International AIDS society conference 2023 summary.

AIM: This article summarizes key research presented at the International AIDS Society (IAS) Conference in Brisbane, held in July 2023. CO-MORBIDITIES: The REPRIEVE Trial as a conference highlight, demonstrating significantly fewer major cardiovascular events amongst people with HIV who were randomized to pitavastatin compared to placebo. Key data on weight, hypertension and incident diabetes are also summarized. ANTIRETROVIRAL THERAPY: Novel data on doravirine and islatravir are described as are trials demonstrating efficacy dolutegravir/lamivudine first-line in people without baseline resistance testing and in suppressed switch amongst people with historic lamivudine resistance. HIV CURE: The sixth case of HIV cure secondary to stem cell transplantation is summarized, as are new insights into the central nervous system as an HIV reservoir.

Multicentre service evaluation of injectable cabotegravir and rilpivirine delivery and outcomes across 12 UK clinics (SHARE LAI-net).

INTRODUCTION: Long-acting injectable cabotegravir + rilpivirine (CAB + RPV LAI) was approved for use in virally suppressed adults in the England and Wales national health service in November 2021. We describe a service evaluation of delivery processes and outcomes in 12 clinics. METHODS: Centres populated a database using information from local policies and clinical records. Services were asked to describe approval processes, clinic pathways, and adherence to national guidelines. Additional data were collected on reasons for regimen choice, treatment discontinuations, and management of viraemia. RESULTS: In total, 518 adults from 12 clinics were approved for CAB + RPV LAI between February 2022 and December 2023. Of the 518 people approved for CAB + RPV LAI, 423 received at least one injection. Median duration on CAB + RPV was 7.5 months (interquartile range 3.7-11.3). In total, 97% of injections were administered within the ±7-day window. Virological failure occurred in 0.7%, and 6% discontinued CAB + RPV. CONCLUSION: In this large UK-based cohort, robust approval processes and clinic protocols facilitated on-time injections and low rates of both discontinuation and virological failure.

Practical management of complexity in older people with HIV: approaching an international consensus.

ABSTRACTGlobally the community of people with HIV is ageing, and some of these have increasingly complex care needs, with a known excess of non-HIV related comorbidities and related issues including consequent polypharmacy. At the 2022 International AIDS Conference in Montréal, Canada, the "Silver Zone" was created in the Global Village as a safe space for older people with HIV. As part of the Silver Zone activities, a session discussing global models of care for in this group was held. HIV treatment providers and advocates from diverse resource settings and with a diversity of expertise were invited to share their experience, reflections, and ideas, and this consensus statement was formed based on these discussions. Different approaches to care emerged, based on local needs and resources, and it became clear that issues of complexity and frailty need not be age limited. Despite clear regional differences, some common themes became apparent, and a consensus was established on basic principles that may be considered in diverse settings. These are discussed here, with agreement on necessary proximal steps to develop bespoke person-centred care models.

Asked to be a sperm donor: disclosure dilemmas of gay men living with HIV.

Previous research has documented the various challenges people living with HIV face as they navigate intimate relationships, including what is often referred to as disclosure. In studies of gay, bisexual and other men who have sex with men, the issue of telling or not telling others about an HIV-positive status has been examined primarily in relation to communication with sexual partners, with few studies focusing on other aspects of intimacy. Drawing on interviews with gay men living with HIV, conducted in four clinics in London, this article explores the narratives of men who have been asked by female friends about the possibility of being a sperm donor. The narratives highlight layers of complexity which have received little attention, not only in research on HIV but also in studies of sperm donation and co-parenting. The article advances dialogue between these two largely separate bodies of work. Our data suggest that reluctance to share an HIV-positive status with others can be an important factor in deciding how to answer the 'sperm donor question'. Examining reproductive relationships of a specific kind - those based on friendships between women and gay men - the article develops the understanding of how secrecy about HIV shapes intimate lives.

Frailty in people living with HIV: an update.

