The scale-up of antiretroviral therapy (ART) is expected to raise adult life expectancy in populations with high HIV prevalence. Using data from a population cohort of over 101,000 individuals in ...rural KwaZulu-Natal, South Africa, we measured changes in adult life expectancy for 2000—2011. In 2003, the year before ART became available in the public-sector health system, adult life expectancy was 49.2 years; by 2011, adult life expectancy had increased to 60.5 years—an 11.3-year gain. Based on standard monetary valuation of life, the survival benefits of ART far outweigh the costs of providing treatment in this community. These gains in adult life expectancy signify the social value of ART and have implications for the investment decisions of individuals, governments, and donors.
The landmark HIV Prevention Trials Network (HPTN) 052 trial in HIV-discordant couples demonstrated unequivocally that treatment with antiretroviral therapy (ART) substantially lowers the probability ...of HIV transmission to the HIV-uninfected partner. However, it has been vigorously debated whether substantial population-level reductions in the rate of new HIV infections could be achieved in "real-world" sub-Saharan African settings where stable, cohabiting couples are often not the norm and where considerable operational challenges exist to the successful and sustainable delivery of treatment and care to large numbers of patients. We used data from one of Africa's largest population-based prospective cohort studies (in rural KwaZulu-Natal, South Africa) to follow up a total of 16,667 individuals who were HIV-uninfected at baseline, observing individual HIV seroconversions over the period 2004 to 2011. Holding other key HIV risk factors constant, individual HIV acquisition risk declined significantly with increasing ART coverage in the surrounding local community. For example, an HIV-uninfected individual living in a community with high ART coverage (30 to 40% of all HIV-infected individuals on ART) was 38% less likely to acquire HIV than someone living in a community where ART coverage was low (<10% of all HIV-infected individuals on ART).
Summary
Evidence for the effect of preconception and periconceptional risk factors on childhood outcomes such as obesity and other non‐communicable diseases (NCDs) in later life is growing. Issues ...such as maternal malnutrition need to be addressed before pregnancy, to prevent a transgenerational passage of risk of NCDs. The aim of this review was to evidence for preconception interventions to prevent obesity and other risk factors for NCDs in children. A search for systematic reviews of interventions in the preconception period published between 2006 and 2018 was conducted on academic databases. Fifteen reviews were included, two of the reviews also included pregnant women. None of the reviews directly reported on obesity or NCD outcomes in children. Results suggest that exercise‐ and diet‐based interventions significantly reduced maternal weight postpartum, weight gain during pregnancy, and improved prevention and control of gestational diabetes. Balanced protein energy supplementation during and before pregnancy was associated with an increase in mean birth weight and reduction of low birth weight babies. There is a dearth of evidence for preconception programmes that follow up on childhood outcomes related to a risk of NCDs. Nevertheless, results suggest that women who received preconception interventions were more likely to have improved pregnancy‐related and behavioural outcomes.
Introduction: To systematically review the literature on mother‐to‐child transmission in breastfed infants whose mothers received antiretroviral therapy and support the process of updating the World ...Health Organization infant feeding guidelines in the context of HIV and ART.
Methods: We reviewed experimental and observational studies; exposure was maternal HIV antiretroviral therapy (and duration) and infant feeding modality; outcomes were overall and postnatal HIV transmission rates in the infant at 6, 9, 12 and 18 months. English literature from 2005 to 2015 was systematically searched in multiple electronic databases. Papers were analysed by narrative synthesis; data were pooled in random effects meta‐analyses. Postnatal transmission was assessed from four to six weeks of life. Study quality was assessed using a modified Newcastle‐Ottawa Scale (NOS) and GRADE.
Results and discussion: Eleven studies were identified, from 1439 citations and review of 72 s. Heterogeneity in study methodology and pooled estimates was considerable. Overall pooled transmission rates at 6 months for breastfed infants with mothers on antiretroviral treatment (ART) was 3.54% (95% CI: 1.15–5.93%) and at 12 months 4.23% (95% CI: 2.97–5.49%). Postnatal transmission rates were 1.08 (95% CI: 0.32–1.85) at six and 2.93 (95% CI: 0.68–5.18) at 12 months. ART was mostly provided for PMTCT only and did not continue beyond six months postpartum. No study provided data on mixed feeding and transmission risk.
