Hospital and community care costs for people newly diagnosed of living with HIV in London, UK.

This study of people newly diagnosed of living with HIV (ND-PLHIV) calculated the use, cost and outcome of HIV services at a London HIV centre. ND-PLHIV were followed July 2017-October 2018. Hospital data included inpatient days (IP), outpatient (OP), dayward (DW) visits, tests and procedures, and anti-retroviral drugs (ARVs). Community services were recorded in daily diaries. Mean per patient-year (MPPY) use was multiplied by unit costs. 13.6 MPPY (95%CI 12.4-14.9) OP visits, 0.4 MPPY (95%CI 0.1-0.7) IP days, 0.09 MPPY (95%CI 0.01-0.2) DW visits and 4.6 MPPY community services (95%CI 3.4-5.8). Total annual costs per patient-year (CPPY) was £11,483 (95%CI £10,369-12,597): ARVs comprised 63% and community services 2%. White participants used fewer hospital and more community services compared with minority ethnic community (MEC) participants. Costs for White ND-PLHIV was £10,778 CPPY (95%CI £9629-11,928); £13,214 (95%CI £10,656-15,772) for MEC ND-PLHIV (p < 0.06). Annual costs were inversely related to CD4 count at entry (r = -5.58, p = 0.02); mean CD4 count was 476 cells/mm3 (95%CI 422-531) versus 373 cells/mm3 (95%CI 320-425) for White and MEC participants respectively (p = 0.03). Annual costs for ND-PLHIV with CD4 ≤ 350 cells/mm3 was £2478 PPY higher compared with CD4 count >350 cells/mm3 (p = 0.04).

The efficiency of the EmERGE pathway of care for people living with HIV in England.

This study estimated the efficiency of implementing the EmERGE Pathway of Care for people living with medically stable HIV in Brighton, UK; an App enables individuals to communicate with caregivers via their smart-phone. Individual data on the use of HIV outpatient services were collected one-year pre- and post-implementation of EmERGE. Unit costs of HIV outpatient services were calculated and linked with mean use of services per patient year. Primary outcomes were CD4 count and viral load; patient activation and quality-of-life measures were secondary outcomes. 565 participants were followed up April 2017 - October 2018: 93% men, mean age at recruitment 47.0 years (95%CI:46.2-47.8). Outpatient visits decreased by 9% from 5.6 (95%CI:5.4-5.8) to 5.1 (95%CI:4.9-5.3). Face-to-face visits decreased and virtual visits increased. Annual costs decreased by 9% from £751 (95%CI: £722-£780) to £678 (95%CI: £653-£705). Including anti-retroviral drugs, total annual cost decreased from £7,343 (95%CI: £7,314-7,372) to £7,270 (95%CI: £7,245-7,297): ARVs costs comprised 90%. EmERGE was a cost-saving intervention, patients remained engaged and clinically stable. Annual costs were reduced, but ARVs continue to dominate costs. Extension of EmERGE to other people with chronic conditions, could produce greater efficiencies but these needs to be evaluated and monitored over time.

Efficiency of the EmERGE Pathway to provide continuity of care for Spanish people living with medically stable HIV.

OBJECTIVE: Calculate the efficiency of the EmERGE Pathway of Care for medically stable people living with HIV at the Hospital Clínic-IDIBAPS, Barcelona, Spain. METHODS: 546 study participants were followed between 1st July 2016 and 30th October 2019 across three HIV outpatient clinics, but the virtual clinic was closed during the second year. Unit costs were calculated, linked to mean use outpatient services per patient year, one-year before and after the implementation of EmERGE. Costs were combined with primary and secondary outcomes. RESULTS: Annual costs across HIV-outpatient services increased by 8%: €1073 (95%CI €999-€1157) to €1158 (95%CI €1084-€1238). Annual cost of ARVs was €7,557; total annual costs increased by 1% from €8430 (95%CI €8356-8514) to €8515 (95%CI €8441-8595). Annual cost for 433 participants managed in face-to-face (F2F) clinics decreased by 5% from €958 (95%CI 905-1018) to €904 (95%CI 863-945); participants transferred from virtual to F2F outpatient clinics (V2F) increased their annual cost by a factor of 2.2, from €115 (95%CI 94-139) to €251 (95%CI 219-290). No substantive changes were observed in primary and secondary outcomes. CONCLUSION: EmERGE Pathway is an efficient and acceptable intervention. Increases in costs were caused by internal structural changes. The cost reduction observed in F2F clinics were off-set by the transfer of participants from the virtual to the F2F clinics due to the closure of the virtual clinic during the second year of the Study. Greater efficiencies are likely to be achieved by extending the use of the Pathway to other PLHIV.