PURPOSE OF REVIEW: The HIV population is ageing with rising rates of frailty though strategies of how best to manage it remain ill-defined. It also remains unclear what the prevalence of frailty is within this cohort, how best to diagnose it and what factors are associated. RECENT FINDINGS: The prevalence of frailty remains unclear because of heterogenous results. Routine screening in those 50+ is recommended and whilst the Fried Frailty Phenotype is currently preferred the Clinical Frailty Scale could be considered. No biomarkers are currently recommended. Looking at associated factors, HIV neurocognitive impairment and long-term alcohol usage has been shown to be associated with developing frailty whilst those who are frail have been shown to be less active and more likely to fall. NAFLD with fibrosis has been shown to be an indicator of metabolic age and the Pooled Cohort Equations has been shown to be more effective in diagnosing cardiovascular risk in frail people living with HIV. SUMMARY: Whilst the prevalence of frailty differs between countries, with the addition of prefrailty, this represents a large proportion of people living with HIV. Services must ensure strategies are in place to support those living with HIV and frailty. Further longitudinal studies are required.

What problems associated with ageing are seen in a specialist service for older people living with HIV?

OBJECTIVES: By 2030 the majority of the people living with HIV in the United Kingdom will be over the age of 50. HIV services globally must adapt to manage people living with HIV as they age. Currently these services are often designed based on data from the wider population or from the experiences of HIV clinicians. This article aims to help clinicians designing inclusive HIV services by presenting the most common needs identified during the first year of a specialist clinic for older people living with HIV at the Ian Charleson Day Centre, Royal Free Hospital in London, United Kingdom. METHODS: The records of all thirty-five patients attending the inaugural nine sessions were reviewed. RESULTS: The median age of attendees was 69 (53-93) with 77% being male, 63% being White, 49% being heterosexual and 97% being virally suppressed respectively. The majority (83%) met the criteria for frailty using the Fried frailty phenotype. Eighteen issues linked to ageing were identified with the most common being affective symptoms (51%), memory loss (37%) and falls (29%). CONCLUSIONS: Whilst older people living with HIV are a heterogeneous group frailty is common and appears to present earlier. HIV services either need to adapt to meet these additional needs or must support users in transitioning to existing services. We feel that our multidisciplinary model is successful in identifying problems associated with ageing in people living with HIV and could be successfully replicated elsewhere.

Descriptive account of 18 adults with known HIV infection hospitalised with SARS-CoV-2 infection.

OBJECTIVE: To report on the clinical characteristics and outcome of 18 people living with HIV (PLWH) hospitalised with SARS-CoV-2 infection in a London teaching hospital. METHODS: The hospital notes of 18 PLWH hospitalised with SARS-CoV-2 infection were retrospectively reviewed alongside data concerning their HIV demographics from an established HIV Database. RESULTS: The majority (16/18) had positive PCR swabs for SARS-CoV-2, and two had negative swabs but typical COVID-19 imaging and history. Most were male (14/18, 78%), median age 63 years (range 47-77 years). Two-thirds were migrants, nine (50%) of Black, Asian and minority ethnicity (BAME). All were diagnosed with HIV for many years (range 8-31 years), and all had an undetectable HIV viral load (<40 copies/mL). The median CD4 prior to admission was 439 (IQR 239-651), and 10/16 (63%) had a CD4 nadir below 200 cells/mm3. Almost all (17/18) had been diagnosed with at least one comorbidity associated with SARS-CoV-2 prior to admission. 3/18 patients died. None received mechanical ventilation. Hospital stay and clinical course did not appear prolonged (median 9 days). CONCLUSIONS: Our data suggest that PLWH may not necessarily have prolonged or complex admissions to hospital when compared with the general hospital and national population admitted with COVID-19. Many had low nadir CD4 counts and potentially impaired functional immune restoration. The PLWH group was younger than generally reported for COVID-19, and the majority were male with multiple complex comorbidities. These patients had frequent contact with hospital settings increasing potential for nosocomial acquisition and increased risk of severe COVID-19.

Discussing parenthood with gay men diagnosed with HIV: a qualitative study of patient and healthcare practitioner perspectives.

