Showing papers by "Marie-Louise Newell published in 2016"

Uptake of Home-Based HIV Testing, Linkage to Care, and Community Attitudes about ART in Rural KwaZulu-Natal, South Africa : Descriptive Results from the First Phase of the ANRS 12249 TasP Cluster-Randomised Trial

Abstract: Authors Collins C. Iwuji, Joanna Orne-Gliemann, Joseph Larmarange, Nonhlanhla Okesola, Frank Tanser, Rodolphe Thiebaut, Claire Rekacewicz, Marie-Louise Newell, Francois Dabis for the ANRS 12249 TasP trial group Abstract Background 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 (...)

Access to HIV care in the context of universal test and treat: challenges within the ANRS 12249 TasP cluster-randomized trial in rural South Africa

Abstract: Introduction: We aimed to quantify and identify associated factors of linkage to HIV care following home-based HIV counselling and testing (HBHCT) in the ongoing ANRS 12249 treatment-as-prevention (TasP) cluster-randomized trial in rural KwaZulu-Natal, South Africa. Methods: Individuals ]16 years were offered HBHCT; those who were identified HIV positive were referred to cluster-based TasP clinics and offered antiretroviral treatment (ART) immediately (five clusters) or according to national guidelines (five clusters). HIV care was also available in the local Department of Health (DoH) clinics. Linkage to HIV care was defined as TasP or DoH clinic attendance within three months of referral among adults not in HIV care at referral. Associated factors were identified using multivariable logistic regression adjusted for trial arm. Results: Overall, 1323 HIV-positive adults (72.9% women) not in HIV care at referral were included, of whom 36.9% (n 0488) linked to care B3 months of referral (similar by sex). In adjusted analyses (n 01222), individuals who had never been in HIV care before referral were significantly less likely to link to care than those who had previously been in care (B33% vs. !42%, p B0.001). Linkage to care was lower in students (adjusted odds-ratio [aOR] 00.47; 95% confidence interval [CI] 0.24A0.92) than in employed adults, in adults who completed secondary school (aOR 00.68; CI 0.49A0.96) or at least some secondary school (aOR 00.59; CI 0.41A0.84) versus 5 primary school, in those who lived at 1 to 2 km (aOR 00.58; CI 0.44A0.78) or 2A5 km from the nearest TasP clinic (aOR 00.57; CI 0.41A0.77) versus B1 km, and in those who were referred to clinic after ]2 contacts (aOR 00.75; CI 0.58A0.97) versus those referred at the first contact. Linkage to care was higher in adults who reported knowing an HIV-positive family member (aOR 01.45; CI 1.12A1.86) versus not, and in those who said that they would take ART as soon as possible if they were diagnosed HIV positive (aOR 02.16; CI 1.13A4.10) versus not. Conclusions: Fewer than 40% of HIV-positive adults not in care at referral were linked to HIV care within three months of HBHCT in the TasP trial. Achieving universal test and treat coverage will require innovative interventions to support linkage to HIV care. Keywords: HIV/AIDS; home-based HIV counselling and testing; linkage to care; universal test and treat; South Africa.

Exclusive Breastfeeding and Cognition, Executive Function, and Behavioural Disorders in Primary School-Aged Children in Rural South Africa: A Cohort Analysis

Abstract: Background: exclusive breastfeeding (EBF) is associated with early child health; longer-term benefits for child development remain inconclusive. We examine associations between EBF, HIV exposure, and other maternal/child factors, with cognitive and emotional-behavioural development in children aged 7-11 years. Methods and findings: the Vertical Transmission Study (VTS) supported EBF in HIV-positive and negative women; between 2012-2014 HIV-negative VTS children (332 HIV-exposed, 574 HIV-unexposed) were assessed on cognition (KABC-II), executive function (NEPSY-II), and emotional-behavioural functioning (CBCL). We developed population means by combining the VTS sample with 629 same-aged HIV-negative children from the local Demographic Platform. For each outcome we split the VTS sample into scores above or at/below each population mean and modelled each outcome using logistic regression analyses, overall and stratified by child sex. There was no demonstrated effect of EBF on overall cognitive functioning. EBF was associated with fewer conduct disorders overall (aOR0.44 [95%CI 0.3-0.7] p Conclusions: EBF was associated with fewer than average conduct disorders, and weakly with improved cognitive development in boys. Efforts to improve stimulation at home, reduce maternal stress, and enable creche attendance are likely to improve executive function and emotional-behavioural development of children.

