Incident HIV among pregnant and breast-feeding women in sub-Saharan Africa: a systematic review and meta-analysis

OBJECTIVES: A previous meta-analysis reported high HIV incidence among pregnant and breast-feeding women in sub-Saharan Africa (SSA), but limited evidence of elevated risk of HIV acquisition during pregnancy or breast-feeding when compared with nonpregnant periods. The rapidly evolving HIV prevention and treatment landscape since publication of this review may have important implications for maternal HIV incidence. DESIGN: Systematic review and meta-analysis. METHODS: We searched four databases and abstracts from relevant conferences through 1 December 2018, for literature on maternal HIV incidence in SSA. We used random-effects meta-analysis to summarize incidence rates and ratios, and to estimate 95% prediction intervals. We evaluated potential sources of heterogeneity with random-effects meta-regression. RESULTS: Thirty-seven publications contributed 100 758 person-years of follow-up. The estimated average HIV incidence rate among pregnant and breast-feeding women was 3.6 per 100 person-years (95% prediction interval: 1.2--11.1), while the estimated average associations between pregnancy and risk of HIV acquisition, and breast-feeding and risk of HIV acquisition, were close to the null. Wide 95% prediction intervals around summary estimates highlighted the variability of HIV incidence across populations of pregnant and breast-feeding women in SSA. Average HIV incidence appeared associated with age, partner HIV status, and calendar time. Average incidence was highest among studies conducted pre-2010 (4.1/100 person-years, 95% prediction interval: 1.1--12.2) and lowest among studies conducted post-2014 (2.1/100 person-years, 95% prediction interval: 0.7--6.5). CONCLUSION: Substantial HIV incidence among pregnant and breast-feeding women in SSA, even in the current era of combination HIV prevention and treatment, underscores the need for prevention tailored to high-risk pregnant and breast-feeding women

Two strategies for partner notification and partner HIV self-testing reveal no evident predictors of male partner HIV testing in antenatal settings: A secondary analysis

BackgroundTo meet global targets for the elimination of mother-to-child HIV transmission, tailored approaches to HIV testing strategies need prioritizing. Herein, we sought to identify individual-level factors associated with male partner HIV testing.MethodsWe conducted a secondary analysis of data from two parallel randomized trials of pregnant women living with HIV and those HIV-negative in Lusaka, Zambia. Across both trials, control groups received partner notification services only, while intervention groups received partner notification services plus HIV self-test kits for their partners. Associations between baseline factors and male partner testing were estimated using a probability difference. The outcome of interest was uptake of male partner HIV testing of any kind within 30 days of randomization.ResultsThe parent study enrolled 326 participants. Among the 151 women in the control groups, no clear associations were noted between maternal or male partner characteristics and reported uptake of male partner HIV testing. There were positive trends favouring partner testing among women who completed primary school education, had larger households (>2 members), and whose partners were circumcised. Likewise, no clear predictors of male partner testing were identified among the 149 women in the intervention groups. However, negative trends favouring no testing were noted among older, multiparous women from larger households.ConclusionNo consistent predictors for male partner HIV testing across two compared strategies were observed. Our findings suggest that differentiated strategies for male partner HIV testing may not be necessary. Instead, consideration should be given to universal approaches when bringing such services to scale

Addition of HIV self-test kits to partner notification services to increase HIV testing of male partners of pregnant women in Zambia: two parallel randomised trials