BACKGROUND: Research on HIV and reproduction has focused largely on women and heterosexual men. This article examines whether it is relevant to address parenthood in HIV care with gay men and what ways of doing so are most appropriate. METHODS: Qualitative interviews were conducted at four London clinics with 25 men living with HIV, aged 20-45, who did not have children, and 16 HIV clinicians. A thematic analysis identified potential reasons why parenthood was rarely discussed with gay men in HIV care. RESULTS: Two sets of ideas contributed to a lack of conversations about parenthood: clinicians' ideas about what matters to gay men and men's ideas about what it means to be HIV-positive. Both sets of ideas largely excluded having children, with patients and practitioners similarly unlikely to raise the topic of parenthood in the clinic. Contrary to what clinician commonly assumed, many men expressed interest in receiving more information, highlighting the importance of reassuring people upon diagnosis that it is possible to become parents while living with HIV. CONCLUSIONS: Parenting desires and intentions were rarely discussed with men in HIV care. Our findings illuminate the potentially beneficial effects of emphasising that having children is a possibility at diagnosis, regardless of patients' gender or sexuality. Conveying this information seems meaningful, not only to men who want to become parents in the future but also to others, as it appears to alleviate fears about mortality and ill health.

Can HIV-positive gay men become parents? How men living with HIV and HIV clinicians talk about the possibility of having children.

It is now established that people living with HIV who have an undetectable viral load and adhere to antiretroviral treatment cannot transmit HIV to their sexual partners. Previous research has shown that 'being undetectable' changes how HIV-positive gay men experience their sex lives. But how does it affect gay men's reproductive behaviours? And what influence does it have on views about parenthood at a time when gay fatherhood has become more socially accepted and publicly visible? Drawing on qualitative interviews with patients and clinicians at four HIV clinics in London, we identify differences in how interviewees talked about the possibility of having children for HIV-positive men. Both groups, unprompted, frequently referred to sperm washing as a method enabling safe conception. However, whereas clinicians talked about sperm washing as an historical technique, which is no longer necessary, patients spoke of it as a current tool. The men rarely mentioned being undetectable as relevant to parenthood and, when prompted, some said that they did not fully understand the mechanics of HIV transmission. Our findings offer new insights into how biomedical knowledge is incorporated into people's understandings of living with HIV, raising important questions about how the meanings of being undetectable are communicated.

Person-centred care and HIV: challenges and solutions.

Person-centred consultations (PCCs) are fundamental to effective healthcare communication, and its use is embedded within key clinical guidance. There are three aspects to PCC: use of the best available research evidence, clinical expertise of the clinician and the patient's circumstances, goals, values and wishes. Balancing theses three aspects in the context of HIV prevention and management can be challenging, and we use three case examples to highlight these.

Simple screening for neurocognitive impairment in routine HIV outpatient care: is it deliverable?

Routine screening for psychological and cognitive difficulties is recommended in BHIVA guidelines but screening questions are not specified and studies give varied recommendations. Our aim was to see if simple screening in the routine clinic could help better direct our referrals to psychology and highlight those patients requiring, and likely to benefit from, further assessment. We introduced brief questions to assess neurocognitive impairment (NCI) and mood into routine HIV visits, with an onward referral pathway for further investigation for those screening positive. Routine attendees to HIV outpatient care over 12 weeks completed brief screening for depression (PHQ-2) and anxiety (GAD-2) and answered three short questions to screen for possible neurocognitive impairment (NCI-3Q). Patients screening positive underwent further screening via our psychologists and/or referral for neuropsychometric testing. Patient demographics, HIV markers and treatment history were recorded. 97 HIV outpatients were screened; 44 (45%) initially screened positive for NCI and/or mood. 29/44 (66%) were referred for further screening and/or psychological assessment and 21/29 (72%) of those engaged. The Montreal Cognitive Assessment (MoCA) and International HIV Dementia Scale (IHDS) were conducted on seven patients; four of these received full neuropsychometric testing. A detectable viral load was associated with positive neurocognitive screening. Rates of NCI and mood disorder among those who were tested were consistent with previous studies. The PHQ-2 and GAD-2 did detect mood problems; however, our results suggest the NCI-3Q questions alone are not good at detecting those with possible NCI. Screening for NCI remains practically difficult in the routine outpatient setting and this pilot supports the need for clearer guidelines on detecting HIV related NCI.