Mortality risk and associated factors in HIV-exposed, uninfected children.

Abstract: Objective: Although with increasing maternal ART, the number of children newly infected with HIV has declined, possible increased mortality in the large number of HEU children may be of concern. We quantified mortality risks among HEU children and reviewed associated factors. Methods: Systematic search of electronic databases (PubMed, Scopus). We included all studies reporting mortality of HEU children to age 60 months and associated factors. Relative risk of mortality between HEU and HUU children was extracted where relevant. Inverse variance methods were used to adjust for study size. Random-effects models were fitted to obtain pooled estimates. Results: Fourteen studies were included in the meta-analysis and thirteen in the review of associated factors. The pooled cumulative mortality in HEU children was 5.5% (95% CI: 4.0-7.2; I2=?94%) at 12 months (11 studies) and 11.0% (95% CI: 7.6-15.0; I2?=?93%) at 24 months (4 studies). The pooled risk ratios for the mortality in HEU children compared to HUU children in the same setting were 1.9 (95% CI: 0.9-3.8; I2=?93%) at 12 months (4 studies) and 2.4 (95% CI: 1.1-5.1; I2=?93%) at 24 months (3 studies). Conclusion: Compared to HUU children, mortality risk in HEU children was about double at both age points, although the association was not statistically significant at 12 months. Interpretation of the pooled estimates is confounded by considerable heterogeneity between studies. Further research is needed to inform the impact of maternal death and breastfeeding on the survival of HEU infants in the context of maternal ART, where current evidence is limited.

Factors associated with pre-ART loss-to-follow up in adults in rural KwaZulu-Natal, South Africa: a prospective cohort study

Abstract: Timely initiation of antiretroviral treatment (ART) requires sustained engagement in HIV care before treatment eligibility. We assessed loss to follow-up (LTFU) correlates in HIV-positive adults accessing HIV treatment and care, not yet ART-eligible (CD4 >500 cells/mm 3 ).

Children and HIV - a hop (hopefully), a skip (lamentably) and a jump (ideally)?

Abstract: The noted children’s human rights lawyer, Michael Freeman, posed the provocative question of whether the world viewed children as “beings or becomings?” (Freeman, 2015). This encapsulates some of the challenges and dilemmas in the way children infected or affected by HIV are served. Narratives around “investing for the future” and “tomorrow’s generation” are in line with an idea that children are becoming adults, becoming human – but obscure their current needs and understate the place of children as current active agents. An equity focus, as called for in this special issue of AIDS Care, would support the needs of children as beings. The end of 2015 saw the end of the Millennium Development Goals (MDGs), and achievements inclusive of substantial reduction of mother-to-child transmission (MTCT) of HIV, prevention of HIV and decrease in HIV incidence as well as expansion of HIV treatment and care programmes globally, but in particular in the most-affected countries of Sub-Saharan Africa (SSA). Yet there are situations where outcomes for children are wanting. These include the unacceptably high 30% MTCT in the Democratic Republic of the Congo (Edmonds et al., 2015; United Nations General Assembly Special Session [UNGASS], 2014) where decentralisation has not ensured higher proportions of pregnant women receiving the full package of interventions at antenatal care, Zimbabwe struggling to reduce national vertical transmission rates to under 5%, being 9.6% in 2013 (UNAIDS, 2014a) and Burundi’s modelled at 24.5% (UNGASS, 2015). Children continue to lag in the equity response, with, compared to adults, fewer children on treatment, 76.9% of adults versus 46% of children in Zimbabwe and 12% in Burundi (UNAIDS, 2014a). It is also notable that fewer children are tested for HIV, and that children receive consistently fewer mentions or considerations in plans, policies and future agendas (Sherr, Cluver, Tomlinson, & Coovadia, 2015). Even those organising the 2016 high-level UN meeting’s civil society consultations forgot that children were part of civil society. Newer antiretroviral treatment (ART) drugs are not formulated for children, making administration and ultimately adherence even more of a challenge. Young girls remain disproportionately affected by HIV compared to boy children (Singh, Rai, & Kumar, 2013). In 2014, 220,000 (190,000 in SSA) children below the age of 15 years were living with HIV globally, nearly all of whom became infected through MTCT. The prevalence of HIV among pregnant women varies from less than 1% in resource-rich settings of Western Europe, America and Asia to over 40% in some areas of southern Africa (UNAIDS, 2014b). Although the UN has prioritised the virtual elimination of vertically-acquired HIV, the complex machinery and interplay of policy, implementation and review needs to be further expanded for this final goal to be met – achievable as evidenced by the dramatic downturn of children infected at birth as recorded in many settings. ByMarch 2015, 15million people had been initiated onto ART globally, nearly 11 million in SSA; it is unclear how many remain on treatment and how many of these are virally suppressed. About 40% of HIV-infected adults were estimated to have accessed ART, but only 32%, or even less, of children; in 2014 nearly three-quarters of pregnant women living with HIV had access to ART for the prevention of mother-to-child transmission (PMTCT) – again high numbers although universal access is not yet enjoyed everywhere. Elimination would require a complete cascade of programmatic provision to ensure universal and appropriately regular HIV testing of all pregnant women to ensure identification of HIV early in pregnancy, followed by comprehensive roll out of appropriate HIV care, ART and support. Better still, not only should HIV-negative pregnant women in high-prevalence areas be tested regularly, but also their households including their partners – this has been reported to halve HIV acquisition (Fatti, Ngonzo, & Grimwood, 2013) in these most vulnerable women. The 2010 WHO PMTCT B+ regime, which included sustained ART for life for pregnant or lactating women once diagnosed, contributes to preventing MTCT during pregnancy and postnatally and reduced transmission to sexual partners – thus indirectly protecting fatherhood as well. WHO recommendations relating to treatment eligibility have been expanded over time, with the most recent, September 2015, guidelines suggesting starting ART immediately upon HIV diagnosis for all, irrespective of clinical or immunological disease progression. This new recommendation thus merges PMTCT with optimal treatment of HIV-infected women. And now there is pre-exposure prophylaxis which could be a valuable adjunct to safer/barrier sex in further protecting women and reducing HIV transmission in discordant couples. All these elements can contribute to provision for safe and healthy families – the bedrock of child development and positive child environments. MTCT can occur before, during and after delivery. With the use of ART in the prevention of MTCT, rates of MTCT

