"I have failed to separate my HIV from this pain": the challenge of managing chronic pain among people with HIV

Pain is a highly prevalent and burdensome symptom among people with HIV (PWH). This study aims to identify how the experience of living with HIV and chronic pain influences pain beliefs, health-seeking and pain management. Thirty-nine purposively sampled PWH with chronic pain (sample characteristics = 61% women, 79% Black, Asian and minority ethnic groups, 18% men who have sex with men, 45-54 median age category) participated in focus groups in London. Focus groups were co-facilitated with community members. Transcripts wereanalysed using a thematic approach. Findings revealed that HIV stigma, fractured care pathways, and general practitioners' lack of HIV training are barriers to supported pain management. Unaddressed pain results in poorer mental health and reduced quality of life, which has important clinical implications for HIV treatment adherence. Creating HIV-specific pain resources, activating social networks, and pain self-management techniques are potential solutions. Person-centred assessment and HIV training is needed to help clinicians identify PWH with chronic pain. Clear guidelines need to be developed to identify which health service providers are responsible for chronic pain management in PWH. This study generated a refined version of the Fear Avoidance Model that introduces a dimension of HIV-specific behaviours that impact PWHs seeking chronic pain management

Improved kidney function in patients who switch their protease inhibitor from atazanavir or lopinavir to darunavir

OBJECTIVE: Atazanavir (ATV) and lopinavir (LPV) have been associated with kidney disease progression in HIV positive patients, with no data reported for darunavir (DRV). We examined kidney function in patients who switched their protease inhibitor from ATV or LPV to DRV. DESIGN: Cohort study. METHODS: Data were from the UK CHIC study. We compared pre and post switch estimated glomerular filtration rate (eGFR) slopes (expressed in ml/min per 1.73 m2 per year) in all switchers and those with rapid eGFR decline (>5 ml/min per 1.73 m2 per year) on ATV or LPV. Mixed-effects models were adjusted for age, gender, ethnicity, eGFR at switch and time updated CD4þ cell count, HIV RNA and cumulative tenofovir (tenofovir disoproxil fumarate) exposure. RESULTS: Data from 1430 patients were included. At the time of switching to DRV, median age was 45 years, 79% were men, 76% had an undetectable viral load, and median eGFR was 93 ml/min per 1.73 m2 . Adjusted mean (95% confidence interval) pre and post switch eGFR slopes were 0.84 (1.31, 0.36) and 1.23 (0.80, 1.66) for ATV (P < 0.001), and 0.57 (1.09, 0.05) and 0.62 (0.28, 0.96) for LPV (P < 0.001). Stable or improved renal function was observed in patients with rapid eGFR decline on ATV or LPV who switched to DRV [15.27 (19.35, 11.19) and 3.72 (1.78, 5.66), P < 0.001 for ATV, 11.93 (14.60, 9.26) and 0.87 (0.54, 2.27), P < 0.001 for LPV]. Similar results were obtained if participants who discontinued tenofovir disoproxil fumarate at the time of switch were excluded. CONCLUSIONS: We report improved kidney function in patients who switched from ATV or LPV to DRV, suggesting that DRV may have a more favourable renal safety profile

Sexual risk and HIV testing disconnect in men who have sex with men (MSM) recruited to an online HIV self-testing trial.

OBJECTIVES: We report the frequency of previous HIV testing at baseline in men who have sex with men (MSM) who enrolled in an HIV self-testing (HIVST) randomized controlled trial [an HIV self-testing public health intervention (SELPHI)]. METHODS: Criteria for enrolment were age ≥ 16 years, being a man (including trans men) who ever had anal intercourse (AI) with a man, not being known to be HIV positive and having consented to national HIV database linkage. Using online survey baseline data (2017-2018), we assessed associations with never having tested for HIV and not testing in the previous 6 months, among men who reported at least two recent condomless AI (CAI) partners. RESULTS: A total of 10 111 men were randomized; the median age was 33 years [interquartile range (IQR) 26-44 years], 89% were white, 20% were born outside the UK, 0.8% were trans men, 47% were degree educated, and 8% and 4% had ever used and were currently using pre-exposure prophylaxis (PrEP), respectively. In the previous 3 months, 89% reported AI and 72% reported CAI with at least one male partner. Overall, 17%, 33%, 54%, and 72% had tested for HIV in the last 3 months, 6 months, 12 months and 2 years, respectively; 13% had tested more than 2 years ago and 15% had never tested. Among 3972 men reporting at least two recent CAI partners, only 22% had tested in the previous 3 months. Region of residence and education level were independently associated with recent HIV testing. Among current PrEP users, 15% had not tested in the previous 6 months. CONCLUSIONS: Most men in SELPHI, particularly those reporting at least two CAI partners and current PrEP users, were not testing in line with current UK recommendations. The results of the trial will inform whether online promotion of HIVST addresses ongoing testing barriers