Background Testing men for HIV during their partner's pregnancy can guide couples-based HIV prevention and treatment, but testing rates remain low. We investigated a combination approach, using evidence-based strategies, to increase HIV testing in male partners of HIV-positive and HIV-negative pregnant women. Methods We did two parallel, unmasked randomised trials, enrolling pregnant women who had an HIV-positive test result documented in their antenatal record (trial 1) and women who had an HIV-negative test result documented in their antenatal record (trial 2) from an antenatal setting in Lusaka, Zambia. Women in both trials were randomly assigned (1:1) to the intervention or control groups using permuted block randomisation. The control groups received partner notification services only, including an adapted version for women who were HIV-negative; the intervention groups additionally received targeted education on the use of oral HIV self-test kits for their partners, along with up to five oral HIV self-test kits. At the 30 day follow-up we collected information from pregnant women about their primary male partner's HIV testing in the previous 30 days at health-care facilities, at home, or at any other facility. Our primary outcome was reported male partner testing at a health facility within 30 days following randomisation using a complete-case approach. Women also reported male partner HIV testing of any kind (including self-testing at home) that occurred within 30 days. Randomisation groups were compared via probability difference with a corresponding Wald-based 95% CI. The trial is registered at ClinicalTrials.gov (NCT04124536) and all enrolment and follow-up has been completed. Findings From Oct 28, 2019, to May 26, 2020, 116 women who were HIV-positive (trial 1) and 210 women who were HIV-negative (trial 2) were enrolled and randomly assigned to study groups. Retention at 30 days was 100 (86%) in trial 1 and 200 (95%) in trial 2. Women in the intervention group were less likely to report facility-based male partner HIV testing in trial 1 (3 [6%] of 47 vs 15 [28%] of 53, estimated probability difference –21·9% [95% CI –35·9 to –7·9%]) and trial 2 (3 [3%] of 102 vs 33 [34%] of 98, estimated probability difference –30·7% [95% CI –40·6 to –20·8]). However, reported male partner HIV testing of any kind was higher in the intervention group than in the control group in trial 1 (36 [77%] of 47 vs 19 [36%] of 53, estimated probability difference 40·7% [95% CI 23·0 to 58·4%]) and trial 2 (80 [78%] of 102 vs 54 [55%] of 98, estimated probability difference 23·3% [95% CI 10·7 to 36·0%]) due to increased use of HIV self-testing. Overall, 14 male partners tested HIV-positive. Across the two trials, three cases of intimate partner violence were reported (two in the control groups and one in the intervention groups). Interpretation Our combination approach increased overall HIV testing in male partners of pregnant women but reduced the proportion of men who sought follow-up facility-based testing. This combination approach might reduce linkages to health care, including for HIV prevention, and should be considered in the design of comprehensive HIV programmes

Acceptability of a Combination Adherence Strategy to Support HIV Antiretroviral Therapy and Pre-exposure Prophylaxis Adherence During Pregnancy and Breastfeeding in Malawi

In two parallel pilot studies, we implemented a combination adherence intervention of patient-centered counselling and adherence supporter training, tailored to support HIV treatment (i.e., antiretroviral therapy) or prevention (i.e., pre-exposure prophylaxis, or PrEP) during pregnancy and breastfeeding. Using a mixed-methods approach, we evaluated the intervention's acceptability. We investigated engagement, satisfaction, and discussion content via survey to all 151 participants assigned to the intervention arm (51 women living with HIV, 100 PrEP-eligible women without HIV). We also conducted serial in-depth interviews with a subgroup (n = 40) at enrollment, three months, and six months. In the quantitative analysis, the vast majority reported high satisfaction with intervention components and expressed desire to receive it in the future, if made available. These findings were supported in the qualitative analysis, with favorable comments about counselor engagement, intervention content and types of support received from adherence supporters. Overall, these results demonstrate high acceptability and provide support for HIV status-neutral interventions for antiretroviral adherence

IMPLEmenting a clinical practice guideline for acute low back pain evidence-based manageMENT in general practice (IMPLEMENT) : cluster randomised controlled trial study protocol

