, five clusters in the intervention arm (immediate ART offered to all HIV-positive adults) and five clusters in the control arm (ART offered according to national guidelines, i.e., CD4 count ≤ 350 cells/μl) contributed to the first phase of the trial. Households were visited every 6 mo. Following informed consent and administration of a study questionnaire, each resident adult (≥16 y) was asked for a finger-prick blood sample, which was used to estimate HIV prevalence, and offered a rapid HIV test using a serial HIV testing algorithm. All HIV-positive adults were referred to the trial clinic in their cluster. Those not linked to care 3 mo after identification were contacted by a linkage-to-care team. Study procedures were not blinded. In all, 12,894 adults were registered as eligible for participation (5,790 in intervention arm; 7,104 in control arm), of whom 9,927 (77.0%) were contacted at least once during household visits. HIV status was ever ascertained for a total of 8,233/9,927 (82.9%), including 2,569 ascertained as HIV-positive (942 tested HIV-positive and 1,627 reported a known HIV-positive status). Of the 1,177 HIV-positive individuals not previously in care and followed for at least 6 mo in the trial, 559 (47.5%) visited their cluster trial clinic within 6 mo. In the intervention arm, 89% (194/218) initiated ART within 3 mo of their first clinic visit. In the control arm, 42.3% (83/196) had a CD4 count ≤ 350 cells/μl at first visit, of whom 92.8% initiated ART within 3 mo. Regarding attitudes about ART, 93% (8,802/9,460) of participants agreed with the statement that they would want to start ART as soon as possible if HIV-positive. Estimated baseline HIV prevalence was 30.5% (2,028/6,656) (95% CI 25.0%, 37.0%). HIV prevalence, uptake of home-based HIV testing, linkage to care within 6 mo, and initiation of ART within 3 mo in those with CD4 count ≤ 350 cells/μl did not differ significantly between the intervention and control clusters. Selection bias related to noncontact could not be entirely excluded., Conclusions: Home-based HIV testing was well received in this rural population, although men were less easily contactable at home; immediate ART was acceptable, with good viral suppression and retention. However, only about half of HIV-positive people accessed care within 6 mo of being identified, with nearly two-thirds accessing care by 12 mo. The observed delay in linkage to care would limit the individual and public health ART benefits of universal testing and treatment in this population., Trial Registration: ClinicalTrials.gov NCT01509508.

Introduction: Remarkable strides have been made in controlling the HIV epidemic, although not enough to achieve epidemic control. More recently, interest in biomedical HIV control approaches has increased, but substantial challenges with the HIV cascade of care hinder successful implementation. We summarise all available HIV prevention methods and make recommendations on how to address current challenges., Discussion: In the early days of the epidemic, behavioural approaches to control the HIV dominated, and the few available evidence-based interventions demonstrated to reduce HIV transmission were applied independently from one another. More recently, it has become clear that combination prevention strategies targeted to high transmission geographies and people at most risk of infections are required to achieve epidemic control. Biomedical strategies such as male medical circumcision and antiretroviral therapy for treatment in HIV-positive individuals and as pre-exposure prophylaxis in HIV-negative individuals provide immense promise for the future of HIV control. In resource-rich settings, the threat of HIV treatment optimism resulting in increased sexual risk taking has been observed and there are concerns that as ART roll-out matures in resource-poor settings and the benefits of ART become clearly visible, behavioural disinhibition may also become a challenge in those settings. Unfortunately, an efficacious vaccine, a strategy which could potentially halt the HIV epidemic, remains elusive., Conclusion: Combination HIV prevention offers a logical approach to HIV control, although what and how the available options should be combined is contextual. Therefore, knowledge of the local or national drivers of HIV infection is paramount. Problems with the HIV care continuum remain of concern, hindering progress towards the UNAIDS target of 90-90-90 by 2020. Research is needed on combination interventions that address all the steps of the cascade as the steps are not independent of each other. Until these issues are addressed, HIV elimination may remain an unattainable goal., Competing Interests: CI has received honoraria for services rendered to Gilead Sciences. All other authors declare no competing interest.

Background: Although some prior studies have provided evidence to question the historical belief that pulmonary vascular resistance index ⩾6 Wood Units×m2 should be a contraindication to heart transplantation in children, no national analyses specific to the modern area have addressed this question., Methods: Data were analysed for paediatric heart transplant recipients from 1 January, 2002 to 1 September, 2012 (n=699). The relationship between pulmonary vascular resistance and all-cause 30-day mortality was evaluated using univariate and multivariate analyses., Results: The 30-day mortality included 10 patients (1.43%), which is lower than in the previous analyses. Receiver operating curve analysis of pulmonary vascular resistance index as a predictor of mortality yielded a cut-off value of 3.37 Wood Units×m2, but the area under the curve and specificity of this threshold was weaker than in previous analyses. Whereas pulmonary vascular resistance index treated as a dichotomised variable was a significant predictor of mortality in univariate (odds ratio 4.92, 95% confidence interval 1.04-23.33, p=0.045) and multivariate (odds ratio 5.26, 95% confidence interval 1.07-25.80, p=0.041) analyses, pulmonary vascular resistance index treated as a continuous variable was not a significant predictor of mortality in univariate (p=0.12) or multivariate (p=0.11) analyses., Conclusions: The relationship between pulmonary vascular resistance and post-heart transplant mortality in children is less convincing in this analysis of a comprehensive, contemporary database than in previous series. This suggests the possibility that modern improvements in the management of post-transplant right ventricular dysfunction have mitigated the contribution of pulmonary hypertension to early mortality.