Cerebrospinal fluid exposure of efavirenz and its major metabolites when dosed at 400 mg and 600 mg once daily: a randomized controlled trial.

BACKGROUND: The optimal penetration of antiretroviral agents into the central nervous system may be a balance between providing adequate drug exposure to inhibit human immunodeficiency virus (HIV) replication while avoiding concentrations associated with neuronal toxicities. METHODS: Cerebrospinal fluid (CSF) exposure of efavirenz and the metabolites 7-hydroxy (7OH) and 8-hydroxy (8OH) efavirenz were assessed after at least 12 weeks of therapy in HIV-infected subjects randomized to commence antiretroviral regimens containing efavirenz at either 400 mg or 600 mg once daily. RESULTS: Of 28 subjects (14 and 14 on efavirenz 400 mg and 600 mg, respectively), CSF HIV RNA was undetectable in all. Geometric mean CSF efavirenz, 7OH-, and 8OH-efavirenz concentrations (with 90% confidence intervals [CIs]) for the 400-mg and 600-mg dosing groups were 16.5 (13-21) and 19.5 (15-25) ng/mL; 0.6 (.4-.9) and 0.6 (.4-1) ng/mL; and 5.1 (4.0-6.4) and 3.1 (2.1-4.4) ng/mL, respectively. Efavirenz concentration in CSF was >0.51 ng/mL (proposed CSF 50% maximal inhibitory concentration for wild-type virus) in all subjects, and 8OH-efavirenz concentration in CSF was >3.3 ng/mL (a proposed toxicity threshold) in 11 of 14 and 7 of 14 subjects randomized to the 400 mg and 600 mg doses of efavirenz, respectively. Whereas CSF efavirenz concentration was significantly associated with plasma concentration (P < .001) and cytochrome P450 2B6 genotype (CSF efavirenz GG to GT/TT geometric mean ratio, 0.56 [90% CI, .42-.74]), CSF 8OH-efavirenz concentration was not (P = .242 for association and CSF 8OH-efavirenz GG to GT/TT geometric mean ratio, 1.52 [90% CI, .97-2.36]). CONCLUSIONS: With both doses of efavirenz studied, CSF concentrations were considered adequate to inhibit HIV replication, although concentrations of 8OH-efavirenz were greater than those reportedly associated with neuronal toxicity. CSF exposure of 8OH-efavirenz was not dependent on plasma exposure and, as we postulate, may be subject to saturable pharmacokinetic effects. CLINICAL TRIALS REGISTRATION: NCT01011413.

The pharmacokinetic profile of raltegravir-containing antiretroviral therapy in HIV-infected individuals over 60 years of age.

BACKGROUND: Antiretroviral safety and efficacy and may differ in older versus younger HIV-infected patients. The objective of this study was to assess the pharmacokinetic (PK) profile in older HIV-infected subjects (>60 years) switching combination antiretroviral therapy (cART) to a raltegravir (RAL) containing regimen. METHODS: Nineteen HIV-infected patients over 60 years of age on effective cART (HIV-RNA < 50 copies/ml) were enrolled in this prospective 24-week study. On day 1, patients switched to tenofovir/emtricitabine (245/200 mg once daily) and RAL (400 mg twice daily). On day 28, intensive PK sampling was undertaken in a fasted state and RAL plasma concentrations determined. Neurocognitive function was assessed at baseline and week 24 using a neuropsychological battery. RAL PK parameters were compared to those of two younger historical HIV-infected control groups that received twice-daily RAL co-administered with darunavir/ritonavir (DRV/r) 800/100 once daily by nonlinear mixed effects modelling. RESULTS: In HIV-infected subjects over the age of 60 (mean ± SD age: 66 ± 3.4 years, n = 19) switching to a RAL containing regimen, we observed no safety concerns, no plasma virological rebounds, and no differences in RAL apparent oral clearance when compared to younger HIV-infected populations (mean ± SD age: 41 ± 9.2 years, n = 38) based on population pharmacokinetic analysis. After 24 weeks of study therapy a decline in cognitive function was observed [change in (SD) global score of (0.91 (1.3), P = 0.018]. CONCLUSIONS: No significant changes in RAL exposure associated with age were observed.

