Lower healthcare costs associated with the use of a single-pill ARV regimen in the UK, 2004-2008.

Aim: Investigate the cost and effects of a single-pill versus two- or three pill first-line antiretroviral combinations in reducing viral load, increasing CD4 counts, and first-line failure rate associated with respective regimens at 6 and 12 months.

Methods: Patients on first-line TDF+3TC+EFV, TDF+FTC+EFV, Truvada®+EFV or Atripla® between 1996-2008 were identified and viral load and CD4 counts measured at baseline, six and twelve months respectively. Factors that independently predicted treatment failure at six and twelve months were derived using multivariate Cox's proportional hazard regression analyses.

The cost-effectiveness of early access to HIV services and starting cART in the UK 1996-2008.

Aim: To calculate use, cost and cost-effectiveness of people living with HIV (PLHIV) starting routine treatment and care before starting combination antiretroviral therapy (cART) and PLHIV starting first-line 2NRTIs+NNRTI or 2NRTIs+PI(boosted), comparing PLHIV with CD4≤200 cells/mm3 and CD4>200 cells/mm3. Few studies have calculated the use, cost and cost-effectiveness of routine treatment and care before starting cART and starting cART above and below CD4 200 cells/mm3.

Methods: Use, costs and cost-effectiveness were calculated for PLHIV in routine pre-cART and starting first-line cART, comparing CD4≤200 cells/mm3 with CD4>200 cells/mm3 (2008 UK prices).

Cost-effectiveness of early treatment with first-line NNRTI-based HAART regimens in the UK, 1996-2006.

Aim: Calculate time to first-line treatment failure, annual cost and cost-effectiveness of NNRTI versus PIboosted first-line HAART regimens in the UK, 1996-2006.

Background: Population costs for HIV services are increasing in the UK and interventions need to be effective and efficient to reduce or stabilize costs. 2NRTIs + NNRTI regimens are cost-effective regimens for first-line HAART, but these regimens have not been compared with first-line PI(boosted) regimens.

Rising population cost for treating people living with HIV in the UK, 1997-2013.

Background: The number of people living with HIV (PLHIV) is increasing in the UK. This study estimated the annual population cost of providing HIV services in the UK, 1997-2006 and projected them 2007-2013.

Methods: Annual cost of HIV treatment for PLHIV by stage of HIV infection and type of ART was calculated (UK pounds, 2006 prices).

Treatment outcome and cost-effectiveness of different highly active antiretroviral therapy regimens in the UK (1996-2002).

The aim of this study was to estimate the outcome and cost-effectiveness per life-year-gained (LYG) of first-, second- and third-line non-nucleoside reverse transcriptase inhibitors (NNRTI) versus protease inhibitor (PI) containing highly active antiretroviral therapy regimens. Hospital care costs (2002 US dollars discounted 3.5% per annum) were linked to treatment failure times.

Survival following HIV infection of a cohort followed up from seroconversion in the UK.

Objectives: To estimate changes over calendar time in survival following HIV seroconversion in the era of HAART and to provide updated survival estimates.

Methods: Using data from a UK cohort of persons with well estimated dates of HIV seroconversion, we analysed time from seroconversion to death from any cause using Cox models, adjusted for prognostic factors. Kaplan-Meier methods were then used to determine the expected survival in each calendar period.

An immune control model for viral replication in the CNS during presymptomatic HIV infection.

The brain is targeted by human immunodeficiency virus type 1 (HIV-1) during the course of untreated infection, leading to cognitive impairment, neurological damage and HIV encephalitis (HIVE). To study early dynamics of HIV entry into the brain, we examined a unique autopsy series of samples obtained from 15 untreated individuals who died in the presymptomatic stages of infection from non-HIV causes. HIV was detected and quantified by limiting dilution PCR and genetically characterized in the V3 region of env.

Do HIV disease progression and HAART response vary among injecting drug users in Europe?

Prior to HAART availability, there was no evidence of a geographical variation in HIV disease progression among injecting drug users (IDU) from different European regions. Nowadays, factors of importance regarding HIV disease progression in the face of HAART availability, such as HAART access, adherence, and the organization of care for IDU may differ across Europe. Therefore we studied HIV disease progression in a European study of IDU with known dates of HIV-seroconversion.