Developing a Bayesian adaptive design for a phase I clinical trial: a case study for a novel HIV treatment

The design of phase I studies is often challenging, because of limited evidence to inform study protocols. Adaptive designs are now well established in cancer but much less so in other clinical areas. A phase I study to assess the safety, pharmacokinetic profile and antiretroviral efficacy of C34-PEG4-Chol, a novel peptide fusion inhibitor for the treatment of HIV infection, has been set up with Medical Research Council funding. During the study workup, Bayesian adaptive designs based on the continual reassessment method were compared with a more standard rule-based design, with the aim of choosing a design that would maximise the scientific information gained from the study. The process of specifying and evaluating the design options was time consuming and required the active involvement of all members of the trial's protocol development team. However, the effort was worthwhile as the originally proposed rule-based design has been replaced by a more efficient Bayesian adaptive design. While the outcome to be modelled, design details and evaluation criteria are trial specific, the principles behind their selection are general. This case study illustrates the steps required to establish a design in a novel context

Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance

Objectives In subjects with transmitted thymidine analogue mutations (TAMs), boosted PIs (PI/b) are often chosen to overcome possible resistance to the NRTI backbone. However, data to guide treatment selection are limited. Our aim was to obtain firmer guidance for clinical practice using real-world cohort data. Methods We analysed 1710 subjects who started a PI/b in combination with tenofovir or abacavir plus emtricitabine or lamivudine, and compared their virological outcomes with those of 4889 patients who started an NNRTI (predominantly efavirenz), according to the presence of ≥1 TAM as the sole form of transmitted drug resistance. Results Participants with ≥1 TAM comprised predominantly MSM (213 of 269, 79.2%), subjects of white ethnicity (206 of 269, 76.6%) and HIV-1 subtype B infections (234 of 269, 87.0%). Most (203 of 269, 75.5%) had singleton TAMs, commonly a revertant of T215Y or T215F (112 of 269, 41.6%). Over a median of 2.5 years of follow-up, 834 of 6599 (12.6%) subjects experienced viraemia (HIV-1 RNA >50 copies/mL). The adjusted HR for viraemia was 2.17 with PI/b versus NNRTI-based therapy (95% CI 1.88–2.51; P < 0.001). Other independent predictors of viraemia included injecting drug use, black ethnicity, higher viral load and lower CD4 cell count at baseline, and receiving abacavir instead of tenofovir. Resistance showed no overall impact (adjusted HR 0.77 with ≥1 TAM versus no resistance; 95% CI 0.54–1.10; P = 0.15). Conclusions In this cohort, patients harbouring ≥1 TAM as the sole form of transmitted drug resistance gained no apparent virological advantage from starting first-line ART with a PI/b

Associations between baseline characteristics, CD4 cell count response and virological failure on first-line efavirenz

Objectives The aim of this study was to investigate associations between baseline characteristics and CD4 cell count response on first-line antiretroviral therapy and risk of virological failure (VF) with or without drug resistance. Methods We conducted an analysis of UK Collaborative HIV Cohort data linked to the UK HIV Drug Resistance Database. Inclusion criteria were viral sequence showing no resistance prior to initiation of first-line efavirenz + tenofovir disoproxil fumarate + emtricitabine and virological suppression within 6 months. Outcomes of VF (≥200 copies/mL) with or without drug resistance were assessed using a competing risks approach fitted jointly with a model for CD4 cell count recovery. Hazard ratios for each VF outcome were estimated for baseline CD4 cell count and viral load and characteristics of CD4 cell count response using latent variables on a standard normal scale. Results A total of 3640 people were included with 338 VF events; corresponding viral sequences were available in 134 with ≥1 resistance mutation in 36. VF with resistance was associated with lower baseline CD4 (0.30, 0.09–0.62), lower CD4 recovery (0.04, 0.00–0.17) and higher CD4 variability (4.40, 1.22–12.68). A different pattern of associations was observed for VF without resistance, but the strength of these results was less consistent across sensitivity analyses. Cumulative incidence of VF with resistance was estimated to be <2% at 3 years for baseline CD4 ≥350 cells/μL. Conclusion Lower baseline CD4 cell count and suboptimal CD4 recovery are associated with VF with drug resistance. People with low CD4 cell count before ART or with suboptimal CD4 recovery on treatment should be a priority for regimens with high genetic barrier to resistance