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Introduction The worldview in relation to patient care has shifted from conquering diseases to improving overall wellbeing and quality of life. We examined treatment aspirations among people living with HIV (PLHIV). Methods In all, 2389 PLHIV were surveyed in the 25-country 2019 Positive Perspectives Study. Descriptive and multivariable analyses were used to explore attitudes towards treatment. Results Participants were from: Northern America (USA, Canada), 21.8% (520/2389); Europe, 46.8% (1119/2389); and other international regions, 31.4% (750/2389). Factors associated with some level of dissatisfaction with HIV medication among those otherwise fully satisfied with their HIV management included being on a multi-tablet regimen (AOR=2.76; 95% CI: 1.93–3.96), reporting polypharmacy (AOR=2.10; 95% CI: 1.45–3.03), and experiencing side effects from current HIV medication (AOR=2.12; 95% CI: 1.49–3.02). Of seven improvements to HIV medications assessed, the percentage ranking each attribute, as the first or second most important, was: ‘reduced long-term impact on my body’ (46.7%); ‘longer-lasting medicine so I don’t have to take it every day’ (43.1%); ‘fewer side effects’ (40.5%); ‘less HIV medicine each day but just as effective’ (25.4%); ‘less chance of affecting other medicines’ (21.6%); ‘no food restrictions/ requirements’ (14.0%); and ‘smaller pills’ (8.7%). Overall, 77.1% (1842/2389) believed ‘future advances in HIV treatment will improve my overall wellbeing’, 72.2% (1726/2389) were ‘open to taking an HIV treatment composed of fewer medicines’, while 54.7% (1306/2389) expressed openness towards longer-acting (non-daily) HIV medication. Compared to those not fully satisfied with either their HIV medication or management, those fully satisfied with both reported significantly higher prevalence of optimal treatment adherence (89.2% [372/417] vs 69.5% [763/1098]) and optimal overall health (70.3% [293/417] vs 47.8% [525/1098]) (all p