Systemic non-Hodgkin lymphoma in individuals with known dates of HIV seroconversion: incidence and predictors.

Objectives: To investigate temporal changes in the risk of non-Hodgkin lymphoma (NHL) and estimate NHL incidence in risk groups and the prognostic role of these risks and current, nadir and time-weighted average CD4 cell count.

Methods: Secular trends in time from HIV seroconversion to an NHL diagnosis was estimated using Cox models from data pooled from the 22 seroconverter cohorts in the CASCADE collaboration for three periods (pre-1997, 1997-1998, 1999-2002), adjusting for age at seroconversion, exposure category and sex.

Results: Of 7103 seroconverters, 129 developed NHL.

Does drug abuse influence the microglial response in AIDS and HIV encephalitis?

Objectives: To investigate the pathological evidence for a possible interaction between drugs of abuse and HIV infection in terms of microglial responses in early and late HIV/AIDS, and to discuss the possible long-term consequences of microglial activation in chronic HIV infection.

Design: This brain pathology study compared age and sex-matched control patients with HIV-negative intravenous drug users, and with HIV-positive drug users both in the presymptomatic stage and with AIDS. A further group of non-drug-using AIDS patients was included.

Delayed diagnosis of HIV infection in ophthalmic practice.

The introduction of potent antiretroviral drug combinations has transformed human immunodeficiency virus/acquired immunodeficiency disease syndrome (HIV/AIDS) from an intractable and rapidly fatal disease to a chronic manageable illness with prolonged life survival for many patients. This paper discusses the ophthalmic and medical histories of two young female patients who presented with 'atypical' optic neuropathy and toxoplasma gondii retinochoroiditis and were later found to be HIV infected. We discuss the need for increased vigilance in the ophthalmic community for suspecting HIV infection to allow optimal management of the ophthalmic and systemic manifestations of the disease spectrum associated with HIV/AIDS.

Spread of hepatitis C virus among European injection drug users infected with HIV: a phylogenetic analysis.

To describe the spread of hepatitis C virus (HCV) among HCV/human immunodeficiency virus (HIV)-coinfected injection drug users (IDUs), the molecular epidemiology of HCV was studied among 108 IDUs from 7 European countries. Phylogenetic analysis based on the NS5B region showed great sequence variation of HCV within each country and no clear phylogenetic clustering by geographic region. The most prevalent subtypes were 1a and 3a, but the percentage of genotype 4 was also relatively high, ranging from 7% in northern Europe to 24% in southern Europe.

Limited effect of highly active antiretroviral therapy among HIV-positive injecting drug users on the population level.

There is evidence that HIV-positive injecting drug users benefit less than other risk groups from highly active antiretroviral therapy that has been available since 1996. In this multicentre European study the impact of the availability of highly active antiretroviral therapy on the progression rates to AIDS and death among injecting drug users with a documented date of HIV seroconversion is studied. After highly active antiretroviral therapy became available the risk of AIDS and death for injecting drug users decreased by 28% and 36%, which is less than has been reported for other risk groups.

Tuberculosis risk varies with the duration of HIV infection: a prospective study of European drug users with known date of HIV seroconversion.

Background: It is not known whether the risk of active tuberculosis disease varies with the length of time that individuals are infected with HIV.

Objective: To study how, independently of CD4 T cell count, the risk of tuberculosis varies with the duration of HIV infection.

Methods: Using Poisson regression analysis, the incidence of and risk factors for tuberculosis were studied in 683 injecting drug users (IDU) with a documented date of HIV seroconversion followed in seven cohorts in six European countries until 1998.

Changes over calendar time in the risk of specific first AIDS-defining events following HIV seroconversion, adjusting for competing risks.

Background: Although studies have reported large reductions in the risks of AIDS and death since the introduction of potent anti-retroviral therapies, few have evaluated whether this has been similar for all AIDS-defining diseases. We wished to evaluate changes over time in the risk of specific AIDS-defining diseases, as first events, using data from individuals with known dates of HIV seroconversion.

