Articles tagged as "Europe"

Changes in sexual risk behaviour and sustained HIV incidence among MSM in the UK

Sexual behaviours, HIV testing, and the proportion of men at risk of transmitting and acquiring HIV in London, UK, 2000-13: a serial cross-sectional study.

Aghaizu A, Wayal S, Nardone A, Parsons V, Copas A, Mercey D, Hart G, Gilson R, Johnson AM. Lancet HIV. 2016 Sep;3(9):e431-40. doi: 10.1016/S2352-3018(16)30037-6. Epub 2016 Jul 14.

Background: HIV incidence in men who have sex with men (MSM) in the UK has remained unchanged over the past decade despite increases in HIV testing and antiretroviral therapy (ART) coverage. In this study, we examine trends in sexual behaviours and HIV testing in MSM and explore the risk of transmitting and acquiring HIV.

Methods: In this serial cross-sectional study, we obtained data from ten cross-sectional surveys done between 2000 and 2013, consisting of anonymous self-administered questionnaires and oral HIV antibody testing in MSM recruited in gay social venues in London, UK. Data were collected between October and January for all survey years up to 2008 and between February and August thereafter. All men older than 16 years were eligible to take part and fieldworkers attempted to approach all MSM in each venue and recorded refusal rates. Data were collected on demographic and sexual behavioural characteristics. We analysed trends over time using linear, logistic, and quantile regression.

Findings: Of 13 861 questionnaires collected between 2000 and 2013, we excluded 1985 (124 had completed the survey previously or were heterosexual reporting no anal intercourse in the past year, and 1861 did not provide samples for antibody testing). Of the 11 876 eligible MSM recruited, 1512 (13%) were HIV positive, with no significant trend in HIV positivity over time. 35% (531 of 1505) of HIV-positive MSM had undiagnosed infection, which decreased non-linearly over time from 34% (45 of 131) to 24% (25 of 106; p=0.01), while recent HIV testing (ie, in the past year) increased from 26% (263 of 997) to 60% (467 of 777; p<0.0001). The increase in recent testing in undiagnosed men (from 29% to 67%, p<0.0001) and HIV-negative men (from 26% to 62%, p<0.0001) suggests that undiagnosed infection might increasingly be recently acquired infection. The proportion of MSM reporting unprotected anal intercourse (UAI) in the past year increased from 43% (513 of 1187) to 53% (394 of 749; p<0.0001) and serosorting (exclusively) increased from 18% (207 of 1132) to 28% (177 of 6369; p<0.0001). 268 (2%) of 11 570 participants had undiagnosed HIV and reported UAI in the past year were at risk of transmitting HIV. Additionally 259 (2%) had diagnosed infection and reported UAI and non-exclusive serosorting in the past year. Although we did not collect data on antiretroviral therapy or viral load, surveillance data suggests that a small proportion of men with diagnosed infection will have detectable viral load and hence might also be at risk of transmitting HIV. 2633 (25%) of 10 364 participants were at high risk of acquiring HIV (defined as HIV-negative MSM either reporting one or more casual UAI partners in the past year or not exclusively serosorting). The proportions of MSM at risk of transmission or acquisition changed little over time (p=0.96 for MSM potentially at risk of transmission and p=0.275 for MSM at high risk of acquiring HIV). Undiagnosed men reporting UAI and diagnosed men not exclusively serosorting had consistently higher partner numbers than did other MSM over the period (median ranged from one to three across surveys in undiagnosed men reporting UAI, two to ten in diagnosed men not exclusively serosorting, and none to two in other men).

Interpretation: An increasing proportion of undiagnosed HIV infections in MSM in London might have been recently acquired, which is when people are likely to be most infectious. High UAI partner numbers of MSM at risk of transmitting HIV and the absence of a significant decrease in the proportion of men at high risk of acquiring the infection might explain the sustained HIV incidence. Implementation of combination prevention interventions comprising both behavioural and biological interventions to reduce community-wide risk is crucial to move towards eradication of HIV.

