J. Roy Robertson

Mismatched human leukocyte antigen alleles protect against heterosexual HIV transmission

Summary: 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 < .02), suggesting that allogeneic immune responses may confer a degree of protection against HIV infection. Analysis of the frequencies of specific alleles at the A, B, and DR loci revealed a significantly higher frequency of HLA DR5 among exposed uninfected individuals, relative to population controls.

The Epidemiology of HIV Infection in Edinburgh Related to the Injecting of Drugs: An Historical Perspective and New Insight Regarding the Past Incidence of HIV Infection Derived from Retrospective HIV Antibody Testing of Stored Samples of Serum

The pattern of sudden explosive outbreaks of HIV infection among drug users has been seen in several countries but is as yet incompletely understood. The epidemic of injecting drugs in Edinburgh was associated with at least four overlapping epidemics of blood-borne viruses (hepatitis B, C, D and HIV). Only hepatitis B was initially recognized, being followed by HIV and latterly hepatitis C. Retrospective HIV testing of stored samples of serum from clinically diagnosed patients with HIV has allowed the HIV epidemic to be delineated and more accurate seroconversion dates identified for most of the patients. There is evidence to suggest that the explosive drug-related Edinburgh HIV epidemic may have been self-terminating and that the epidemic in male drug users preceded that in female drug users by around 3 months. We suggest that the self-terminating nature of this epidemic may have been related to changes in drug injecting behaviour or to varying infectivity of the virus. This latter possibility should be explored in future studies of HIV transmission.

β2-microglobulin levels in drug users : the influence of risk behaviour

beta 2-microglobulin (beta 2M) levels were measured in 217 Edinburgh drug users to assess their usefulness as a marker for HIV-related disease. Eighty HIV-seronegative drug injectors had significantly higher levels than 100 HIV-seronegative blood-donor controls. Amongst 137 asymptomatic HIV-seropositive drug users, those who were defined as continued drug users had significantly higher beta 2M levels and percentages of CD3+ T lymphocytes with DR Class II expression than non-injecting drug users. beta 2M levels correlated with the percentage of activated DR+ CD3+ T lymphocytes. These findings indicate that changes in beta 2M levels may reflect differences in drug-injecting behaviour and are not influenced solely by HIV status or progression. These changes in beta 2M probably represent differing degrees of immunostimulation resulting from the antigenic challenges afforded by continued or frequent drug injection. It is important to establish normal ranges for beta 2M from HIV-seronegative controls who are matched with respect to risk group and behaviour. All these factors should be taken into account if beta 2M is to be used as a marker of HIV progression.

Toxicology of Scotland's drugs-related deaths in 2000–2007: Presence of heroin, methadone, diazepam and alcohol by sex, age-group and era

Scotland has a new database on drugs-related deaths (DRDs). We review the prior toxicology and demography of Scotlands DRDs in 2000–2007. Each DRD was cross-classified by the presence/absence of heroin (H); methadone (M); diazepam (D); and alcohol (A). Comparisons were made by era (2000–2002, 2003–2005 and 2006–2007), sex and age-group (under 35 years and 35+ years). Data were for 1007 DRDs in 2000–2002 (180 female); 1011 in 2003–2005 (206 female); and 875 in 2006 and 2007 (149 female). DRDs citing diazepam decreased from around half in 2000–2002 to only 18% by 2006 and 2007 (95% CI: 15–21%). The presence of alcohol decreased also, for males, down from 43% of 827 DRDs in 2000–2002 (95% CI: 40–46%) to 35% of 726 DRDs in 2006 and 2007 (95% CI: 31–38%). The presence of heroin and alcohol were positively associated; of heroin and methadone strongly negatively. Alcohols co-presence was age related: present in 53% of 598 male heroin-DRDs at 35+ years of age but in only 36% of 974 male heroin-DRDs under 35 years of age. Neither methadone nor heroin was present in a third of all female DRDs (183/535) and a fifth of male DRDs (460/2358). In 101 female and 276 male DRDs, none of H, M, D or A was mentioned. Periodically, the toxicology and demography of a countrys DRDs should be analysed together, as here for Scotland, to highlight idiosyncrasies or insights. That alcohols co-presence at heroin-DRDs was age related adds to several reasons for (ageing) heroin injectors to moderate their alcohol intake.

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. Results show that with ongoing HAART availability, the risk of HIV disease progression has continued to decrease. When accounting for pre-AIDS death (in AIDS analyses) and non-natural deaths (suicide, overdose, accidents and homicide, in analyses of death) which are common among IDU, the risk of AIDS and death has decreased by as much as 65% and 75%, respectively, in 2000/2001. Results show little geographic variation in progression to AIDS. All-cause mortality was higher in IDU from Glasgow than elsewhere, while in the Valencian region (Spain) IDU were at a significantly lower risk of non-natural deaths. The timing of HAART initiation by treatment-naïve IDU likewise differed across Europe: IDU in Amsterdam, Innsbruck, and Edinburgh started at significantly lower CD4 counts than IDU in Paris, Geneva, Glasgow, and the Valencian region, but the subsequent short-term immune response was similar. In conclusion, the risk in progression to AIDS or natural death is similar across western Europe although IDU across Europe differ in other factors, such as the risk of non-natural death and the timing of HAART initiation.

