Incident HIV during pregnancy and early postpartum period: a population-based cohort study in a rural area in KwaZulu-Natal, South Africa

BACKGROUND: The evidence on the effect of pregnancy on acquiring HIV is conflicting, with studies reporting both higher and lower HIV acquisition risk during pregnancy when prolonged antiretroviral therapy was accessible. The aim of this study was to assess the pregnancy effect on HIV acquisition where antiretroviral therapy was widely available in a high HIV prevalence setting. METHODS: This is a retrospective cohort study nested within a population-based surveillance to determine HIV incidence in HIV-uninfected women from 15 to 49 years from 2010 through 2015 in rural KwaZulu-Natal. HIV incidence per 100 person-years according to pregnancy status (not pregnant, pregnant, to eight weeks postpartum) were measured in 5260 HIV-uninfected women. Hazard ratios (HR) were estimated by Cox proportional hazards regression with pregnancy included as a time varying variable. RESULTS: Overall, pregnancy HIV incidence was 4.5 per 100 person-years (95% CI 3.4-5.8), higher than non-pregnancy (4.0; 95% CI 3.7-4.3) and postpartum incidences (4.2 per 100 person-years; 95% CI 2.3-7.6). However, adjusting for age, and demographic factors, pregnant women had a lower risk of acquiring HIV (HR 0.4; 95% CI 0.2-0.9, P = 0.032) than non-pregnant women; there were no differences between postpartum and non-pregnant women (HR 1.2; 95% CI 0.4-3.2; P = 0.744). In models adjusting for the interaction of age and gravidity, pregnant women under 25 years with two or more pregnancies had a 2.3 times greater risk of acquiring HIV than their older counterparts (95% CI 1.3-4.3; P = 0.008). CONCLUSIONS: Pregnancy had a protective effect on HIV acquisition. Elevated HIV incidence in younger women appeared to be driven by those with higher gravidity. The sexual and biological factors in younger women should be explored further in order to design appropriate HIV prevention interventions

The political context of AIDS-related stigma and knowledge in a South African township

The purpose of this study was to examine the presentation of AIDS-related stigma and knowledge within the political context of the South African government\'s response to the AIDS epidemic. It was during the 2000 - 2004 period that key government officials publicly challenged the orthodox views of HIV/AIDS, with the South African president, Thabo Mbeki, actively positing the primary role of poverty and other socio-economic stressors in the progression of the AIDS epidemic. This discursive position had real-time effects for AIDS policy-making and ultimately delayed the implementation of a national antiretroviral (ARV) rollout programme. Consequently this position was criticised by commentators in the media and elsewhere for contributing to an already widespread climate of AIDS stigmatisation and misinformation. To shed more light on these claims we conducted a survey in 2005 in Atteridgeville, a South African township, and compared results with those of a similar survey conducted shortly after ARV medications became available in 2004. Results indicated a reduction in AIDS stigma levels across the 1-year period, and that those participants who endorsed contentious political views (such as those expressed by key government officials) were more likely to have a higher level of AIDS-related stigma than those who disagreed. Nevertheless, this study cautions against drawing a causal relationship between the South African government\'s position and AIDS-stigmatising attitudes, and suggests that further political and social factors be accounted for in an attempt to gain a fuller understanding of this seemingly complex relationship. Keywords: HIV/AIDS, AIDS-related stigma, South African government, AIDS debate, antiretroviral rollout, Atteridgeville.SAHARA J Vol. 5 (2) 2008: pp. 74-8

HIV seroconcordance among heterosexual couples in rural KwaZulu-Natal, South Africa: a population-based analysis

Introduction High levels of HIV seroconcordance at the population level reduce the potential for effective HIV transmission. However, the level of HIV seroconcordance is largely unknown among heterosexual couples in sub‐Saharan Africa. We aimed to quantify the population level HIV seroconcordance in stable heterosexual couples in rural South Africa. Methods We followed adults (≥15 years old) using a population‐based, longitudinal and open surveillance system in KwaZulu‐Natal, South Africa, from 2003 to 2016. Sexual partnerships and HIV status were confirmed via household surveys and annual HIV surveillance. We calculated the proportions of HIV seroconcordance and serodiscordance in stable sexual partnerships and compared them to the expected proportions under the assumption of random mixing using individual‐based microsimulation models. Among unpartnered individuals, we estimated the incidence rates and hazard of sexual partnership formation with HIV‐positive or HIV‐negative partners by participants' own time‐varying HIV status. Competing risks survival regressions were fitted adjusting for sociodemographic and clinical factors. We also calculated Newman's assortativity coefficients. Results A total of 18,341 HIV‐negative and 11,361 HIV‐positive individuals contributed 154,469 person‐years (PY) of follow‐up. Overall, 28% of the participants were in stable sexual partnerships. Of the 677 newly formed stable sexual partnerships, 7.7% (95% CI: 5.8 to 10.0) were HIV‐positive seroconcordant (i.e. both individuals in the partnership were HIV‐positive), which was three times higher than the expected proportion (2.3%) in microsimulation models based on random mixing. The incidence rates of sexual partnership formation were 0.54/1000PY with HIV‐positive, 1.12/1000PY with HIV‐negative and 2.65/1000PY with unknown serostatus partners. HIV‐positive individuals had 2.39 (95% CI: 1.43 to 3.99) times higher hazard of forming a sexual partnership with an HIV‐positive partner than did HIV‐negative individuals after adjusting for age, opposite‐sex HIV prevalence (by 5‐years age groups), HIV prevalence in the surrounding community, ART coverage and other sociodemographic factors. Similarly, forming a sexual partnership with an HIV‐negative partner was 1.47 (95% CI: 1.01 to 2.14) times higher in HIV‐negative individuals in the adjusted model. Newman's coefficient also showed that assortativity by participant and partner HIV status was moderate (r = 0.35). Conclusions A high degree of population level HIV seroconcordance (both positive and negative) was observed at the time of forming new sexual partnerships. Understanding factors driving these patterns may help the development of strategies to bring the HIV epidemic under control