Efficiency of the EmERGE Pathway to provide continuity of care for Spanish people living with medically stable HIV.

OBJECTIVE: Calculate the efficiency of the EmERGE Pathway of Care for medically stable people living with HIV at the Hospital Clínic-IDIBAPS, Barcelona, Spain. METHODS: 546 study participants were followed between 1st July 2016 and 30th October 2019 across three HIV outpatient clinics, but the virtual clinic was closed during the second year. Unit costs were calculated, linked to mean use outpatient services per patient year, one-year before and after the implementation of EmERGE. Costs were combined with primary and secondary outcomes. RESULTS: Annual costs across HIV-outpatient services increased by 8%: €1073 (95%CI €999-€1157) to €1158 (95%CI €1084-€1238). Annual cost of ARVs was €7,557; total annual costs increased by 1% from €8430 (95%CI €8356-8514) to €8515 (95%CI €8441-8595). Annual cost for 433 participants managed in face-to-face (F2F) clinics decreased by 5% from €958 (95%CI 905-1018) to €904 (95%CI 863-945); participants transferred from virtual to F2F outpatient clinics (V2F) increased their annual cost by a factor of 2.2, from €115 (95%CI 94-139) to €251 (95%CI 219-290). No substantive changes were observed in primary and secondary outcomes. CONCLUSION: EmERGE Pathway is an efficient and acceptable intervention. Increases in costs were caused by internal structural changes. The cost reduction observed in F2F clinics were off-set by the transfer of participants from the virtual to the F2F clinics due to the closure of the virtual clinic during the second year of the Study. Greater efficiencies are likely to be achieved by extending the use of the Pathway to other PLHIV.

Correction to: CSF inflammatory markers and neurocognitive function after addition of maraviroc to monotherapy darunavir/ritonavir in stable HIV patients: the CINAMMON study.

Due to a production error the bottom portion of Figure 1 was omitted. The corrected figure is given below.

CSF inflammatory markers and neurocognitive function after addition of maraviroc to monotherapy darunavir/ritonavir in stable HIV patients: the CINAMMON study.

CINAMMON is a phase IV, open-label, single-arm, pilot study assessing maraviroc (MVC) in the central nervous system (CNS) when added to darunavir/ritonavir monotherapy (DRV/r) in virologically suppressed HIV-infected subjects. CCR5 tropic participants on DRV/r were recruited. Participants remained on DRV/r for 12 week (w) (control phase). MVC 150 mg qd was added w12-w36 (intervention phase). Lumbar puncture (LP) and neurocognitive function (Cogstate) examinations scheduled at baseline, w12 and w36; MRI before w12, again at w36. Primary endpoint was CSF inflammatory marker changes during intervention phase. Secondary endpoints included changes in NC function and MRI parameters. CSF/plasma DRV/r concentrations measured at w12 and w36, MVC at w36. Nineteen patients recruited, 15 completed (17M, 2F). Dropouts: headache (2), knee problem (could not attend, 1), personal reasons (1). Mean age (range) 45.4 years (27.2-65.1), 13/19 white, 10/19 MSM. No changes in selected CSF markers were seen w12-w36. Overall NC function did not improve w12-w36: total age adjusted z score improved by 0.27 (weighted paired t test; p = 0.11); for executive function only, age adjusted z score improved by 0.54 (p = 0.03). MRI brain parameters unchanged. DRV plasma:CSF concentration ratio unchanged between w12 (132) and w36 (112; p = 0.577, Wilcoxon signed-rank). MVC plasma:CSF concentration ratio was 35 at w36. No changes in neuroinflammatory markers seen. In this small study, addition of 24w MVC 150 mg qd to stable DRV/r monotherapy showed possible improvement in executive function with no global NC effect. Learning effect cannot be excluded. This effect should be further evaluated.