Methods: Using a competing risks proportional hazards model on pooled data from 20 cohorts (CASCADE), we evaluated time from HIV seroconversion to each first AIDS-defining disease (16 groups) and to death without AIDS for four calendar periods, adjusting for exposure category, age, sex, acute infection, and stratifying by cohort.

HIV and drug misuse in the Edinburgh cohort.

The Edinburgh cohort of intravenous drug users (IVDUs) became infected with HIV between 1983 and 1984. Before the era of effective therapy, many of these infected IVDUs displayed cognitive impairments on progressing to AIDS and were found to have HIV encephalitis (HIVE). Full autopsies were conducted on these patients, providing an opportunity to study the intersecting pathology of pure HIVE and drug use.

Changes in the cause of death among HIV positive subjects across Europe: results from the EuroSIDA study.

Objectives: The causes of death among HIV-positive patients may have changed since the introduction of highly active antiretroviral therapy (HAART). We investigated these changes, patients who died without an AIDS diagnosis and factors relating to pre-AIDS deaths.

Methods: Analyses of 1826 deaths among EuroSIDA patients, an observational study of 8556 patients.

Identification of shared populations of human immunodeficiency virus type 1 infecting microglia and tissue macrophages outside the central nervous system.

Infection of microglia and other cells of the macrophage/monocyte lineage in the central nervous system (CNS) by human immunodeficiency virus type I (HIV-1) underlies the development of giant cell encephalitis (GCE). It is currently unknown whether GCE depends on the emergence of virus populations specifically adapted to replicate in cells of the monocyte/macrophage lineage and whether this also leads to the specific targeting of macrophages in other nonlymphoid tissues. Autopsy samples from lymph node, brain (frontal region), lung, and full-thickness colon sections were obtained from nine study subjects with GCE and from nine without.

Mismatched human leukocyte antigen alleles protect against heterosexual HIV transmission.

Genetic variation at the human leukocyte antigen (HLA) loci has been shown to be an important risk factor for progression to HIV disease, but its significance in infection is less well understood. We have investigated its role in HIV transmission in a cohort of individuals at risk for heterosexual infection. Analysis of over 80 individuals revealed that that the degree of concordance at HLA A, B, and DR loci differs significantly between transmitting and nontransmitting couples at risk for heterosexual HIV transmission (p <.

Using phylogenetic analysis to trace HIV-1 migration among western European injecting drug users seroconverting from 1984 to 1997.

Objective: To reconstruct the epidemiological relationships of the HIV epidemics among injecting drug users (IDU) in western Europe.

Methods: HIV env V3 sequences of and epidemiological data were obtained from 145 IDU who seroconverted in three sequential periods: 1984-1988, 1989-1992 and 1993-1997. The sequences were phylogenetically analysed and examined for signature patterns characteristic of northern European IDU, including the conserved GGC codon in the V3 loop.

Historical HIV prevalence in Edinburgh Prison: a database-linkage study.

Background: The prevalence of HIV in prisons is often higher than in the surrounding community, because prisons contain a high proportion of injecting drug users (IDUs). Reliable estimation of HIV prevalence in UK prisons only began in the 1990s. Edinburgh, Scotland, experienced a major IDU-related HIV epidemic which began in 1983.

Infections with Mycobacterium tuberculosis and Mycobacterium avium among HIV-infected patients after the introduction of highly active antiretroviral therapy. EuroSIDA Study Group JD.

The impact of highly active antiretroviral therapy (HAART) among human immunodeficiency virus (HIV)-infected patients on the incidences of mycobacterial infections has not been studied in detail. We assessed incidences of mycobacterial diseases among HIV- infected patients following the introduction of HAART, using data from the EuroSIDA study, a European, multicenter observational cohort of more than 7,000 patients. Overall incidences of Mycobacterium tuberculosis (TB) and Mycobacterium avium complex (MAC) were 0.

Cerebral infarction in adult AIDS patients: observations from the Edinburgh HIV Autopsy Cohort.

Background And Purpose: Autopsy series of patients with AIDS have found a 4% to 29% prevalence of cerebral infarction. Little is known of the prevalence of cerebral infarction when not associated with non-HIV central nervous system (CNS) infection, lymphoma, or cardioembolic sources. Clinical correlation has seldom been available.