Early antiretroviral treatment reduces risk of bacille Calmette-Guerin immune reconstitution adenitis

SETTING: Two centres in Soweto and Cape Town, South Africa. OBJECTIVE: To assess the effects of timing of initiation of antiretroviral treatment (ART) and other factors on the risk of bacille Calmette-Guerin (BCG) related regional adenitis due to immune reconstitution inflammatory syndrome (BCG-IRIS) in human immunodeficiency virus (HIV) infected infants. DESIGN: HIV-infected infants aged 6-12 weeks with CD4 count >= 25% enrolled in the Children with HIV Early Antiretroviral Therapy (CHER) Trial received early (before 12 weeks) or deferred (after immunological or clinical progression) ART; infants with CD4 count 750000 copies/ml at initiation. Incidence of BCG-IRIS was 10.9 and 54.3 per 100 person-years (py) among infants with CD4 count >= 25% at enrolment receiving early (at median age 7.4 weeks) vs. deferred (23.2 weeks) ART, respectively (HR 0.24, 95% CI 0.11-0.53, P < 0.001). Infants with CD4 count <25% receiving early ART had intermediate incidence (41.7/100 py). Low CD4 counts and high HIV-1 RNA at initiation were the strongest independent risk factors for BCG-IRIS. CONCLUSIONS: Early ART initiation before immunological and/or clinical progression substantially reduces the risk of BCG-IRIS regional adenitis

Prevalence of dengue fever virus antibodies and associated risk factors among residents of El-Gadarif state, Sudan

Abstract Background Dengue fever, caused by dengue virus (DENV), has become one of the most important mosquito-borne viral diseases with a steady rise in global incidence, including the Sudan. Sporadic cases and frequent acute febrile illness outbreaks, compatible with Dengue fever, have been reported in El-Gadarif State, Sudan. However, diagnosis was based almost exclusively on clinical signs without confirmatory laboratory investigations. Despite the magnitude of the problem in El-Gadarif State, no information is currently available with regard to the epidemiology of the disease in this State. El-Gadarif State is one of the largest commercial centers in the Sudan. The objective of the present investigation is to estimate the prevalence of DENV antibodies, and determine the potential risk factors associated with seropositivity among residents of El-Gadarif State. Methods A cross sectional study was conducted in a total of 701residents randomly selected from all 10 localities in El-Gadarif State. The sera from the 701 residents were tested for the presence of DENV-specific immunoglobulin G (IgG) antibodies using a commercially available Anti-dengue IgG enzyme-linked immunosorbent assay (ELISA). Results Among the 701 residents, 334 residents (47.6%) were seropositive for DENV. Mosquito control (OR = 2.73, CI = 1.37–5.87, p-value = 0.001); low income (OR = 2.31, CI: 1.71–6.36, p value = 0.032); sleeping out-doors (OR = 3.73, CI = 2.63–6.23, p-value = 0.013), and localities were determined as potential risk factors for contracting DENV infection. Conclusions The prevalence rate of DENV antibodies among residents of El-Gadarif State is significantly high (47.6%). Further epidemiologic studies including, distribution of mosquito vectors and implementation of improved surveillance are urgently warranted for better prediction and prevention of a possible DENV outbreak in El-Gadarif State, Sudan

Early time-limited antiretroviral therapy versus deferred therapy in South African infants infected with HIV: results from the children with HIV early antiretroviral (CHER) randomised trial

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Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV-1 infection 2015: optimizing health in preparation for adult life.

The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV-1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short-term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long-term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first- and second-line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART 'pipeline' of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained

Enhanced infection prophylaxis reduces mortality in severely immunosuppressed HIV-infected adults and older children initiating antiretroviral therapy in Kenya, Malawi, Uganda and Zimbabwe: the REALITY trial

Meeting abstract FRAB0101LB from 21st International AIDS Conference 18–22 July 2016, Durban, South Africa. Introduction: Mortality from infections is high in the first 6 months of antiretroviral therapy (ART) among HIV‐infected adults and children with advanced disease in sub‐Saharan Africa. Whether an enhanced package of infection prophylaxis at ART initiation would reduce mortality is unknown. Methods: The REALITY 2×2×2 factorial open‐label trial (ISRCTN43622374) randomized ART‐naïve HIV‐infected adults and children >5 years with CD4 <100 cells/mm3. This randomization compared initiating ART with enhanced prophylaxis (continuous cotrimoxazole plus 12 weeks isoniazid/pyridoxine (anti‐tuberculosis) and fluconazole (anti‐cryptococcal/candida), 5 days azithromycin (anti‐bacterial/protozoal) and single‐dose albendazole (anti‐helminth)), versus standard‐of‐care cotrimoxazole. Isoniazid/pyridoxine/cotrimoxazole was formulated as a scored fixed‐dose combination. Two other randomizations investigated 12‐week adjunctive raltegravir or supplementary food. The primary endpoint was 24‐week mortality. Results: 1805 eligible adults (n = 1733; 96.0%) and children/adolescents (n = 72; 4.0%) (median 36 years; 53.2% male) were randomized to enhanced (n = 906) or standard prophylaxis (n = 899) and followed for 48 weeks (3.8% loss‐to‐follow‐up). Median baseline CD4 was 36 cells/mm3 (IQR: 16–62) but 47.3% were WHO Stage 1/2. 80 (8.9%) enhanced versus 108(12.2%) standard prophylaxis died before 24 weeks (adjusted hazard ratio (aHR) = 0.73 (95% CI: 0.54–0.97) p = 0.03; Figure 1) and 98(11.0%) versus 127(14.4%) respectively died before 48 weeks (aHR = 0.75 (0.58–0.98) p = 0.04), with no evidence of interaction with the two other randomizations (p > 0.8). Enhanced prophylaxis significantly reduced incidence of tuberculosis (p = 0.02), cryptococcal disease (p = 0.01), oral/oesophageal candidiasis (p = 0.02), deaths of unknown cause (p = 0.02) and (marginally) hospitalisations (p = 0.06) but not presumed severe bacterial infections (p = 0.38). Serious and grade 4 adverse events were marginally less common with enhanced prophylaxis (p = 0.06). CD4 increases and VL suppression were similar between groups (p > 0.2). Conclusions: Enhanced infection prophylaxis at ART initiation reduces early mortality by 25% among HIV‐infected adults and children with advanced disease. The pill burden did not adversely affect VL suppression. Policy makers should consider adopting and implementing this low‐cost broad infection prevention package which could save 3.3 lives for every 100 individuals treated