Impact of physical activity programs and services for older adults: a rapid review.

BACKGROUND: Knowledge of which physical activity programs are most effective for older adults in different sub-populations and contexts is limited. The objectives of this rapid review were to: 1) Overview evidence evaluating physical activity programs/services for older adults; and 2) Describe impact on physical activity, falls, intrinsic capacity (physical domain), functional ability (physical, social, and cognitive/emotional domains), and quality of life. METHODS: We conducted a rapid review of primary studies from 350 systematic reviews identified in a previous scoping review (March 2021: PEDro, MEDLINE, CINAHL, Cochrane Database). For Objective 1, we included intervention studies investigating physical activity programs/services in adults ≥ 60 years. Of these, we included good quality (≥ 6/10 PEDro scale) randomised controlled trials (RCTs) with ≥ 50 participants per group in Objective 2. RESULTS: Objective 1: Of the 1421 intervention studies identified from 8267 records, 79% were RCTs, 87% were in high income countries and 39% were good quality. Objective 2: We identified 87 large, good quality RCTs (26,861 participants). Overall activity promotion, structured exercise and recreation/sport had positive impacts (≥ 50% between-group comparisons positive) across all outcome domains. For overall activity promotion (21 intervention groups), greatest impacts were on physical activity (100% positive) and social outcomes (83% positive). Structured exercise (61 intervention groups) had particularly strong impacts on falls (91% positive), intrinsic capacity (67% positive) and physical functioning (77% positive). Recreation/sport (24 intervention groups) had particularly strong impacts on cognitive/emotional functioning (88% positive). Multicomponent exercise (39 intervention groups) had strong impacts across all outcomes, particularly physical activity (95% positive), falls (90% positive) and physical functioning (81% positive). Results for different populations and settings are presented. CONCLUSION: Evidence supporting physical activity for older adults is positive. We outline which activity types are most effective in different populations and settings.

Economic evaluation of physical activity mass media campaigns across the globe: a systematic review.

BACKGROUND: Physical activity mass media campaigns can deliver physical activity messages to many people, but it remains unclear whether they offer good value for money. We aimed to investigate the cost-effectiveness, cost-utility, and costs of physical activity mass media campaigns. METHODS: A search for economic evaluations (trial- or model-based) and costing studies of physical activity mass media campaigns was performed in six electronic databases (June/2021). The authors reviewed studies independently. A GRADE style rating was used to assess the overall certainty of each modelled economic evaluation. Results were summarised via narrative synthesis. RESULTS: Twenty-five studies (five model-based economic evaluations and 20 costing studies) were included, and all were conducted in high-income countries except for one costing study that was conducted in a middle-income country. The methods and assumptions used in the model-based analyses were highly heterogeneous and the results varied, ranging from the intervention being more effective and less costly (dominant) in two models to an incremental cost of US$130,740 (2020 base year) per QALY gained. The level of certainty of the models ranged from very low (n = 2) to low (n = 3). Overall, intervention costs were poorly reported. CONCLUSIONS: There are few economic evaluations of physical activity mass media campaigns available. The level of certainty of the models was judged to be very low to low, indicating that we have very little to little confidence that the results are reliable for decision making. Therefore, it remains unclear to what extent physical activity mass media campaigns offer good value for money. Future economic evaluations should consider selecting appropriate and comprehensive measures of campaign effectiveness, clearly report the assumptions of the models and fully explore the impact of assumptions in the results. REVIEW REGISTRATION: https://bit.ly/3tKSBZ3.

Economic evaluations of fall prevention exercise programs: a systematic review.

