HIV and weight stigma

HIV-associated wasting has declined with access to antiretrovirals (ARVs). However, weight gain and metabolic syndrome continue to increase across people with HIV.¹ Access to more effective and tolerable ARVs has increased virologic suppression and immunologic recovery, leading to increased life span.¹ The benefit of ARVs on morbidity and mortality outweighs the risk for potential side effects from ARVs. However, as people with HIV age and life span increases, the effect of weight gain and other metabolic abnormalities must be considered.²

Weight gain associated with HIV includes the “return to health” phenomenon and the effects of ARVs.^1,3 Older ARVs were associated with lipodystrophy.² Weight gain and the impact of ARVs on insulin resistance contribute to developing type 2 diabetes in people with HIV.^2,4,5 Metabolic syndrome, a cluster of risk factors for cardiovascular diseases and type 2 diabetes, also may occur.¹ In addition, inflammation linked to abdominal obesity may contribute to neurocognitive impairment.¹ The impact of immune dysfunction and dysregulation on adipose tissue affects health outcomes.⁶ Individuals at lower weight have differing adipose tissue immune function and inflammation compared with those at higher weight and at higher weight with HIV.⁶ Metabolic abnormalities may lead to nonalcoholic fatty liver disease. The effects of gestational weight gain in people who have HIV must also be considered.^7,8 Blood pressure also has been affected during the first year of ARV therapy and beyond.^3,9

A growing body of literature is seeking to guide the use of integrase strand transfer inhibitors (INSTIs), tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and their association with potential weight gain in people with HIV who are treatment-naive and treatment-experienced.^2,10 INSTIs have been reported to have effects on gene expression and the secretion of adipokines and cytokines.¹¹ Instead of switching to INSTIs, there is some evidence demonstrating that preexisting weight gain and low levels of physical activity influence additional weight gain with ARVs.¹² The actual mechanism for weight gain with INSTIs, especially in addition to TAF, has not yet been elucidated.¹³ In addition, the true reversibility of weight gain is not known. Risk factors for weight gain, such as race and sex, have been reported.²

Exposure to thymidine analogs and didanosine is associated with insulin resistance.¹⁴ High-circulating leptin is associated with a higher homeostatic model assessment of insulin resistance and high-sensitivity C-reactive protein independent of fat depot size.¹⁵ This factor suggests that greater adipocyte lipid content contributes to impaired glucose tolerance and systemic inflammation. Insulin resistance was associated with a clinical cut point of 5% weight gain after switching to an INSTI-based regimen.¹⁶ Monitoring for incident type 2 diabetes is warranted for all people with HIV on any ARV regimen.¹⁷

Switching to 2-drug regimens with dolutegravir-lamivudine (Dovato, ViiV Healthcare) or dolutegravir-rilpivirine (Juluca, ViiV Healthcare) has been associated with an improved lipid profile.¹⁸ Many switch studies show a decrease in weight and cholesterol markers with a switch to TDF or the opposite when switching to TAF.^2,19-23 However, the clinical implications of these switches need to be considered. Current guidelines do not recommend switching ARVs due to potential weight gain.²⁴

Stigma

Healthcare providers need to be aware of the stigmatization of weight.²⁵ Weight stigma has a damaging effect on health, including disordered eating, sleep disturbance, and exercise avoidance. Cortisol levels increased in response to exposure to weight-stigmatizing scenarios in laboratory experiments.²⁵ Individuals who experience weight discrimination have higher levels of C-reactive protein. Moreover, adolescents who experience this stigma are more likely to develop obesity, type 2 diabetes, and cardiovascular disease. There is an increase in all-cause mortality for those experiencing stigma.²⁵

Unfortunately, healthcare professionals may continue this stigma through implicit and explicit bias. Stereotypes toward those who are overweight or obese include laziness, lack of intelligence, and a lack of willpower and self-control.²⁵ Some providers may even attempt to use stigma to encourage weight loss. Healthcare professionals also over-attribute health conditions and comorbidities to weight, often missing the opportunity to diagnose an underlying medical condition.²⁵ When the stigma surrounding HIV is added to weight stigma, health outcomes likely are diminished further.

There are also racial disparities in the health status of people with HIV. There is a relationship between weight, race, and cardiovascular risk.²⁶ Data suggest that race should be included as a main effect in statistical models. Currently, it is often used as a covariant to adjust for race and ethnicity. Risk factors that are socio-behavioral or lifestyle related need to be addressed with appropriate interventions. Specific risk factors include alcohol use, osteoporosis, previous AIDS-defining events, and polypharmacy.²⁷

The effect of weight in people with HIV has changed throughout the HIV epidemic, and short-term health outcomes have given way to long-term health consequences. Patient-specific factors should be considered when initiating and switching ARVs. A personalized approach is essential in conjunction with the evidence presented in the guidelines. Lifestyle and pharmacologic and surgical management of people with HIV who are overweight and obese should be considered.

By Milena Murray, PharmD, MSc, BCIDP, AAHIVP, FCCP

References

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