Background: Evidence generated from reliable research is not frequently implemented into clinical practice. Evidence-based clinical practice guidelines are a potential vehicle to achieve this. A recent systematic review of implementation strategies of guideline dissemination concluded that there was a lack of evidence regarding effective strategies to promote the uptake of guidelines. Recommendations from this review, and other studies, have suggested the use of interventions that are theoretically based because these may be more effective than those that are not. An evidencebased clinical practice guideline for the management of acute low back pain was recently developed in Australia. This provides an opportunity to develop and test a theory-based implementation intervention for a condition which is common, has a high burden, and for which there is an evidence-practice gap in the primary care setting. Aim: This study aims to test the effectiveness of a theory-based intervention for implementing a clinical practice guideline for acute low back pain in general practice in Victoria, Australia. Specifically, our primary objectives are to establish if the intervention is effective in reducing the percentage of patients who are referred for a plain x-ray, and improving mean level of disability for patients three months post-consultation. Methods/Design: This study protocol describes the details of a cluster randomised controlled trial. Ninety-two general practices (clusters), which include at least one consenting general practitioner, will be randomised to an intervention or control arm using restricted randomisation. Patients aged 18 years or older who visit a participating practitioner for acute non-specific low back pain of less than three months duration will be eligible for inclusion. An average of twenty-five patients per general practice will be recruited, providing a total of 2,300 patient participants. General practitioners in the control arm will receive access to the guideline using the existing dissemination strategy. Practitioners in the intervention arm will be invited to participate in facilitated face-to-face workshops that have been underpinned by behavioural theory. Investigators (not involved in the delivery of the intervention), patients, outcome assessors and the study statistician will be blinded to group allocation. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN012606000098538 (date registered 14/03/2006).The trial is funded by the NHMRC by way of a Primary Health Care Project Grant (334060). JF has 50% of her time funded by the Chief Scientist Office3/2006). of the Scottish Government Health Directorate and 50% by the University of Aberdeen. PK is supported by a NHMRC Health Professional Fellowship (384366) and RB by a NHMRC Practitioner Fellowship (334010). JG holds a Canada Research Chair in Health Knowledge Transfer and Uptake. All other authors are funded by their own institutions

Combination adherence strategy to support HIV antiretroviral therapy and pre-exposure prophylaxis adherence during pregnancy and breastfeeding: protocol for a pair of pilot randomised trials.

INTRODUCTION To realise the expected gains from prevention of mother-to-child HIV transmission initiatives, adherence to preventative and therapeutic antiretroviral regimens is critical and interventions deployable in busy programmatic settings with a high HIV burden are needed. Based on formative research, we developed an approach that integrates patient-centred counselling and engagement of an adherence supporter for pregnant and breastfeeding women initiating HIV treatment (ie, antiretroviral therapy (ART)) or biomedical HIV prevention (ie, pre-exposure prophylaxis (PrEP)). METHODS Tonse Pamodzi 2 is a pilot study designed to provide acceptability, fidelity and clinical outcomes data on a set of behavioural interventions for adherence support. The study comprises two parallel randomised trials, enrolling HIV-positive pregnant women initiating ART (Trial 1, n=100) and HIV-negative pregnant women with risk of HIV acquisition and willing to initiate PrEP (Trial 2, n=200). Within each trial, participants are randomised 1:1 to either the intervention or control group. The Tonse Pamodzi adherence intervention comprises patient-centred counselling (adapted Integrated Next Step Counseling(iNSC)) and external adherence support tailored to the clinical context (ie, for ART or PrEP). Participants randomly assigned to the control group receive standard counselling based on local HIV guidelines. Participants are followed for 6 months. To assess intervention acceptability, we will employ a mixed method approach to describe participant engagement, satisfaction, and discussion content. We will audit and score recorded counselling sessions to evaluate the implementation fidelity of iNSC sessions. We will also assess clinical outcomes at 3 and 6 months for both Trial 1 (retention in care and viral suppression of HIV) and Trial 2 (retention in care, and plasma and intracellular tenofovir drug concentrations). ETHICS AND DISSEMINATION The study protocol was approved by the Malawi National Health Science Research Committee (19/05/2334) and the University of North Carolina at Chapel Hill Institutional Review Board (19-1060). TRIAL REGISTRATION NUMBER NCT04330989

Combination HIV prevention during pregnancy and the post-partum period in Malawi and Zambia: a mathematical modelling analysis