OBJECTIVE: To investigate cost-effectiveness and costs of fall prevention exercise programmes for older adults. DESIGN: Systematic review. DATA SOURCES: Medline, Embase, Web of Science, Scopus, National Institute for Health Research Economic Evaluation Database, Health Technology Assessment database, Tufts Cost-Effectiveness Analysis Registry, Research Papers in Economics and EconLit (inception to May 2022). ELIGIBILITY CRITERIA FOR STUDY SELECTION: Economic evaluations (trial-based or model-based) and costing studies investigating fall prevention exercise programmes versus no intervention or usual care for older adults living in the community or care facilities, and reporting incremental cost-effectiveness ratio (ICER) for fall-related outcomes or quality-adjusted life years (QALY, expressed as cost/QALY) and/or intervention costs. RESULTS: 31 studies were included. For community-dwelling older adults (21 economic evaluations, 6 costing studies), results ranged from more effective and less costly (dominant) interventions up to an ICER of US$279 802/QALY gained and US$11 986/fall prevented (US$ in 2020). Assuming an arbitrary willingness-to-pay threshold (US$100 000/QALY), most results (17/24) were considered cost-effective (moderate certainty). The greatest value for money (lower ICER/QALY gained and fall prevented) appeared to accrue for older adults and those with high fall risk, but unsupervised exercise appeared to offer poor value for money (higher ICER/QALY). For care facilities (two economic evaluations, two costing studies), ICERs ranged from dominant (low certainty) to US$35/fall prevented (moderate certainty). Overall, intervention costs varied and were poorly reported. CONCLUSIONS: Most economic evaluations investigated fall prevention exercise programmes for older adults living in the community. There is moderate certainty evidence that fall prevention exercise programmes are likely to be cost-effective. The evidence for older adults living in care facilities is more limited but promising. PROSPERO REGISTRATION NUMBER: PROSPERO 2020 CRD42020178023.

2020 WHO guidelines on physical activity and sedentary behaviour for children and adolescents aged 5-17 years: summary of the evidence.

BACKGROUND: The World Health Organization (WHO) released in 2020 updated global guidelines on physical activity and sedentary behaviour for children, adolescents, adults, older adults and sub-populations such as pregnant and postpartum women and those living with chronic conditions or disabilities. OBJECTIVE: To summarize the evidence on the associations between physical activity, sedentary behaviour, and health-related outcomes used to inform the 2020 WHO guidelines on physical activity and sedentary behaviour for children and adolescents aged 5-17 years. METHODS: The update of the WHO guideline recommendations for children and adolescents utilized and systematically updated the evidence syntheses on physical activity and sedentary behaviour conducted for the 2016 Canadian 24-Hour Movement Guidelines for Children and Youth, the 2019 Australian 24-Hour Movement Guidelines for Children and Young People (5-17 years), and the 2018 Physical Activity Guidelines for Americans, Second Edition. Systematic reviews published from 2017 up to July 2019 that addressed the key questions were identified, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to rate the certainty of the evidence for the entire body of evidence. RESULTS: The updated literature search yielded 21 relevant systematic reviews. The evidence base reviewed (i.e., existing and new systematic reviews) provided evidence that greater amounts and higher intensities of physical activity as well as different types of physical activity (i.e., aerobic and muscle and bone strengthening activities) are associated with improved health outcomes (primarily intermediate outcomes). There was sufficient evidence to support recommendations on limiting sedentary behaviours, which was not addressed in the 2010 WHO guidelines. However, there is still insufficient evidence available to fully describe the dose-response relationships between physical activity or sedentary behaviour and health outcomes, and whether the associations vary by type or domain of physical activity or sedentary behaviour. CONCLUSIONS: Addressing the identified research gaps will better inform guideline recommendations in children and adolescents, and future work should aim to prioritize these areas of research. In the meantime, investment and leadership is needed to scale up known effective policies and programs aimed at increasing activity in children and adolescents.

New global guidelines on sedentary behaviour and health for adults: broadening the behavioural targets.

BACKGROUND: In 2018, the World Health Organisation (WHO) commenced a program of work to update the 2010 Global Recommendations on Physical Activity for Health, for the first-time providing population-based guidelines on sedentary behaviour. This paper briefly summarizes and highlights the scientific evidence behind the new sedentary behaviour guidelines for all adults and discusses its strengths and limitations, including evidence gaps/research needs and potential implications for public health practice. METHODS: An overview of the scope and methods used to update the evidence is provided, along with quality assessment and grading methods for the eligible new systematic reviews. The literature search update was conducted for WHO by an external team and reviewers used the AMSTAR 2 (Assessment of Multiple Systematic Reviews) tool for critical appraisal of the systematic reviews under consideration for inclusion. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was used to rate the certainty (i.e. very low to high) of the evidence. RESULTS: The updated systematic review identified 22 new reviews published from 2017 up to August 2019, 14 of which were incorporated into the final evidence profiles. Overall, there was moderate certainty evidence that higher amounts of sedentary behaviour increase the risk for all-cause, cardiovascular disease (CVD) and cancer mortality, as well as incidence of CVD, cancer, and type 2 diabetes. However, evidence was deemed insufficient at present to set quantified (time-based) recommendations for sedentary time. Moderate certainty evidence also showed that associations between sedentary behaviour and all-cause, CVD and cancer mortality vary by level of moderate-to-vigorous physical activity (MVPA), which underpinned additional guidance around MVPA in the context of high sedentary time. Finally, there was insufficient or low-certainty systematic review evidence on the type or domain of sedentary behaviour, or the frequency and/or duration of bouts or breaks in sedentary behaviour, to make specific recommendations for the health outcomes examined. CONCLUSIONS: The WHO 2020 guidelines are based on the latest evidence on sedentary behaviour and health, along with interactions between sedentary behaviour and MVPA, and support implementing public health programmes and policies aimed at increasing MVPA and limiting sedentary behaviour. Important evidence gaps and research opportunities are identified.

