Psychological morbidity and parenting stress in mothers of primary school children by timing of acquisition of HIV infection: a longitudinal cohort study in rural South Africa.

Longitudinal maternal mental health data are needed from high HIV prevalence settings. The Siyakhula Cohort (SC) is a population-based cohort of HIV-positive and negative mothers (n=1506) with HIV-negative children (n=1536) from rural South Africa. SC includes 767 HIV-negative mothers; 465 HIV-positive in pregnancy; 272 HIV-positive since pregnancy (n=2 missing HIV status). A subgroup (n=890) participated in a non-randomized breastfeeding intervention [Vertical Transmission Study (VTS)]; the remaining (n=616) were resident in the same area and received antenatal care at the time of the VTS, but were not part of the VTS, instead receiving the standard of care Prevention of Mother-to-Child Transmission (PMTCT) Programme. In secondary analysis we investigated the prevalence of, and factors associated with, psychological morbidity amongst mothers who were still the primary caregiver of the child (1265 out of 1506) at follow-up (7-11 years post-birth). We measured maternal depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder Scale-7) and parenting stress (Parenting Stress Index-36), using standardized cut-offs and algorithms. In total, 75 (5.9%) mothers met criteria for depression, 37 (2.9%) anxiety and 134 (10.6%) parenting stress. Using complete case logistic regression (n=1206 out of 1265 mothers) as compared to being HIV-negative, testing HIV-positive in pregnancy doubled odds of depression [adjusted odd ratios (aOR)=1.96 [1.0-3.7] P=0.039]. Parenting stress was positively associated with acquisition of HIV after pregnancy (aOR=3.11 [1.9-5.2] P<0.001) and exposure to household crime (aOR=2.02 [1.3-3.2] P=0.003); negatively associated with higher maternal education (aOR=0.29 [0.1-0.8] P=0.014), maternal employment (aOR=0.55 [0.3-0.9] P=0.024). Compared with the standard of care PMTCT, VTS mothers had reduced odds of parenting stress (aOR=0.61 [0.4-0.9] P=0.016). Integrating parental support into mostly bio-medical treatment programmes, during and beyond pregnancy, is important.

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

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 ß2 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.

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.

Time to eligibility for antiretroviral therapy in adults with CD4 cell count > 500 cells/µL in rural KwaZulu-Natal, South Africa.

OBJECTIVES: Understanding of progression to antiretroviral therapy (ART) eligibility and associated factors remains limited. The objectives of this analysis were to determine the time to ART eligibility and to explore factors associated with disease progression in adults with early HIV infection. METHODS: HIV-infected adults (≥ 18 years old) with CD4 cell count > 500 cells/µl were enrolled in the study at three primary health care clinics, and a sociodemographic, behavioural and partnership-level questionnaire was administered. Participants were followed 6-monthly and ART eligibility was determined using a CD4 cell count threshold of 350 cells/µl. Kaplan - Meier and Cox proportional hazard regression modelling were used in the analysis. RESULTS: A total of 206 adults contributed 381 years of follow-up; 79 (38%) reached the ART eligibility threshold. Median time to ART eligibility was shorter for male patients (12.0 months) than for female patients (33.9 months). Male sex [adjusted hazard ratio (aHR) 3.13; 95% confidence interval (CI) 1.82-5.39], residing in a household with food shortage in the previous year (aHR 1.58; 95% CI 0.99-2.54), and taking nutritional supplements in the first 6 months after enrolment (aHR 2.06; 95% CI 1.11-3.83) were associated with shorter time to ART eligibility. Compared with reference CD4 cell count ≤ 559 cells/µl, higher CD4 cell count was associated with longer time to ART eligibility [aHR 0.46 (95% CI 0.25-0.83) for CD4 cell count 560-632 cells/µl; aHR 0.30 (95% CI 0.16-0.57) for CD4 cell count 633-768 cells/µl; and aHR 0.17 (95% CI 0.08-0.38) for CD4 cell count > 768 cells/µl]. CONCLUSIONS: Over one in three adults with CD4 cell count > 500 cells/µl became eligible for ART at a CD4 cell count threshold of 350 cells/µl over a median of 2 years. The shorter time to ART eligibility in male patients suggests a possible need for sex-specific pre-ART care and monitoring strategies.

Who cares? Implications of care-giving and -receiving by HIV-infected or -affected older people on functional disability and emotional wellbeing.