Conclusions: There is evidence of substantially reduced postnatal HIV transmission risk under the cover of maternal ART. However, transmission risk increased once PMTCT ART stopped at six months, which supports the current World Health Organization recommendations of life‐long ART for all.
When patients receive an intervention based on whether they score below or above some threshold value on a continuously measured random variable, the intervention will be randomly assigned for ...patients close to the threshold. The regression discontinuity design exploits this fact to estimate causal treatment effects. In spite of its recent proliferation in economics, the regression discontinuity design has not been widely adopted in epidemiology. We describe regression discontinuity, its implementation, and the assumptions required for causal inference. We show that regression discontinuity is generalizable to the survival and nonlinear models that are mainstays of epidemiologic analysis. We then present an application of regression discontinuity to the much-debated epidemiologic question of when to start HIV patients on antiretroviral therapy. Using data from a large South African cohort (2007–2011), we estimate the causal effect of early versus deferred treatment eligibility on mortality. Patients whose first CD4 count was just below the 200 cells/μL CD4 count threshold had a 35% lower hazard of death (hazard ratio = 0.65 95% confidence interval = 0.45–0.94) than patients presenting with CD4 counts just above the threshold. We close by discussing the strengths and limitations of regression discontinuity designs for epidemiology.
Objectives
To examine the association between maternal body mass index (BMI) and gestational weight gain (GWG) and adverse birth outcomes in HIV‐infected and HIV‐uninfected women.
Methods
In an urban ...South African community, 2921 consecutive HIV‐infected and HIV‐uninfected pregnant women attending primary healthcare services were assessed at their first antenatal visit. A subset of HIV‐infected women enrolled in a longitudinal study was assessed three times during pregnancy. All women had birth outcome data from medical records and study questionnaires. In analyses, the associations between BMI, GWG, maternal factors and adverse birth outcomes were assessed with logistic regression models.
Results
The estimated pre‐pregnancy BMI median was 29 kg/m2 (IQR, 24–34) overall, 29 kg/m2 (IQR, 24–34) for HIV‐uninfected and 28 kg/m2 (IQR, 24–34) for HIV‐infected women; HIV prevalence was 38%. In adjusted models, increased BMI in the overall cohort was positively associated with age, haemoglobin and parity at first antenatal visit. Maternal obesity was associated with increased likelihood of having high birthweight (aOR 2.54, 95% CI 1.39–4.66) and large size for gestational age (aOR 1.66, 95% CI 1.20–2.31) infants. In the subset cohort, GWG was associated with increased likelihood of spontaneous preterm delivery (aOR 4.35, 95% CI 1.55–12.21) and high birthweight (aOR 3.00, 95% CI 1.22–7.34) infants.
Conclusion
Obesity during pregnancy is prevalent in this setting and appears associated with increased risk of adverse birth outcomes in both HIV‐infected and HIV‐uninfected women. Weight management interventions targeting women of child‐bearing age are needed to promote healthy pregnancies and reduce adverse birth outcomes.
Objectifs
Examiner l'association entre l'indice de masse corporelle maternelle (IMC) et le gain de poids gestationnel (GPG) et les résultats de naissance défavorables chez les femmes infectées et non infectées par le VIH.
Méthodes
Dans une communauté urbaine sud‐africaine, 2921 femmes enceintes consécutives infectées et non infectées par le VIH visitant les services de soins de santé primaires ont été évaluées lors de leur première visite prénatale. Un sous‐ensemble de femmes infectées par le VIH inscrites à une étude longitudinale a été évalué trois fois pendant la grossesse. Toutes les femmes avaient des données sur les résultats à la naissance provenant des dossiers médicaux et des questionnaires d'étude. Dans les analyses, les associations entre l'IMC, le GPG, les facteurs maternels et les résultats de naissance défavorables ont été évalués en utilisant des modèles de régression logistique.