'Gay bowel syndrome': relic or real (and returning) phenomenon?

PURPOSE OF REVIEW: This article aims to review the term 'gay bowel syndrome', including the recent research looking at increased rates of bowel infections in men who have sex with men (MSM), particularly in light of the recent Shigella outbreaks in MSM in London and New York, and considers whether 'gay bowel syndrome' is a syndrome that really exists and is worthy of further research and specific treatment, or whether the term continues to be obsolete and not useful. RECENT FINDINGS: Little or no recent research exists around the concept of a specific syndrome affecting the bowels of MSM. Rather, there seems to be a clustering of diseases in certain high-risk groups, especially those in urban areas with multiple sexual partners, recreational drug use, and possible concomitant HIV infection. SUMMARY: All healthcare practitioners (including non-sexual health/HIV specialists) need to consider careful and thorough history taking (including sexual history) to identify those at risk.

Systematic Review: Strategies for Improving HIV Testing and Detection Rates in European Hospitals.

Undiagnosed HIV infection is a prominent clinical issue throughout Europe that requires the continuous attention of all healthcare professionals and policymakers to prevent missed testing opportunities and late diagnosis. This systematic review aimed to evaluate interventions to increase HIV testing rates and case detection in European hospitals. Out of 4598 articles identified, 29 studies fulfilled the selection criteria. Most of the studies were conducted in single Western European capital cities, and only one study was from Eastern Europe. The main interventions investigated were test-all and indicator-condition-based testing strategies. Overall, the prevalence of undiagnosed HIV was well above 0.1%. The studied interventions increased the HIV testing rate and the case detection rate. The highest prevalence of undiagnosed HIV was found with the indicator-condition-driven testing strategy, whereas the test-all strategy had the most profound impact on the proportion of late diagnoses. Nevertheless, the HIV testing rates and case-finding varied considerably across studies. In conclusion, effective strategies to promote HIV testing in European hospitals are available, but relevant knowledge gaps regarding generalizability and sustainability remain. These gaps require the promotion of adherence to HIV testing guidelines, as well as additional larger studies representing all European regions.

Real world use of dolutegravir two drug regimens.

BACKGROUND: Since 2015, we prescribed dolutegravir (DTG)-based two drug regimens (DTG-2DR) for 620 people [total cohort 3133 (19.8%)]. METHOD: Clinic database search 1 January 15 to 31 October 21. Demographic, tolerability and HIV related data analysed. RESULTS: In total, 620 people identified; 561 had complete data. 446 male (79.5%); median age 54 years (interquartile range 46, 59). 343 (61.1%) MSM. Nine people who initiated naïvely achieved viral suppression (100%). 546/552 (99.0%) switched or continued and were suppressed at data censor. 460/552 (83.3%) received DTG-lamivudine (DTG/3TC), 74/552 (13.4%) received DTG-rilpivirine (DTG/RPV) and 18/552 (3.3%) received DTG-emtricitabine (DTG/FTC). 70 (12.5%) switched off DTG-2DR (55 DTG/3TC, 13 DTG/RPV, two DTG/FTC) due to side-effects. 41 episodes of blip (1 off >50 copies/ml) occurred in 30 people (5.3%). 11/41 on DTG-RPV [ n  = 7 multi-tablet regimen (MTR), n  = 4 single tablet regimen (STR)]. 27/41 DTG-3TC, 3/41 DTG/FTC ( n  = 26 MTR, n  = 4 STR). Six people (1.1%) failed (confirmed viral load >200 copies/ml or persistent low level viraemia) ( n  = 4 DTG-3TC STR, n  = 1 DTG-3TC MTR, n  = 1 DTG-RPV MTR). Four failures due to low level viraemia, one due to non-adherence and one due to high viral load. Resistance tests performed for 5/6 - mutations detected only in latter person with high viral load failure (on DTG-3TC MTR) who developed triple class resistance. CONCLUSION: Majority of experience is in DTG/3TC stable switch. Minority of patients developed side-effects. Low number of virological failures, one developed integrase inhibitor resistance. Viral failure associated with MTR, commensurate with trial data showing no failure with resistance if DTG/3TC STR used. Overall DTG-2DR demonstrates high efficacy in real-world setting.