This paper examines how care-giving to adults and/or children and care-receiving is associated with the health and wellbeing of older people aged 50+ in rural South Africa. Data used are from a cross-sectional survey adapted from World Health Organization's Study on Global Ageing and Adult Health (SAGE) conducted in 2009/10 in rural South Africa. Bivariate statistics and multivariate logistical regression were used to assess the relationship between care-giving and/or care-receiving with functional disability, quality of life or emotional wellbeing, and self-rated health status, adjusted for socio-demographic factors. Sixty-three per cent of 422 older people were care-givers to at least one young adult or child; 27 per cent of older people were care-givers due to HIV-related reasons in young adults; 84 per cent of participants were care-recipients mainly from adult children, grandchildren and spouse. In logistic regressions adjusting for sex, age, marital status, education, receipt of grants, household headship, household wealth and HIV status, care-giving was statistically significantly associated with good functional ability as measured by ability to perform activities of daily living. This relationship was stronger for older people providing care-giving to adults than to children. In contrast, care-givers were less likely to report good emotional wellbeing; again the relationship was stronger for care-givers to adults than children. Simultaneous care-giving and -receiving was likewise associated with good functional ability, but about a 47 per cent lower chance of good emotional wellbeing. Participants who were HIV-infected were more likely to be in better health but less likely to be receiving care than those who were HIV-affected. Our findings suggest a strong relationship between care-giving and poor emotional wellbeing via an economic or psychological stressor pathway. Interventions that improve older people's socio-economic circumstances and reduce financial hardship as well as those that provide social support would go some way towards mitigating this relationship.

Barriers to antiretroviral treatment initiation in rural KwaZulu-Natal, South Africa.

OBJECTIVES: Although antiretroviral therapy (ART) has been freely available since 2004 in South Africa, not all those who are eligible initiate ART. We aimed to investigate individual and household characteristics as barriers to ART initiation in men and women in rural KwaZulu-Natal. METHODS: Adults ≥ 16 years old living within a sociodemographic surveillance area (DSA) who accessed the local HIV programme between 2007 and 2011 were included in the study. Individual and household factors associated with ART initiation within 3 months of becoming eligible for ART were investigated using multivariable logistic regression stratified by sex and after exclusion of individuals who died before initiating ART. RESULTS: Of the 797 men and 1598 women initially included, 8% and 5.5%, respectively, died before ART initiation and were excluded from further analysis. Of the remaining 733 men and 1510 women, 68.2% and 60.2%, respectively, initiated ART ≤ 3 months after becoming eligible (P = 0.34 after adjustment for CD4 cell count). In men, factors associated with a higher ART initiation rate were being a member of a household located < 2 km from the nearest HIV clinic and being resident in the DSA at the time of ART eligibility. In women, ART initiation was more likely in those who were not pregnant, in members of a household where at least one person was on ART and in those with a high wealth index. CONCLUSIONS: In this rural South African setting, barriers to ART initiation differed for men and women. Supportive individual- and household-level interventions should be developed to guarantee rapid ART initiation taking account gender specificities.

Prevalence and correlates of depression among HIV-infected and -affected older people in rural South Africa.

BACKGROUND: Little is known about depression in older people in sub-Saharan Africa, the associated impact of HIV, and the influence on health perceptions. OBJECTIVES: Examine the prevalence and correlates of depression; explore the relationship between depression and health perceptions in HIV-infected and -affected older people. METHODS: In 2010, 422 HIV-infected and -affected participants aged 50+ were recruited into a cross-sectional study. Nurse professionals interviewed participants and a diagnosis of depressive episode was derived from the Composite International Diagnostic Interview (Depression module) using the International Classification of Diseases diagnostic criteria and categorised as major (MDE) or brief (BDE). RESULTS: Overall, 42.4% (n=179) had a depressive episode (MDE: 22.7%, n=96; BDE: 19.7%, n=83). Prevalence of MDE was significantly higher in HIV-affected (30.1%, 95% CI 24.0-36.2%) than HIV-infected (14.8%, 95% CI 9.9-19.7%) participants; BDE was higher in HIV-infected (24.6%, 95% CI 18.7-30.6%) than in HIV-affected (15.1%, 95% CI 10.3-19.8%) participants. Being female (aOR 3.04, 95% CI 1.73-5.36), receiving a government grant (aOR 0.34, 95% CI 0.15-0.75), urban residency (aOR 1.86, 95% CI 1.16-2.96) and adult care-giving (aOR 2.37, 95% CI 1.37-4.12) were significantly associated with any depressive episode. Participants with a depressive episode were 2-3 times more likely to report poor health perceptions. LIMITATIONS: Study limitations include the cross-sectional design, limited sample size and possible selection biases. CONCLUSIONS: Prevalence of depressive episodes was high. Major depressive episodes were higher in HIV-affected than HIV-infected participants. Psycho-social support similar to that of HIV treatment programmes around HIV-affected older people may be useful in reducing their vulnerability to depression.