Advancing the global physical activity agenda: recommendations for future research by the 2020 WHO physical activity and sedentary behavior guidelines development group.

BACKGROUND: In July, 2019, the World Health Organization (WHO) commenced work to update the 2010 Global Recommendations on Physical Activity for Health and established a Guideline Development Group (GDG) comprising expert public health scientists and practitioners to inform the drafting of the 2020 Guidelines on Physical Activity and Sedentary Behavior. The overall task of the GDG was to review the scientific evidence and provide expert advice to the WHO on the amount of physical activity and sedentary behavior associated with optimal health in children and adolescents, adults, older adults (> 64 years), and also specifically in pregnant and postpartum women and people living with chronic conditions or disabilities. METHODS: The GDG reviewed the available evidence specific to each sub-population using systematic protocols and in doing so, identified a number of gaps in the existing literature. These proposed research gaps were discussed and verified by expert consensus among the entire GDG. RESULTS: Evidence gaps across population sub-groups included a lack of information on: 1) the precise shape of the dose-response curve between physical activity and/or sedentary behavior and several of the health outcomes studied; 2) the health benefits of light-intensity physical activity and of breaking up sedentary time with light-intensity activity; 3) differences in the health effects of different types and domains of physical activity (leisure-time; occupational; transportation; household; education) and of sedentary behavior (occupational; screen time; television viewing); and 4) the joint association between physical activity and sedentary time with health outcomes across the life course. In addition, we acknowledge the need to conduct more population-based studies in low- and middle-income countries and in people living with disabilities and/or chronic disease, and to identify how various sociodemographic factors (age, sex, race/ethnicity, socioeconomic status) modify the health effects of physical activity, in order to address global health disparities. CONCLUSIONS: Although the 2020 WHO Guidelines for Physical Activity and Sedentary Behavior were informed by the most up-to-date research on the health effects of physical activity and sedentary time, there is still substantial work to be done in advancing the global physical activity agenda.

World Health Organization 2020 guidelines on physical activity and sedentary behaviour.

OBJECTIVES: To describe new WHO 2020 guidelines on physical activity and sedentary behaviour. METHODS: The guidelines were developed in accordance with WHO protocols. An expert Guideline Development Group reviewed evidence to assess associations between physical activity and sedentary behaviour for an agreed set of health outcomes and population groups. The assessment used and systematically updated recent relevant systematic reviews; new primary reviews addressed additional health outcomes or subpopulations. RESULTS: The new guidelines address children, adolescents, adults, older adults and include new specific recommendations for pregnant and postpartum women and people living with chronic conditions or disability. All adults should undertake 150-300 min of moderate-intensity, or 75-150 min of vigorous-intensity physical activity, or some equivalent combination of moderate-intensity and vigorous-intensity aerobic physical activity, per week. Among children and adolescents, an average of 60 min/day of moderate-to-vigorous intensity aerobic physical activity across the week provides health benefits. The guidelines recommend regular muscle-strengthening activity for all age groups. Additionally, reducing sedentary behaviours is recommended across all age groups and abilities, although evidence was insufficient to quantify a sedentary behaviour threshold. CONCLUSION: These 2020 WHO guidelines update previous WHO recommendations released in 2010. They reaffirm messages that some physical activity is better than none, that more physical activity is better for optimal health outcomes and provide a new recommendation on reducing sedentary behaviours. These guidelines highlight the importance of regularly undertaking both aerobic and muscle strengthening activities and for the first time, there are specific recommendations for specific populations including for pregnant and postpartum women and people living with chronic conditions or disability. These guidelines should be used to inform national health policies aligned with the WHO Global Action Plan on Physical Activity 2018-2030 and to strengthen surveillance systems that track progress towards national and global targets.

The cost of inaction on physical inactivity to public health-care systems: a population-attributable fraction analysis.

