Exercise as a preventive and therapeutic strategy for non-communicable diseases in people living with HIV: evidence, mechanisms and clinical implications

Abstract

Objective

To synthesise evidence on exercise for preventing and managing non-communicable diseases (NCDs) among HIV clients, emphasising sub-Saharan Africa.

Design

Narrative review.

Data sources

Meta-analyses, randomised trials, cohort studies, mechanistic investigations and implementation reports involving adolescents and adults aged 15+ Priority was given to cardiometabolic, musculoskeletal, neurocognitive, immunological, behavioural, safety, feasibility and low- and middle-income country outcomes.

Rationale

People living with HIV face elevated risk of cardiovascular disease, heart failure and type 2 diabetes due to persistent immune activation, chronic inflammation and treatment related metabolic effects. Exercise is a scalable, low-cost intervention with broad benefits.

Results

Aerobic and combined aerobic plus resistance training performed ≥3 times weekly for ≥5 weeks improves cardiorespiratory fitness and functional capacity with moderate effects, without adverse effects on CD4 or viral load. Resistance and concurrent training increase strength and lean mass and may attenuate bone mineral density loss. Exercise reduces depressive symptoms, improves quality of life and benefits attention and executive function. Mechanistic studies report reduced pro inflammation, improved endothelial function, enhanced mitochondrial capacity and greater antioxidant defence. Feasibility is high with appropriate screening and progression and with adaptations for neuropathy, frailty, pregnancy, low bone density and multimorbidity. Task shifting, digital or community delivery improve uptake despite limited evidence.

Conclusions

Exercise should be integrated into HIV and NCD care using frequency, intensity, time and type principles. Programmes require risk stratification, age and sex sensitivity and behaviour change support. Further research should evaluate mechanistic endpoints, high-intensity interval training dosing, pragmatic delivery models and economic outcomes in low- and middle-income countries.

WHAT IS ALREADY KNOWN ON THIS TOPIC

• In sub-Saharan Africa, the number of people with HIV and other chronic illnesses who use exercise as an affordable treatment to prevent and manage their condition is increasing. All types of competitive physical activities are supported by evidence from several non-contradictory research.

WHAT THIS STUDY ADDS

• This study asserts that exercise provides non-pharmacological prevention and management of non-communicable diseases (NCDs) and provides benefits to function and mental health of people living with HIV.

• This study highlights the need for HIV patients with numerous comorbidities—of NCDs to mental health—to be treated with innovative yet affordable methods.

• Shows evidence of cost-effectiveness trials among HIV-positive individuals, pointing to a crucial direction for studies that focus on stigma and gender.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• There is evidence of exercise regimens that should focus on approach including those supported by mHealth and digital tools. There is potential for research trials on the best techniques for long-term management. Practitioners might test multiple strategies through multisectoral policies in education and health.

Background

Exercise is a cost-effective, scalable intervention with proven cardiometabolic, musculoskeletal and neurocognitive benefits, making it particularly valuable in addressing the rising non-communicable disease (NCD) burden among people living with HIV (PLWH).¹ Compared with uninfected individuals, PLWH face significantly higher risks for several NCDs, including approximately 1.8-fold higher heart failure risk, 1.5-fold greater cardiovascular disease risk and 1.3-fold higher type 2 diabetes incidence.2,4 While antiretroviral therapy (ART) has transformed HIV into a chronic condition, it does not eliminate NCD risk.

Structured exercise programmes, whether supervised, community-based or home-delivered, can improve functional capacity, cardiometabolic profiles and mental health outcomes.⁵ This narrative review with scoping elements focuses on adults and adolescents (≥15 years) in the contemporary ART era (integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF) widely used), incorporating global data with emphasis on sub-Saharan Africa, where HIV prevalence is highest.⁶ The review addresses: the epidemiology of NCDs in PLWH, biological pathways linking HIV/ART to NCD risk and evidence for exercise as a preventive and therapeutic strategy, alongside clinical and implementation considerations.