BMI and All-Cause Mortality in a Population-Based Cohort in Rural South Africa

OBJECTIVE: This study evaluates the association between BMI and all-cause and cause-specific mortality in South Africa. METHODS: Prospective, population-based observational cohort data from rural South Africa were analyzed. BMI was measured in 2010. Demographic characteristics were recorded and deaths were verified with verbal autopsy interview. The InterVA-5 tool was used to assign causes of death. HIV testing was conducted annually. Cox proportional hazards models were fit to estimate the effect of BMI on all-cause and cause-specific mortality, accounting for the competing risk of death from other causes. Models were adjusted for sociodemographic characteristics and HIV status, and inverse probability weighting for survey nonparticipation was used. RESULTS: The cohort consisted of 9,728 individuals. In adjusted models, those with BMI of 25.0 to 29.9 kg/m2 or 30.0 to 34.9 kg/m2 had a lower hazard of death (adjusted hazard ratio: 0.80; 95% CI: 0.69-0.92 and adjusted hazard ratio: 0.75; 95% CI: 0.60-0.93, respectively) compared with those with BMI of 18.5 to 24.9 kg/m^{2}. CONCLUSIONS: Individuals in South Africa who meet clinically defined criteria for overweight or obesity had a lower risk of all-cause mortality than those with a normal BMI. These findings were stronger for women and communicable conditions

Tests of achromatic phase shifters performed on the SYNAPSE test bench: a progress report

The achromatic phase shifter (APS) is a component of the Bracewell nulling interferometer studied in preparation for future space missions (viz. Darwin/TPF-I) focusing on spectroscopic study of Earth-like exo-planets. Several possible designs of such an optical subsystem exist. Four approaches were selected for further study. Thales Alenia Space developed a dielectric prism APS. A focus crossing APS prototype was developed by the OCA, Nice, France. A field reversal APS prototype was prepared by the MPIA in Heidelberg, Germany. Centre Spatial de Li\`ege develops a concept based on Fresnel's rhombs. This paper presents a progress report on the current work aiming at evaluating these prototypes on the SYNAPSE test bench at the Institut d'Astrophysique Spatiale in Orsay, France

Sociobehavioural and community predictors of unsuppressed viral load: multi-level results from a hyper-endemic rural South African population

OBJECTIVE: Extensive antiretroviral therapy scale-up is expected to prevent onward transmission of HIV by reducing the overall community viral load. Despite multiple studies about predictors of detectable viral load derived from clinical setting, to date, no study has established such predictors using a population-based viral load survey in a sub-Saharan African hyperendemic setting to inform interventions designed to halt HIV transmission. We used one of Africa's largest prospective cohorts in rural KwaZulu-Natal Province, South Africa, to establish the key sociodemographic, behavioral and community predictors of unsuppressed viral load at the population level. METHODS: We collected 5454 viral load measurements from a population-based viral load survey of 3892 women living with HIV from a rural population during 2011, 2013 and 2014. Multilevel logistic regression models were fitted to examine the risk predictors of unsuppressed viral load. RESULTS: Among women living with HIV in this population, the prevalence of unsuppressed viral load was 69% in 2011, 58% in 2013 and 53% in 2014. Although time since HIV infection was associated with lower risk for virologic detection [adjusted odds ratio (aOR) = 0.91,0.87-0.94], young women (aOR = 2.59,1.47-4.55) with extensive external migration history (aOR = 1.25,1.02-1.54), greater number of sexual partners (aOR = 1.30,1.02-1.67), and longer history of residing in an HIV incidence hotspot community were more likely to experience unsuppressed viral load (aOR = 1.12,1.06-1.19). CONCLUSION: Young women, number of sexual partners, transiency and longer residence in an HIV hotspot community are important determinants of unsuppressed viral load in a hyperendemic rural African setting. To substantially reduce the persistently high transmission potential in these settings, targeted interventions to address these risk factors will be essential for both individual and population health gains

Tracking external introductions of HIV using phylodynamics reveals a major source of infections in rural KwaZulu-Natal, South Africa

