Understanding participant perspectives around HIV-1 cure-related studies involving antiretroviral analytical treatment interruptions in the United Kingdom.

Background: To test efficacy, HIV cure-related trials often require a period of intensively monitored interruption of antiretroviral therapy (ART) (analytical treatment interruption or ATI). As individuals who started ART during primary HIV-1 infection (PHI) are often recruited, we have asked people already enrolled into an observational PHI study about their willingness and concerns around participating in cure-related studies involving ATIs. Methods: People who were diagnosed with PHI and started ART, attending two London HIV clinics, provided informed consent to complete a digital survey in clinic between 21/07/21 to October 31, 2023. Questions comprised sociodemographics, motivations, concerns and practical considerations influencing willingness to participate in studies involving ATIs. Hierarchical clustering of responses was performed using the 'pheatmap' R statistical package and ranked from most to least concerned. Responses were cross-referenced with enrolment into an ATI study which recruited from this cohort. Results: Of 352 eligible participants, 75 completed the survey. The majority were white, cisgender men who have sex with men, 34/75 (45 %) were born outside the UK. 29 (39 %) expressed interest in joining ATI studies. Participants who were interested or unsure in joining ATI studies were primarily motivated (53/65, 82 % very or moderately interested) by an altruistic desire to help scientific research. Across all participants, onward HIV transmission was the predominant concern (67/75, 89 % very or moderately concerned), and similar levels of concerns reported if the HIV-1 viral load threshold to restarting ART was increased from 500 to 50 000 copies/mL. Most participants preferred weekly (23/65, 35 %) or fortnightly (11/65, 17 %) viral load monitoring during an ATI. Before taking part in a study involving an ATI, participants stated they would prefer to discuss this with their HIV doctor (55/65, 85 %). Conclusion: In this small survey, 39 % of respondents expressed interest in joining studies involving ATIs, primarily for altruistic reasons. Participants were more interested in joining a potential ATI study if a novel intervention was included than simply an ATI alone. The main concern expressed was risk of viral transmission. To inform practical and study design considerations for future ATI studies, unrestricted access for mitigation of transmission risk should be included, and regular, frequent viral load monitoring is preferred.

Immunotherapeutic approaches to HIV cure and remission.

PURPOSE OF REVIEW: Despite improvements in the effectiveness of antiretroviral therapy (ART), there are still unmet needs for people living with HIV which drive the search for a cure for HIV infection. The goal of this review is to discuss the challenges and recent immunotherapeutic advances towards developing a safe, effective and durable cure strategy for HIV. RECENT FINDINGS: In recent years, advances have been made in uncovering the mechanisms of persistence of latent HIV and in developing more accurate assays to measure the intact proviral reservoir. Broadly neutralising antibodies and modern techniques to enhance antibody responses have shown promising results. Other strategies including therapeutic vaccination, latency reversal agents, and immunomodulatory agents have shown limited success, but newer interventions including engineered T cells and other immunotherapies may be a potent and flexible strategy for achieving HIV cure. SUMMARY: Although progress with newer cure strategies may be encouraging, challenges remain and it is essential to achieve a high threshold of safety and effectiveness in the era of safe and effective ART. It is likely that to achieve sustained HIV remission or cure, a multipronged approach involving a combination of enhancing both adaptive and innate immunity is required.

Feasibility randomized-controlled trial of online acceptance and commitment therapy for painful peripheral neuropathy in people living with HIV: The OPEN study.

