Consensus statement on the role of health systems in advancing the long-term well-being of people living with HIV.

Health systems have improved their abilities to identify, diagnose, treat and, increasingly, achieve viral suppression among people living with HIV (PLHIV). Despite these advances, a higher burden of multimorbidity and poorer health-related quality of life are reported by many PLHIV in comparison to people without HIV. Stigma and discrimination further exacerbate these poor outcomes. A global multidisciplinary group of HIV experts developed a consensus statement identifying key issues that health systems must address in order to move beyond the HIV field's longtime emphasis on viral suppression to instead deliver integrated, person-centered healthcare for PLHIV throughout their lives.

Cost effectiveness of testing HIV infected individuals for TB in a low TB/HIV setting.

OBJECTIVES: Guidelines recommend routine testing for latent TB infection (LTBI) in people living with HIV. However there are few cost-effectiveness studies to justify this in contemporary high resource, low TB/HIV incidence settings. We sought to assess the uptake, yield and cost-effectiveness of testing for latent and active TB. METHODS: Adults attending an ambulatory HIV clinic in London, UK were prospectively recruited by stratified selection and tested for TB infection using symptom questionnaires, chest radiograph (CXR), tuberculin skin test (TST), T-Spot.TB and induced sputum. From this, 30 testing strategies were compared in a cost-effectiveness model including probabilistic sensitivity analysis using Monte Carlo simulation. RESULTS: 219 subjects were assessed; 95% were using antiretroviral therapy (ART). Smear negative, culture positive TB was present in 0.9% asymptomatic subjects, LTBI in 9%. Only strategies testing those from subSaharan Africa with a TST or interferon gamma release assay (IGRA) with or without CXR, or testing those from countries with a TB incidence of >40/100,000 with TST alone were cost-effective using a £30,000/QALY threshold. CONCLUSIONS: Cost-effectiveness analysis in an adult HIV cohort with high ART usage suggests there is limited benefit beyond routine testing for latent TB in people from high and possibly medium TB incidence settings.

Liver test abnormalities in patients with HIV mono-infection: assessment with simple noninvasive fibrosis markers.

BACKGROUND: Patients with HIV mono-infection may develop chronic liver disease due to a number of factors including hepatic steatosis. We estimated the prevalence and predictors of hepatic steatosis and fibrosis in a cohort of HIV-mono-infected patients with persistently deranged liver function tests. METHODS: Of 2398 consecutive patients at one UK clinical center, 156 (6.5%) had persistently abnormal transaminases in at least two measurements six months apart. We used APRI and FIB4 scores to determine the presence of significant and/or advanced fibrosis in this group as well as its potential associations. RESULTS: Mean age was 47.5±8.5 years and 91% (142/156) were males. Diabetes mellitus was present in 11% of patients; hypertension in 18%; and dyslipidemia in 52%. Almost all were on antiretroviral therapy (ART) (97%) and most were virologically suppressed (94%). Steatosis was detected by ultrasound in 71% of patients. The prevalence of FIB4≤1.45, 1.46-3.24 and >3.25 was 67%, 29% and 4%, respectively, and that of APRI≤0.5, 0.51-1.49 and >1.5 was 52%, 45% and 3% respectively. In multivariate analysis, only cumulative ART exposure was associated with FIB4>1.45 (odds ratio [OR] 1.008, 95% confidence interval [CI] 1.000-1.016), while APRI>0.5 was associated with higher alanine aminotransferase levels (OR 1.033, 95%CI 1.015-1.510). Twenty patients had a liver biopsy, of whom 13 had non-alcoholic fatty liver disease (NAFLD). CONCLUSIONS: Elevated transaminases are often present in HIV-mono-infected patients and this may be associated with NAFLD and/or ART. Non-invasive screening for the presence of NAFLD and fibrosis in all HIV-mono-infected patients as part of their routine clinical management should be further explored.

Decreasing cost effectiveness of testing for latent TB in HIV in a low TB incidence area.

Testing for latent tuberculosis infection (LTBI) in HIV-infected persons in low tuberculosis (TB) incidence areas is often recommended. Using contemporary, clinical data, we report the yield and cost-effectiveness of testing all HIV attendees, two current UK strategies and no LTBI testing. Economic modelling was performed utilising 10-year follow up data from a large HIV clinical cohort. Outcomes were numbers of cases of active TB and incremental cost per quality-adjusted life year (QALY) gained. Between 2000 and 2010, 256 people were treated for TB/HIV co-infection. 72 (28%) occurred ≥3 months after HIV diagnosis and may have been prevented by LTBI testing. Between 2000 and 2005, the incremental cost per QALY gained for the British HIV Association (BHIVA) and UK National Institute of Care Excellence (NICE) strategies, and testing all clinic attendees was €6270, €6998 and €33,473, respectively. These rose to €9332, €32,564 and €74,067, respectively, between 2005 and 2010. Probabilistic sensitivity analysis suggested that at a threshold of €24,000 per additional QALY, the most cost-effective strategies would be NICE or testing all in 2000-2005 and BHIVA during 2005-2010. Both UK testing regimens missed cases but are cost-effective compared with no testing. Using recent data, they all became more expensive, suggesting that alternative or more targeted TB testing strategies must be considered.

Analysis of minimum target prices for production of entecavir to treat hepatitis B in high- and low-income countries.

BACKGROUND: In 2013, an estimated 686,000 people died from hepatitis B virus (HBV) infection worldwide. Mass treatment programmes for hepatitis B will require very low drug costs. International treatment guidelines recommend first-line monotherapy with either entecavir or tenofovir disoproxil fumarate (TDF). While the basic patent on TDF expires in 2017/8, entecavir is already generic in several countries, including the US. The chemical structure of entecavir is related to abacavir, which costs <$200 per person-year in low-income countries. METHODS: The clinical efficacy, chemical structures, daily doses, routes of chemical synthesis, costs of raw materials and patent expiry dates were analysed for entecavir and TDF. Costs of sustainable, generic production were calculated for entecavir, and compared with published originator and generic prices in high- and low-income countries. RESULTS: With a daily dose of 0.5 mg, one year's supply of entecavir treatment requires <0.2 g of active pharmaceutical ingredient (API) per person, estimated to cost $4/year, based on quotations of API production from generic suppliers. With an additional $20 per year for formulation/packaging and a 50% profit margin, entecavir was estimated to cost a minimum of $36/person-year, substantially lower than current originator and generic prices. Entecavir is no longer under patent protection in the USA, China, Brazil and South Africa, with European expiry in 2017. Given differences in daily dosing, production volumes for entecavir would be 600 times lower than TDF (300 mg once daily) for treating the same numbers of patients. CONCLUSIONS: Mass treatment for hepatitis B with generic entecavir could be achieved at very low cost in all countries, provided that important projections can be met in terms of pricing for the API and finished dosage form.