Despite increasing access to antiretrovirals, HIV incidence in rural KwaZulu-Natal remains among the highest ever reported in Africa. While many epidemiological factors have been invoked to explain such high incidence, widespread human mobility and viral movement suggest that transmission between communities may be a major source of new infections. High cross-community transmission rates call into question how effective increasing the coverage of antiretroviral therapy locally will be at preventing new infections, especially if many new cases arise from external introductions. To help address this question, we use a phylodynamic model to reconstruct epidemic dynamics and estimate the relative contribution of local transmission versus external introductions to overall incidence in KwaZulu-Natal from HIV-1 phylogenies. By comparing our results with population-based surveillance data, we show that we can reliably estimate incidence from viral phylogenies once viral movement in and out of the local population is accounted for. Our analysis reveals that early epidemic dynamics were largely driven by external introductions. More recently, we estimate that 35 per cent (95% confidence interval: 20-60%) of new infections arise from external introductions. These results highlight the growing need to consider larger-scale regional transmission dynamics when designing and testing prevention strategies

Robust averaging protects decisions from noise in neural computations

An ideal observer will give equivalent weight to sources of information that are equally reliable. However, when averaging visual information, human observers tend to downweight or discount features that are relatively outlying or deviant (‘robust averaging’). Why humans adopt an integration policy that discards important decision information remains unknown. Here, observers were asked to judge the average tilt in a circular array of high-contrast gratings, relative to an orientation boundary defined by a central reference grating. Observers showed robust averaging of orientation, but the extent to which they did so was a positive predictor of their overall performance. Using computational simulations, we show that although robust averaging is suboptimal for a perfect integrator, it paradoxically enhances performance in the presence of “late” noise, i.e. which corrupts decisions during integration. In other words, robust decision strategies increase the brain’s resilience to noise arising in neural computations during decision-making

I-SceI-Mediated Double-Strand Break Does Not Increase the Frequency of Homologous Recombination at the Dct Locus in Mouse Embryonic Stem Cells

Targeted induction of double-strand breaks (DSBs) at natural endogenous loci was shown to increase the rate of gene replacement by homologous recombination in mouse embryonic stem cells. The gene encoding dopachrome tautomerase (Dct) is specifically expressed in melanocytes and their precursors. To construct a genetic tool allowing the replacement of Dct gene by any gene of interest, we generated an embryonic stem cell line carrying the recognition site for the yeast I-SceI meganuclease embedded in the Dct genomic segment. The embryonic stem cell line was electroporated with an I-SceI expression plasmid, and a template for the DSB-repair process that carried sequence homologies to the Dct target. The I-SceI meganuclease was indeed able to introduce a DSB at the Dct locus in live embryonic stem cells. However, the level of gene targeting was not improved by the DSB induction, indicating a limited capacity of I-SceI to mediate homologous recombination at the Dct locus. These data suggest that homologous recombination by meganuclease-induced DSB may be locus dependent in mammalian cells

Possible involvement of caveolin in attenuation of cardioprotective effect of ischemic preconditioning in diabetic rat heart

<p>Abstract</p> <p>Background</p> <p>Nitric oxide (NO) has been noted to produce ischemic preconditioning (IPC)-mediated cardioprotection. Caveolin is a negative regulator of NO, which inhibits endothelial nitric oxide synthase (eNOS) by making caveolin-eNOS complex. The expression of caveolin is increased during diabetes mellitus (DM). The present study was designed to investigate the involvement of caveolin in attenuation of the cardioprotective effect of IPC during DM in rat.</p> <p>Methods</p> <p>Experimental DM was induced by single dose of streptozotocin (50 mg/Kg, <it>i.p</it>,) and animals were used for experiments four weeks later. Isolated heart was mounted on Langendorff's apparatus, and was subjected to 30 min of global ischemia and 120 min of reperfusion. IPC was given by four cycles of 5 min of ischemia and 5 min of reperfusion with Kreb's-Henseleit solution (K-H). Extent of injury was measured in terms of infarct size by triphenyltetrazolium chloride (TTC) staining, and release of lactate dehydrogenase (LDH) and creatin kinase-MB (CK-MB) in coronary effluent. The cardiac release of NO was noted by measuring the level of nitrite in coronary effluent.</p> <p>Results</p> <p>IPC- induced cardioprotection and release of NO was significantly decreased in diabetic rat heart. Pre-treatment of diabetic rat with daidzein (DDZ) a caveolin inhibitor (0.2 mg/Kg/s.c), for one week, significantly increased the release of NO and restored the attenuated cardioprotective effect of IPC. Also perfusion of sodium nitrite (10 μM/L), a precursor of NO, significantly restored the lost effect of IPC, similar to daidzein in diabetic rat. Administration of 5-hydroxy deaconate (5-HD), a mito K_ATPchannel blocker, significantly abolished the observed IPC-induced cardioprotection in normal rat or daidzein and sodium nitrite perfused diabetic rat heart alone or in combination.</p> <p>Conclusions</p> <p>Thus, it is suggested that attenuation of the cardioprotection in diabetic heart may be due to decrease the IPC mediated release of NO in the diabetic myocardium, which may be due to up -regulation of caveolin and subsequently decreased activity of eNOS.</p