INTRODUCTION: Despite widespread success in reducing vertical HIV transmission, most antenatal care (ANC) programmes in eastern and southern Africa have not emphasized primary prevention of maternal HIV acquisition during pregnancy and lactation/breastfeeding. We hypothesized that combination HIV prevention interventions initiated alongside ANC could substantially reduce maternal HIV incidence. METHODS: We constructed a multi-state model describing male-to-female HIV transmission in steady heterosexual partnerships during pregnancy and lactation/breastfeeding, with initial conditions based on population distribution estimates for Malawi and Zambia in 2020. We modelled individual and joint increases in three HIV prevention strategies at or soon after ANC initiation: (1) HIV testing of male partners, resulting in HIV diagnosis and less condomless sex among those with previously undiagnosed HIV; (2) initiation (or re-initiation) of suppressive antiretroviral therapy (ART) for male partners with diagnosed but unsuppressed HIV; and (3) adherent pre-exposure prophylaxis (PrEP) for HIV-negative female ANC patients with HIV-diagnosed or unknown-status male partners. We estimated the percentage of within-couple, male-to-female HIV transmissions that could be averted during pregnancy and lactation/breastfeeding with these strategies, relative to base-case conditions in which 45% of undiagnosed male partners become newly HIV diagnosed via testing, 75% of male partners with diagnosed but unsuppressed HIV initiate/re-initiate ART and 0% of female ANC patients start PrEP. RESULTS: Increasing uptake of any single strategy by 20 percentage points above base-case levels averted 10%-11% of maternal HIV acquisitions during pregnancy and lactation/breastfeeding in the model. Joint uptake increases of 20 percentage points in two interventions averted an estimated 19%-23% of transmissions, and with a 20-percentage-point increase in uptake of all three interventions, 29% were averted. Strategies achieving 95% male testing, 90% male ART initiation/re-initiation and 40% female PrEP use reduced incident infections by 45%. CONCLUSIONS: Combination HIV prevention strategies provided alongside ANC and sustained through the post-partum period could substantially reduce maternal HIV incidence during pregnancy and lactation/breastfeeding in eastern and southern Africa

Prescribing patterns in dementia: a multicentre observational study in a German network of CAM physicians

<p>Abstract</p> <p>Background</p> <p>Dementia is a major and increasing health problem worldwide. This study aims to investigate dementia treatment strategies among physicians specialised in complementary and alternative medicine (CAM) by analysing prescribing patterns and comparing them to current treatment guidelines in Germany.</p> <p>Methods</p> <p>Twenty-two primary care physicians in Germany participated in this prospective, multicentre observational study. Prescriptions and diagnoses were reported for each consecutive patient. Data were included if patients had at least one diagnosis of dementia according to the 10th revision of the International Classification of Diseases during the study period. Multiple logistic regression was used to determine factors associated with a prescription of any anti-dementia drug including <it>Ginkgo biloba</it>.</p> <p>Results</p> <p>During the 5-year study period (2004-2008), 577 patients with dementia were included (median age: 81 years (IQR: 74-87); 69% female). Dementia was classified as unspecified dementia (57.2%), vascular dementia (25.1%), dementia in Alzheimer's disease (10.4%), and dementia in Parkinson's disease (7.3%). The prevalence of anti-dementia drugs was 25.6%. The phytopharmaceutical <it>Ginkgo biloba </it>was the most frequently prescribed anti-dementia drug overall (67.6% of all) followed by cholinesterase inhibitors (17.6%). The adjusted odds ratio (AOR) for receiving any anti-dementia drug was greater than 1 for neurologists (AOR = 2.34; CI: 1.59-3.47), the diagnosis of Alzheimer's disease (AOR = 3.28; CI: 1.96-5.50), neuroleptic therapy (AOR = 1.87; CI: 1.22-2.88), co-morbidities hypertension (AOR = 2.03; CI: 1.41-2.90), and heart failure (AOR = 4.85; CI: 3.42-6.88). The chance for a prescription of any anti-dementia drug decreased with the diagnosis of vascular dementia (AOR = 0.64; CI: 0.43-0.95) and diabetes mellitus (AOR = 0.55; CI: 0.36-0.86). The prescription of <it>Ginkgo biloba </it>was associated with sex (female: AOR = 0.41; CI: 0.19-0.89), patient age (AOR = 1.06; CI: 1.02-1.10), treatment by a neurologist (AOR = 0.09; CI: 0.03-0.23), and the diagnosis of Alzheimer's disease (AOR = 0.07; CI: 0.04-0.16).</p> <p>Conclusions</p> <p>This study provides a comprehensive analysis of everyday practice for treatment of dementia in primary care in physicians with a focus on CAM. The prescribing frequency for anti-dementia drugs is equivalent to those found in other German studies, while the administration of <it>Ginkgo biloba </it>is significantly higher.</p