Background and Objectives: Pulmonary hypertension (PH) has been associated with substantial morbidity and mortality in children, but existing analyses of inpatient care are limited to small single-institution series or focused registries representative of selected patient subgroups. We examined US national data on pediatric PH hospitalizations to determine trends in volume, demographics, procedures performed during admission, and resource utilization., Methods: Retrospective cohort study using a national administrative database of pediatric hospital discharges: the Kids' Inpatient Database., Results: Children with PH accounted for 0.13% of the 43 million pediatric hospitalizations in the United States between 1997 and 2012, and discharges demonstrated an increasing trend over the study period (P < .0001). Cumulative, inflation-adjusted national hospital charges for PH hospitalizations rose (P = .0003) from $926 million in 1997 to $3.12 billion in 2012. Patients with PH without associated congenital heart disease (CHD) comprised an increasing and majority (56.4%) proportion over the study period (P < .0001), children without associated CHD admitted at urban teaching hospitals comprised the fastest-growing subgroup. In-hospital, all-cause mortality was high (5.9%) in children with PH, but demonstrated a decreasing trend (P < .0001)., Conclusions: Morbidity and mortality of pediatric PH continue to represent substantial and growing health care burdens. Shifts in case mix toward PH not associated with CHD, toward noncardiac procedures, and toward care in urban teaching hospitals will increase pressure to manage resource utilization in this small but growing patient group and to improve expertise and define excellence in PH care across a wide range of clinical settings., (Copyright © 2015 by the American Academy of Pediatrics.)

Background: Some have suggested that children undergoing cardiac surgery who receive angiotensin-converting enzyme (ACE) inhibitors experience a greater degree of hypotension after anesthesia induction and in the immediate postcardiopulmonary bypass period than children who did not receive these drugs. Therefore, we examined the effect of ACE inhibitor/angiotensin II receptor blocker (ARB) therapy on intraoperative hemodynamics and vasopressor use in pediatric patients undergoing cardiac surgery., Methods: In a retrospective cohort study of patients younger than 18 years who underwent cardiopulmonary bypass between March 1, 2010, and April 1, 2011, we compared intraoperative hemodynamics and vasopressor use between patients who received preoperative ACE inhibitor/ARB therapy and those who did not. The primary outcome was vasoactive infusion score after cardiopulmonary bypass., Results: The occurrence of hypotension did not differ significantly between the ACE inhibitor/ARB group and the control group during induction of anesthesia or at any time point after cardiopulmonary bypass. At 0, 30, 60, and 90 minutes after cessation of cardiopulmonary bypass, patients on ACE inhibitor/ARB therapy tended to have a higher vasoactive infusion score (7.1, 7.6, 9.4, and 11.3) than patients in the control group (6.3, 6.1, 6.0, and 6.7). Although this difference became more pronounced over time, it did not reach statistical significance., Conclusion: The use of preoperative ACE inhibitors and ARBs in pediatric patients undergoing cardiac surgery did not significantly increase the incidence of hypotension after induction of anesthesia and did not increase significantly the vasoconstrictor requirements upon weaning from cardiopulmonary bypass; however, additional prospective studies are needed., (© The Author(s) 2014.)

Objective: To explore the impact of expanded eligibility criteria for antiretroviral therapy (ART) on median CD4⁺ cell count at ART initiation and early mortality on ART., Methods: Analyses included all adults (≥16 years) initiated on first-line ART between August 2004 and July 2012. CD4⁺ cell count threshold 350 cells per microliter for all adults was implemented in August 2011. Early mortality was defined as any death within 91 days of ART initiation. Trends in baseline CD4⁺ cell count and early mortality were examined by year (August to July) of ART initiation. Competing risks analysis was used to examine early mortality., Results: A total of 19,080 adults (67.6% female) initiated ART. Median CD4⁺ cell count at ART initiation was 110-120 cells per microliter over the first 6 years, increasing marginally to 145 cells per microliter in 2010-2011 and more significantly to 199 cells per microliter in 2011-2012. Overall, there were 875 deaths within 91 days of ART initiation; early mortality rate was 19.4 per 100 person-years [95% confidence interval (CI) 18.2 to 20.7]. After adjustment for sex, age, baseline CD4⁺ cell count, and concurrent tuberculosis (TB), there was a 46% decrease in early mortality for those who initiated ART in 2011-2012 compared with the reference period 2008-2009 (subhazard ratio, 0.54; 95% CI: 0.41 to 0.71)., Conclusions: Since the expansion of eligibility criteria, there is evidence of earlier access to ART and a significant reduction in early mortality rate in this primary health care programme. These findings provide strong support for national ART policies and highlight the importance of earlier ART initiation for achieving reductions in HIV-related mortality.

