HIV therapeutics stand at an inflection point. With viral suppression now routinely achievable for many patients, attention is shifting towards other more long-term outcomes such as comorbidities, treatment complexity and equitable access to medicines. Gerry Hughes reports from a recent British HIV Association meeting, which summarised key findings from the Conference on Retroviruses and Opportunistic Infections 2026.
HIV care has transformed over the past two decades. Effective antiretroviral therapy has made durable viral suppression achievable for many people living with HIV. However, this still very much depends on geographical location, with certain populations continuing to experience disparities in access to care and therapeutics.
A recent UK Health Security Agency annual HIV statistics report shows that 95% of people living with HIV in England are diagnosed, 99% of those diagnosed receive treatment and 98% achieve viral suppression. These are important metrics in meeting the 95-95-95 targets from the United Nations Programme on HIV/AIDS.
Yet important gaps remain. In 2024, 3,043 new HIV diagnoses were reported in the UK. Despite a modest reduction in diagnoses compared to 2023 figures, late diagnosis continues to affect a substantial proportion of individuals, accounting for 42% of new cases in England.
This has important clinical consequences: individuals diagnosed late are around 10 times more likely to die within a year compared with those diagnosed promptly.
In parallel, the demographic profile of people receiving care is shifting. More than half of individuals in HIV care in England are now aged 50 years or older, reflecting both improved survival and the long-term nature of treatment.
The Conference on Retroviruses and Opportunistic Infections (CROI) 2026 reflected an evolution in clinical priorities – many associated with this shifting patient demographic. Viral suppression remains essential, but it is no longer sufficient on its own. Increasingly, attention is focused on treatment burden, comorbidity and the long-term sustainability of care.
Expanding HIV treatment options and simplification strategies
Presenting at the British HIV Association (BHIVA) ‘Best of CROI’ Virtual Feedback Meeting, Dr Tristan Barber, consultant in HIV medicine at the Royal Free London NHS Foundation Trust, outlined emerging strategies aimed at reducing treatment burden while maintaining durable virological suppression.
Dr Barber highlighted data from a phase 2 study evaluating once-weekly oral islatravir, a nucleoside reverse transcriptase translocation inhibitor, in combination with the first-in-class capsid inhibitor lenacapavir, in virologically suppressed individuals.
Participants were randomised either to switch immediately to weekly islatravir/lenacapavir or to continue daily bictegravir/emtricitabine/tenofovir alafenamide with a delayed switch.
‘The summary here is that weekly oral islatravir and lenacapavir maintained high rates of virologic suppression through to 96 weeks, and no emergent resistance to islatravir or lenacapavir was detected,’ Dr Barber observed. ‘There was good adherence in both groups. And this combination is now being investigated in the phase 3 ISLEND-1 and ISLEND-2 studies.’
Findings from the ARTISTRY-1 and -2 trials also highlighted the potential for treatment simplification. In the phase 3 randomised ARTISTRY-1 trial, switching to a bictegravir/lenacapavir single tablet regimen was compared with continuation of complex antiretroviral regimens in virologically suppressed individuals.
The population was notably treatment-experienced, with 77% receiving protease inhibitor-based therapy at baseline, with a high prevalence of comorbidities, treatment experience, resistance-associated mutations and high pill burden.
Through to 48 weeks, switching maintained virological suppression and demonstrated non-inferiority, with no treatment-emergent resistance and stable CD4 counts.
Reflecting on the importance of such studies in an evolving HIV demographic, Dr Barber noted that many of these participants had ‘switched away from a booster with potentially positive metabolic impacts, as well as the avoidance of drug-drug interactions, particularly as they age’.
Managing innovative treatments in complex patients
Long-acting injectable therapy is another transformative development in the evolution of HIV treatment, offering an alternative to daily oral dosing.
Real-world data, however, highlight variabilities in treatment outcomes. Dr Marta Boffito, consultant physician at Chelsea and Westminster Hospital, outlined a study of 114 patients with 195 corresponding plasma samples, which demonstrated substantial variation in drug concentrations of long-acting cabotegravir and rilpivirine.
Lower cabotegravir, but not rilpivirine, concentrations were associated with detectable viral loads, potentially related to the greater importance of cabotegravir in treatment success.
These findings underscore a key challenge. Outcomes observed in clinical trials may not fully translate into routine practice, particularly in populations with complex social or clinical circumstances. Variability in pharmacokinetics, adherence to injection schedules and administration technique may all influence outcomes.
Approaches such as therapeutic drug monitoring could become increasingly important in ensuring the effectiveness of long-acting therapies in real-world settings.
Dr Boffito also discussed data from CROI 2026 on the changing demographic of HIV care, noting the growing importance of managing comorbidity and polypharmacy.
METHOD is a phase 2 trial investigating adjunctive metformin with standard tuberculosis (TB) therapy in people with HIV, evaluating safety, tolerability, time to infection clearance and pulmonary outcomes.
In a study of 80 METHOD participants receiving TB treatment, including 43 on metformin, exposure to key anti-TB agents was reduced in those receiving metformin. Isoniazid bioavailability was 15.9% lower and rifampicin bioavailability 24% lower, resulting in an overall reduction in drug exposure.