Résultats
L'IMC médian estimé avant la grossesse était globalement de 29 kg/m2 (IQR, 24‐34) pour les femmes non infectées par le VIH et 28 kg/m2 (IQR, 24 ‐34) pour celles infectées par le VIH; La prévalence du VIH était de 38%. Dans les modèles ajustés, l'augmentation de l'IMC dans la cohorte globale était positivement associée à l'âge, à l'hémoglobine et à la parité lors de la première visite prénatale. L'obésité maternelle a été associée à une augmentation de la probabilité d'avoir un nourrisson avec un poids élevé à la naissance (ORa 2,54, IC95%: 1,39‐4,66) et une grande taille pour l’âge gestationnel (ORa 1,66, IC95%: 1,20‐2,31). Dans la cohorte du sous‐ensemble, le GPG était associé à une probabilité accrue d'accouchement prématuré spontané (aOR 4,35, IC95%: 1,55‐12,21) et à des nourrissons avec un poids de naissance élevé (aOR 3,00, IC95%: 1,22‐7,34).
ConclusionL'obésité pendant la grossesse est répandue dans ce contexte et semble associée à un risque accru d'accouchements défavorables chez les femmes infectées et non infectées par le VIH. Des interventions de prise en charge du poids ciblant les femmes en âge de procréer sont nécessaires pour promouvoir des grossesses saines et réduire les issues de naissance défavorables.
Objectives
Pregnancy and post‐partum viral load suppression is critical to prevent mother‐to‐child HIV transmission and ensure maternal health. We measured viraemia risk before, during and after ...pregnancy in HIV‐infected women.
Methods
Between 2010 and 2015, 1425 HIV‐infected pregnant women on lifelong antiretroviral therapy (ART) for at least six months pre‐pregnancy were enrolled in a cohort study in rural KwaZulu‐Natal, South Africa. Odds ratios were estimated in multilevel logistic regression, with pregnancy period time‐varying.
Results
Over half of 1425 women received tenofovir‐based regimens (n = 791). Median pre‐pregnancy ART duration was 2.1 years. Of 988 women (69.3%) with pre‐pregnancy viral loads, 82.0%, 6.8% and 11.2% had VL <50, 50‐999 and ≥1000 copies/ml, respectively. During pregnancy and at six, 12 and 24 months, viral load was ≥1000 copies/ml in 15.2%, 15.7%, 17.8% and 16.6% respectively; viral load <50 was 76.9%, 77%, 75.5% and 75.8%, respectively. Adjusting for age, clinical and pregnancy factors, viraemia risk (viral load ≥50 copies/ml) was not significantly associated with pregnancy adjusted OR (aOR) 1.31; 95% CI 0.90‐1.92, six months (aOR 1.30; 95% CI 0.83‐2.04), 12 months (aOR 0.96; 95% CI 0.58‐1.58) and 24 months (aOR 1.40; 95% CI 0.89‐2.22) post‐partum. Adjusting for ART duration–pregnancy period interaction, viraemia risk was 1.8 during pregnancy and twofold higher post‐partum.
Conclusions
While undetectable viral load before pregnancy through post‐partum was common, the UNAIDS goal to suppress viraemia in 90% of women was not met. Women on preconception ART remain vulnerable to viraemia; additional support is required to prevent mother‐to‐child HIV transmission and maintain maternal health.
Objectifs
La suppression de la charge virale pendant la grossesse et après l'accouchement est essentielle pour prévenir la transmission mère‐enfant du VIH et assurer la santé maternelle. Nous avons mesuré le risque de virémie avant, pendant et après la grossesse chez les femmes infectées par le VIH.
Méthodes
Entre 2010 et 2015, 1425 femmes enceintes infectées par le VIH, sous traitement antirétroviral (ART) à vie pendant au moins six mois avant la grossesse ont été incluses dans une étude de cohorte dans le KwaZulu‐Natal, en Afrique du Sud. Les odds ratios ont été estimés dans une régression logistique à multi niveaux, avec des périodes de grossesse variables.