Assessing the role of peripheral CD8 T cells in neurocognitive impairment in HIV-infected men who have sex with men: data from the MSM Neurocog Study.

Studies have suggested CD8 lymphocytes may be a possible marker for inflammation, which is believed to be a contributing factor to neurocognitive impairment. Individuals enrolled in the MSM Neurocog Study were analysed. Those with depression, anxiety or mood disorders were excluded. Individuals with neurocognitive impairment were identified using the Brief NeuroCognitive Screen and compared to those with normal scores. CD4 and CD8 T cell values and CD4:CD8 ratios were compared between groups. In all, 144 men, aged 18-50 years, were included in the analysis. Twenty were diagnosed with neurocognitive impairment. We were unable to identify any significant difference between current, nadir or peak CD4 and CD8 counts. CD4:CD8 ratios and CD4:CD8 ratio inversion (<1) were also found to be similar between both groups. However, neurocognitive impairment subjects were 8% more likely to have inversion of CD4:CD8 ratio and higher median peak CD8 cell counts reported compared to non-impaired subjects. Analysis of data from the MSM Neurocog Study, demonstrated trends in peripheral CD8 counts and CD4:CD8 ratios. However, we are unable to demonstrate any significant benefit. Plasma biomarkers of neurocognitive impairment in HIV-infected subjects would be of great benefit over current methods of invasive CSF analysis and technical neuroimaging used in the diagnosis of neurocognitive impairment. Future, prospective, longitudinal work with large numbers of neurocognitive impairment subjects is required to further investigate the role of peripheral CD8 T cells as markers of neurocognitive impairment.

Clinical predictors of rectal lymphogranuloma venereum infection: results from a multicentre case-control study in the U.K.

OBJECTIVE: Since 2003, over 2000 cases of lymphogranuloma venereum (LGV) have been diagnosed in the U.K. in men who have sex with men (MSM). Most cases present with proctitis, but there are limited data on how to differentiate clinically between LGV and other pathology. We analysed the clinical presentations of rectal LGV in MSM to identify clinical characteristics predictive of LGV proctitis and produced a clinical prediction model. DESIGN: A prospective multicentre case-control study was conducted at six U.K. hospitals from 2008 to 2010. Cases of rectal LGV were compared with controls with rectal symptoms but without LGV. METHODS: Data from 98 LGV cases and 81 controls were collected from patients and clinicians using computer-assisted self-interviews and clinical report forms. Univariate and multivariate logistic regression was used to compare symptoms and signs. Clinical prediction models for LGV were compared using receiver operating curves. RESULTS: Tenesmus, constipation, anal discharge and weight loss were significantly more common in cases than controls. In multivariate analysis, tenesmus and constipation alone were suggestive of LGV (OR 2.98, 95% CI 0.99 to 8.98 and 2.87, 95% CI 1.01 to 8.15, respectively) and that tenesmus alone or in combination with constipation was a significant predictor of LGV (OR 6.97, 95% CI 2.71 to 17.92). The best clinical prediction was having one or more of tenesmus, constipation and exudate on proctoscopy, with a sensitivity of 77% and specificity of 65%. CONCLUSIONS: This study indicates that tenesmus alone or in combination with constipation makes a diagnosis of LGV in MSM presenting with rectal symptoms more likely.

Screening for HIV-related neurocognitive impairment in clinical practice: challenges and opportunities.