Predictors of tuberculosis (TB) and antiretroviral (ARV) medication non-adherence in public primary care patients in South Africa: A cross sectional study

Background: Despite the downward trend in the absolute number of tuberculosis (TB) cases since 2006 and the fall in the incidence rates since 2001, the burden of disease caused by TB remains a global health challenge. The co-infection between TB and HIV adds to this disease burden. TB is completely curable through the intake of a strict anti-TB drug treatment regimen which requires an extremely high and consistent level of adherence.The aim of this study was to investigate factors associated with adherence to anti-TB and HIV treatment drugs. Methods: A cross-sectional survey method was used. Three study districts (14 primary health care facilities in each) were selected on the basis of the highest TB caseload per clinic. All new TB and new TB retreatment patients were consecutively screened within one month of anti-tuberculosis treatment. The sample comprised of 3107 TB patients who had been on treatment for at least three weeks and a sub-sample of the total sample were on both anti-TB treatment and anti-retro-viral therapy(ART) (N = 757). Data collection tools included: a Socio-Demographic Questionnaire; a Post-Traumatic-Stress-Disorder (PTSD) Screen; a Psychological Distress Scale; the Alcohol Use Disorder Identification Test (AUDIT); and self-report measures of tobacco use, perceived health status and adherence to anti-TB drugs and ART. Results: The majority of the participants (N = 3107) were new TB cases with a 55.9% HIV co-infection rate in this adult male and female sample 18 years and older. Significant predictors of non-adherence common to both anti-TB drugs and to dual therapy (ART and anti-TB drugs) included poverty, having one or more co-morbid health condition, being a high risk for alcohol mis-use and a partner who is HIV positive. An additional predictor for non-adherence to anti-TB drugs was tobacco use. Conclusions: A comprehensive treatment programme addressing poverty, alcohol mis-use, tobacco use and psycho-social counseling is indicated for TB patients (with and without HIV). The treatment care package needs to involve not only the health sector but other relevant government sectors, such as social development.IS

Evaluation of a Theory-Informed Implementation Intervention for the Management of Acute Low Back Pain in General Medical Practice: The IMPLEMENT Cluster Randomised Trial

Introduction: This cluster randomised trial evaluated an intervention to decrease x-ray referrals and increase giving advice to stay active for people with acute low back pain (LBP) in general practice. Methods: General practices were randomised to either access to a guideline for acute LBP (control) or facilitated interactive workshops (intervention). We measured behavioural predictors (e.g. knowledge, attitudes and intentions) and fear avoidance beliefs. We were unable to recruit sufficient patients to measure our original primary outcomes so we introduced other outcomes measured at the general practitioner (GP) level: behavioural simulation (clinical decision about vignettes) and rates of x-ray and CT-scan (medical administrative data). All those not involved in the delivery of the intervention were blinded to allocation. Results: 47 practices (53 GPs) were randomised to the control and 45 practices (59 GPs) to the intervention. The number of GPs available for analysis at 12 months varied by outcome due to missing confounder information; a minimum of 38 GPs were available from the intervention group, and a minimum of 40 GPs from the control group. For the behavioural constructs, although effect estimates were small, the intervention group GPs had greater intention of practising consistent with the guideline for the clinical behaviour of x-ray referral. For behavioural simulation, intervention group GPs were more likely to adhere to guideline recommendations about x-ray (OR 1.76, 95%CI 1.01, 3.05) and more likely to give advice to stay active (OR 4.49, 95%CI 1.90 to 10.60). Imaging referral was not statistically significantly different between groups and the potential importance of effects was unclear; rate ratio 0.87 (95%CI 0.68, 1.10) for x-ray or CT-scan. Conclusions: The intervention led to small changes in GP intention to practice in a manner that is consistent with an evidence-based guideline, but it did not result in statistically significant changes in actual behaviour. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN01260600009853