Résultats
Plus de la moitié des 1425 femmes ont reçu un traitement à base de ténofovir (n = 791). La durée médiane de l’ART avant la grossesse était de 2,1 ans. Sur 988 femmes (69,3%) ayant des charges virales avant la grossesse, 82,0%, 6,8% et 11,2% avaient respectivement des valeurs de <50, entre 50 et 999, et ≥1000 copies/ml. Pendant la grossesse et à six, 12 et 24 mois, la charge virale était ≥1000 copies/ml chez 15,2%, 15,7%, 17,8% et 16,6% respectivement; elle était <50 chez 76,9%, 77%, 75,5% et 75,8%, respectivement. En ajustant pour l’âge, les facteurs cliniques et de grossesse, le risque de virémie (charge virale ≥ 50 copies/ml) n’était pas significativement associé à la grossesse OR ajusté (aOR)= 1,31; IC95%: 0,90‐1,92, à six mois (aOR= 1,30; IC95%: 0,83‐2,04), à 12 mois (aOR= 0,96; IC95% : 0,58‐1,58) et à 24 mois (aOR= 1,40; IC95%: 0,89‐2,22) après l'accouchement. En ajustant pour l'interaction entre la durée de l’ART et la période de grossesse, le risque de virémie était de 1,8 pendant la grossesse et de deux fois plus élevé après l'accouchement.
Conclusions
Alors qu'une charge virale indétectable avant la grossesse et jusqu'au post‐partum était courante, l'objectif de l’ONUSIDA de supprimer la virémie chez 90% des femmes n’était pas atteint. Les femmes sous TAR avant la conception restent vulnérables à la virémie. Un soutien supplémentaire est nécessaire pour prévenir la transmission mère‐enfant du VIH et maintenir la santé maternelle.
Introduction
HIV treatment guidelines now recommend antiretroviral therapy (ART) initiation regardless of CD4 count to maximize benefit both for the individual and society. It is unknown whether the ...initiation of ART at higher CD4 counts would affect adherence levels. We investigated whether initiating ART at higher CD4 counts was associated with sub‐optimal adherence (<95%) during the first 12 months of ART.
Methods
A prospective cohort study nested within a two‐arm cluster‐randomized trial of universal test and treat was implemented from March 2012 to June 2016 to measure the impact of ART on HIV incidence in rural KwaZulu‐Natal. ART was initiated regardless of CD4 count in the intervention arm and according to national guidelines in the control arm. ART adherence was measured monthly using a visual analogue scale (VAS) and pill counts (PC). HIV viral load was measured at ART initiation, three and six months, and six‐monthly thereafter. We pooled data from participants in both arms and used random‐effects logistic regression models to examine the association between CD4 count at ART initiation and sub‐optimal adherence, and assessed if adherence levels were associated with virological suppression.
Results
Among 900 individuals who initiated ART ≥12 months before study end, median (IQR) CD4 at ART initiation was 350 cells/mm3 (234, 503); median age was 34.6 years (IQR 27.4 to 46.4) and 71.7% were female. Adherence was sub‐optimal in 14.7% of visits as measured by VAS and 20.7% by PC. In both the crude analyses and after adjusting for potential confounders, adherence was not significantly associated with CD4 count at ART initiation (adjusted OR for linear trend in sub‐optimal adherence with every 100 cells/mm3 increase in CD4 count: 1.00, 95% CI 0.95 to 1.05, for VAS, and 1.03, 95% CI 0.99 to 1.07, for PC). Virological suppression at 12 months was 97%. Optimal adherence by both measures was significantly associated with virological suppression (p < 0.001 for VAS; p = 0.006 for PC).
Conclusions
We found no evidence that higher CD4 counts at ART initiation were associated with sub‐optimal ART adherence in the first 12 months. Our findings should alleviate concerns about adherence in individuals initiating ART at higher CD4 counts, however long‐term outcomes are needed. ClinicalTrials.gov NCT01509508.
The 2015 WHO recommendation of antiretroviral therapy (ART) for all immediately following HIV diagnosis is partially based on the anticipated impact on HIV incidence in the surrounding population. We ...investigated this approach in a cluster-randomised trial in a high HIV prevalence setting in rural KwaZulu-Natal. We present findings from the first phase of the trial and report on uptake of home-based HIV testing, linkage to care, uptake of ART, and community attitudes about ART.