With increasingly successful management of HIV, focus has shifted away from AIDS-related complications to other chronic co-morbidities. For HIV-related cognitive problems, the true aetiopathogenesis and epidemiology remains unclear. Rather than a systematic review, this paper presents the challenges and the opportunities we faced in establishing our own clinical service. Papers were identified using Pubmed and the terms "screening", "HIV" and "neurocognitive". This article covers the background of HIV-associated neurocognitive disorders (HAND) with a focus on HIV-related neurocognitive impairment (NCI), detailing classification, prevalence, diagnostic categories and diagnostic uncertainties. Screening is discussed, including a comparison of the available screening tools for cognitive deficits in HIV-infected patients and the importance of practice effects. Discussed also are the normal ranges and the lack thereof and potential investigations for those found to have impairments. We conclude by discussing the role of NCI screening in routine clinical care at the current time.

Non-cirrhotic portal hypertension in HIV-infected individuals.

Non-cirrhotic portal hypertension (NCPH) has been associated with didanosine (ddI) exposure. We aimed to determine the number of individuals with NCPH within our cohort and define their characteristics. We identified individuals within our cohort with NCPH and performed a retrospective case note review. Cumulative antiretroviral therapy (ART) use was calculated and a statistical analysis performed to compare exposure to the rest of the clinic cohort for the same time period. Where available, data was collated on FibroScan®, echocardiography and coagulation profile. Seventeen patients were identified. Upper gastrointestinal bleeding was the most common presenting feature. Liver biopsy showed mild portal or periportal fibrosis in 13 (81%) and four with features of nodular regenerative hyperplasia. There was significantly greater exposure to ddl in this group (59.5 months) compared to the rest of the HIV cohort (21.1 months) P = <0.001. Eleven subjects has a liver elastography performed, six (55%) had a result greater than 9.6 kPa (consistent with greater than F2 disease by Metavir scoring). Echocardiography was performed in seven patients: four met criteria for pulmonary hypertension. This is consistent with other cohorts demonstrating an association between the didanosine exposure and NCPH. Our data also suggest an increased risk of pulmonary hypertension.

Interventions to increase access to STI services: a study of England's 'high-impact changes' across three central London clinics.

BACKGROUND: Increasing access to sexual health services is a key objective for the Department of Health in England and Wales. In 2006 it published 10 high-impact changes (HICs) designed to enhance 48 h access to genitourinary medicine services. However, there is limited evidence on the effectiveness of the proposed interventions. OBJECTIVE: To evaluate the implementation of five HICs in three sexual health clinics over 4 years. These HICs included a text message results service, nurse-delivered asymptomatic service, clinic refurbishment, a centralised booking service and an electronic appointment system. METHODS: The effect of HICs was evaluated by measuring clinical activity, number of sexual health screens performed, and patients seen within 48 h. These data were obtained from the clinic database, mandatory reports and Health Protection Agency waiting time surveys, respectively. RESULTS: The median number of new patients seen per month increased from 3635 to 4263 following the implementation of the five HICs. The follow-up/new patient ratio fell from 0.67 to 0.21 during the study. The biggest fall corresponded to a rise in patients receiving results by text message, from 0% to 40%. Only the centralised booking service was associated with a significant increase in the number of new patients seen. DISCUSSION: Providing results by text message was associated with a reduced number of follow-up patients, while implementation of a centralised booking service coincided with a significant increase in patient access. Further research is required to evaluate the relative importance of the other HICs.

The frequency and reasons for antiretroviral switching with specific antiretroviral associations: the SWITCH study.