In 2023, more than 30 million of the 39.9 million PLWH were receiving ART, the majority in sub-Saharan Africa.⁷ As life expectancy increases, multimorbidity management, including NCD prevention, has become central to HIV care. HIV treatment goals have shifted toward multimorbidity management as a result of the growing burden of non-communicable diseases (NCDs) and extended life expectancy brought about by antiretroviral medication.⁸ According to meta-analyses and large cohort studies, PLWH have a 1.5-fold increased risk of cardiovascular disease and a 1.8-fold increased risk of heart failure when compared with those who are HIV-negative.^{9 10} The prevalence of hypertension ranges from 12% to 42%, diabetes from 2% to 14% and dyslipidaemia from 20% to 50%, with rates varying by ART regimen and region.¹¹ Osteopenia and osteoporosis affect up to 67% of PLWH, particularly post-menopausal women and older men on long-term ART.¹² Mental health disorders, especially depression, occur in 20%–40% of PLWH, compounding NCD risks and undermining treatment adherence.¹³ These patterns reflect both traditional risk factors and HIV/ART-specific contributors, highlighting the importance of exercise as a modifiable factor within integrated care models.

The elevated NCD risk in PLWH results from persistent immune activation, chronic low-level inflammation (‘inflammageing’), and ART-related metabolic effects.¹⁴ Even with viral suppression, biomarkers such as IL-6 and C-reactive protein remain elevated, driving endothelial dysfunction, atherogenesis and myocardial remodelling.¹⁵ Certain ART regimens, particularly INSTIs such as dolutegravir and bictegravir, and TAF, are associated with clinically significant weight gain and adverse shifts in glucose and lipid metabolism.^{16 17} Switching from tenofovir disoproxil fumarate to TAF has been associated with increases in triglycerides and total cholesterol, elevating estimated cardiovascular risk.¹⁸ Altered body composition characterised by visceral adiposity with peripheral lipoatrophy further exacerbates insulin resistance.¹⁹ Mitochondrial toxicity from certain ART agents contributes to muscle dysfunction and oxidative stress, while ART-associated bone mineral density (BMD) loss remains a prevalent complication.¹²

HIV-Induced DNA ageing and risk of NCDs

HIV infection accelerates biological ageing through pathways such as telomere shortening, mitochondrial dysfunction and epigenetic modifications that promote premature cellular senescence and chronic inflammation. Evidence shows that PLWH exhibit markedly increased epigenetic age, averaging 5–7 years older than HIV-negative individuals, with changes detectable as early as 3 years after seroconversion.^{20 21} This molecular ageing is strongly associated with higher risks of cardiovascular disease, neurocognitive impairment, diabetes and cancer, and even predicts mortality in HIV-associated malignancies.²² These processes contribute to ‘inflammageing’, persistent immune activation and immunometabolic dysfunction, intensifying vulnerability to NCDs. Importantly, this accelerated ageing creates modifiable physiological targets for exercise: regular physical activity can attenuate oxidative stress, enhance mitochondrial capacity and increase telomerase activity, thereby counteracting key mechanisms driving age-related decline in people with HIV.

HIV infection accelerates biological ageing at the DNA level through mechanisms such as telomere shortening and epigenetic modifications. These processes contribute to premature cellular senescence, immune dysfunction and systemic inflammation, which in turn increase vulnerability to NCDs. For example, Levine et al.²⁰ demonstrated that PLWH exhibited an average epigenetic age increase of 5.2 years in blood and 7.4 years in brain tissue compared with HIV-negative individuals. Similarly, a systematic review by Sehl and colleagues confirmed that 22 out of 25 studies consistently reported accelerated epigenetic ageing in HIV-positive cohorts.²³ This accelerated molecular ageing has been linked to higher risks of cardiovascular disease, neurocognitive impairment, diabetes and cancers, underscoring how HIV-associated DNA ageing contributes directly to the rising NCD burden among people with HIV.

HIV-related DNA ageing and chronic disease outcomes are further highlighted by studies examining survival and morbidity. Breen and colleagues found that individuals within 3 years of HIV seroconversion already displayed epigenetic age acceleration of 1.9 to 4.8 years, demonstrating the rapid onset of molecular ageing.²¹ Importantly, this accelerated ageing is not only a biomarker but also a predictor of clinical outcomes. For example, Horvath and Levine observed that higher epigenetic age in people with HIV-associated cancers was strongly associated with increased mortality risk.²² These findings suggest that HIV-induced DNA ageing is a mechanistic pathway linking infection with the early onset and severity of NCDs. All these mechanisms create a pathophysiological environment in which exercise interventions can target inflammation, improve endothelial function, enhance insulin sensitivity, optimise body composition and preserve bone health.

