The history of pre‐exposure prophylaxis (PrEP) is notable for being a community rather than industry‐driven development. This talk will review this history, covering factors that include community demand, study results, regulatory challenges, commercial interests and practical issues of public health. It will also look at some of the controversies that appear to limit broader access, and important changes since US approval for PrEP in 2012. If PrEP had been discovered in the 1980s, the demand for access is likely to have been very different and it would now be universally available. Yet in many health settings, the willingness to include the option of PrEP appears to be inversely correlated with the increasingly impressive data showing its effectiveness. The limitations of condoms are shown in continued rates of new HIV infections in high‐risk populations. These rates have remained persistently high for the last decade, even with the dramatic impact of treatment as prevention (TasP) on reducing further transmission. Within the last year, the polarized debate about PrEP appears to be shifting to a middle ground focused on individual choice. Together with TasP, this has started a new dialogue on the potential benefits on quality of life. This has brought a new focus on the cumulative and largely unmeasured impact for HIV negative gay men who live for decades focused on a fear of HIV. Looking forwards, the rate‐limiting steps of cost and adherence have the potential to be overcome with lower priced generic tenofovir in 2017 and the development of long‐acting formulations.
IntroductionThe evolving HIV epidemic, coupled with advances in HIV treatment, has resulted in an ageing HIV‐diagnosed population. It has been suggested that adverse physical and psychological effects of HIV may be higher among older people. However, few studies have examined the effect of older age on well‐being for people with HIV.Materials and MethodsThe ASTRA study included 3258 HIV‐diagnosed individuals (2248 MSM; 373 heterosexual men; 637 women) recruited from eight UK clinics in 2011–12 (64% response rate). Participants completed a questionnaire that included standard inventories on symptoms and health‐related quality of life (HrQoL). Associations of age group with: physical symptom distress (reporting significant distress for ≥1 of 26 symptoms), depression and anxiety (score ≥10 on PHQ‐9 and GAD‐7, respectively) and HrQoL problem (reporting problems on ≥1 of 5 Eurqol‐5D domains) were assessed; adjustment was made for gender/sexuality and time with diagnosed HIV.ResultsOf all participants, 87% were taking ART, 76% had VL ≤50c/mL and 19% had CD4 <350/mm3. Mean age was 45 years (range 18–88) with 5% <30, 23% 30–39, 43% 40–49, 22% 50–59 and 7% ≥60 years. The most prevalent distressing physical symptoms were: lack of energy/tiredness (26%), difficulty sleeping (24%), muscle‐ache/joint pain (21%) and pain (18%). With older age, there was no clear trend in prevalence of physical symptom distress, but prevalence of depression and anxiety decreased, while prevalence of HrQoL problems increased. This pattern remained after adjustment for gender/sexuality and time diagnosed with HIV. The increase with age in overall prevalence of HrQoL problem was due to increased problems for "mobility," "self‐care" and "performing usual activities" domains, not an increase in "depression/anxiety." Longer time with diagnosed HIV was strongly associated with higher prevalence of all symptoms measures and HrQoL problem (p<0.001 for trend, adjusted models).ConclusionsPhysical and psychological symptoms are common among people living with HIV, but the burden of these symptoms is not highest among the older age group. While HrQoL tended to worsen with older age, physical symptom distress did not, and mental health improved. This may reflect greater resilience in older adults, or the potential for "successful ageing": maintaining mental health despite age‐related health losses.
AbstractIntroductionThe International AIDS Society convened a multidisciplinary committee of experts in December 2020 to provide guidance and key considerations for the safe and ethical management of clinical trials involving people living with HIV (PLWH) during the SARS‐CoV‐2 pandemic. This consultation did not discuss guidance for the design of prevention studies for people at risk of HIV acquisition, nor for the programmatic delivery of antiretroviral therapy (ART).DiscussionThere is strong ambition to continue with HIV research from both PLWH and the research community despite the ongoing SARS‐CoV‐2 pandemic. How to do this safely and justly remains a critical debate. The SARS‐CoV‐2 pandemic continues to be highly dynamic. It is expected that with the emergence of effective SARS‐CoV‐2 prevention and treatment strategies, the risk to PLWH in clinical trials will decline over time. However, with the emergence of more contagious and potentially pathogenic SARS‐CoV‐2 variants, the effectiveness of current prevention and treatment strategies may be compromised. Uncertainty exists about how equally SARS‐CoV‐2 prevention and treatment strategies will be available globally, particularly for marginalized populations, many of whom are at high risk of reduced access to ART and/or HIV disease progression. All of these factors must be taken into account when deciding on the feasibility and safety of developing and implementing HIV research.ConclusionsIt can be assumed for the foreseeable future that SARS‐CoV‐2 will persist and continue to pose challenges to conducting clinical research in PLWH. Guidelines regarding how best to implement HIV treatment studies will evolve accordingly. The risks and benefits of performing an HIV clinical trial must be carefully evaluated in the local context on an ongoing basis. With this document, we hope to provide a broad guidance that should remain viable and relevant even as the nature of the pandemic continues to develop.