BACKGROUND: Physical inactivity is an important modifiable risk factor for non-communicable diseases (NCDs) and mental health conditions. We aimed to estimate the public health-care costs associated with these diseases because of physical inactivity, which will help policy makers to prioritise investment in policy actions to promote and enable more people to be more active. METHODS: We used a population-attributable fraction formula to estimate the direct public health-care costs of NCDs and mental health conditions for 2020-30. The disease outcomes that we included were incident cases of coronary heart disease, stroke, type 2 diabetes, hypertension, cancer (breast, colon, bladder, endometrial, oesophageal, gastric, and renal), dementia, and depression in adults aged at least 18 years. We used the most recent health and economic data evidence available for 194 countries. FINDINGS: 499·2 million new cases of preventable major NCDs would occur globally by 2030 if the prevalence of physical inactivity does not change, with direct health-care costs of INT$520 billion. The global cost of inaction on physical inactivity would reach approximately $47·6 billion per year. Although 74% of new cases of NCDs would occur in low-income and middle-countries, high-income countries would bear a larger proportion (63%) of the economic costs. The cost of treatment and management of NCDs varied-although dementia accounted for only 3% of new preventable NCDs, the disease corresponded to 22% of all costs; type 2 diabetes accounted for 2% of new preventable cases but 9% of all costs; and cancers accounted for 1% of new preventable cases but 15% of all costs. INTERPRETATION: This health and economic burden of physical inactivity is avoidable. Further investments in and implementation of known and effective policy interventions will support countries to reach the Sustainable Development Goal of reduction of NCD mortality by 2030. FUNDING: None.

The First Global Physical Activity and Sedentary Behavior Guidelines for People Living With Disability.

BACKGROUND: The World Health Organization has released the first global public health guidelines on physical activity and sedentary behavior for people living with disability. This paper presents the guidelines, related processes, and evidence, and elaborates upon how the guidelines can support inclusive policy, practice, and research. METHODS: Methods were consistent with the World Health Organization protocols for developing guidelines. Systematic reviews of the evidence on physical activity for health for people living with disability were appraised, along with a consideration of the evidence used to inform the general 2020 World Health Organization guidelines. RESULTS: Evidence supported the development of recommendations for people living with disability, stressing that there are no major risks to engaging in physical activity appropriate to an individual's current activity level, health status, and physical function, and that the health benefits accrued generally outweigh the risks. They also emphasize the benefits of limiting sedentary behavior. CONCLUSIONS: The guidelines mark a positive step forward for disability inclusion, but considerable effort is needed to advance the agenda. This paper highlights key considerations for the implementation of the new recommendations for people living with disability, in line with the human rights agenda underpinning the Global Action Plan on Physical Activity 2018-2030 and allied policies.

Global Public Health Guidelines on Physical Activity and Sedentary Behavior for People Living With Chronic Conditions: A Call to Action.

BACKGROUND: In 2020, the World Health Organization (WHO) released global guidelines on physical activity (PA) and sedentary behavior, for the first time providing population-based recommendations for people living with selected chronic conditions. This article briefly presents the guidelines, related processes and evidence, and, importantly, considers how they may be used to support research, practice, and policy. METHODS: A brief overview of the scope, agreed methods, selected chronic conditions (adults living with cancer, hypertension, type 2 diabetes, and human immunodeficiency virus), and appraisal of systematic review evidence on PA/sedentary behavior is provided. Methods were consistent with World Health Organization protocols for developing guidelines. RESULTS: Moderate to high certainty evidence (varying by chronic condition and outcome examined) supported that PA can reduce the risk of disease progression or premature mortality and improve physical function and quality of life in adults living with chronic conditions. Direct evidence on sedentary behavior was lacking; however, evidence extrapolated from adult populations was considered applicable, safe, and likely beneficial (low certainty due to indirectness). CONCLUSIONS: Clinical and public health professionals and policy makers should promote the World Health Organization 2020 global guidelines and develop and implement services and programs to increase PA and limit sedentary behavior in adults living with chronic conditions.

Cross-sectional examination of 24-hour movement behaviours among 3- and 4-year-old children in urban and rural settings in low-income, middle-income and high-income countries: the SUNRISE study protocol.

