The 31st Conference on Retroviruses and Opportunistic Infections (CROI 2024) was held in Denver, Colorado over 3–6 March 2024 (https://www.croiconference.org/croi-2024-resources). The CROI conference is a forum for both basic scientists and clinical investigators to present their research findings in HIV, hepatitis, SARS-CoV-2, mpox and other viral infections and their related conditions. The conference had a mixture of plenary sessions, oral abstract presentations, themed discussions, interactive symposia, and poster presentations. Out of a total of 1902 submitted abstracts, 1067 were selected for presentation.
The author attended CROI as part of a team presenting research results from DolPHIN-2, a trial evaluating the safety and efficacy of dolutegravir when initiated in late pregnancy (Malaba et al, 2022), and results from the AGILE clinical trial platform, an early phase clinical trial platform for the treatment of COVID-19 (Griffiths et al, 2020). This report summarises findings from the conference sessions attended.
Combatting complications of HIV
People living with HIV have an increased risk of cardiovascular disease (CVD) compared with the general population due to a combination of traditional risk factors, the HIV virus and exposure to antiretroviral therapy (Feinstein et al, 2019). Hypertension is the most common modifiable CVD risk factor (GBD [Global Burden of Disease] 2021 Causes of Death Collaborators, 2024). Blood pressure can be controlled through weight loss, reducing salt intake and reducing alcohol consumption, but for many people, antihypertensive medication is the most effective long-term means of lowering blood pressure (Blood Pressure Lowering Treatment Trialists’ Collaboration, 2008). The following strategies to prevent CVD complications were presented.
Longenecker (2024a) presented a strategy on how a nurse-led multi-component intervention improved blood pressure and cholesterol in people living with HIV. The EXTRA-CVD trial took place in the USA over 12 months and randomised 297 people receiving HIV therapy with hypertension and hyperlipidaemia to either a prevention nurse intervention group or a generic prevention education group. The prevention nurse intervention group used a strategy with four components:
- Nurse-led care coordination
- Nurse-managed medication protocols and adherence support
- Home blood pressure monitoring
- Electronic medical record support tools.
The study showed that the people receiving the intervention achieved lower non-HDL (high-density lipoprotein) cholesterol levels and lower blood pressure with an increase in treatment for hypertension. It was unclear if the prevention nurses were HIV specialist nurses or cardiovascular specialist nurses. The study is now published (Longenecker et al, 2024b) and suggests that we should be considering adding nurses dedicated to comorbidity management to clinics, dependent on funding.
Yan et al (2024) presented the results from a randomised controlled trial conducted in Haiti, which evaluated the early initiation of antihypertensive treatment as a strategy to prevent cardiovascular disease. Amlodipine was started if the systolic blood pressure was greater than 130mmHg and a reduction in blood pressure was observed in comparison with participants receiving standard care. The addition of an extra tablet was not considered a burden. It was concluded that lowering the threshold for initiating antihypertensive treatment for people living with HIV could be an important tool in preventing CVD.
Hickey et al (2024a) looked at a community-based intervention for the management of severe hypertension (BP≥160/100) in Kenya and Uganda. The study randomised 200 participants and compared clinician-directed, community health worker-facilitated telehealth home visits for blood pressure and medication delivery to clinicbased hypertension care. Blood pressure was significantly improved in the community-based group after 48 weeks, as was retention in care.
Further data were presented from the REPRIEVE study. The main study showed that people with HIV who received pitavastatin had a lower risk of a major adverse cardiovascular event compared with taking a placebo (Grinspoon et al, 2023). The first sub-study presented looked at the mechanistic pathway of pitavastatin (Kolossváry et al, 2024). The study found that pitavastatin increased expression of key proteins and in particular PCOLCE, which was associated with a significant decrease (31%, P=0.002) in noncalcified plaque. The second sub-study (Erlandson et al, 2024) reported on the effect pitavastatin has on physical function and found that there were no significant differences between those receiving pitavastatin and placebo. It was concluded that the findings support the long-term safety of statin therapy on muscle, when used for primary prevention in people living with HIV.
New oral drugs
There were two presentations of new drugs still in clinical development, which have the potential to be administered orally once a week for HIV treatment. One is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) from Merck (MK-8527) and the other is an integrase inhibitor (INSTI) from Gilead (GS1720). The data presented were from phase I trials and showed good antiviral responses. There is still further research required before we see these drugs available in clinic.
The phase I trial of MK-8527 showed that a single dose as low as 0.5mg achieved viral load decreases and that the safety, efficacy and pharmacokinetics support continued clinical investigation (Carstens et al, 2024).