Abstract access  

Editor’s notes: Despite wide-scale ART coverage, HIV incidence among gay men and other men who have sex with men remains high in many high-income countries, and is increasing in some locations. Although expanded testing and treatment are expected to lower HIV incidence, there are concerns that changes in risk behaviour may offset the impact of ART on HIV transmission. In this paper, the authors illustrate that among gay men and other men who have sex with men in London, the proportion who had tested for HIV in the past year increased considerably over the period 2000 and 2013, with a corresponding decrease in the numbers with undiagnosed HIV.  However, there were increasing rates of condomless anal intercourse in both HIV-negative and HIV-positive men.  Furthermore, men living with HIV who were undiagnosed, and men who were not exclusively serosorting (having sex with partners of the presumed same HIV status), reported increased numbers of sexual partners over the period of the surveys. Despite the increases in recent HIV testing, three percent of men in 2013 incorrectly perceived themselves to be HIV negative. This suggests that many men who are undiagnosed may be recent infections, so could be at high risk of transmission. Previous modelling studies have illustrated that increased sexual risk behaviour, particular among people who are unaware that they are HIV positive, could account for the observed increase in incidence in gay men and other men who have sex with men. The findings of this study demonstrate the importance of core groups to the continued transmission of HIV. Test and treat programmes alone may not be sufficient to reduce HIV incidence in gay men and other men who have sex with men populations. There is the need for appropriately tailored combination prevention programmes in order to make real gains against HIV among gay men and other men who have sex with men.

Europe
United Kingdom
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The limits of HIV disclosure for women in 27 countries

The association between HIV disclosure status and perceived barriers to care faced by women living with HIV in Latin America, China, central/eastern Europe, and western Europe/Canada.

Loutfy M, Johnson M, Walmsley S, Samarina A, Vasquez P, Hao-Lan H, Madihlaba T, Martinez-Tristani M, van Wyk J. AIDS Patient Care STDS. 2016 Sep;30(9):435-44. doi: 10.1089/apc.2016.0049. Epub 2016 Aug 23.

Generally, women are less likely than men to disclose their HIV status. This analysis examined the relationship between HIV disclosure and (1) perceived barriers to care and (2) quality of life (QoL) for women with HIV. The ELLA (EpidemioLogical study to investigate the popuLation and disease characteristics, barriers to care, and quAlity of life for women living with HIV) study enrolled HIV-positive women aged ≥18 years. Women completed the 12-item Barriers to Care Scale (BACS) questionnaire. QoL was assessed using the Health Status Assessment. BACS and QoL were stratified by dichotomized HIV disclosure status (to anyone outside the healthcare system). Multilevel logistic regression analysis was used to identify factors associated with disclosure. Of 1945 patients enrolled from Latin America, China, central/eastern Europe, and western Europe/Canada between July 2012 and September 2013, 1929 were included in the analysis (disclosed, n = 1724; nondisclosed, n = 205). Overall, 55% of patients lived with a husband/partner, 53% were employed, and 88% were receiving antiretroviral therapy. Patients who were with a serodiscordant partner were more likely to disclose (p = 0.0003). China had a disproportionately higher percentage of participants who did not disclose at all (nearly 30% vs. <15% for other regions). Mean BACS severity scores for medical/psychological service barriers and most personal resource barriers were significantly lower for the disclosed group compared with the nondisclosed group (p ≤ 0.02 for all). Compared with the disclosed group, the nondisclosed group reported statistically significantly higher (p ≤ 0.03) BACS item severity scores for 8 of the 12 potential barriers to care. The disclosed group reported better QoL. Overall, HIV nondisclosure was associated with more severe barriers to accessing healthcare by women with HIV.

Abstract Full-text [free] access

Editor’s notes: This study drew women participants from Latin America, China, central and eastern Europe and from western Europe and Canada.  China was the only Asian country included and no African countries were included. This is important background information since the first sentence of the abstract ‘women are less likely than men to disclose HIV status’ is less likely to be true for, for example, parts of Africa. The study did not include men. So, no comparison can therefore be made with men’s disclosure behaviour. Nevertheless, the paper draws on data from 27 countries. Most women in the study did have access to ‘efficacious, well-tolerated’ antiretroviral therapy. A number of women, most notably in China, did not disclose their HIV status outside the health care system. Many women disclosed their status to a limited extent (only to some family and close friends). Non-disclosure affected access to health care as well as more general support. This pattern of non- or limited disclosure and barriers to access to care is replicated in many other places. The findings in this paper point to the importance globally of tackling stigma and providing a supportive health care and social setting for people living with HIV, so they can benefit fully from the treatment and care that is available.

