Exploring the concept of unmet need within sexual and reproductive health in England: A qualitative Delphi exercise.

BACKGROUND: Unmet need within sexual and reproductive health (SRH) is a concept that is difficult to define and measure. This qualitative Delphi exercise was used to ascertain the opinions of SRH professionals on the conceptualisation and measurement of unmet need within SRH. METHODS: This exercise was carried out in two rounds. In the first round, respondents responded narratively to three prompts, which were then used to create a series of statements. In the second round, participants responded narratively to the statements created in the first round. Responses from both rounds were then coded and analysed thematically. RESULTS: Participants felt that an understanding of unmet need is an important part of SRH service design and provision, and believed that certain populations are often underrepresented within the datasets that are used to assess unmet need. Many respondents felt that a full understanding of unmet need within SRH would only come from involvement of relevant stakeholders in the process of investigating unmet need, and that qualitative methods may also have a role to play in gaining a more holistic understanding of unmet need within SRH. CONCLUSIONS: Respondents within this study felt that unmet need is complex concept that has a significant impact on service delivery and the outcomes and experiences of the most vulnerable populations. We need to improve our understanding of unmet need and prioritise stakeholder voices if we want to create interventions that address unmet need within SRH.

Inequalities in sexual and reproductive outcomes among women aged 16-24 in England (2012-2019).

BACKGROUND: Women aged 16-24 in England have a high burden of sexual and reproductive morbidity, with particularly poor outcomes among people living in more deprived areas (including racially minoritised populations). This analysis used national data to examine the disparities within sexual and reproductive outcomes among this population and to assess whether the patterns of inequality were consistent across all outcomes. METHODS: Within this ecological study, univariable and multivariable Poisson regression analyses of neighbourhood-level data from national data sets were carried out to investigate the relationships of deprivation and ethnicity with each of six dependent variables: gonorrhoea and chlamydia testing rates, gonorrhoea and chlamydia test positivity rates, and abortion and repeat abortion rates. RESULTS: When comparing Index of Multiple Deprivation (IMD) decile 1 (most deprived) and IMD decile 10 (least deprived), chlamydia (RR 0.65) and gonorrhoea (0.79) testing rates, chlamydia (0.70) and gonorrhoea (0.34) positivity rates, abortion rates (0.45) and repeat abortion rates (0.72) were consistently lower in IMD decile 10 (least deprived). Similarly, chlamydia (RR 1.24) and gonorrhoea positivity rates (1.92) and repeat abortion rates (1.31) were higher among black women than white women. Results were similar when both ethnicity and deprivation were incorporated into multivariable analyses. CONCLUSION: We found similar patterns of outcome inequality across a range of sexual and reproductive outcomes, despite multiple differences in the drivers of each outcome. Our analysis suggests that there are broad structural causes of inequality across sexual and reproductive health that particularly impact the health of deprived and black populations.

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.

Assessment of trabecular bone score, an index of bone microarchitecture, in HIV positive and HIV negative persons within the HIV UPBEAT cohort.

INTRODUCTION: Increased prevalence of low bone mineral density (BMD) and increased fracture incidence are observed in persons living with HIV (PLWH). The trabecular bone score (TBS) is a novel index of bone microarchitecture which improves fracture prediction independent of BMD. METHODS: The HIV UPBEAT study is a single centre, prospective cohort study that enrolled subjects with and without HIV from similar sociodemographic backgrounds for annual assessments of bone health. TBS was derived from lumbar spine (LS) dual-energy X-ray absorptiometry images. Univariate and multivariable linear regression was used to assess relationships between baseline TBS, BMD, sociodemographic and clinical factors. RESULTS: 463 subjects (201 HIV positive) were included; PLWH were younger and more likely male, of non-African ethnicity and current smokers. HIV was associated with a mean reduction of 0.037 [-0.060, -0.013] (p = 0.002) in TBS. Lower TBS was also associated with male gender, non-African ethnicity, current smoking status and lower LS BMD. HIV remained associated with lower TBS after adjustment for LS BMD, age, gender and ethnicity. However, adjustment for current smoking significantly attenuated the association between HIV and TBS, with further adjustment for higher bone turnover markers largely explaining any residual association. Among the sub-group of PLWH, exposure to protease inhibitors and lower nadir CD4+ T-cell counts were both predictors of lower TBS. CONCLUSIONS: PLWH have lower TBS independent of LS BMD. However, this is largely explained by higher current smoking rates and higher bone turnover in those with HIV. Exposure to PI, but not tenofovir disproxil fumarate, also contributed to lower TBS in those with HIV.

Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries: a prospective, observational study.

