South Africa has the largest population of PLWH globally, with a prevalence of 17% in
adults or 7.2 million PLWH. The rapid scale-up of ART programs has resulted in >6 million
PLWH on treatment, significant gains in life expectancy, and a large population of aging
PLWH. With increasing life expectancy, obesity and type 2 diabetes have become growing
threats for PLWH in South Africa and globally. One recent study found that 63% of PLWH
are overweight or obese, and 6% have diabetes in this setting.
This elevated risk of obesity in PLWH in South Africa is likely due to a confluence of
both general considerations and HIV-specific factors. First, South Africa has experienced
an accelerated background epidemic of metabolic disease in the general population with a
prevalence of overweight and obesity that is nearly equal to that of high-income
countries. Additionally, the International Diabetes Federation estimates that
approximately 15.5 million adults are living with diabetes in the African Region, and
projects it to grow to 41 million by 2045. As part of this background epidemic of
metabolic disease, South Africa is also experiencing a nutrition transition, with
widespread availability of processed and refined foods as well as sugar-sweetened
beverages.
Regarding HIV-specific issues, in 2019 the first-line ART regimen for the South African
national HIV treatment program transitioned to TLD. TLD is generally very safe and
well-tolerated and has a high barrier to HIV resistance but this transition to this
regimen has been associated with risk of excess weight gain at the population level. Both
clinical trials and observational studies conducted in South Africa have shown
substantial increases in body weight in those who are initiating this ART regimen newly
and among those who are suppressed and switched, especially women. Given this, there is a
growing risk of obesity in PLWH in this context and a need for management strategies to
address this increasingly prevalent comorbidity.
Preventing the metabolic complications of HIV in South Africa and worldwide requires
urgent solutions. To date, obesity management and diabetes prevention have largely
consisted of behavioural interventions such as the Diabetes Prevention Program and
related lifestyle modification efforts, focused on improving diet and increasing physical
activity. However, in the past several years, novel anti-obesity pharmacologic agents
such as the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown enormous
promise for obesity management and diabetes prevention in people who are HIV-negative
(8-10). However, this drug class has a very limited evidence base in PLWH and relatively
scant data from sub-Saharan African populations.
Currently, liraglutide is the only GLP-1 RA approved for obesity management in South
Africa and this protocol proposes to use the drug for its labelled indication of "weight
loss in addition to diet and exercise in adults aged 18 and above who have: (1) a BMI of
30 or greater (obese) or (2) a BMI of greater than 27 and less than 30 (overweight) and
weight related health problems (such as diabetes, high blood pressure,
hypercholesterolemia, or obstructive sleep apnoea).
This evidence gap motivates further inquiry into GLP-1 RAs such as liraglutide as one
potential approach to obesity management and prevention of diabetes in PLWH who have
comorbid obesity in South Africa, with implications for PLWH in other contexts. In this
proposal, the investigators seek to further this important area of inquiry by evaluating
the acceptability of liraglutide along with lifestyle counselling in PLWH who have
obesity and are stable on dolutegravir-based ART in South Africa.