Towards universal ARV access: Achievements and challenges in Free State Province, South Africa

Objective. To study the progress and challenges with regard to universal antiretroviral (ARV) access in Free State Province, South Africa. Methods. Data from the first 4 years of the public sector ARV roll-out and selected health system indicators were used. Data were collected from the public sector ARV database in Free State Province for new patients on ARVs, average waiting times and median CD4 counts at the start of treatment. Information on staff training, vacancy rates and funding allocations for the ARV roll-out was obtained from official government reports. Projections were made of expected new ARV enrolments for 2008 and 2009 and compared with goals set by the National Strategic Plan (NSP) to achieve universal access to ARVs by 2011. Results. New ARV enrolments increased annually to 25% of the estimated need by the end of 2007. Average waiting times to enrolment decreased from 5.82 months to 3.24 months. Median CD4 counts at enrolment increased from 89 to 124 cells/μl. There is a staff vacancy rate of 38% in the ARV programme and an inadequate increase in budget allocations. Conclusion. The current vertical model of ARV therapy delivery is unlikely to raise the number of new enrolments sufficiently to achieve the goals of universal access by 2011 as envisaged by the NSP. The Free State is implementing a project (STRETCH trial) to broaden the ARV roll-out in an attempt to increase access to ARVs

Retrospective cohort study evaluating clinical, biochemical and pharmacological prognostic factors for prostate cancer progression using primary care data

This is the final version. Available on open access from BMJ Publishing group via the DOI in this recordObjectives – To confirm the association of previously reported prognostic factors with future progression of localised prostate cancer using primary care data and identify new potential prognostic factors for further assessment in prognostic model development and validation. Design – Retrospective cohort study, employing Cox proportional hazards regression controlling for age, PSA, and Gleason score, stratified by diagnostic stage. Setting – Primary care in England Participants – Males with localised prostate cancer diagnosed between 01/01/1987 and 31/12/2016 within the Clinical Practice Research Datalink database, with linked data from the National Cancer Registration and Analysis Service and Office for National Statistics. Primary and Secondary outcomes – Primary outcome measure was prostate cancer mortality. Secondary outcomes measures were all-cause mortality and commencing systematic therapy. Up13 staging after diagnosis was not used as a secondary outcome owing to significant missing data. Results 10,901 males (mean age 74.38 +/- 9.03 years) with localised prostate cancer were followed up for a mean of 14.12 (+/- 6.36) years. 2,331 (21.38%) men underwent systemic therapy and 3,250 (31.65%) died, including 1,250 (11.47%) from prostate cancer. Factors associated with an increased risk of prostate cancer mortality included age; high PSA; current or ex-smoker; ischaemic heart disease; high C-Reactive Protein; high ferritin; low haemoglobin; high blood glucose; and low albumin. Conclusions This study identified several new potential prognostic factors for prostate cancer progression, as well as confirming some known prognostic factors, in an independent primary care data set. Further research is needed to develop and validate a prognostic model for prostate cancer progression.Can Test Collaborative/CRU

Differences in access and patient outcomes across antiretroviral treatment clinics in the Free State province: A prospective cohort study

Objective. To assess differences in access to antiretroviral treatment (ART) and patient outcomes across public sector treatment facilities in the Free State province, South Africa. Design. Prospective cohort study with retrospective database linkage. We analysed data on patients enrolled in the treatment programme across 36 facilities between May 2004 and December 2007, and assessed percentage initiating ART and percentage dead at 1 year after enrolment. Multivariable logistic regression was used to estimate associations of facility-level and patient-level characteristics with both mortality and treatment status. Results. Of 44 866 patients enrolled, 15 219 initiated treatment within 1 year; 8 778 died within 1 year, 7 286 before accessing ART. Outcomes at 1 year varied greatly across facilities and more variability was explained by facility-level factors than by patient-level factors. The odds of starting treatment within 1 year improved over calendar time. Patients enrolled in facilities with treatment initiation available on site had higher odds of starting treatment and lower odds of death at 1 year compared with those enrolled in facilities that did not offer treatment initiation. Patients were less likely to start treatment if they were male, severely immunosuppressed (CD4 count ≤50 cells/μl), or underweight

Temperature effects on zoeal morphometric traits and intraspecific variability in the hairy crab Cancer setosus across latitude

International audiencePhenotypic plasticity is an important but often ignored ability that enables organisms, within species-specific physiological limits, to respond to gradual or sudden extrinsic changes in their environment. In the marine realm, the early ontogeny of decapod crustaceans is among the best known examples to demonstrate a temperature-dependent phenotypic response. Here, we present morphometric results of larvae of the hairy crab , the embryonic development of which took place at different temperatures at two different sites (Antofagasta, 23°45′ S; Puerto Montt, 41°44′ S) along the Chilean Coast. Zoea I larvae from Puerto Montt were significantly larger than those from Antofagasta, when considering embryonic development at the same temperature. Larvae from Puerto Montt reared at 12 and 16°C did not differ morphometrically, but sizes of larvae from Antofagasta kept at 16 and 20°C did, being larger at the colder temperature. Zoea II larvae reared in Antofagasta at three temperatures (16, 20, and 24°C) showed the same pattern, with larger larvae at colder temperatures. Furthermore, larvae reared at 24°C, showed deformations, suggesting that 24°C, which coincides with temperatures found during strong EL Niño events, is indicative of the upper larval thermal tolerance limit.   is exposed to a wide temperature range across its distribution range of about 40° of latitude. Phenotypic plasticity in larval offspring does furthermore enable this species to locally respond to the inter-decadal warming induced by El Niño. Morphological plasticity in this species does support previously reported energetic trade-offs with temperature throughout early ontogeny of this species, indicating that plasticity may be a key to a species' success to occupy a wide distribution range and/or to thrive under highly variable habitat conditions

Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies

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

Associations of modern initial antiretroviral drug regimens with all-cause mortality in adults with HIV in Europe and North America: a cohort study

Background: Over the past decade, antiretroviral therapy (ART) regimens that include integrase strand inhibitors (INSTIs) have become the most commonly used for people with HIV starting ART. Although trials and observational studies have compared virological failure on INSTI-based with other regimens, few data are available on mortality in people with HIV treated with INSTIs in routine care. Therefore, we compared all-cause mortality between different INSTI-based and non-INSTI-based regimens in adults with HIV starting ART from 2013 to 2018. Methods: This cohort study used data on people with HIV in Europe and North America from the Antiretroviral Therapy Cohort Collaboration (ART-CC) and UK Collaborative HIV Cohort (UK CHIC). We studied the most common third antiretroviral drugs (additional to nucleoside reverse transcriptase inhibitor) used from 2013 to 2018: rilpivirine, darunavir, raltegravir, elvitegravir, dolutegravir, efavirenz, and others. Adjusted hazard ratios (aHRs; adjusted for clinical and demographic characteristics, comorbid conditions, and other drugs in the regimen) for mortality were estimated using Cox models stratified by ART start year and cohort, with multiple imputation of missing data. Findings: 62 500 ART-naive people with HIV starting ART (12 422 [19·9%] women; median age 38 [IQR 30–48]) were included in the study. 1243 (2·0%) died during 188 952 person-years of follow-up (median 3·0 years [IQR 1·6–4·4]). There was little evidence that mortality rates differed between regimens with dolutegravir, elvitegravir, rilpivirine, darunavir, or efavirenz as the third drug. However, mortality was higher for raltegravir compared with dolutegravir (aHR 1·49, 95% CI 1·15–1·94), elvitegravir (1·86, 1·43–2·42), rilpivirine (1·99, 1·49–2·66), darunavir (1·62, 1·33–1·98), and efavirenz (2·12, 1·60–2·81) regimens. Results were similar for analyses making different assumptions about missing data and consistent across the time periods 2013–15 and 2016–18. Rates of virological suppression were higher for dolutegravir than other third drugs. Interpretation: This large study of patients starting ART since the introduction of INSTIs found little evidence that mortality rates differed between most first-line ART regimens; however, raltegravir-based regimens were associated with higher mortality. Although unmeasured confounding cannot be excluded as an explanation for our findings, virological benefits of first-line INSTIs-based ART might not translate to differences in mortality. Funding: US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council

Engaging Men in Prevention and Care for HIV/AIDS in Africa

Ed Mills and colleagues argue that a more balanced approach to gender is needed so that both men and women are involved in HIV treatment and prevention

Reduced Cortisol and Metabolic Responses of Thin Ewes to an Acute Cold Challenge in Mid-Pregnancy: Implications for Animal Physiology and Welfare

Background: Low food availability leading to reductions in Body Condition Score (BCS; 0 indicates emaciation and 5 obesity) in sheep often coincides with low temperatures associated with the onset of winter in New Zealand. The ability to adapt to reductions in environmental temperature may be impaired in animals with low BCS, in particular during pregnancy when metabolic demand is higher. Here we assess whether BCS affects a pregnant animal’s ability to cope with cold challenges. Methods: Eighteen pregnant ewes with a BCS of 2.760.1 were fed to attain low (LBC: BCS2.360.1), medium (MBC: BCS3.260.2) or high BCS (HBC: BCS3.660.2). Shorn ewes were exposed to a 6-h acute cold challenge in a climate-controlled room (wet and windy conditions, 4.460.1uC) in mid-pregnancy. Blood samples were collected during the BCS change phase, acute cold challenge and recovery phase. Results: During the BCS change phase, plasma glucose and leptin concentrations declined while free fatty acids (FFA) increased in LBC compared to MBC (P,0.01, P,0.01 and P,0.05, respectively) and HBC ewes (P,0.05, P,0.01 and P,0.01, respectively). During the cold challenge, plasma cortisol concentrations were lower in LBC than MBC (P,0.05) and HBC ewes (P,0.05), and FFA and insulin concentrations were lower in LBC than HBC ewes (P,0.05 and P,0.001, respectively). Leptin concentrations declined in MBC and HBC ewes while remaining unchanged in LBC ewes (P,0.01). Glucose concentrations and internal body temperature (Tcore) increased in all treatments, although peak Tcore tended to be higher in HBC ewes (P,0.1). During the recovery phase, T4 concentrations were lower in LBC ewes (P,0.05). Conclusion: Even though all ewes were able to increase Tcore and mobilize glucose, low BCS animals had considerably reduced cortisol and metabolic responses to a cold challenge in mid-pregnancy, suggesting that their ability to adapt to cold challenges through some of the expected pathways was reduced

Cost-Effectiveness of Early Versus Standard Antiretroviral Therapy in HIV-Infected Adults in Haiti

This cost-effectiveness study comparing early versus standard antiretroviral treatment (ART) for HIV, based on randomized clinical trial data from Haiti, reveals that the new WHO guidelines for early ART initiation can be cost-effective in resource-poor settings