DOSAGE of exercise AND MITIGATION OF HIV-Related DNA CHANGES

Regular physical activity is a powerful non-pharmacological strategy for slowing DNA ageing and reducing NCD risks among people with HIV. Exercise has been shown to preserve telomere length, enhance telomerase activity and reduce oxidative stress, all of which counteract molecular ageing. For instance, Werner and colleagues found that long-term endurance training increased telomerase activity and the expression of telomere-stabilising proteins in leucocytes, delaying cellular senescence.²⁴ Similarly, Tucker reported that highly active individuals had significantly longer telomeres, biologically equivalent to approximately 9 years of reduced cellular ageing, compared with sedentary peers.²⁵ A meta-analysis by Song and Kim further confirmed that aerobic exercise interventions lasting more than 6 months significantly attenuated telomere shortening in adults. These findings suggest that structured exercise interventions may play a critical role in reducing the burden of NCDs by mitigating the DNA ageing processes accelerated by HIV infection.

For PLWH, the full spectrum of exercise modalities aerobic, resistance, high-intensity interval training (HIIT) and concurrent (combined) training can be prescribed using FITT principles (frequency, intensity, time, type), with progression from a minimal effective dose of ~3 sessions/week for ≥5 weeks (20–60 min/session) toward guideline targets (≥150 min/week moderate or ≥75 min/week vigorous aerobic activity plus ≥2 resistance sessions) as shown in table 1.26,28 Aerobic training (moderate continuous or intervals) improves cardiorespiratory fitness (CRF) andfunctional capacity; resistance training adds muscle strength and favourable shifts in body composition and can be used at lower external loads with blood-flow restriction when pain, neuropathy or frailty limit classic loading.²⁹

Table 1. Examples of exercise dosing protocols used in studies involving PLWH.

Prescription	Repetitions	Number of sets	Total duration	Authors
Less than 3 weeks	Variable	2 resistance sets	≥5 weeks (90–150 min)	Ozemek et al; O’Brien et al Zech et al26 28 31
Between 3 and 5 weeks		≥2 resistance sets	≥5 weeks (20–60 min)	Zech et al31
6-week low volume	Variable	1–3 sets	≥5 weeks (20–60 min)	Ramírez-Marrero et al30

PLWH, people living with HIV.

HIIT is feasible in PLWH, though responses may vary by sex and disease phenotype; in a 6-week low-volume HIIT programme among Hispanic women, VO₂ peak gains were less consistent in HIV+than HIV– participants, underscoring heterogeneity and the need to individualise intensity and recovery.³⁰ Concurrent training is frequently optimal for cardiometabolic risk, pairing aerobic (moderate/vigorous or HIIT) with multijoint resistance (1–3 sets, 8–15 reps, 6–8 exercises) two or more days/week.^{26 31} Flexibility and mind-body approaches (eg, yoga, aerobic dance) can complement mobility, balance and symptom control but should not replace cardio-metabolic dosing. Home vs facility-based delivery can be mixed; supervision improves adherence and safety, while mobile health ‘Mhealth’/tele-exercise (texts, wearables, app-guided HIIT) shows promise, but evidence for hard cardiometabolic endpoints in PLWH remains limited and heterogeneous.³²

Exercise is safe and beneficial for medically stable PLWH on effective ART regimen, with trials and reviews reporting no adverse effects on cluster of difference 4 (CD4) count or viral load and low serious-event rates when screened appropriately.²⁸ Preparticipation checks should verify viral suppression, recent CD4 trend, cardiovascular risk, anaemia, symptomatic peripheral neuropathy and bone health (osteopenia/osteoporosis), with temporary deferral during acute opportunistic infections (OIs), uncontrolled fever or severe anaemia; weight-bearing and impact progressions should be conservative when BMD is low.¹² Several trials required CD4≥200–500 cells/µL and undetectable/low viral load as inclusion thresholds, which, while not universal cutoffs, illustrate conservative screening used in research.³⁰

ART and exercise interactions are generally favourable, but clinicians should monitor for INSTI/TAF-associated weight gain and dyslipidaemia, which may influence training goals, and for neuropathy, myopathy or fatigue, which can alter modality choice and recovery windows.⁹ Programmes should include adverse event monitoring, use rate of perceived exertion (RPE) and heart rate to titrate internal load, and consider lower-load BFR resistance or cycle/elliptical substitutions in painful neuropathy; return to exercise after intercurrent illness should be gradual, with re-screening for OIs as per national HIV guidelines.