The phase Ia and Ib results of GS-1720 were presented (Fichtenbaum et al, 2024). Potent antiviral activity was exhibited with partial analysis of resistance showing no treatment emergent INSTI resistance at lower doses. GS-1720 was well tolerated with a favourable safety profile.
Results were also presented from a phase II study of a weekly oral combination of islatravir (NRTTI) and lenacapavir (capsid inhibitor) (Colson et al, 2024). The combination was well tolerated, and the majority of people remained virological suppressed (94%) at 24 weeks. The two discontinuations due to adverse events were not related to the combination. The study is still ongoing and the additional long-term data will be presented at a later date. It was concluded that islatravir and lenacapavir has the potential to become the first oral weekly complete regimen for HIV treatment.
Long-acting injectables
There were a number of presentations on long-acting injectables. Notably, the plenary session by Charles Flexner looked back over the past 10 years at the development of long-acting drugs and how they work. He opened and closed his presentation with ‘People don't fail drugs, drugs fail people’. There is still more to come from longer-acting treatments with new drugs and formulations. Currently, the combination of cabotegravir and rilpivirine (long-acting CAB/RPV) is the only licensed long-acting injectable for the treatment of HIV.
The CARES trial (Kityo et al, 2024) reported on the use of long-acting CAB/RPV in Africa following a switch from oral therapy. It was shown to be safe and effective at 48 weeks even with sparse viral load monitoring. It is hoped that the study will be the first steps of incorporating long-acting therapy into African HIV treatment programmes.
The LATITUDE study (Rana et al, 2024) specifically looked at people with a history of poor adherence to oral treatment regimens and randomised them to receive either long-acting CAB/RPV or continue on oral treatment. The study took place in the USA and enrolled 434 participants. There were no exclusions based on CD4 count, HIV viral load, active substance or alcohol use or unstable housing. Comprehensive adherence support and financial incentives were provided to achieve viral suppression before the participants could switch to the long-acting combination. The study was stopped early, and all participants were offered long-acting CAB/RPV as this was found to be superior to standard care oral HIV treatment. This study showed that clinical trials are feasible in this population, with the results supporting the use of long-acting injectables.
A poster presentation showed that a high proportion (81%) of people starting long-acting CAB/RPV with detectable viral loads were suppressed at 48 weeks (Hickey et al, 2024b). Overall, 93% of participants remained virologically suppressed on long-acting CAB/RPV or an alternative regimen. These data were from a retrospective clinical cohort analysis. This analysis along with other reported studies has led to the release of updated treatment guidelines by International Antiviral Society-USA (IAS-USA), which states that long-acting CAB/RPV may be considered for people with viraemia who are unable to take oral treatment, have a high risk of HIV disease progression and the virus is susceptible to both CAB and RPV (Sax et al, 2024). This differs from the BHIVA guidelines, which recommend that people have a viral load suppression of <50copies/mL for at least 6 months (Waters et al, 2022).
Antiretrovirals in pregnancy
Results from the DolPHIN-2 trial secondary endpoint analyses and infant follow-up study were presented. The DolPHIN-2 trial (NCT03249181) randomised pregnant women initiating antiretroviral therapy from 28 weeks gestation to dolutegravir or efavirenz with tenofovir and lamivudine/emtricitabine. Poster presentations showed that both regimens exhibited similar association between adherence and viral load suppression, which highlights the need for addressing non-adherence to treatment during the critical postpartum period (Malaba et al, 2024a). No association was seen with dolutegravir and increase in blood pressure during the 72-week postpartum period (Malaba et al, 2024b). No differences were observed between the efavirenz- or dolutegravir-containing regimens on rates of depression, anxiety and sleep disorders in pregnancy and the postpartum period (van der Wekken-Pas et al, 2024a). Rates of depression and poor sleep quality were high, mainly at time of diagnosis and during transition into motherhood, which further emphasises the need for peripartum support for women diagnosed with HIV during pregnancy (van der Wekken-Pas et al, 2024b).
The DolPHIN-2 sub-study followed up the infants born to the mothers taking part in the main trial. The infants underwent developmental assessments and neuroimaging to look at the effects of HIV and antiretroviral treatment. The neuroimaging sub-study showed that there were no significant differences in brain volume in children (aged 3 to 4 years old) who were exposed to HIV and whose mothers received dolutegravir versus those whose mothers received efavirenz (Bradford et al, 2024). Additionally, the brain volumes were comparable to children who had not been exposed to HIV or antiretrovirals in utero (Bradford et al, 2024).
Summary
There was a wide range of topics presented at CROI 2024 that included safety of antiretrovirals in pregnancy, antiretrovirals in the paediatric population, broadly neutralising antibodies, weight gain, cognitive function, mental health, and ageing. The findings presented can be used to inform the evidence-based practice of the HIV specialist nurse.