HIV treatment and obesity have become increasingly interconnected as modern antiretroviral therapy (ART) transforms HIV into a manageable chronic condition. Whilst ART enables people living with HIV to achieve near-normal life expectancy, certain regimens—particularly those containing integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF)—are associated with significant weight gain. Obesity prevalence among people living with HIV in the UK now mirrors or exceeds that of the general population, at 25–30%. This creates unique metabolic and cardiovascular risks that require careful monitoring and individualised management strategies balancing viral suppression with long-term metabolic health.

How HIV Treatment Affects Body Weight and Metabolism

Antiretroviral therapy (ART) has transformed HIV from a life-threatening condition into a manageable chronic illness, enabling people living with HIV to achieve near-normal life expectancy. However, modern ART regimens have been associated with changes in body weight and metabolic function. Research indicates that certain antiretroviral medications, particularly integrase strand transfer inhibitors (INSTIs) such as dolutegravir and bictegravir, are linked to greater weight gain compared to older drug classes. The nucleoside reverse transcriptase inhibitor (NRTI) backbone also plays an important role: tenofovir alafenamide (TAF) is associated with more weight gain than tenofovir disoproxil fumarate (TDF), whilst older regimens containing efavirenz may have had relative weight-suppressive effects.

The mechanisms underlying ART-related weight gain are multifactorial and not yet fully understood. Some antiretroviral drugs may influence appetite regulation, though the precise pathways remain under investigation. Additionally, the restoration of health following ART initiation—often termed the 'return to health' effect—naturally leads to weight gain as immune function improves and chronic inflammation subsides. This represents a positive outcome for individuals who were previously experiencing HIV-related wasting. It is important to note that not all people on the same ART regimen will experience clinically significant weight gain; individual responses vary considerably due to genetic, environmental, and behavioural factors.

Metabolic changes associated with ART extend beyond simple weight gain. Some medications can affect insulin sensitivity, lipid profiles, and fat distribution patterns. Certain protease inhibitors and older NRTIs have been particularly associated with metabolic complications, including dyslipidaemia and insulin resistance. The British HIV Association (BHIVA) and European AIDS Clinical Society (EACS) guidelines emphasise the importance of monitoring metabolic parameters regularly—at baseline and at least annually, with more frequent checks if abnormalities are detected. Monitoring should include weight, body mass index (BMI), waist circumference, blood pressure, fasting glucose, and lipid levels to identify and address changes early in the treatment course.

Why Obesity Occurs in People Living with HIV

The development of obesity in people living with HIV represents a complex interplay of medication effects, immune restoration, lifestyle factors, and demographic characteristics. Historically, HIV infection was associated with weight loss and wasting syndrome; however, obesity prevalence among people living with HIV in the UK now mirrors or exceeds that of the general population. Data from UK cohorts suggest rates between 25% and 30%, though prevalence varies by population and setting.

Key contributing factors include:

• Antiretroviral medication effects: Certain ART regimens, particularly those containing INSTIs and TAF-based backbones, have demonstrated associations with significant weight gain. Women and individuals of Black African or Caribbean ethnicity appear particularly susceptible to INSTI-related weight gain in some studies, though the reasons for these disparities remain under investigation and individual responses are heterogeneous. Switching from efavirenz-based regimens may also be followed by weight gain.

• Immune reconstitution: Successful viral suppression and CD4 cell recovery lead to 'return-to-health' weight restoration. As chronic inflammation resolves and overall health improves, the body's nutritional status normalises, often resulting in weight gain that may progress to obesity if not monitored.

• Lifestyle and socioeconomic factors: People living with HIV may face barriers to maintaining healthy weight, including mental health challenges, socioeconomic disadvantage, reduced physical activity due to fatigue or comorbidities, and limited access to nutritional support.

• Ageing and comorbidities: As the HIV-positive population ages on long-term ART, age-related metabolic changes combine with medication effects and accumulated comorbidities to increase obesity risk.

• Other medical causes: Secondary causes of weight gain—such as hypothyroidism, Cushing's syndrome, or concurrent medications (e.g., corticosteroids, antipsychotics)—should be considered and investigated where clinically indicated.