BACKGROUND: Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals. METHODS: In this observational study, we used data from prospective studies of HIV-positive individuals in Europe (France, Greece, the Netherlands, Spain, Switzerland, and the UK) and North and South America (Brazil, Canada, and the USA) in The HIV-CAUSAL Collaboration and The Centers for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies that differ in the threshold used to measure CD4 cell count and HIV RNA viral load every 3-6 months (when below the threshold) or every 9-12 months (when above the threshold). The strategies were defined by the threshold CD4 counts of 200 cells per µL, 350 cells per µL, and 500 cells per µL. Using inverse probability weighting to adjust for baseline and time-varying confounders, we estimated hazard ratios (HRs) of death and of AIDS-defining illness or death, risk ratios of virological failure, and mean differences in CD4 cell count. FINDINGS: 47 635 individuals initiated an antiretroviral therapy regimen between Jan 1, 2000, and Jan 9, 2015, and met the eligibility criteria for inclusion in our study. During follow-up, CD4 cell count was measured on average every 4·0 months and viral load every 3·8 months. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1091 had AIDS-defining illnesses or died (267 in threshold 200 strategy, 365 in threshold 350, and 459 in threshold 500). Compared with threshold 500, the mortality HR was 1·05 (95% CI 0·86-1·29) for threshold 200 and 1·02 (0·91·1·14) for threshold 350. Corresponding estimates for death or AIDS-defining illness were 1·08 (0·95-1·22) for threshold 200 and 1·03 (0·96-1·12) for threshold 350. Compared with threshold 500, the 24 month risk ratios of virological failure (viral load more than 200 copies per mL) were 2·01 (1·17-3·43) for threshold 200 and 1·24 (0·89-1·73) for threshold 350, and 24 month mean CD4 cell count differences were 0·4 (-25·5 to 26·3) cells per µL for threshold 200 and -3·5 (-16·0 to 8·9) cells per µL for threshold 350. INTERPRETATION: Decreasing monitoring to annually when CD4 count is higher than 200 cells per µL compared with higher than 500 cells per µL does not worsen the short-term clinical and immunological outcomes of virally suppressed HIV-positive individuals. However, more frequent virological monitoring might be necessary to reduce the risk of virological failure. Further follow-up studies are needed to establish the long-term safety of these strategies. FUNDING: National Institutes of Health.

Is there continued evidence for an association between abacavir usage and myocardial infarction risk in individuals with HIV? A cohort collaboration.

BACKGROUND: In March 2008, the D:A:D study published results demonstrating an increased risk of myocardial infarction (MI) for patients on abacavir (ABC). We describe changes to the use of ABC since this date, and investigate changes to the association between ABC and MI with subsequent follow-up. METHODS: A total of 49,717 D:A:D participants were followed from study entry until the first of an MI, death, 1 February 2013 or 6 months after last visit. Associations between a person's 10-year cardiovascular disease (CVD) risk and the likelihood of initiating or discontinuing ABC were assessed using multivariable logistic/Poisson regression. Poisson regression was used to assess the association between current ABC use and MI risk, adjusting for potential confounders, and a test of interaction was performed to assess whether the association had changed in the post-March 2008 period. RESULTS: Use of ABC increased from 10 % of the cohort in 2000 to 20 % in 2008, before stabilising at 18-19 %. Increases in use pre-March 2008, and subsequent decreases, were greatest in those at moderate and high CVD risk. Post-March 2008, those on ABC at moderate/high CVD risk were more likely to discontinue ABC than those at low/unknown CVD risk, regardless of viral load (≤1,000 copies/ml: relative rate 1.49 [95 % confidence interval 1.34-1.65]; >1,000 copies/ml: 1.23 [1.02-1.48]); no such associations were seen pre-March 2008. There was some evidence that antiretroviral therapy (ART)-naïve persons at moderate/high CVD risk post-March 2008 were less likely to initiate ABC than those at low/unknown CVD risk (odds ratio 0.74 [0.48-1.13]). By 1 February 2013, 941 MI events had occurred in 367,559 person-years. Current ABC use was associated with a 98 % increase in MI rate (RR 1.98 [1.72-2.29]) with no difference in the pre- (1.97 [1.68-2.33]) or post- (1.97 [1.43-2.72]) March 2008 periods (interaction P = 0.74). CONCLUSIONS: Despite a reduction in the channelling of ABC for patients at higher CVD risk since 2008, we continue to observe an association between ABC use and MI risk. Whilst confounding cannot be fully ruled out, this further diminishes channelling bias as an explanation for our findings.

Hepatitis delta virus testing, epidemiology and management: a multicentre cross-sectional study of patients in London.