An integrated approach to improving the availability and utilisation of tuberculosis healthcare in rural South Africa.

BACKGROUND: Patients with tuberculosis (TB) face several challenges in accessing care, and an integrated service that includes HIV testing could be preferable for them and ensure timely HIV treatment initiation and optimal TB care. OBJECTIVES: To investigate factors, including uptake of the offer of HIV testing, associated with availability and utilisation of healthcare by TB patients in a rural programme devolved to primary care in Hlabisa sub-district, KwaZulu-Natal. METHODS: Three hundred TB patients were randomly selected in a two-stage-sampling scheme with five primary healthcare clinic (PHC) sampling units selected with probability proportional to size. Data were collected using a structured questionnaire. We describe key availability and utilisation factors and analyse factors associated with being offered an HIV test in multiple regressions controlling for sex, age, education, employment and marital status. RESULTS: Most patients (75.2%) received care for a first episode of TB, mainly pulmonary. Nearly all (94.3%) were offered an HIV test during their current TB treatment episode, patients using their closest clinic being substantially more likely to have been offered HIV testing than those not using their closest clinic (adjusted odds ratio 12.79, p=0.05). About one-fifth (20.3%) of patients did not take medication under observation, and 3.4% reported missing taking their tablets at some stage. Average travelling time to the clinic and back was 2 hours, most patients (56.8%) using minibus taxis. CONCLUSION: We demonstrate high HIV testing rates among TB patients in a rural public programme, suggesting appropriate management of HIV-TB co-infected patients. We describe healthcare availability and utilisation factors that can inform the proposed district management teams for PHC re-engineering on areas needing improvement.

HIV status and participation in HIV surveillance in the era of antiretroviral treatment: a study of linked population-based and clinical data in rural South Africa.

OBJECTIVE: To examine whether HIV status affects participation in a population-based longitudinal HIV surveillance in the context of an expanding HIV treatment and care programme in rural South Africa. METHOD: We regressed consent to participate in the HIV surveillance during the most recent fieldworker visit on HIV status (based on previous surveillance participation or enrollment in pre-antiretroviral treatment (pre-ART) care or ART in the local HIV treatment and care programme), controlling for sex, age and year of the visit (N = 25,940). We then repeated the regression using the same sample but, in one model, stratifying HIV-infected persons into three groups (neither enrolled in pre-ART care nor receiving ART; enrolled in pre-ART care but not receiving ART; receiving ART) and, in another model, additionally stratifying the group enrolled in pre-ART and the group receiving ART into those with CD4 count ≤ 200/µl (i.e. the ART eligibility threshold at the time) vs. those with CD4 count >200/µl. RESULTS: HIV-infected individuals were significantly less likely to consent to participate in the surveillance than HIV-uninfected individuals [adjusted odds ratio (aOR), 0.74; 95% confidence interval, 0.70-0.79, P < 0.001], controlling for other factors. Persons who were receiving ART were less likely to consent to participate (aOR, 0.75, 0.68-0.84, P < 0.001) than those who had never sought HIV treatment or care (aOR, 0.82, 0.75-0.89, P < 0.001), but more likely to consent than persons enrolled in pre-ART care (aOR 0.62, 0.56-0.69, P < 0.001). Those with CD4 count ≤ 200/µl were significantly less likely to consent to participate than those with CD4 count >200/µl in both the group enrolled in pre-ART and the group receiving ART. CONCLUSION: As HIV test results are not made available to participants in the HIV surveillance, our findings agree with the hypothesis that HIV-infected persons are less likely than HIV-uninfected persons to participate in HIV surveillance because they fear the negative consequences of others learning about their HIV infection. Our results further suggest that the increased knowledge of HIV status that accompanies improved ART access can reduce surveillance participation of HIV-infected persons, but that this effect decreases after ART initiation, in particular in successfully treated patients.

Use of dried blood spots for the determination of genetic variation of interleukin-10, killer immunoglobulin-like receptor and HLA class I genes.

Optimal methods for using dried blood spots (DBSs) for population genetics-based studies have not been well established. Using DBS stored for 8 years from 21 pregnant South African women, we evaluated three methods of gDNA extraction with and without whole-genome amplification (WGA) to characterize immune-related genes: interleukin-10 (IL-10), killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I. We found that the QIAamp DNA mini kit yielded the highest gDNA quality (P< 0.05; Wilcoxon signed rank test) with sufficient yield for subsequent analyses. In contrast, we found that WGA was not reliable for sequence-specific primer polymerase chain reaction (SSP-PCR) analysis of KIR2DL1, KIR2DS1, KIR2DL5 and KIR2DL3 or high-resolution HLA genotyping using a sequence-based approach. We speculate that unequal template amplification by WGA underrepresents gene repertoires determined by sequence-based approaches.