It is important to note that whilst there is strong observational evidence linking certain ART regimens with weight gain, individual responses vary considerably, highlighting the role of genetic, environmental, and behavioural factors in obesity development.

Managing Weight Gain Whilst on Antiretroviral Therapy

Effective weight management for people living with HIV requires a collaborative, individualised approach that balances viral suppression with metabolic health. The primary goal remains maintaining undetectable viral load, but this should not preclude addressing weight-related concerns that affect quality of life and long-term health outcomes.

Monitoring and early intervention form the cornerstone of management. BHIVA and EACS guidelines recommend baseline and regular (at least annual) weight and BMI measurements, with more frequent monitoring if abnormalities are detected. More detailed metabolic assessments—including waist circumference, blood pressure, fasting glucose, and lipid profiles—should be conducted at baseline and at least annually, or more frequently if clinically indicated. Early identification of weight gain allows for timely intervention before obesity develops. Rapid or unexplained weight gain should prompt screening for secondary causes, including thyroid function tests, medication review, and assessment for fluid retention.

Lifestyle modifications remain the first-line approach for managing ART-related weight gain. Dietary interventions should focus on balanced, nutrient-dense eating patterns rather than restrictive diets, which may be difficult to sustain. Referral to a dietitian with experience in HIV care can provide tailored nutritional guidance. Physical activity recommendations should be individualised based on fitness level, comorbidities, and personal preferences, with a target of at least 150 minutes of moderate-intensity activity weekly, as per UK Chief Medical Officers' guidelines. Signposting to NHS tier 2 weight management services (community-based lifestyle programmes) may be appropriate for individuals with a BMI ≥30 kg/m² (or ≥27.5 kg/m² for people of South Asian, Chinese, other Asian, Middle Eastern, Black African, or African-Caribbean family background) who have not responded to initial advice.

Medication review may be appropriate for individuals experiencing problematic weight gain. Switching from an INSTI-based or TAF-containing regimen to an alternative ART combination might be considered, though this decision must carefully weigh the risks of virological failure or drug resistance against potential metabolic benefits. Evidence that switching away from INSTIs leads to substantial weight loss is limited and uncertain. Any treatment modification should be undertaken only after thorough discussion between patient and HIV specialist, ensuring the new regimen maintains virological efficacy whilst addressing tolerability concerns. BHIVA, EACS, and local multidisciplinary teams provide guidance on appropriate ART switches in the context of tolerability issues, including weight gain. When considering any new medication or supplement, clinicians should check the University of Liverpool HIV Drug Interactions resource to identify potential interactions with ART.

Health Risks of Obesity in People Living with HIV

Obesity in people living with HIV carries significant health implications that extend beyond those experienced by the general population. The combination of excess adiposity, chronic HIV infection (even when virally suppressed), long-term ART exposure, and ageing creates a unique risk profile for cardiovascular and metabolic complications.

Cardiovascular disease represents a leading cause of morbidity and mortality among people living with HIV in the UK. Obesity compounds the already elevated cardiovascular risk associated with HIV infection and certain antiretroviral medications. Excess weight contributes to hypertension, dyslipidaemia, and insulin resistance—all established cardiovascular risk factors. NICE guidance on cardiovascular disease prevention emphasises the use of QRISK3 for risk assessment in UK primary care, with HIV status considered as an additional risk factor. The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) risk calculator may also be used as an HIV-specific adjunct tool in specialist settings.

Type 2 diabetes occurs at higher rates in people living with HIV compared to the general population, with obesity serving as a major modifiable risk factor. The combination of ART-related metabolic effects and excess adiposity significantly increases diabetes risk. BHIVA and EACS recommend baseline and annual screening with fasting glucose; HbA1c may underestimate glycaemia in some people living with HIV and should be interpreted with caution. Screening is particularly important for those with additional risk factors including family history, ethnicity (South Asian, Black African, or Caribbean background), or concurrent use of medications known to affect glucose metabolism.

Non-alcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction-associated steatotic liver disease (MASLD), has emerged as an important comorbidity, with obesity, metabolic syndrome, and certain antiretroviral drugs all contributing to hepatic steatosis. NICE guidance recommends calculating the Fibrosis-4 (FIB-4) score to assess liver fibrosis risk; individuals with intermediate or high scores should be referred for transient elastography and, if indicated, to hepatology services. People living with HIV who are co-infected with hepatitis B or C face particularly high risks of progressive liver disease when obesity is present.