Between 9 March 2012 and 22 May 2014, five clusters in the intervention arm (immediate ART offered to all HIV-positive adults) and five clusters in the control arm (ART offered according to national guidelines, i.e., CD4 count ≤ 350 cells/μl) contributed to the first phase of the trial. Households were visited every 6 mo. Following informed consent and administration of a study questionnaire, each resident adult (≥16 y) was asked for a finger-prick blood sample, which was used to estimate HIV prevalence, and offered a rapid HIV test using a serial HIV testing algorithm. All HIV-positive adults were referred to the trial clinic in their cluster. Those not linked to care 3 mo after identification were contacted by a linkage-to-care team. Study procedures were not blinded. In all, 12,894 adults were registered as eligible for participation (5,790 in intervention arm; 7,104 in control arm), of whom 9,927 (77.0%) were contacted at least once during household visits. HIV status was ever ascertained for a total of 8,233/9,927 (82.9%), including 2,569 ascertained as HIV-positive (942 tested HIV-positive and 1,627 reported a known HIV-positive status). Of the 1,177 HIV-positive individuals not previously in care and followed for at least 6 mo in the trial, 559 (47.5%) visited their cluster trial clinic within 6 mo. In the intervention arm, 89% (194/218) initiated ART within 3 mo of their first clinic visit. In the control arm, 42.3% (83/196) had a CD4 count ≤ 350 cells/μl at first visit, of whom 92.8% initiated ART within 3 mo. Regarding attitudes about ART, 93% (8,802/9,460) of participants agreed with the statement that they would want to start ART as soon as possible if HIV-positive. Estimated baseline HIV prevalence was 30.5% (2,028/6,656) (95% CI 25.0%, 37.0%). HIV prevalence, uptake of home-based HIV testing, linkage to care within 6 mo, and initiation of ART within 3 mo in those with CD4 count ≤ 350 cells/μl did not differ significantly between the intervention and control clusters. Selection bias related to noncontact could not be entirely excluded.
Home-based HIV testing was well received in this rural population, although men were less easily contactable at home; immediate ART was acceptable, with good viral suppression and retention. However, only about half of HIV-positive people accessed care within 6 mo of being identified, with nearly two-thirds accessing care by 12 mo. The observed delay in linkage to care would limit the individual and public health ART benefits of universal testing and treatment in this population.
ClinicalTrials.gov NCT01509508.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background Exclusive breastfeeding, though better than other forms of infant feeding and associated with improved child survival, is uncommon. We assessed the HIV-1 transmission risks and ...survival associated with exclusive breastfeeding and other types of infant feeding. Methods 2722 HIV-infected and uninfected pregnant women attending antenatal clinics in KwaZulu Natal, South Africa (seven rural, one semiurban, and one urban), were enrolled into a non-randomised intervention cohort study. Infant feeding data were obtained every week from mothers, and blood samples from infants were taken monthly at clinics to establish HIV infection status. Kaplan-Meier analyses conditional on exclusive breastfeeding were used to estimate transmission risks at 6 weeks and 22 weeks of age, and Cox's proportional hazard was used to quantify associations with maternal and infant factors. Findings 1132 of 1372 (83%) infants born to HIV-infected mothers initiated exclusive breastfeeding from birth. Of 1276 infants with complete feeding data, median duration of cumulative exclusive breastfeeding was 159 days (first quartile Q1 to third quartile Q3, 122–174 days). 14·1% (95% CI 12·0–16·4) of exclusively breastfed infants were infected with HIV-1 by age 6 weeks and 19·5% (17·0–22·4) by 6 months; risk was significantly associated with maternal CD4-cell counts below 200 cells per μL (adjusted hazard ratio HR 3·79; 2·35–6·12) and birthweight less than 2500 g (1·81, 1·07–3·06). Kaplan-Meier estimated risk of acquisition of infection at 6 months of age was 4·04% (2·29–5·76). Breastfed infants who also received solids were significantly more likely to acquire infection than were exclusively breastfed children (HR 10·87, 1·51–78·00, p=0·018), as were infants who at 12 weeks received both breastmilk and formula milk (1·82, 0·98–3·36, p=0·057). Cumulative 3-month mortality in exclusively breastfed infants was 6·1% (4·74–7·92) versus 15·1% (7·63–28·73) in infants given replacement feeds (HR 2·06, 1·00–4·27, p=0·051). Interpretation The association between mixed breastfeeding and increased HIV transmission risk, together with evidence that exclusive breastfeeding can be successfully supported in HIV-infected women, warrant revision of the present UNICEF, WHO, and UNAIDS infant feeding guidelines.
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