Across randomised and controlled studies in adults with HIV, aerobic or combined aerobic resistance training performed ≥3×/week for≥5 weeks yields moderate improvements in VO₂ max/CRF and functional capacity; a meta-analysis reported VO₂ max SMD ≈0.66 and 6 min walk SMD ≈1.11 vs controls, favouring exercise.³¹ O’Brien and colleagues also found significant gains in VO₂ max, strength and body composition (increased lean mass; reduced %fat) with no deleterious effects on CD4 or viral load.²⁸ Among older PLWH (≥50 years), pooled data show clinically meaningful gains in walking capacity (Cohen’s d ≈0.47), with mixed or non-significant pooled effects for VO₂ max and weight, pointing to the need for adequately powered, age-specific trials.³³ Some studies suggest blood pressure reductions and favourable lipid or glycaemic trends following structured training, though precision varies by regimen and population; resistance training improves strength and may aid body composition without consistent changes in interleukin-6 (IL-6)/tumour necrosis factor-alpha (TNF-α), while blood flow restriction resistance training can produce acute cardiometabolic benefits at lower loads.^{29 34}

Comparative efficacy signals support concurrent training for combined outcomes and HIIT for time-efficient improvements in CRF, but PLWH-specific HIIT evidence remains limited; in women with HIV, low-volume HIIT improved workloads and time-to-exhaustion but not group mean VO₂ peak.³⁰ Dose response patterns are consistent with general guidelines of higher adherence and progression towards ≥150 min/week plus ≥2 resistance sessions yield larger CRF and body-composition gains; supervision and mixed modal programmes enhance effects, particularly in multimorbidity.

Clinical effectiveness on musculoskeletal and functional outcomes

CRF evidence

Structured aerobic and concurrent training improves functional capacity and cardiorespiratory performance in PLWH. Meta-analytic evidence shows that the 6 min walk test typically increases by 30 to 60 m, representing a large effect (standardised mean difference ≈ 1.11) and clinically meaningful gains in daily mobility.³¹ Improvements in VO₂ max fall within the moderate range, with standardised mean differences close to 0.66 across trials. These gains translate into better independence and reduced frailty risk, especially in older adults.

Muscle strength and body composition evidence

Resistance and combined training produce moderate to large increases in muscle strength, with a pooled standardised mean difference of about 0.78 (moderate to large effect) after eight or more weeks of training.³⁴ These adaptations are accompanied by improvements in lean mass and reductions in total fat mass. Although BMD remains a major challenge for PLWH because of chronic inflammation, tenofovir based treatment and hormonal changes, regular resistance and high impact training can slow its decline, even though gains are generally smaller compared with HIV negative groups.¹²

Inflammation and immune function evidence

Exercise supports immune recovery without compromising viral suppression. Moderate intensity aerobic and resistance training can maintain or increase CD4 cell counts, with average increases of 30 to 50 cells per µL in several trials, and can improve the CD4 to CD8 ratio, a marker associated with reduced morbidity.²⁸ Regular training reduces inflammatory markers such as IL-6, TNF-α and C reactive protein while increasing anti-inflammatory mediators.³⁴ Mechanistic studies show improvements in endothelial function, mitochondrial capacity and reduced T cell senescence, all of which contribute to slower immunological ageing and lower cardiovascular disease risk.³⁵ Viral load remains stable, confirming the immunological safety of well prescribed exercise. Evidence for long term cardiometabolic endpoints and HIIT responses, particularly among women and older adults, remains inconsistent.