BACKGROUND: We investigated the reasons for switching antiretroviral regimens, an issue rarely addressed in cohort studies. METHODS: An observed toxicity switch rate (OTSR) was calculated by Poisson regression using the number of days individuals received each individual antiretroviral drug. RESULTS: Of 3333 individuals receiving HAART, a total of 14% of regimens were switched, the majority occurring after 6 months of therapy. Toxicity was the major reason for switching (61%) and there were no major statistically significant differences in OTSR between the protease inhibitor (OTSR 26.4, 95% CI 18.3-37) and non-nucleoside reverse transcriptase inhibitor (OTSR 22.2, 95% CI 13.6-34.4) based regimes. For individual antiretrovirals, stavudine and zidovudine had significantly higher "switch" scores than all other drugs. CONCLUSIONS: There were no differences between the major HAART classes in OTSR. We suggest that newer antiretrovirals will require differentiation in terms of longer-term toxicity, as this is the major reason for switching.

Sexual health of adults working in pornographic films.

We report the frequency of sexually transmitted infections (STIs) diagnosed in performers in the adult pornographic film industry. Over a 13 month period, 445 STI screens were performed in 115 patients, 56 women and 59 men. All reported unprotected sex during filming. Seventy-five percent (86) had at least one sexual partner outside work, and 90% used condoms inconsistently with them. Women worked exclusively with women (23%), men only (38%) or both genders (39%). Almost all men (97%) worked exclusively heterosexually. Thirty-eight percent (44/115) were diagnosed with 77 STIs, including non-specific urethritis (51), gonorrhoea (10), chlamydia (6) and genital warts (6). Gonorrhoea was found exclusively at the pharynx in three heterosexual men. There were no cases of HIV, syphilis, hepatitis B or hepatitis C. Monthly screening and certification is a working requirement for this population but STIs are common in an industry where unprotected sex is the norm.

Reduced glomerular filtration rate but sustained virologic response in HIV/hepatitis B co-infected individuals on long-term tenofovir.

Reports have described a decrease in glomerular filtration rate (eGFR) associated with tenofovir disoproxil fumarate (TDF) use in HIV positive individuals. However, no study has examined renal function over a prolonged period in HIV/hepatitis B virus (HBV) co-infected patients. We assessed the long-term durability and toxicity of TDF in a cohort of 39 e antigen (eAg) positive co-infected patients commenced on TDF 245 mg daily either in addition to or as part of standard antiretroviral therapy. Immunological and virological parameters were followed to 260 weeks, with the median follow-up period being 251 weeks (range 69-290 weeks). eGFR was calculated using the Modification in Diet in Renal Disease equation. On treatment at 260 weeks, 88% (14/16) had HIV viral load <50 copies/mL, median CD4 count rose from 318 to 532 cells/mm(3), median alanine aminotransferase (ALT) fell from 61 IU/L to 42 IU/L, with 35% (7/20) having a normal ALT, median HBV DNA fell from 69 x 10(6) copies/mL to 500 copies/mL, with 75% (12/16) having an undetectable HBV DNA level and 55% (6/11) becoming eAg negative. Of those with detectable HBV DNA, none had TDF resistance mutations. The eGFR declined by 22.19 mL/min/1.73 mm(2) from baseline (P = 0.023) over this period, which was unaffected by protease inhibitor use, baseline CD4 count, ALT or HBV DNA level. Three patients discontinued TDF therapy due to renal dysfunction. In conclusion, TDF has sustained efficacy but is associated with a significant decline in eGFR. Further larger studies are required to clarify this observation.

Impact of different low-dose ritonavir regimens on lipids, CD36, and adipophilin expression.

We investigated the relationship between ritonavir concentrations and changes in lipids, vascular inflammation markers, CD36, and adipophilin expression in volunteers randomly assigned to groups receiving 100 mg of ritonavir once daily or twice daily. In both groups decreases in high-density lipoprotein (HDL) (6%, P = 0.010; and 10%, P < 0.001, respectively) and CD36 (14%, P = 0.012; and 16%, P = 0.006, respectively) and increases in the vascular inflammation marker sCD40L (12%, P = 0.008; 19%, P = 0.003, respectively) were seen. Increases in adipophilin (30%, P = 0.044) and triglycerides (32%, P = 0.044) were seen only in the group receiving ritonavir twice daily. The ritonavir concentration in the plasma correlated with changes in triglycerides, HDL, and adipophilin (r = 0.34, P = 0.030; r = 0.33, P = 0.040; and r = 0.4, P = 0.01, respectively).