Mortality related to novel psychoactive substances in Scotland, 2012: An exploratory study

BACKGROUND The growth of novel psychoactive substances (NPS) over the last decade, both in terms of availability and consumption, is of increasing public health concern. Despite recent increases in related mortality, the circumstances surrounding and characteristics of individuals involved in NPS deaths at a population level remain relatively unknown. METHODS The Scottish National Drug Related Death Database (NDRDD) collects a wide-range of data relating to the nature and circumstances of individuals who have died a drug-related death (DRD). We conducted exploratory descriptive analysis of DRDs involving NPS recorded by the NDRDD in 2012. Statistical testing of differences between sub-groups was also conducted where appropriate. RESULTS In 2012, we found 36 DRDs in Scotland to have NPS recorded within post-mortem toxicology. However, in only 23 of these cases were NPS deemed by the reporting pathologist to be implicated in the actual cause of death. The majority of NPS-implicated DRDs involved Benzodiazepine-type drugs (13), mainly Phenazepam (12). The remaining 10 NPS-implicated deaths featured a range of different Stimulant-type drugs. The majority of these NPS-implicated deaths involved males and consumption of more than one drug was recorded by toxicology in all except one case. NPS-implicated deaths involving Benzodiazepine-type NPS drugs appeared to involve older individuals known to be using drugs for a considerable period of time, many of whom had been in prison at some point in their lives. They also typically involved combinations of opioids and benzodiazepines; no stimulant drugs were co-implicated. Deaths where stimulant-type NPS drugs were implicated appeared to be a younger group in comparison, all consuming two or more Stimulant-type drugs in combination. CONCLUSION This exploratory study provides an important insight into the circumstances surrounding and characteristics of individuals involved in NPS deaths at a population level. It identifies important issues for policy and practice, not least the prominent role of unlicensed benzodiazepines in drug-related mortality, but also the need for a range of harm reduction strategies to prevent future deaths.

Risk-factors for methadone-specific deaths in Scotland's methadone-prescription clients between 2009 and 2013*

Highlights • Powerful analysis of a national cohort’s 362 methadone-specific deaths.• Scottish cohort of 33,128 methadone-prescription clients in 2009–2013.• Steeper age-gradient than for all drugs-related deaths.• No gender differential in the hazard of methadone-specific deaths.• Increased hazard at the highest quintile for quantity of methadone prescribed.

External data required timely response by the Trial Steering-Data Monitoring Committee for the NALoxone InVEstigation (N-ALIVE) pilot trial

The prison-based N-ALIVE pilot trial had undertaken to notify the Research Ethics Committee and participants if we had reason to believe that the N-ALIVE pilot trial would not proceed to the main trial. In this paper, we describe how external data for the third year of before/after evaluation from Scotlands National Naloxone Programme, a related public health policy, were anticipated by eliciting prior opinion about the Scottish results in the month prior to their release as official statistics. We summarise how deliberations by the N-ALIVE Trial Steering-Data Monitoring Committee (TS-DMC) on N-ALIVEs own interim data, together with those on naloxone-on-release (NOR) from Scotland, led to the decision to cease randomization in the N-ALIVE pilot trial and recommend to local Principal Investigators that NOR be offered to already-randomized prisoners who had not yet been released.

Ageing opioid users' increased risk of methadone-specific death in the UK

Background The first evidence that the hazard ratio (HR) for methadone-specific death rises more steeply with age-group than for all drug-related deaths (DRDs) came from Scotland’s cohort of 33,000 methadone-prescription clients. We aim to examine, for England, whether illicit opioid users’ risk of methadone-specific death increases with age; and to pool age-related HRs for methadone-specific deaths with those for Scotland’s methadone-prescription clients. Methods The setting is all services in England that provide publicly-funded, structured treatment for illicit opioid users, the methodology linkage of the English National Drug Treatment Monitoring System and mortality database, and key measurements are DRDs, methadone-specific DRDs, or heroin-specific DRDs, by age-group and gender, with proportional hazards adjustment for substances used, injecting status and periods in/out of treatment. Results Linkage was achieved for 129,979 adults receiving prescribing treatment modalities for opioid dependence during April 2005 to March 2009 and followed-up for 378,009 person-years (pys). There were 1,266 DRDs: 271 methadone-specific (7 per 10,000 pys: irrespective of gender) and 473 heroin-specific (15 per 10,000 pys for males, 7 for females). Methadone-specific DRD-rate per 10,000 person-years was 3.5 (95% CI: 2.7–4.4) at 18–34 years, 8.9 (CI: 7.3–10.5) at 35–44 years and 18 (CI: 13.8–21.2) at 45+ years; heroin-specific DRD-rate was unchanged with age. Relative to 25–34 years, pooled HRs for UK clients’ methadone-specific deaths were: 0.87 at <25 years (95% CI: 0.56–1.35); 2.14 at 35–44 years (95% CI: 1.76–2.60); 3.75 at 45+ years (95% CI: 2.99–4.70). Conclusion International testing and explanation are needed of UK’s sharp age-related increase in the risk of methadone-specific death. Clients should be alerted that their risk of methadone-specific death increases as they age.