Age, sex and gender sensitive perspectives

Some differences in exercise responses reflect general physiological sex differences, while others stem from HIV-specific hormonal and metabolic effects. Men often show larger absolute strength and VO₂ max improvements, whereas women tend to show better endurance capacity and lipid oxidation.³⁶ Men usually experience more rapid reductions in visceral adiposity, while women often maintain fat-free mass more effectively during weight loss interventions.⁹ Bone health requires special consideration. Postmenopausal women and men with hypogonadism typically show slower responses, so exercise should be accompanied by nutritional and sometimes pharmacological support.¹²

Exercise needs shift across the life course. Adolescents and young adults benefit from programmes that emphasise skill development and prevention of early cardiometabolic risk.⁵ Adults above 50 years often present with multimorbidity and reduced muscle quality, making combined strength, balance and aerobic work important for maintaining independence.³⁷ Exercise during pregnancy is generally safe when medically cleared. Recommended precautions include avoiding prolonged supine positions after 20 weeks and reducing impact loading when pelvic girdle pain or obstetric complications are present.³⁸ Co-infections such as tuberculosis or hepatitis B and C may require additional recovery time and careful intensity adjustments.⁹

Implementation for adherence, behaviour change and maintenance

Implementation requires structured frameworks such as the Reach, Effectiveness, Adoption, Implementation, Maintenance framework and the Template for Intervention Description and Replication guide to support intervention design, delivery and reporting.³⁹ Community-based, low resource strategies have demonstrated feasibility within African settings. Examples include peer-led walking groups in Mozambique, community resistance circuits using filled water jugs in Niger and supervised aerobic-dance sessions in South Africa.⁵ These approaches reduce cost and increase cultural acceptability.

Task shifting to trained non-specialist workers can enhance reach in routine HIV care.³² Incorporating exercise counselling into ART visits supports behaviour change and improves linkage to ongoing activity. Digital tools such as SMS prompts, wearable trackers and app-guided interval training programmes are promising for younger and working adults. Fidelity monitoring should include adherence to frequency and intensity, documentation of adaptations and participant feedback.

Long-term maintenance is supported by behavioural frameworks such as the Capability, Opportunity, Motivation and Behaviour model and Self-Determination Theory, which emphasises autonomy, competence and relatedness. Motivational interviewing has been effective for identifying personal goals, reducing barriers and improving physical activity uptake and continuation.⁴⁰ Habit formation strategies such as pairing exercise with daily routines or environmental cues provide stability. Peer support enhances accountability and reduces stigma for many PLWH. Peer-led models have shown strong adherence effects in both high- and low-resource settings.³²

Economic considerations

Economic data remain limited for PLWH. Existing modelling studies suggest that structured exercise integrated into HIV care may be cost-effective for preventing cardiovascular disease and diabetes according to WHO benchmarks.⁴¹ Community-based and task-shifted models reduce staff and infrastructure costs and appear to be more sustainable in low- and middle-income settings.⁵ Although pharmacological prevention often produces quicker cardiometabolic effects, exercise provides broader benefits including functional performance and mental health. Few direct cost-effectiveness trials have been conducted among PLWH, highlighting an important research gap.

Economic evaluations FOR measurement and reporting standards

Evidence on the economic impact of exercise interventions in PLWH is limited but emerging. Modelling studies suggest that structured physical activity, when integrated into HIV care, may be cost-effective for NCD prevention, depending on the delivery model and context, particularly for cardiovascular disease and type 2 diabetes, when measured against WHO’s cost-effectiveness thresholds.⁴¹ From a health system perspective, the budget impact of adding exercise programmes to HIV clinics is modest compared with pharmacological prevention, particularly if delivered via group or community-based formats. Downstream savings from reduced NCD events, including fewer hospitalisations and lower medication costs, can offset programme expenses within 3–5 years in high-prevalence settings.⁴¹

In low- and middle-income countries (LMICs), task-shifted and community-led delivery models further improve cost-effectiveness by reducing personnel and infrastructure demands.⁵ Comparative analyses with pharmacological prevention suggest that while drugs like statins or antihypertensives may achieve faster reductions in risk, exercise provides broader benefits across metabolic, mental health and functional domains, making it an attractive investment for multisectoral health policy. It was also noted that there was a scarcity of PLWH-specific cost-effectiveness trials and very few direct cost-effective trials exist in PLWH populations, underscoring the need for economic evaluation alongside pragmatic trials.