Natural killer cell responses during SARS-CoV-2 infection and vaccination in people living with HIV-1.

Natural killer (NK) cell subsets with adaptive properties are emerging as regulators of vaccine-induced T and B cell responses and are specialized towards antibody-dependent functions contributing to SARS-CoV-2 control. Although HIV-1 infection is known to affect the NK cell pool, the additional impact of SARS-CoV-2 infection and/or vaccination on NK cell responses in people living with HIV (PLWH) has remained unexplored. Our data show that SARS-CoV-2 infection skews NK cells towards a more differentiated/adaptive CD57+FcεRIγ- phenotype in PLWH. A similar subset was induced following vaccination in SARS-CoV-2 naïve PLWH in addition to a CD56bright population with cytotoxic potential. Antibody-dependent NK cell function showed robust and durable responses to Spike up to 148 days post-infection, with responses enriched in adaptive NK cells. NK cell responses were further boosted by the first vaccine dose in SARS-CoV-2 exposed individuals and peaked after the second dose in SARS-CoV-2 naïve PLWH. The presence of adaptive NK cells associated with the magnitude of cellular and humoral responses. These data suggest that features of adaptive NK cells can be effectively engaged to complement and boost vaccine-induced adaptive immunity in potentially more vulnerable groups such as PLWH.

Virologic Response to Dolutegravir Plus Lamivudine in People With Suppressed Human Immunodeficiency Virus Type 1 and Historical M184V/I: A Systematic Literature Review and Meta-analysis.

Background: To investigate the impact of the M184V/I mutation on virologic response to dolutegravir plus lamivudine (DTG + 3TC) in suppressed-switch populations, a meta-analysis was performed using virologic outcomes from people with human immunodeficiency virus type 1 (PWH) with and without M184V/I before DTG + 3TC switch in real-world studies identified via systematic literature review. Sensitivity analyses were performed using data from PWH with M184V/I in interventional studies identified via targeted literature review. Methods: Single-arm meta-analyses using common- and random-effects models were used to estimate proportions of PWH with virologic failure (VF) among real-world populations with and without M184V/I and interventional study participants with M184V/I at 24, 48, and 96 weeks. Results: Literature reviews identified 5 real-world studies from 3907 publications and 51 abstracts meeting inclusion criteria and 5 interventional studies from 1789 publications and 3 abstracts. All time points had low VF incidence in PWH with M184V/I (real-world: 1.43%-3.81%; interventional: 0.00%) and without (real-world: 0.73%-2.37%). Meta-analysis-estimated proportions (95% confidence interval) with VF were low at weeks 24, 48, and 96, respectively, for PWH with M184V/I (real-world: 0.01 [.00-.04], 0.03 [.01-.06], and 0.04 [.01-.07]; interventional: 0.00 [.00-.02], 0.00 [.00-.01], and 0.00 [.00-.03]) and without (real-world: 0.00 [.00-.02], 0.02 [.01-.04], and 0.02 [.00-.05]). One real-world study (n = 712) reported treatment-emergent M184V at VF in 1 of 652 (0.15%) PWH without prior M184V/I. Conclusions: Results suggest that prior M184V/I has minimal impact on virologic suppression after switching to DTG + 3TC and provide reassurance when considering switching regimens in virologically suppressed PWH with incomplete treatment history or limited treatment options.