HIV pre-exposure prophylaxis and its implementation in the PrEP Impact Trial in England: a pragmatic health technology assessment.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV acquisition. To enable routine commissioning of PrEP in England, we aimed to establish population need, duration of need, PrEP uptake, and duration of use in attendees of sexual health services (SHS) in England. METHODS: The Impact Trial was a prospective, open-label, single-arm, multicentre trial conducted at 157 SHS across England between Oct 13, 2017, and July 12, 2020. Clinicians assessed HIV-negative attendees for their risk of HIV acquisition to identify those who were eligible to participate and receive either daily or event-based oral PrEP (tenofovir disoproxil maleate with emtricitabine), as appropriate. Eligible participants were aged 16 years or older, considered HIV-negative on the day of enrolment, and willing to adhere to the trial procedures. Non-trial attendees are mutually exclusive of trial participants and included SHS attendees who were not recruited to the Impact Trial at any point. They include HIV-negative individuals aged 16 years or older who attended a participating SHS at least once after recruitment at that SHS had begun and before Feb 29, 2020. The main outcomes assessed were PrEP need, uptake, and use, and HIV and sexually transmitted infection (STI) incidence. Data are presented up to Feb 29, 2020, before the introduction of COVID-19 control measures. The study is registered with ClinicalTrials.gov, NCT03253757. FINDINGS: In this analysis, we include 21 356 of 24 268 participants enrolled before Feb 29, 2020. 20 403 participants (95·5%) were men who have sex with men (MSM). Uptake of PrEP among SHS attendees clinically assessed and coded as eligible was 21 292 (57·1%) of 37 289. 18 400 trial participants had at least one post-enrolment visit and a median of 361 days of follow-up (IQR 143-638); 14 039 (75·9%) of these had enough PrEP prescribed to provide protection for 75% of their follow-up time. Among MSM, HIV incidence was 0·13 (95% CI 0·08-0·19) per 100 person-years in trial participants (27 seroconversions) and 0·95 (95% CI 0·88-1·03) per 100 person-years in non-trial attendees (587 seroconversions; proportionate reduction of 86·8%, 95% CI 80·2-91·6). 18 607 bacterial STIs were recorded (incidence 68·1 per 100 person-years in trial participants who were MSM). 4343 (24·4%) MSM participants were diagnosed with two or more STIs, accounting for 14 800 (79·5%) of all 18 607 diagnoses. INTERPRETATION: PrEP need was higher than initially estimated by an expert stakeholder group. The high proportion of follow-up time protected by PrEP suggests that the need for protection persisted throughout trial participation for most participants. HIV incidence among MSM trial participants was low. The large unmet need for PrEP suggests that greater provision is required to maximise the potential of a national programme. The high incidence of bacterial STIs among participants, concentrated within a subgroup of PrEP users, presents an opportunity for tailored STI control measures. FUNDING: NHS England.

FRAX assessment in people ageing with HIV.

OBJECTIVES: Current British HIV Association (BHIVA) guidelines recommend the use of FRAX for the routine assessment of bone fracture risk in people living with HIV over 50 years of age every 3 years. Bone mineral density measurement with dual-energy X-ray absorptiometry (DXA) scan is recommended for those with increased fracture risk (FRAX major > 10%). Our objectives were to estimate the prevalence of and risk factors for osteoporosis in a population of PLWH aged > 50 years and assess the utility of FRAX in predicting the presence of DXA-proven osteoporosis in this cohort. METHODS: This was a cross-sectional study of a cohort of PLWH aged > 50 years attending the Chelsea and Westminster Hospital and who had a DXA scan between January 2009 and December 2018. FRAX scores were calculated using the Sheffield algorithm. Multiple regression models and Cohen's kappa values were used to assess risk factors for osteoporosis and agreement between FRAX and DXA scan results, respectively. RESULTS: In all, 744 patients were included (92.9% male, mean age 56 ± 5 years). The prevalence rates of osteoporosis (at DXA scans) and osteopenia were 12.2% and 63.7%, respectively. FRAX major was > 10% in only two patients, while 90/91 (98.9%) patients with osteoporosis had a normal FRAX score. The presence of osteoporosis was significantly associated with low body mass index and estimated glomerular filtration rate (p < 0.05). CONCLUSION: Our results indicate that FRAX scores did not predict the presence of osteoporosis in our population of PLWH over 50 years of age and therefore FRAX scores may not be the appropriate tool to define eligibility to perform DXA scans in PLWH.

Multimodality assessment of sleep outcomes in people living with HIV performed using validated sleep questionnaires.

Studies conducted in people living with HIV (PLHIV) report high rates of sleep disturbance, without a clear explanation as to cause or effect. Therefore, we proposed use of multiple validated questionnaires that would allow a more comprehensive evaluation of sleep quality in PLHIV. We administered eight validated sleep and wellbeing questionnaires, recording different aspects of sleep in order to provide a comprehensive description of sleep quality, quantity, daytime functioning, wakefulness, and general wellbeing. Associations with demographics and clinical data were analyzed by univariable/multivariable analyses. Of 254 subjects 99% were male (98% men who have sex with men), 88% white, mean age 41 (SD ± 9.9) years, HIV duration eight years (SD ± 6.3), 94% were on antiretroviral therapy, mean CD4 cell count was 724 cells/mm3, 81% had HIV RNA<40 copies/ml, 72% were university educated, and 60% used 'chemsex' drugs. Almost half (45%) reported poor sleep quality, 22% insomnia, 21% daytime sleepiness, and 33% fatigue. As individual factors, HIV duration ≥10 years, anxiety, depression, and recreational drug use were associated with poor quality sleep, fatigue, and poorer functional outcomes (p ≤ 0.05). The prevalence of sleep disturbance was high in our cohort of PLHIV. Sleep disturbance was associated with longer duration of HIV infection, depression, anxiety, and recreational drug use.

Genetic and functional mitochondrial assessment of HIV-infected patients developing HAART-related hyperlactatemia.

BACKGROUND: Mitochondrial damage of HIV and antiretrovirals, especially nucleoside-analogue interference on mitochondrial DNA (mtDNA) replication, is reported to underlay highly active antiretroviral therapy (HAART)-related hyperlactatemia, but scarce approaches have been performed to correlate clinical manifestations and mitochondrial abnormalities. METHODS: We obtained lymphocytes and monocytes of 26 HIV-infected and treated patients who developed hyperlactatemia and after recovery, 28 nonhyperlactatemic HIV subjects on HAART, 31 naive individuals, and 20 uninfected controls. Mitochondrial replication and transcription analysis were performed by quantitative real-time PCR, mitochondrial translation quantification by western blot and mitochondrial enzymatic activities by spectrophotometry. RESULTS: Mitochondrial parameters decreased during hyperlactatemia and improved at recovery. Mitochondrial replication and transcription species were reduced (P = 0.16 and P = 0.71), but the most significant decay was observed on mitochondrial protein content (P < 0.05) and mitochondrial complexes III and IV activities (P < 0.01 and P < 0.001). During hyperlactatemia lactate level correlated complexes III and IV function (P < 0.05). After recovery mitochondrial parameters achieved values of nonhyperlactatemic HIV individuals, which were lower than ranges of naive subjects and uninfected controls. CONCLUSIONS: HIV and HAART-related hyperlactatemia is associated with a general mitochondrial impairment which reverts after recovery. Mitochondrial biochemistry show a better correlation with lactate levels than mitochondrial genetics suggesting that mitochondrial function could be a better marker of hyperlactatemia development than mtDNA content.