Standardisation of outcome measurement is critical to synthesising exercise evidence in PLWH. Heterogeneity in outcome measures limits comparability across studies; a core set would improve meta-analytic synthesis. Core outcome sets should include CRF (eg, VO₂ max or 6MWT), muscle strength (handgrip dynamometry, 1RM tests), body composition (DXA, bioimpedance) and health-related quality of life (eg, SF-36, WHOQOL-HIV).⁴² Biomarkers, including CD4 count, CD4/CD8 ratio, IL-6, TNF-α, CRP, fasting glucose, HbA1c and lipid panels, capture immunometabolism adaptations. Selecting functional tests, such as gait speed, sit-to-stand and balance assessments, helps evaluate independence and fall risk in older PLWH. For quantifying physical activity, device-based measures (accelerometers, pedometers) offer greater validity and granularity than self-report, though cost and feasibility in LMICs remain limiting factors.⁴³ In LMIC settings, simple tools such as handgrip dynamometry, pedometers and low-cost bioimpedance devices may balance validity and feasibility.

Clinical practice guidance ON health equity and context in LMIC settings

In LMICs, where the majority of PLWH reside, implementing exercise programmes faces access and infrastructure barriers, including limited sports facilities, limited health worker capacity and inadequate integration into primary care.⁵ Cost constraints for both individuals and health systems often prioritise ART provision over preventive interventions such as structured exercise. Rural–urban disparities are marked: rural PLWH may have fewer exercise facilities but greater opportunities for community walking or farming-related physical activity, whereas urban PLWH may face safety concerns and overcrowding that limit outdoor activity.⁴⁴

Stigma, both HIV-related and gender-based, can deter participation in group or public exercise, necessitating privacy-sensitive and culturally adapted programming. In sub-Saharan Africa, community-based, low-resource models, such as peer-led walking groups or resistance training using improvised equipment, have demonstrated feasibility and acceptability in countries like Mozambique, Niger and South Africa.⁵ Practical low-resource resistance options include sand-filled water bottles, jerry cans, elastic resistance bands, rice or flour bags, concrete blocks and simple bodyweight circuits (eg, sit-to-stands, wall push-ups, step-ups). These tools allow for progressive overload and full-body resistance training without gym infrastructure.

Screening checklists should include cardiovascular risk assessment, musculoskeletal status, immune profile (CD4 count, viral load) and comorbidities before exercise initiation. Sample 12-week protocols can be tailored:

• Aerobic: 150 min/week at 60%–75% HRmax, progressing to intervals as tolerated for 8 to 12 weeks as shown in table 2.

• Resistance: Multijoint exercises for major muscle groups, starting at 50%–60% 1RM and progressing by 5%–10% every 2–4 weeks.

• HIIT: 4×4 min bouts at 85%–90% HRmax with 3 min active recovery, 2–3×/week (only for clinically stable individuals). Monitoring schedules should reassess cardiovascular, metabolic and functional outcomes every 12–16 weeks to guide progression and ensure safety.

Table 2. A sample 8–12-week exercise protocol that improves exercise outcomes.

Type of exercise training	Duration (minutes)	Percentage HR maximum	Variations
Aerobic	150 min	60%–75%	Every 4–6 weeks
Resistance	90 min	50%–60%	Every 2–4 weeks
High-intensity interval	30 min with 3 min active recovery	85%–90%	Every 2–3×/week Contraindicated only for clinically stable individuals

Research gaps and future agenda

Despite growing evidence, critical gaps remain. Few large pragmatic trials have evaluated exercise interventions in PLWH within routine care or across diverse LMIC settings. There is a need for mechanistic studies exploring mitochondrial function, endothelial repair and neurocognitive plasticity in response to different training modalities. Long-term outcomes, including sustained reductions in NCD risk and mortality, are underreported. The optimal HIIT dosing for PLWH remains uncertain, particularly in older adults and those with multimorbidity. Future research should address sex-specific and age-specific protocols, as well as adaptations for pregnancy, disability and co-infections. Implementation studies in LMICs should integrate economic evaluation to inform policy uptake, and harmonisation of data collection protocols would facilitate meta-analyses and guideline development. Leveraging digital health tools for remote monitoring and adherence tracking offers opportunities for scale, but effectiveness in resource-constrained settings requires rigorous testing.

Strengths of this review

• Integrates clinical, mechanistic, behavioural and implementation evidence with a focus on sub-Saharan Africa.

• Provides practical guidance on exercise dosing and screening considerations for diverse populations, including older adults and women.

Limitations of this review

• Limited by heterogeneity of interventions and outcomes and a paucity of long-term trials reporting hard NCD endpoints and costs.