Dr Boffito said: ‘It can become a very complex, multi drug-drug interaction scenario, if we add the dolutagravir to the picture. So, this is really to highlight the importance of looking at multiple drug-drug interactions, but also looking at pharmacodynamic data, and looking at viral load response, and also TB treatment response.’
Cardiovascular risk and HIV: an evolving clinical priority
As the life expectancy trajectory for many, but not all, HIV patients increases, non-communicable diseases are becoming a major determinant of long-term outcomes.
Professor Yvonne Gilleece, consultant in HIV medicine and sexual health at University Hospitals Sussex NHS Foundation Trust, reported data from the REPRIEVE study, involving 7,769 participants across five global regions, describing the scale of cardiovascular risk for HIV patients.
Among this low-to-moderate cardiovascular disease risk population, 36% of participants had hypertension at baseline, of whom 56% were receiving treatment, 12% were diagnosed but untreated, and 32% had elevated blood pressure at baseline.
Hypertension was more common in women than men (39% vs 34%) and was strongly associated with obesity, affecting 51% of individuals with obesity compared with 26% of those with normal body mass index.
Among those with diagnosed hypertension, 61% achieved blood pressure control below 140/90 mmHg, with lower control rates in women.
Professor Gilleece also highlighted data from a large cohort study examining cerebral small vessel disease and large artery disease, and the differential effects of modifiable risk factors on cerebrovascular injury in women and men with HIV.
Small vessel, but not large artery, disease was more prevalent in women than men, with a 2.93-fold higher burden. These findings reinforce the need for more systematic identification and management of cardiovascular risk factors as part of routine care, particularly for women.
Reflecting on sex differences in cardiovascular outcomes, Professor Gilleece commented: ‘For me, women are the group we need to watch in the context of cardiovascular risk.’
INSTIs and cardiovascular disease risk
Professor Caroline Sabin, professor of medical statistics and epidemiology at University College London, also focused part of her presentation on cardiovascular disease.
She discussed updated analyses from the International Cohort Consortium of Infectious Disease (RESPOND) collaboration. This study examined the impact of integrase strand transfer inhibitors (INSTIs) and cardiovascular disease risk.
Earlier findings had suggested a potential increase in risk with INSTI use, although results had been inconsistent across studies. The updated analysis used a target trial emulation framework to provide a more robust estimate.
The reanalysis included 7,111 antiretroviral therapy-naive participants, of whom 47% initiated an INSTI-based regimen. In this group, adjusted relative risk of cardiovascular disease was 1.92 at one year, 1.83 at two years and 1.71 at six years.
Among the 22,921 antiretroviral therapy-experienced participants, 49% switched to an INSTI. Here, any increased risk was more transient, with relative risks of 1.41 at one year, 1.26 at two years and 1.02 at six years.
Despite these relative risk signals, absolute risk differences were small, never exceeding 1.23 percentage points. Professor Sabin noted that the clinical relevance of these findings is likely to be limited.
Effectiveness and equity of HIV prevention strategies
Along with treatment approaches, the BHIVA meeting also focused on preventative strategies.
While pre-exposure prophylaxis (PrEP) is highly effective, its population-level impact is evolving. Again, this is alongside shifting patient demographics and persistent inequities in access and uptake.
Dr Michael Rayment, consultant in sexual health and HIV at Chelsea and Westminster Hospital NHS Foundation Trust, presented final eight-year results from the ANRS Prévenir study – a prospective cohort study enrolling individuals at high risk of HIV infection using PrEP.
Men who have sex with men could choose either daily or on-demand PrEP with tenofovir disoproxil fumarate/emtricitabine and switch between regimens. Participants were tested for HIV at baseline, at one month and every three months thereafter.
Overall HIV incidence was low at 0.99 per 1,000 person-years. When outcomes were stratified by daily, on-demand or switching use of PrEP, no differences in HIV acquisition were observed, leading the authors to conclude that on-demand PrEP is as effective as daily dosing.
Programme scale increased substantially over time, with almost 28,000 participants receiving PrEP by study end. While overall new HIV diagnoses declined by 2%, a 33% reduction among men born in France contrasted with a 73% increase among those born abroad.
These findings highlight a persistent gap, as Dr Rayment observed: ‘This is a real lesson learned, I think, around equity, and that only those populations able to access PrEP stand to yield benefits.’
Conclusion
As the BHIVA ‘Best of CROI’ Virtual Feedback Meeting demonstrated, HIV care is entering a more complex and nuanced phase. Viral suppression, once the primary objective, now represents the foundation upon which broader challenges emerge.
Treatment strategies are evolving towards greater simplicity and durability, while long-acting approaches offer new opportunities alongside new uncertainties. At the same time, ageing populations and increasing comorbidity are reshaping the clinical focus of care, with compounding factors such as cardiovascular disease and drug interactions becoming more prominent.
Sustaining progress will depend not only on therapeutic innovation, but on how effectively these advances are integrated into increasingly complex care pathways.
The next phase of HIV care will likely be defined by the ability to move beyond viral control and address the wider determinants of long-term health.
