Factors associated with mortality in HIV-infected people in rural and urban South Africa

PKBackground: Factors associated with mortality in HIV-infected people in sub-Saharan Africa are widely reported. However rural urban disparities and their association with all-cause mortality remain unclear. Furthermore, commonly used classical Cox regression ignores unmeasured variables and frailty. Objective: To incorporate frailty in assessing factors associated with mortality in HIV-infected people in rural and urban South Africa. Design: Using data from a prospective cohort following 6,690 HIV-infected participants from Soweto (urban) and Mpumalanga (rural) enrolled from 2003 to 2010; covariates of mortality were assessed by the integrated nested Laplace approximation method. Results: We enrolled 2,221 (33%) rural and 4,469 (67%) urban participants of whom 1,555 (70%) and 3,480 (78%) were females respectively. Median age (IQR) was 36.4 (31.0 44.1) in rural and 32.7 (28.2 38.1) in the urban participants. The mortality rate per 100 person-years was 11 (9.7 12.5) and 4 (3.6 4.5) in the rural and urban participants, respectively. Compared to those not on HAART, rural participants had a reduced risk of mortality if on HAART for 6 12 (HR: 0.20, 95% CI: 0.10 0.39) and 12 months (HR: 0.10, 95% CI: 0.05 0.18). Relative to those not on HAART, urban participants had a lower risk if on HAART 12 months (HR: 0.35, 95% CI: 0.27 0.46). The frailty variance was significant and 1 in rural participants indicating more heterogeneity. Similarly it was significant but B1 in the urban participants indicating less heterogeneity. Conclusion: The frailty model findings suggest an elevated risk of mortality in rural participants relative to the urban participants potentially due to unmeasured variables that could be biological, socio economic, or healthcare related. Use of robust methods that optimise data and account for unmeasured variables could be helpful in assessing the effect of unknown risk factors thus improving patient management and care in South Africa and elsewhere

Early ART-initiation and longer ART duration reduces HIV-1 proviral DNA levels in children from the CHER trial

Background Reduction of the reservoir of latent HIV-infected cells might increase the possibility of long-term remission in individuals living with HIV. We investigated factors associated with HIV-1 proviral DNA levels in children receiving different antiretroviral therapy (ART) strategies in the children with HIV early antiretroviral therapy (CHER) trial. Methods Infants with HIV  <  12 weeks old with CD4%  ≥  25% were randomized in the CHER trial to early limited ART for 40 or 96 weeks (ART-40 W, ART-96 W), or deferred ART (ART-Def). For ART-Def infants or following ART interruption in ART-40 W/ART-96 W, ART was started/re-started for clinical progression or CD4%  <  25%. In 229 participants, HIV-1 proviral DNA was quantified by PCR from stored peripheral blood mononuclear cells from children who had received  ≥  24 weeks ART and two consecutive undetectable HIV-1 RNA 12–24 weeks apart. HIV-1 proviral DNA was compared between ART-Def and ART-96 W at week 96, and in all arms at week 248. Factors associated with HIV-1 proviral DNA levels were evaluated using linear regression. Findings Longer duration of ART was significantly associated with lower HIV-1 proviral DNA at both 96 (p  =  0.0003) and 248 weeks (p  =  0.0011). Higher total CD8 count at ART initiation was associated with lower HIV-1 proviral DNA at both 96 (p  =  0.0225) and 248 weeks (p  =  0.0398). Week 248 HIV-1 proviral DNA was significantly higher in those with positive HIV-1 serology at week 84 than those with negative serology (p  =  0.0042). Intepretation Longer ART duration is key to HIV-1 proviral DNA reduction. Further understanding is needed of the effects of “immune-attenuation” through early HIV-1 exposure. Funding Wellcome Trust, National Institutes of Health, Medical Research Council

Challenges for Routine Health System Data Management in a Large Public Programme to Prevent Mother-to-Child HIV Transmission in South Africa