INTRODUCTION: 24-hour movement behaviours (physical activity, sedentary behaviour and sleep) during the early years are associated with health and developmental outcomes, prompting the WHO to develop Global guidelines for physical activity, sedentary behaviour and sleep for children under 5 years of age. Prevalence data on 24-hour movement behaviours is lacking, particularly in low-income and middle-income countries (LMICs). This paper describes the development of the SUNRISE International Study of Movement Behaviours in the Early Years protocol, designed to address this gap. METHODS AND ANALYSIS: SUNRISE is the first international cross-sectional study that aims to determine the proportion of 3- and 4-year-old children who meet the WHO Global guidelines. The study will assess if proportions differ by gender, urban/rural location and/or socioeconomic status. Executive function, motor skills and adiposity will be assessed and potential correlates of 24-hour movement behaviours examined. Pilot research from 24 countries (14 LMICs) informed the study design and protocol. Data are collected locally by research staff from partnering institutions who are trained throughout the research process. Piloting of all measures to determine protocol acceptability and feasibility was interrupted by COVID-19 but is nearing completion. At the time of publication 41 countries are participating in the SUNRISE study. ETHICS AND DISSEMINATION: The SUNRISE protocol has received ethics approved from the University of Wollongong, Australia, and in each country by the applicable ethics committees. Approval is also sought from any relevant government departments or organisations. The results will inform global efforts to prevent childhood obesity and ensure young children reach their health and developmental potential. Findings on the correlates of movement behaviours can guide future interventions to improve the movement behaviours in culturally specific ways. Study findings will be disseminated via publications, conference presentations and may contribute to the development of local guidelines and public health interventions.

Development of WHO Guidelines on Physical Activity, Sedentary Behavior, and Sleep for Children Less Than 5 Years of Age.

BACKGROUND: Physical inactivity is a leading risk factor for global mortality and a contributor to the increase in overweight and obesity. The Commission on Ending Childhood Obesity identified the need for guidance on physical activity, particularly for early childhood (<5 y), a period of rapid physical and cognitive development. METHODS: The World Health Organization (WHO) has developed the first global guidelines on physical activity, sedentary, and sleep behaviors, building upon high-quality systematic reviews. The WHO guideline process is a rigorous, systematic, and transparent method for the development of recommendations, using the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision framework. It takes into consideration the strength of the evidence as well as values and preferences, benefits and harms, equity and human rights. RESULTS: The authors summarize the first global guidelines on time spent in physical activity, sedentary behavior (including screen time and time spent restrained), and sleep patterns in infants (birth to 1 y of age), toddlers (1-2.9 y of age), and preschoolers (3-4.9 y of age). CONCLUSIONS: WHO is actively disseminating and supporting implementation of these guidelines by national adoption and adaptation, through links with early childhood development and the Global Action Plan on Physical Activity 2018-2030.

Canadian 24-Hour Movement Guidelines for Adults aged 18-64 years and Adults aged 65 years or older: an integration of physical activity, sedentary behaviour, and sleep.

The Canadian Society for Exercise Physiology assembled a Consensus Panel representing national organizations, content experts, methodologists, stakeholders, and end-users and followed an established guideline development procedure to create the Canadian 24-Hour Movement Guidelines for Adults aged 18-64 years and Adults aged 65 years or older: An Integration of Physical Activity, Sedentary Behaviour, and Sleep. These guidelines underscore the importance of movement behaviours across the whole 24-h day. The development process followed the strategy outlined in the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. A large body of evidence was used to inform the guidelines including 2 de novo systematic reviews and 4 overviews of reviews examining the relationships among movement behaviours (physical activity, sedentary behaviour, sleep, and all behaviours together) and several health outcomes. Draft guideline recommendations were discussed at a 4-day in-person Consensus Panel meeting. Feedback from stakeholders was obtained by survey (n = 877) and the draft guidelines were revised accordingly. The final guidelines provide evidence-based recommendations for a healthy day (24-h), comprising a combination of sleep, sedentary behaviours, and light-intensity and moderate-to-vigorous-intensity physical activity. Dissemination and implementation efforts with corresponding evaluation plans are in place to help ensure that guideline awareness and use are optimized. Novelty First ever 24-Hour Movement Guidelines for Adults aged 18-64 years and Adults aged 65 years or older with consideration of a balanced approach to physical activity, sedentary behaviour, and sleep Finalizes the suite of 24-Hour Movement Guidelines for Canadians across the lifespan.

Operational effectiveness and 36 week HIV-free survival in the South African programme to prevent mother-to-child transmission of HIV-1.