IntroductionTransmission of Hepatitis C virus (HCV) among HIV‐positive men who have sex with men (MSM) in the United Kingdom is ongoing. We explore associations between self‐reported sexual behaviours and drug use with cumulative HCV prevalence, as well as new HCV diagnosis.MethodsASTRA is a cross‐sectional questionnaire study including 2,248 HIV‐diagnosed MSM under care in the United Kingdom during 2011–2012. Socio‐demographic, lifestyle, HIV‐related and sexual behaviour data were collected during the study. One thousand seven hundred and fifty two (≥70%) of the MSM who consented to linkage of ASTRA and clinical information (prior to and post questionnaire) were included. Cumulative prevalence of HCV was defined as any positive anti‐HCV or HCV‐RNA test result at any point prior to questionnaire completion. We excluded 536 participants with clinical records only after questionnaire completion. Among the remaining 1,216 MSM, we describe associations of self‐reported sexual behaviours and recreational drug use in the three months prior to ASTRA with cumulative HCV prevalence, using modified Poisson regression with robust error variances. New HCV was defined as any positive anti‐HCV or HCV‐RNA after questionnaire completion. We excluded 591 MSM who reported ever having a HCV diagnosis at questionnaire, any positive HCV result prior to questionnaire or did not have any HCV tests after the questionnaire. Among the remaining 1,195 MSM, we describe occurrence of new HCV diagnosis during follow‐up according to self‐reported sexual behaviours and recreational drug use three months prior to questionnaire (Fisher's exact test).ResultsCumulative HCV prevalence among MSM prior to ASTRA was 13.3% (95% CI 11.5–15.4). Clinic‐ and age‐adjusted prevalence ratios (95% CI) for cumulative HCV prevalence were 4.6 (3.1–6.7) for methamphetamine, 6.5 (3.5–12.1) for injection drugs, 2.3 (1.6–3.4) for gamma hydroxybutyrate (GHB), 1.6 (1.3–2.0) for nitrites, 1.7 (1.5–2.0) for all condom‐less sex (CLS), 2.1 (1.7–2.5) for CLS‐HIV‐seroconcordant, 1.3 (0.9–1.9) for CLS‐HIV‐serodiscordant, 2.0 (1.6–2.5) for group sex, 1.5 (1.2–1.9) for more than 10 new sexual partners in the past year. Among 1,195 MSM with 2.2 years [IQR 1.5–2.4] median follow‐up, there were 7 new HCV cases during 2,033 person‐years at risk. Incidence was 3.5 per 1,000 person‐years (95% CI 1.6–7.2). New HCV was recorded in 1.3% MSM who used methamphetamine versus 0.5% MSM who did not (p=0.385); 3.7% MSM who injected recreational drugs versus 0.5% MSM who did not (p=0.148); 2.9% MSM who used GHB versus 0.4% MSM who did not (p=0.003); 1.5% MSM who used nitrites versus 0.2% MSM who did not (p=0.019); 1.1% MSM having CLS versus 0.3% MSM who did not (p=0.084); 1.7% MSM having CLS‐HIV‐serodiscordant versus 0.4% MSM who did not (p=0.069); 0.9% MSM who had CLS‐HIV‐seroconcordant versus 0.5% MSM who did not (p=0.318); 0.8% MSM who had group sex versus 0.5% MSM who did not (p=0.463); and 1.6% MSM with =10 new sexual partners in the previous year versus 0.2% MSM with no or up to 9 new partners (p=0.015).ConclusionsSelf‐reported recent use of recreational and injection drugs, condom‐less sex and multiple new sexual partners are associated with pre‐existing HCV infection and, with the exception of injection drugs, appear to be predictive of new HCV co‐infection among HIV‐diagnosed MSM.
AbstractIntroductionSuboptimal ART adherence, despite HIV viral suppression, has been associated with chronic residual inflammation. Whether this association extends to individuals who initiate ART during early HIV infection remains unknown, which was the objective of this study.MethodsPlasma levels of interleukin‐6 (IL‐6), high‐sensitivity C‐reactive protein, serum amyloid A protein (SAA), IL‐27, soluble intercellular adhesion molecule‐1, soluble vascular adhesion molecule‐1, D‐dimer and the CD4+/CD8+ T‐cell ratio, were analysed at baseline and eight months after ART initiation in treatment‐naïve participants with HIV and CD4+ T‐cells >500 cells/mm3 enrolled in the immediate arm of START. Adherence was assessed by seven‐day self‐report. Multivariable linear regression was utilized to analyse the association between ART adherence and each biomarker at the eight‐month visit in participants who achieved virologic suppression (<50 copies/mL).ResultsWe evaluated 1627 participants (422 female) who achieved virologic suppression at the eight‐month visit in the period between 2009 and 2013. Median (IQR) CD4+ T‐cell count before ART was 651 (585, 769) cells/mm3. Incomplete adherence was reported in 109 (7%) participants at the eight month visit. After adjusting for covariates, plasma IL‐6 was 1.12 (95% CI, 1.00 to 1.26; p = 0.047) fold higher in participants reporting incomplete versus 100% adherence. A similar association for SAA was observed in an exploratory analysis (1.29 (95% CI 1.04 to 1.60); p = 0.02). No significant differences in other biomarkers were observed.ConclusionsIncomplete ART adherence was associated with higher IL‐6 levels in individuals who achieved virologic suppression early after ART initiation in START. A potential similar association for SAA requires confirmation. These findings suggest a role for identifying strategies to maximize ART adherence even during virologic suppression. ClinicalTrials.gov number: NCT00867048.