The impact of mode of acquisition on biological markers of paediatric hepatitis C virus infection.

Despite the introduction of blood donor screening, worldwide, children continue to become infected with hepatitis C virus (HCV) via un-sterile medical injections, receipt of unscreened blood and isolated hospital contamination outbreaks. It is plausible that the natural history and disease progression in these children might differ from that of their vertically infected counterparts. Vertically and parenterally HCV-infected children were prospectively followed within the European Paediatric HCV Network and the UK National HCV Register, respectively. Biological profiles were compared. Vertically and parenterally HCV-infected children differed in terms of some key characteristics including the male to female ratio and the proportion of children receiving therapy. Parenterally infected children were more likely to have at least one hepatomegaly event during follow-up, 20%vs 10%. Parenteral infection did not significantly affect the odds of being consistently viraemic (AOR 1.14, P = 0.703) and there was no significant difference in the odds of having consistently elevated ALT levels and mode of acquisition (AOR 0.83, P = 0.748). The proportion of children with 2 or more markers of HCV infection did not differ significantly by mode of acquisition (χ(2) 1.13, P = 0.288). This analysis does not support substantial differences between vertically and parenterally infected groups, but there are specific mechanisms identified requiring further investigation. Given the continued parenteral infection of children worldwide, it is vital that knowledge of disease progression in this group is accurate and that the differences in comparison with vertically infected children are clarified to inform more accurate and individualized clinical management.

British HIV Association and Children's HIV Association position statement on infant feeding in the UK 2011.

To prevent the transmission of HIV infection during the postpartum period, the British HIV Association and Children's HIV Association (BHIVA/CHIVA) continue to recommend the complete avoidance of breast feeding for infants born to HIV-infected mothers, regardless of maternal disease status, viral load or treatment.

Challenges in PMTCT antiretroviral adherence in northern KwaZulu-Natal, South Africa.

BACKGROUND: Women living with HIV in sub-Saharan Africa face significant challenges in accessing HIV care and adhering to antiretroviral therapy. Most reports have focused on issues relating to long-term adherence such as those surrounding stigma and disclosure, hunger, cultural factors, lack of accurate health information, lack of social support, medication side effects and overcrowded health systems. Information related to the challenges facing pregnant women when taking antiretrovirals for prophylactic purposes is limited. The "Kesho Bora Study" is a multicentre prevention of mother-to-child transmission (PMTCT) trial in sub-Saharan Africa evaluating the PMTCT efficacy of triple therapy until cessation of breast feeding compared to short course zidovudine monotherapy in a predominantly breast feeding population. Following unexplained discrepancies during objective adherence assessments, a sub-study was conducted at one site to examine the underlying adherence issues. METHODS: The counselling and clinical notes of all 100 enrolled Zulu women were examined. Extracted information was supplemented by unstructured, free-ranging interviews conducted by trained adherence counsellors on 43 consecutive women attending the trial clinic over a two-week period. Adherence was defined as good (>95% adherence), or poor (<95% adherence). RESULTS: Reasons provided for sub-optimal adherence included therapy misconceptions/misunderstandings, antiretroviral use by relatives, domestic violence, poverty and issues relating to disclosure and stigma. About 61% (57/94) of antenatal women had good adherence with their PMTCT prophylaxis, with no significant difference shown between those taking the long and short course. CONCLUSION: Antenatal women in northern rural KwaZulu-Natal face significant challenges in taking antiretroviral PMTCT prophylaxis.

Prevention of mother-to-child transmission of HIV in resource-rich and -poor settings.

Without prevention, a third of HIV-exposed infants acquire HIV in breastfeeding populations before, during, or after delivery through mother-to-child transmission (MTCT). Whereas MTCT is now a sentinel event in resource-rich countries with antiretroviral prophylaxis, caesarean section, and avoidance of breastfeeding, this is not yet the case in resource-poor settings because breastfeeding is crucial to infant survival. Recent advances in postpartum maternal and infant prophylaxis enables safer breastfeeding, and increasing numbers of women accessing treatment and prevention of MTCT services in sub-Saharan Africa is leading to optimism that MTCT could be eliminated here also, as reflected in the UNAIDS target of 2015.