Association between breast milk fatty acids and HIV-1 transmission through breastfeeding.

Abstract: A residual mother-to-child transmission of HIV through breastfeeding persists despite prophylaxis. We identified breast milk fatty acids (FA) associated with postnatal HIV transmission through breastfeeding in a case-control study. Cases (n=23) were HIV-infected women with an infant who acquired HIV after 6 weeks of age. Controls (n=23) were matched on infant׳s age at sample collection. Adjusting for maternal antenatal plasma CD4 T cell count, cis-vaccenic acid (18:1n-7) and eicosatrienoic acid (20:3n-3) were associated with HIV transmission in opposite dose-response manner: OR (tertile 3 versus tertile 1): 10.8 and 0.16, p for trend=0.02 and 0.03, respectively. These fatty acids correlated with HIV RNA load, T helper-1 related cytokines, IL15, IP10, and β2 microglobulin, positively for cis-vaccenic acid, negatively for eicosatrienoic acid. These results suggested a change in FA synthesis by mammary gland cells leading to increased cis-vaccenic acid in milk of mothers who transmitted HIV to their infant during breastfeeding.

The effect of maternal and child early life factors on grade repetition among HIV exposed and unexposed children in rural KwaZulu-Natal, South Africa.

Abstract: Receiving an education is essential for children living in poverty to fulfil their potential. Success in the early years of schooling is important as children who repeat grade one are particularly at risk for future dropout. We examined early life factors associated with grade repetition through logistic regression and explored reasons for repeating a grade through parent report. In 2012–2014 we re-enrolled children aged 7–11 years in rural KwaZulu-Natal who had been part of an early life intervention. Of the 894 children included, 43.1% had repeated a grade, of which 62.9% were boys. Higher maternal education (aOR 0.44; 95% CI 0.2–0.9) and being further along in the birth order (aOR 0.46; 95% CI 0.3–0.9) reduced the odds of grade repetition. In addition, maternal HIV status had the strongest effect on grade repetition for girls (aOR 2.17; 95% CI 1.3–3.8), whereas for boys, it was a fridge in the household (aOR 0.59; 95% CI 0.4–1.0). Issues with school readiness was the most common reason for repeating a grade according to parental report (126/385, 32.7%), while school disruptions was an important reason among HIV-exposed boys. Further research is needed to elucidate the pathways through which HIV affects girls’ educational outcomes and potentially impacts on disrupted schooling for boys. Our results also highlight the importance of preparation for schooling in the early years of life; future research could focus on gaining a better understanding of mechanisms by which to improve early school success, including increased quality of reception year and investigating the protective effect of older siblings.