Rectal chlamydia--a reservoir of undiagnosed infection in men who have sex with men.

OBJECTIVE: To determine the prevalence of rectal chlamydia infection in a cohort of men who have sex with men (MSM) and the proportion of infection that would be missed without routine screening. METHODS: MSM presenting to four HIV/GUM outpatient clinics at the Chelsea & Westminster Hospital NHS Foundation Trust between 1 November 2005 and 29 September 2006 were offered testing for rectal chlamydia infection in addition to their routine screen for sexually transmitted infections (STIs). Chlamydia trachomatis (CT) tests were performed using the Beckton-Dickinson Probe-Tec Strand Displacement Assay. Positive samples were re-tested at the Sexually Transmitted Bacteria Reference Laboratory, to confirm the result and identify lymphogranuloma venereum (LGV)-associated serovars. RESULTS: A total of 3076 men were screened. We found an 8.2% prevalence of infection with CT (LGV and non-LGV serovars) in the rectum and 5.4% in the urethra. The HIV and rectal chlamydia co-infection rate was 38.1%. The majority of rectal infections (69.2%, (171/247)) were asymptomatic and would have been missed if routine screening had not been undertaken. Of the samples re-tested, 94.2% (227/242) rectal and 91.8% (79/86) urethral specimens were confirmed CT positive and 36 cases of LGV were identified. CONCLUSION: Our data show a high rate of rectal chlamydia infection, in the majority of cases it was asymptomatic. We recommend routine screening for rectal chlamydia in men at risk, as this may represent an important reservoir for the onward transmission of infection.

The role of immune suppression and HHV-8 in the increasing incidence of HIV-associated multicentric Castleman's disease.

BACKGROUND: In HIV cohorts with access to highly active antiretroviral therapy (HAART), the incidence of Kaposi's sarcoma (KS) is falling; however, the incidence of multicentric Castleman's disease (MCD) in HIV has not previously been described. METHODS: The incidence of HIV-associated MCD was calculated from a prospective HIV database with 56 202 patient-years of follow-up and compared with KS. Univariate and multivariate analyses were carried out to identify factors associated with MCD. Plasma human herpesvirus (HHV)-8 DNA levels were measured in HIV-seropositive individuals with newly diagnosed MCD (n = 24), KS (n = 72), HIV-associated lymphoma (n = 74) and HIV-positive controls (n = 53). RESULTS: From 24 cases of HIV-associated MCD, the incidence measured 4.3/10,000 patient-years [95% confidence interval (CI) 2.7-6.4]. The incidence in the pre-HAART (1983-1996), early-HAART (1997-2001) and later HAART (2002-2007) eras were 2.3 (95% CI 0.02-4.2), 2.8 (95% CI 0.9-6.5) and 8.3 (95% CI 4.6-12.6), respectively, representing a statistically significant increase over time (P < 0.05). In contrast, from 1180 cases of KS, the incidence in this cohort decreased with time. Multivariate analysis demonstrated that a nadir CD4 count >200/mm(3), increased age, no previous HAART exposure and non-Caucasian ethnicity were all associated with an increased risk of MCD. Plasma HHV-8 DNA levels were higher in patients with newly diagnosed MCD than with KS, lymphomas or HIV-positive controls (Mann-Whitney U-test, P < 0.0001). CONCLUSIONS: The incidence of HIV-associated MCD is increasing. It appears to occur more frequently in older HIV-positive individuals with well-preserved immune function.

HIV opt-out increases HIV testing in low-risk patients.

We audited the effect of introducing HIV opt-out in a genitourinary medicine clinic in central London, UK. We found that opt-out increased the rate at which HIV testing was offered to low-risk patients and that more tests were done.