Background: Recent changes to South Africa's prevention of mother-to-child transmission of HIV (PMTCT) guidelines have raised hope that the national goal of reducing perinatal HIV transmission rates to less than 5% can be attained. While programmatic efforts to reach this target are underway, obtaining complete and accurate data from clinical sites to track progress presents a major challenge. We assessed the completeness and accuracy of routine PMTCT data submitted to the district health information system (DHIS) in three districts of Kwazulu-Natal province, South Africa. Methodology/Principal Findings: We surveyed the completeness and accuracy of data reported for six key PMTCT data elements between January and December 2007 from all 316 clinics and hospitals in three districts. Through visits to randomly selected sites, we reconstructed reports for the same six PMTCT data elements from clinic registers and assessed accuracy of the monthly reports previously submitted to the DHIS. Data elements were reported only 50.3% of the time and were “accurate” (i.e. within 10% of reconstructed values) 12.8% of the time. The data element “Antenatal Clients Tested for HIV” was the most accurate data element (i.e. consistent with the reconstructed value) 19.8% of the time, while “HIV PCR testing of baby born to HIV positive mother” was the least accurate with only 5.3% of clinics meeting the definition of accuracy. Conclusions/Significance: Data collected and reported in the public health system across three large, high HIV-prevalence Districts was neither complete nor accurate enough to track process performance or outcomes for PMTCT care. Systematic data evaluation can determine the magnitude of the data reporting failure and guide site-specific improvements in data management. Solutions are currently being developed and tested to improve data quality

Thymic Output and CD4 T-Cell Reconstitution in HIV-Infected Children on Early and Interrupted Antiretroviral Treatment: Evidence from the Children with HIV Early Antiretroviral Therapy Trial

Objectives Early treatment of HIV-infected children and adults is important for optimal immune reconstitution. Infants’ immune systems are more plastic and dynamic than older children’s or adults’, and deserve particular attention. This study aimed to understand the response of the HIV-infected infant immune system to early antiretroviral therapy (ART) and planned ART interruption and re-start. Methods Data from HIV-infected children enrolled the CHER trial, starting ART aged between 6 and 12 weeks, was used to explore the effect of ART on immune reconstitution. We used linear and nonlinear regression and mixed-effects models to describe children’s CD4 trajectories and to identify predictors of CD4 count during early and interrupted ART. Results Early treatment arrested the decline in CD4 count but did not fully restore it to the levels observed in HIV-uninfected children. Treatment interruption at 40 or 96 weeks resulted in a rapid decline in CD4 T-cells, which on retreatment returned to levels observed before interruption. Naïve CD4 T-cell count was an important determinant of overall CD4 levels. A strong correlation was observed between thymic output and the stable CD4 count both before and after treatment interruption. Conclusions Early identification and treatment of HIV-infected infants is important to stabilize CD4 counts at the highest levels possible. Once stabilized, children’s CD4 counts appear resilient, with good potential for recovery following treatment interruption. The naïve T-cell pool and thymic production of naive cells are key determinants of children’s CD4 levels.</p

Sexual Risk, Serostatus and Intimate Partner Violence Among Couples During Pregnancy in Rural South Africa

The aim of this study was to describe sexual risk behavior among 239 couples during pregnancy and to examine the relationship of sexual risk behavior with HIV serostatus and intimate partner violence. One-third (31.8 %) of pregnant women and 20.9 % of male partners were HIV positive. HIV risk factors included lack of knowledge of partners’ HIV serostatus, unprotected sexual intercourse and multiple sexual partners. Among men, multivariate logistic regression identified awareness of HIV negative partner status, multiple sexual partners and low levels of partner violence and among women Zulu or Swati ethnicity were associated with unprotected intercourse. HIV positive concordance was associated with protected sex and in multilevel analysis of couples HIV positive status and awareness of the partner’s HIV positive status were associated with protected sex. High levels of HIV risk behaviour was found among couples during pregnancy calling for HIV risk reduction interventions

Les scénarios énergie-climat : mise au point après la crise, Fukushima, Durban…, et les gaz de schiste

Les scénarios énergie-climat : mise au point après la crise, Fukushima, Durban…, et les gaz de schiste / Patrick Criqui, Silvana Mima, Pierre-Olivier Peytral, Jean-Christophe Simon. Futuribles, n° 390, novembre 2012, pp. 5-23. Consulter l’article sur le site de Futuribles : http://www.futuribles.com/fr/viewer/pdf/3927 Présentation du papier par Futuribles : Dans un article publié dans ces colonnes en 2011 (n° 373), Patrick Criqui avait présenté une série de scénarios d’évolution possible sur ..