HIV treatment as prevention: applicable in sub-Saharan Africa?

Abstract: Antiretroviral treatment decreases the risk of HIV acquisition in stable serodiscordant couples and the general population in high HIV prevalence settings. However, HIV elimination will probably not be achieved by one prevention approach to fi t all, but will require a combination of eff ective interventions contextualised to the specifi c epidemic to achieve virtual elimination, defi ned as one new HIV infection per 1000 individuals. In The Lancet Infectious Diseases, Justin Okano and colleagues tested whether treatment as prevention with antiretroviral treatment can eliminate HIV in men who have sex with men in the nationwide Danish HIV cohort study. They used CD4-staged Bayesian backcalculation to estimate the annual incidence in men who have sex with men in Denmark and the number of undiagnosed men who have sex with men likely to continue to transmit HIV infection. The unique civic registration number assigned to all Danish residents allowed linking the relevant registries. Estimated HIV incidence was 1·4 per 1000 men who have sex with men in 2013, close to the elimination threshold, and an estimated 21% of all HIV-infected men who have sex with men in Denmark remained undiagnosed. The incidence reduction was attributed to increasing antiretroviral treatment coverage, with a signifi cant eff ect when treatment coverage reached 35%. However, the context of this study needs to be appreciated; men who have sex with men drive the Danish HIV epidemic, are nearly universally engaged in HIV care, with extensive antiretroviral treatment coverage immediately upon HIV diagnosis, and strict adherence and viral suppression; in these circumstances treatment as prevention works to curb the HIV epidemic. These essential conditions have not been replicated elsewhere in western Europe and this scenario, coupled with behavioural risk compensation reported in men who have sex with men in Denmark and elsewhere in Europe after antiretroviral treatment-associated reduced morbidity and mortality, means treatment as prevention alone is unlikely to be the silver bullet that decision-makers had hoped for. The big question remains whether in heterosexuallydriven HIV epidemics such as in sub-Saharan Africa, treatment as prevention will eventually reduce HIV incidence to such low levels that the end of the epidemic will be in sight. In a rural area in South Africa with high HIV prevalence and incidence and antiretroviral treatment provided only to those with advanced HIV progression, antiretroviral treatment coverage higher than 20% was associated with a reduction in an individual’s risk of HIV acquisition, albeit not to the low levels seen in Danish men who have sex with men. It is unclear whether this was due to later antiretroviral treatment initiation in South Africa than in Denmark, whether a heterosexual epidemic diff ers from that in men who have sex with men and treatment as prevention alone is insuffi cient, or whether adherence, and thus viral suppression, was sub-optimum. UNAIDS coined the 90:90:90 target to provide a structure for treatment as prevention to achieve its goal of epidemic containment: 90% of people to know their HIV status, 90% of HIV-infected people to be on antiretroviral treatment, and 90% of those on antiretroviral treatment to be virally suppressed. In sub-Saharan Africa, concentrated epidemics exist within the generalised HIV epidemic, and it has been suggested that focusing context-specifi c combination interventions to areas of high transmission and people at most risk of HIV infection achieves more eff ect than a uniformly-distributed intervention. Experience from ongoing studies and HIV treatment programmes in sub-Saharan Africa, the region of highest need, shows that HIV care and treatment does not reach all those in need, that vulnerable groups including young people and men are failing to engage with health care, that asymptomatic people might be less likely to engage with, and be retained in, care and that lifelong adherence to antiretroviral treatment might be complex in settings where other health challenges prevail. With antiretroviral treatment-eligibility expansion, also in sub-Saharan Africa, and consequent rapid increase in antiretroviral treatment coverage coupled with adherence and viral suppression rates that are not as good as those recorded in men who have sex with men in Denmark, the crucial question now is whether earlier treatment will lead to drug resistance of the form and prevalence likely to compromise future elimination of HIV. Findings from four ongoing cluster-randomised trials, one of which is due to report later this year, will provide further insight about the eff ectiveness Go do ng /B SI P/ Sc ie nc e Ph ot o Li br ar y