BACKGROUND: Neuropathic pain negatively affects quality of life among people living with HIV (PLWH). This study examined the feasibility of conducting a full-scale randomized-controlled trial of online acceptance and commitment therapy ("ACT OPEN") for neuropathic pain in PLWH. METHODS: Using a parallel-groups design, thirty-eight participants were randomized to ACT OPEN or a waitlist control (2:1). Participants completed standard self-report outcome measures at baseline, and two- and five-months post-randomization. Participants were aware of their allocation, but assessment was blinded. RESULTS: Twenty-five participants were randomized to ACT OPEN and 13 to the control (of 133 referrals). ACT OPEN completion was 69% and two-month trial retention was 82%. Treatment credibility and satisfaction scores for ACT OPEN were comparable to scores reported in previous trials of cognitive-behavioural treatments for pain. Four adverse events were reported during the study, including one serious adverse event; all of these were unrelated to the research procedures. Small to moderate effects and 95% confidence intervals suggest that the true effect may favour ACT OPEN for improvements in pain intensity/interference and depression. CONCLUSIONS: A full-scale RCT of online ACT for pain management in PLWH may be feasible with refinements to trial design to facilitate recruitment. SIGNIFICANCE: Research on pain management in people living with HIV has primarily focused on pharmacological treatments with limited success. This is the first study to show the potential feasibility of a psychological treatment based on acceptance and commitment therapy delivered online and tailored for pain management in people with HIV ("ACT OPEN"). ACT OPEN may be a promising treatment in this population and further evaluation in a full-scale randomized-controlled trial appears warranted. TRIAL REGISTRATION: The trial was registered (clinicaltrials.gov; NCT03584412).

Reasons for delayed antiretroviral therapy (ART) initiation in the era of early ART initiation guidelines: a retrospective service evaluation.

Following changes in national antiretroviral therapy (ART) guidelines removing the CD4 threshold for initiation of ART, we evaluated the time to ART initiation and reasons for delayed or non-initiation. A retrospective notes review of 292 newly diagnosed HIV-positive individuals attending two London clinics between August 2015 and December 2016 was performed. Two hundred and fifty-four of 292 (87%) individuals started ART. Median time to ART initiation was 29 days (range: 0-514). Thirty of 292 (13%) did not start ART. Rates of virological suppression at six months were similar regardless of time to ART initiation. People who inject drugs (16.7% vs. 3.6%) (p = 0.009), having a higher median baseline CD4 cell count (500 vs. 388 cells/mm3, p = 0.001), and having gastrointestinal/liver co-morbidities (23% vs. 9%, p = 0.001) were associated with delayed ART initiation. The cohort not on ART had a higher median baseline CD4 cell count (500 vs. 388 cells/mm3, p < 0.001). Documented reasons for delayed or ART non-initiation included patient's choice, prolonged adjustment periods, and difficulty leaving work. We conclude that delayed or non-initiation of ART was associated with injecting drug use and prolonged adjustment to a new HIV diagnosis. Clinician factors may include lack of urgency with higher baseline CD4 cell counts. Improved linkage to care and drug services pathways may encourage timely ART initiation.

Diagnosis and treatment strategies of tuberculous intestinal perforations: a case series.

Gastrointestinal tuberculosis (TB) may result in intestinal obstruction and perforation, even after antituberculous therapy has been initiated. Despite surgical intervention tuberculous perforation has a high complication and mortality rate, and it is difficult to predict the subgroup of patients with abdominal TB who progress to perforation. In this study, we retrospectively investigated the clinical features that may predict disease progression in patients in our institution who presented abdominal TB over a 5-year period between January 2006 and August 2011, as well as describe an unreported method of managing tuberculous intestinal perforations when resection with end-to-end anastomosis is unfeasible. Six out of 91 patients (6.6%) with abdominal TB developed perforations. Factors linked with increased complications and mortality were age, comorbidities, multiple perforations and length of time between onset of abdominal symptoms and perforation. Four patients (66.7%) had long histories of abdominal symptoms before perforation. Three patients were receiving or had completed antituberculous therapy before developing perforation. Five patients were managed surgically, two underwent laparostomy as both primary closure and end-to-end anastomosis were deemed too risky. Mortality following perforation was 17%. Patients with prolonged abdominal symptoms, even after antituberculous therapy, should raise suspicion for subacute intestinal obstruction. This should be recognized early and surgical intervention considered in order to prevent mortality secondary to perforation. Laparostomy may be an alternative when resection and end-to-end anastomosis is not possible.