Longitudinal effect of CD4 by cotrimoxazole use on malaria incidence among HIV-infected Ugandan adults on antiretroviral therapy: a randomized controlled study.


Kasirye, R; Grosskurth, H; Munderi, P; Levin, J; Anywaine, Z; Nunn, A; Kamali, A; Baisley, K; (2016) Longitudinal effect of CD4 by cotrimoxazole use on malaria incidence among HIV-infected Ugandan adults on antiretroviral therapy: a randomized controlled study. Malar J, 15. p. 361. ISSN 1475-2875 DOI: 10.1186/s12936-016-1426-z

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Abstract

BACKGROUND: An urgent priority in maternal, newborn and child health is to accelerate the scale-up of cost-effective essential interventions, especially during labor, the immediate postnatal period and for the treatment of serious infectious diseases and acute malnutrition.  Tracking intervention coverage is a key activity to support scale-up and in this paper we examine priorities in coverage measurement, distinguishing between essential interventions that can be measured now and those that require methodological development.<br/> METHODS: We conceptualized a typology of indicators related to intervention coverage that distinguishes access to care from receipt of an intervention by the population in need.  We then built on documented evidence on coverage measurement to determine the status of indicators for essential interventions and to identify areas for development.<br/> RESULTS: Contact indicators from pregnancy to childhood were identified as current indicators for immediate use, but indicators reflecting the quality of care provided during these contacts need development. At each contact point, some essential interventions can be measured now, but the need for development of indicators predominates around interventions at the time of birth and interventions to treat infections. Addressing this need requires improvements in routine facility based data capture, methods for linking provider and community-based data, and improved guidance for effective coverage measurement that reflects the provision of high-quality care.<br/> CONCLUSION: Coverage indicators for some essential interventions can be measured accurately through household surveys and be used to track progress in maternal, newborn and child health.  Other essential interventions currently rely on contact indicators as proxies for coverage but urgent attention is needed to identify new measurement approaches that directly and reliably measure their effective coverage.<br/> BACKGROUND: Cardiovascular magnetic resonance (CMR) can provide important structural information in patients undergoing transcatheter aortic valve implantation. Although CMR is considered the standard of reference for measuring ventricular volumes and mass, the relationship between CMR findings of right ventricular (RV) function and outcomes after transcatheter aortic valve implantation has not previously been reported.<br/> METHODS AND RESULTS: A total of 190 patients underwent 1.5 Tesla CMR before transcatheter aortic valve implantation. Steady-state free precession sequences were used for aortic valve planimetry and to assess ventricular volumes and mass. Semiautomated image analysis was performed by 2 specialist reviewers blinded to patient treatment. Patient follow-up was obtained from the Office of National Statistics mortality database. The median age was 81.0 (interquartile range, 74.9-85.5) years; 50.0% were women. Impaired RV function (RV ejection fraction ≤50%) was present in 45 (23.7%) patients. Patients with RV dysfunction had poorer left ventricular ejection fractions (42% versus 69%), higher indexed left ventricular end-systolic volumes (96 versus 40 mL), and greater indexed left ventricular mass (101 versus 85 g/m(2); P<0.01 for all) than those with normal RV function. Median follow-up was 850 days; 21 of 45 (46.7%) patients with RV dysfunction died, compared with 43 of 145 (29.7%) patients with normal RV function (P=0.035). After adjustment for significant baseline variables, both RV ejection fraction ≤50% (hazard ratio, 2.12; P=0.017) and indexed aortic valve area (hazard ratio, 4.16; P=0.025) were independently associated with survival.<br/> CONCLUSIONS: RV function, measured on preprocedural CMR, is an independent predictor of mortality after transcatheter aortic valve implantation. CMR assessment of RV function may be important in the risk stratification of patients undergoing transcatheter aortic valve implantation.<br/> BACKGROUND: The effect of CD4 count on malaria incidence in HIV infected adults on antiretroviral therapy (ART) was assessed in the context of a randomized controlled trial on the effect of stopping cotrimoxazole (CTX).<br/> METHODS: This study presents a sub-analysis of the COSTOP trial (ISRCTN44723643) which was carried out among HIV-infected Ugandan adults stable on ART with CD4 counts ≥250 cells/µl. Participants were randomized (1:1) to continue CTX or stop CTX and receive matching placebo, and were followed up for a minimum of 1 year (median 2.5 years). CD4 counts were measured at baseline, 3 months and then every 6 months. Clinical malaria was defined as fever and a positive blood slide. First, the relationship between current CD4 count during follow-up and malaria among participants on placebo was examined; using random effects Poisson regression to account for repeated episodes. Second, the effect of CD4 count at enrolment, CD4 count at ART initiation, and CD4 count during follow-up on malaria, was assessed within each trial arm; to examine whether the effect of CD4 count differed by CTX use.<br/> RESULTS: 2180 participants were enrolled into the COSTOP trial. The incidence of clinical malaria was approximately four episodes/100 person years in the CTX arm and 14 episodes/100 person years in the placebo arm. There was no evidence of an association of current CD4 and clinical malaria incidence (P = 0.56), or parasitaemia levels (P = 0.24), in the placebo arm. Malaria incidence did not differ by CD4 count at ART initiation, enrolment or during follow up, irrespective of CTX use. When compared with participants in the lowest CD4 stratum, rate ratios within each trial arm were all close to 1, and P values were all above P = 0.30.<br/> CONCLUSIONS: The immune status of HIV infected participants who are stable on ART as measured by CD4 count was not associated with malaria incidence and did not modify the effect of stopping CTX on malaria. The decision of whether to stop or continue CTX prophylaxis for malaria in HIV infected individuals who are stable on ART should not be based on CD4 counts alone. COSTOP trial registration number ISRCTN44723643.<br/>

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
PubMed ID: 27417903
Web of Science ID: 379587700001
URI: http://researchonline.lshtm.ac.uk/id/eprint/2634771

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