BACKGROUND: Hepatitis delta virus (HDV) testing is recommended for all patients with hepatitis B virus (HBV) infection. HDV infection is associated with severe liver disease and interferon is the only available treatment. OBJECTIVES: To determine the rate of anti-HDV antibody testing in HBV patients; and to describe the epidemiology, clinical characteristics and management of HDV-infected patients at four hospitals in London. STUDY DESIGN: The anti-HDV testing rate was estimated by reviewing clinical and laboratory data. Cross-sectional data collection identified HDV-infected patients who had attended the study centres between 2005 and 2012. RESULTS: At a centre with clinic-led anti-HDV testing, 40% (67/168) of HBV patients were tested. Recently diagnosed HBV patients were more likely to be screened than those under long-term follow-up (62% vs 36%, P=0.01). At a centre with reflex laboratory testing, 99.4% (3543/3563) of first hepatitis B surface antigen positive samples were tested for anti-HDV. Across the four study centres there were 55 HDV-infected patients, of whom 50 (91%) had immigrated to the UK and 27 (49%) had evidence of cirrhosis. 31 patients received interferon therapy for HDV with an end of treatment virological response observed in 10 (32%). CONCLUSIONS: The anti-HDV testing rate was low in a centre with clinic-led testing, but could not be evaluated in all centres. The HDV-infected patients were of diverse ethnicity, with extensive histological evidence of liver disease and poor therapeutic responses. Future recommendations include reflex laboratory testing algorithms and a prospective cohort study to optimise the investigation and management of these patients.

Use of surveillance data on HIV diagnoses with HIV-related symptoms to estimate the number of people living with undiagnosed HIV in need of antiretroviral therapy.

BACKGROUND: It is important to have methods available to estimate the number of people who have undiagnosed HIV and are in need of antiretroviral therapy (ART). METHODS: The method uses the concept that a predictable level of occurrence of AIDS or other HIV-related clinical symptoms which lead to presentation for care, and hence diagnosis of HIV, arises in undiagnosed people with a given CD4 count. The method requires surveillance data on numbers of new HIV diagnoses with HIV-related symptoms, and the CD4 count at diagnosis. The CD4 count-specific rate at which HIV-related symptoms develop are estimated from cohort data. 95% confidence intervals can be constructed using a simple simulation method. RESULTS: For example, if there were 13 HIV diagnoses with HIV-related symptoms made in one year with CD4 count at diagnosis between 150-199 cells/mm3, then since the CD4 count-specific rate of HIV-related symptoms is estimated as 0.216 per person-year, the estimated number of person years lived in people with undiagnosed HIV with CD4 count 150-199 cells/mm3 is 13/0.216 = 60 (95% confidence interval: 29-100), which is considered an estimate of the number of people living with undiagnosed HIV in this CD4 count stratum. CONCLUSIONS: The method is straightforward to implement within a short period once a surveillance system of all new HIV diagnoses, collecting data on HIV-related symptoms at diagnosis, is in place and is most suitable for estimating the number of undiagnosed people with CD4 count <200 cells/mm3 due to the low rate of developing HIV-related symptoms at higher CD4 counts. A potential source of bias is under-diagnosis and under-reporting of diagnoses with HIV-related symptoms. Although this method has limitations as with all approaches, it is important for prompting increased efforts to identify undiagnosed people, particularly those with low CD4 count, and for informing levels of unmet need for ART.

Late HIV presentation: epidemiology, clinical implications and management.

Late presentation of HIV is common and is associated with several adverse outcomes including an increased risk of clinical progression, blunted immune recovery on highly active antiretroviral therapy and a greater risk of drug toxicity. Late presenters may have higher rates of poor adherence, exacerbated by the same factors that contribute to their late diagnosis, such as lack of knowledge about HIV and the benefits of highly active antiretroviral therapy. We review the definitions of, risk factors for and subsequent impact of late presentation. Evidence regarding how and when to start antiretroviral therapy, and with which agents, will be discussed, as well as issues surrounding vaccination and opportunistic infection prophylaxis for individuals with a low CD4 count. Finally, strategies to increase HIV testing uptake to reduce late presentation will be summarized.

Cost-utility analysis of primary prophylaxis versus treatment on-demand for individuals with severe haemophilia.

OBJECTIVE: To assess the cost effectiveness of primary prophylaxis with clotting factor instead of treatment following a bleed (on-demand) for individuals with severe haemophilia. DESIGN: Different data sources on the clinical effects and costs of treatments were combined using a Markov model. SETTING: English treatment centres. PERSPECTIVE: UK societal. PARTICIPANTS: Hypothetical cohorts of 100 individuals with severe haemophilia A or B or severe von Willebrands disease. INTERVENTIONS: Primary prophylaxis treatment on-demand with clotting factor. OUTCOME MEASURES: Costs, quality-adjusted life-years (QALYs) and incremental cost per QALY in UK pounds ( pound, 1999/2000 values). RESULTS: The baseline results showed that treating individuals with severe haemophilia A/severe von Willebrands disease or severe haemophilia B with primary prophylaxis instead of treatment on-demand cost an additional pound 46500 and pound 8600 per QALY gained, respectively. However, the results were extremely sensitive to a number of factors including the clotting factor unit cost, the time between prophylactic doses and the discount rate. CONCLUSIONS: Despite the high costs of treatment, primary prophylaxis was cost effective compared with treatment on-demand in some scenarios. Primary prophylaxis is more likely to be cost effective for individuals with severe haemophilia B compared with individuals with severe haemophilia A/severe von Willebrands disease. Further research is required to assess the relationship between methods of clotting factor infusion and health-related quality-of-life.