Background: Antiretroviral therapy (ART) suppresses HIV viral load in all body compartments and so limits the risk of HIV transmission. It has been suggested that ART not only contributes to preventing transmission at individual but potentially also at population level. This trial aims to evaluate the effect of ART initiated immediately after identification/diagnosis of HIV-infected individuals, regardless of CD4 count, on HIV incidence in the surrounding population. The primary outcome of the overall trial will be HIV incidence over two years. Secondary outcomes will include i) socio-behavioural outcomes (acceptability of repeat HIV counselling and testing, treatment acceptance and linkage to care, sexual partnerships and quality of life); ii) clinical outcomes (mortality and morbidity, retention into care, adherence to ART, virologic failure and acquired HIV drug resistance), iii) cost-effectiveness of the intervention. The first phase will specifically focus on the trial's secondary outcomes., Methods/design: A cluster-randomised trial in 34 (2 × 17) clusters within a rural area of northern KwaZulu-Natal (South Africa), covering a total population of 34,000 inhabitants aged 16 years and above, of whom an estimated 27,200 would be HIV-uninfected at start of the trial. The first phase of the trial will include ten (2 × 5) clusters. Consecutive rounds of home-based HIV testing will be carried out. HIV-infected participants will be followed in dedicated trial clinics: in intervention clusters, they will be offered immediate ART initiation regardless of CD4 count and clinical stage; in control clusters they will be offered ART according to national treatment eligibility guidelines (CD4 <350 cells/μL, World Health Organisation stage 3 or 4 disease or multidrug-resistant/extensively drug-resistant tuberculosis). Following proof of acceptability and feasibility from the first phase, the trial will be rolled out to further clusters., Discussion: We aim to provide proof-of-principle evidence regarding the effectiveness of Treatment-as-Prevention in reducing HIV incidence at the population level. Data collected from the participants at home and in the clinics will inform understanding of socio-behavioural, economic and clinical impacts of the intervention as well as feasibility and generalizability., Trial Registration: Clinicaltrials.gov: NCT01509508; South African Trial Register: DOH-27-0512-3974.

Background: Initiating therapy with a low CD4 cell count is associated with a substantially greater risk of disease progression and death than earlier initiation. We examined factors associated with late presentation of HIV using the new European consensus definition (CD4 cell count <350 cells/mm3) and mortality., Methods: Patients newly diagnosed with HIV infection at a UK clinic were recruited from January 1996 to May 2010. Factors associated with late presentation were assessed using logistic regression. Factors associated with mortality rates were analysed using Poisson regression., Results: Of the 1536 included in the analysis, 86% were male and 10% were aged 50 years and older. Half the cohort (49%) had a CD4 cell count below 350 cells/mm3 at presentation ("late presentation"). The frequency of late presentation was highest in those aged 50 years or older and remained unchanged over time (64.3% in 1996-1998 and 65.4% in 2008-2010). In contrast, among those aged less than 50 years, the proportion with late presentation decreased over time (57.1% in 1996-1998 and 38.5% in 2008-2010). Other factors associated with late presentation were African ethnicity and being a male heterosexual.The mortality rate was 15.47/1000 person-years (pyrs) (95%-CI: 13.00-18.41). When compared with younger adults, older individuals had a higher mortality, after adjusting for confounders (rate ratio (RR) = 2.87; 95%-CI: 1.88-4.40)., Conclusions: Older adults were more likely to present late and had a higher mortality. Initiatives to expand HIV testing in clinical and community setting should not neglect individuals aged over 50.

We collected data from 218 HIV-infected men to assess the usefulness of the urethral smear and symptoms in predicting Chlamydia trachomatis infection. Prevalence of urethral chlamydia was 9%. A polymorphonuclear leucocyte (PMNL) count>or=5 was 73% sensitive and 71% specific for C. trachomatis infection. Adjusted odds ratio for risk of chlamydial infection was significant for urethral irritation (7.48; 1.54-36.4), a PMNL count of 20 or more (9.83; 2.52-8.4) and a PMNL count of 5-19 (4.10; 1.34-12.5). We had to perform 50 urethral smears in HIV-positive men without symptoms to treat one case of C. trachomatis at the time of visit. Findings suggest that the presence of symptoms, in particular urethral irritation may be associated with chlamydial urethritis and that the higher the urethral PMNL count, the more likely it is for C. trachomatis to be detected. The findings in this study also lend further support to recent guidelines that urethral microscopy is not useful in asymptomatic men and hence should be abandoned.