OBJECTIVE: Previous studies on the operational effectiveness of programmes to reduce transmission of HIV from mother-to-child (PMTCT) in Africa have generally been hospital-based pilot studies with short follow-up periods. METHOD: Prospective cohort study to evaluate the routine operational effectiveness of the South African National PMTCT Programme, primarily measured by HIV-free survival at 36 weeks post-delivery. Three of eighteen pilot sites participating in the programme were selected as they reflected differences in circumstances, such as HIV prevalence, socioeconomic status and rural-urban location. A total of 665 HIV-positive mothers and their infants were followed. RESULTS: HIV-free survival at 36 weeks varied significantly across sites with 84% in Paarl, 74% in Umlazi and 65% in Rietvlei (P = 0.0003). Maternal viral load was the single most important factor associated with HIV transmission or death [hazard ratio (HR), 1.54; 95% confidence interval (CI), 1.21-1.95]. Adjusting for health system variables (fewer than four antenatal visits and no antenatal syphilis test) explained the difference between Rietvlei and Paarl (crude HR, 2.27; 95% CI, 1.36-3.77; adjusted HR, 1.81; 95% CI, 0.93-3.50). Exposure to breastmilk feeding explained the difference between Umlazi and Paarl (crude HR, 1.74; 95% CI, 1.06-2.84; adjusted HR, 1.41; 95% CI, 0.81-2.48). CONCLUSION: Ever breastfeeding and underlying inequities in healthcare quality within South Africa are predictors of PMTCT programme performance and will need to be addressed to optimize PMTCT effectiveness.

Quantitation of HIV-1 RNA in breast milk by real time PCR.

HIV-1 RNA in breast milk is a strong predictor of HIV-1 transmission through breastfeeding. In the present report, breast milk samples from HIV-1 uninfected donors were spiked with dilution of quantified culture supernatant from HIV-1(NDK) infected PBMC. Two RNA extraction techniques based on silica extraction, Nuclisens (BioMerieux) and Triazol (Qiagen), two techniques based on guanidine thiocynanate/chloroforme extraction, TRIzol (Life Technologie) and Amplicor HIV-1 Monitor (Roche Diagnostic Systems), and one technique based on electrostatic adsorption on iron oxide micro beads (Promega) were compared. HIV-1 RNA was quantitated by real time PCR (LTR gene) and Amplicor HIV-1 Monitor. Combining magnetic micro beads extraction and real time PCR quantitation allowed to correctly quantify breast milk HIV-1 RNA, with a difference between the expected and measured HIV-1 RNA levels always lower than 0.3 log copies/ml. The same combination was confirmed on 25 breast milk samples from HIV-1 infected women collected in Kwazulu-Natal, South Africa, by comparing measurements with those obtained by the Amplicor HIV-1 Monitor (r(2)=0.88). Nucleic acid extraction by magnetic micro beads followed by real time PCR is a reliable, sensitive, rapid and simple procedure to quantify HIV-1 RNA in breast milk and allows for PCR inhibitors found frequently in these samples.

Breastmilk RNA viral load in HIV-infected South African women: effects of subclinical mastitis and infant feeding.

OBJECTIVE: To investigate determinants of breastmilk RNA viral load among HIV-infected South African women, with particular attention to infant feeding mode and subclinical mastitis. DESIGN: Observational, longitudinal study. METHODS: Information on current infant feeding practice and a spot milk sample from each breast were obtained from 145 HIV-infected lactating women at 1, 6 and 14 weeks postpartum. The sodium/potassium (Na+/K+) ratio in milk was taken as an indicator of subclinical mastitis. The association between milk RNA viral load and maternal and infant characteristics was investigated using uni- and multivariate models. RESULTS: Milk viral load was below the limit of detection of the HIV RNA assay (< 200 copies/ml) in 63/185 (34.1%), 73/193 (37.8%) and 68/160 (42.5%) of samples at 1, 6 and 14 weeks, respectively. Multivariate models predicted between 13 and 26% of variability in milk viral load in the first 14 weeks. Low blood CD4 cell count (< 200 x 10(6) cells/l) during pregnancy and raised milk Na+/K+ ratio were significantly associated with raised milk RNA viral load at all times, but there were no consistent associations between infant feeding mode and RNA viral load in milk. There was a non-significant trend for the six infants known to be infected postnatally, compared with the 88 infants who remained uninfected, to have been exposed to breastmilk of higher viral load at each time point. CONCLUSIONS: Breast milk HIV RNA viral load in the first 14 weeks of life varied; high levels were associated with subclinical mastitis and severe maternal immunosuppression. Multivariate models had limited predictive value for milk RNA viral load, illustrating the multiple contributors to viral load.