Additional complications associated with obesity in this population include obstructive sleep apnoea, osteoarthritis, certain cancers, and mental health challenges. The cumulative burden of these conditions significantly impacts quality of life and may complicate HIV management through drug interactions and reduced treatment adherence.

Treatment Options and Support for Weight Management

Comprehensive weight management support for people living with HIV should be integrated into routine HIV care, with access to multidisciplinary services that address the complex interplay between viral control, metabolic health, and overall wellbeing.

Multidisciplinary care teams ideally include HIV physicians, specialist nurses, dietitians, physiotherapists or exercise specialists, and mental health professionals. Many UK HIV clinics now offer integrated metabolic services, though availability varies by region. Patients should enquire about weight management support through their HIV clinic or request referral to appropriate NHS tier 2 (community lifestyle programmes), tier 3 (specialist multidisciplinary weight management services), or tier 4 (bariatric surgery) services, depending on clinical need and local integrated care system (ICS) pathways.

Pharmacological interventions for obesity may be considered when lifestyle modifications prove insufficient and BMI exceeds thresholds specified in NICE guidance. Options include:

• Orlistat: A lipase inhibitor that reduces dietary fat absorption. It may be prescribed when BMI is ≥30 kg/m² (or ≥28 kg/m² with risk factors such as type 2 diabetes or hypertension). It requires commitment to a reduced-fat diet and can cause gastrointestinal side effects. Patients should be monitored for fat-soluble vitamin deficiency and advised to take a multivitamin supplement at a different time of day. Women of childbearing potential should use effective contraception, as orlistat may reduce absorption of oral contraceptives.

• GLP-1 receptor agonists: Semaglutide 2.4 mg (Wegovy) and liraglutide 3 mg (Saxenda) are licensed in the UK for weight management in adults with a BMI ≥30 kg/m² (or ≥27 kg/m² with at least one weight-related comorbidity). Access is determined by NICE technology appraisal criteria and is typically provided through specialist tier 3 or tier 4 weight management services. Treatment duration is defined (usually up to two years for semaglutide), with regular review of efficacy and tolerability. These medications require careful consideration of potential drug interactions with ART; clinicians should consult the University of Liverpool HIV Drug Interactions resource. Women of childbearing potential must use effective contraception, and treatment should be stopped at least two months before a planned pregnancy. GLP-1 receptor agonists are not recommended during breastfeeding. Common side effects include nausea, vomiting, and diarrhoea.

Any pharmacological treatment must be prescribed alongside continued lifestyle interventions and requires regular monitoring of efficacy, tolerability, and adherence. Patients should be advised to report any suspected side effects via the MHRA Yellow Card Scheme (www.mhra.gov.uk/yellowcard or search for 'Yellow Card' in the Google Play or Apple App Store).

Bariatric surgery may be appropriate for individuals with severe obesity (BMI ≥40 kg/m², or ≥35 kg/m² with significant comorbidities such as type 2 diabetes or obstructive sleep apnoea) who have not achieved adequate weight loss through other means. NICE guidance on bariatric surgery applies to people living with HIV, though additional considerations are necessary. Early involvement of an HIV specialist pharmacist is essential, as bariatric procedures can affect absorption of antiretroviral medications. Modified-release formulations should be avoided post-operatively; standard immediate-release formulations are preferred. Therapeutic drug monitoring and regular viral load checks are recommended to ensure continued virological suppression, with ART adjustments made if needed. Patients should be counselled on the lifelong need for nutritional supplementation and follow-up.

Psychological support addresses the emotional and behavioural aspects of weight management, including body image concerns, eating behaviours, and motivation for lifestyle change. Access to counselling or cognitive behavioural therapy may be available through HIV support organisations or NHS psychological services.

Patients experiencing significant weight gain should not hesitate to discuss concerns with their HIV care team, as early intervention offers the best opportunity for successful weight management whilst maintaining optimal virological control.

Frequently Asked Questions