Antiretroviral therapy and preterm delivery-a pooled analysis of data from the United States and Europe.

OBJECTIVE: To investigate reported differences in the association between highly active antiretroviral therapy (HAART) in pregnancy and the risk of preterm delivery among HIV-infected women. DESIGN: Combined analysis of data from three observational studies. SETTING: USA and Europe. POPULATION: A total of 19, 585 singleton infants born to HIV-infected women, 1990-2006. METHODS: Data from the Pediatric Spectrum of HIV Disease project (PSD), a US monitoring study, the European Collaborative Study (ECS), a consented cohort study, and the National Study of HIV in Pregnancy and Childhood (NSHPC), the United Kingdom and Ireland surveillance study. MAIN OUTCOME MEASURE: Preterm delivery rate (<37 weeks of gestation). RESULTS: Compared with monotherapy, HAART was associated with increased preterm delivery risk in the ECS (adjusted odds ratio [AOR] 2.40, 95% CI 1.49-3.86) and NSHPC (AOR 1.43, 95% CI 1.10-1.86), but not in the PSD (AOR 0.92, 95% CI 0.67-1.26), after adjusting for relevant covariates. Because of heterogeneity, data were not pooled for this comparison, but heterogeneity disappeared when HAART was compared with dual therapy (P = 0.26). In a pooled analysis, HAART was associated with 1.5-fold increased odds of preterm delivery compared with dual therapy (95% CI 1.19-1.87, P=0.001), after adjusting for covariates. CONCLUSIONS: Heterogeneity in the association between HAART and preterm delivery was not explained by study design, adjustment for confounders or a standard analytical approach, but may have been the result of substantial differences in populations and data collected. The pooled analysis comparing HAART with dual therapy showed an increased risk of preterm delivery associated with HAART.

Discordance between CD4 cell count and CD4 cell percentage: implications for when to start antiretroviral therapy in HIV-1 infected children.

OBJECTIVE: Antiretroviral therapy (ART) guidelines for HIV-1-infected children specify both absolute CD4 cell count and CD4 percentage thresholds at which consideration should be given to initiating ART. This leads to clinical dilemma when one marker is below the threshold, whereas the other is above. DESIGN: Data were obtained on a large group of children followed longitudinally in trials and cohort studies in Europe and the USA. Follow-up was censored 6 months after the start of any antiretroviral drug other than zidovudine monotherapy. METHODS: Discordance between CD4 cell count and percentage was defined in relation to ART initiation thresholds in World Health Organization (WHO) and European paediatric treatment guidelines. The relative prognostic value of CD4 cell count and percentage for progression to AIDS/death was investigated using time-updated Cox proportional hazards models, stratified by age. RESULTS: Among 3345 children, with a total of 21,815 pairs of CD4 measurements analysed, 980 developed AIDS and/or died after a median follow-up of 1.7 years. Over one-half of children had discordant values of CD4 cell markers at the first visit when one or both treatment thresholds were crossed and approximately one-third had the same pattern of discordance at a subsequent measurement. Models suggested that CD4 percentage had little or no prognostic value over and above that contained in CD4 cell count, irrespective of age. CONCLUSIONS: More emphasis should be placed on CD4 cell count than on CD4 percentage in deciding when to start ART in HIV-1-infected children.

Community-based treatment for multidrug-resistant tuberculosis in rural KwaZulu-Natal, South Africa.

SETTING: Hlabisa health sub-district, KwaZulu-Natal, South Africa. OBJECTIVE: To describe the establishment of a community-based multidrug-resistant tuberculosis (MDR-TB) treatment programme embedded in the district TB control programme and to evaluate whether early outcomes are comparable to those in the traditional hospital-based model of care. DESIGN: Cases who initiated community-based MDR-TB treatment (CM) between March and December 2008 were compared with patients who initiated MDR-TB treatment under the traditional hospital-based model of care (TM) between January 2001 and February 2008. Time to initiation of treatment and time to sputum smear and culture conversion were compared for the two groups in Kaplan-Meier survival curves using the Mantel-Cox log-rank test. RESULTS: Overall, 50 CM cases and 57 TM cases were included; 39 of the 50 CM cases (78.0%) were human immunodeficiency virus positive. The median time to initiation of treatment was 84 days for CM and 106.5 days for TM (P = 0.002). Median time to sputum smear conversion was shorter for CM than TM (59 vs. 92 days, P = 0.055), as was time to sputum culture conversion (85 vs. 119 days, P = 0.002). CONCLUSION: Community-based treatment for MDR-TB can be implemented within the existing TB control programme in rural South Africa and should be scaled up where resources allow.