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Pre-exposure prophylaxis for HIV prevention is cost-effective in the Netherlands

Cost-effectiveness analysis of pre-exposure prophylaxis for HIV-1 prevention in the Netherlands: a mathematical modelling study.

Nichols BE, Boucher CA, van der Valk M, Rijnders BJ, van de Vijver DA. Lancet Infect Dis. 2016 Sep 22. pii: S1473-3099(16)30311-5. doi: 10.1016/S1473-3099(16)30311-5. [Epub ahead of print]

Background: Pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine prevents HIV infections among men who have sex with men (MSM). PrEP can be given on a daily or intermittent basis. Unfortunately, PrEP is not reimbursed in most European countries. Cost-effectiveness analyses of PrEP among MSM in Europe are absent but are key for decision makers to decide upon PrEP implementation.

Methods: We developed a deterministic mathematical model, calibrated to the well-defined Dutch HIV epidemic among MSM, to predict the effect and cost-effectiveness of PrEP. PrEP was targeted to 10% of highly sexually active Dutch MSM over the coming 40 years. Cost-effectiveness ratios were calculated to predict the cost-effectiveness of daily and on-demand PrEP. Cost-effectiveness ratios below euro20 000 were considered to be cost-effective in this analysis.

Findings: Within the context of a stable HIV epidemic, at 80% effectiveness and current PrEP pricing, PrEP can cost as much as euro11 000 (IQR 9400-14 100) per quality-adjusted life-year (QALY) gained when used daily, or as little as euro2000 (IQR 1300-3000) per QALY gained when used on demand. At 80% effectiveness, daily PrEP can be considered cost-saving if the price of PrEP is reduced by 70%, and on-demand PrEP can be considered cost-saving if the price is reduced by 30-40%.

Interpretation: PrEP for HIV prevention among MSM in the Netherlands is cost-effective. The use of PrEP is most cost-effective when the price of PrEP is reduced through on-demand use or through availability of generic PrEP, and can quickly be considered cost-saving.

Abstract access  

Editor’s notes: Evidence surrounding the clinical effectiveness of pre-exposure prophylaxis to prevent HIV infection has been building for years (see HIV This Month January 2016 and February 2015).  This article now adds to the evidence with indications that pre-exposure prophylaxis is also cost-effective in a European setting.

The authors use a deterministic mathematical model to represent the HIV epidemic in the Netherlands among gay men and other men who have sex with men. They estimate the cost and cost-effectiveness of two models of pre-exposure prophylaxis usage: a daily dosage, and an ‘on demand’ dosage.  Their base case analysis found that both usage models fall under a willingness-to-pay ratio of €20 000 per QALY gained over a 40-year time horizon, although the ‘on demand’ model was least expensive at only €2000 (IQR 1300–3000) per QALY gained.  The model reflected some uncertainty around the results. However, very few results from the sensitivity analysis indicated a cost-per-QALY ratio above €20 000. Several scenarios indicated that pre-exposure prophylaxis was cost-saving. 

Pre-exposure prophylaxis was approved by the European Medicines Agency in July 2016, however it is currently not reimbursed by most European governments. This paper provides important evidence to make a case in favour of recommending reimbursement. Although the willingness-to-pay threshold used (€20 000/QALY) does not have any formal recognition in the Netherlands, several independent analyses soliciting the Dutch society’s value of a QALY reflect values much higher than this. As noted in the comment accompanying this paper (Niessen and Jaffar), the potential cost of implementing pre-exposure prophylaxis on a large-scale could be higher than current budgetary priorities allow. Still, this is an important study adding to the mounting evidence that countries should begin to consider how pre-exposure prophylaxis can be made available to people at highest risk of HIV infection.  

Europe
Netherlands
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Weekend breaks on efavirenz-based ART non-inferior in adolescents

BREATHER (PENTA 16) short-cycle therapy (SCT) (5 days on/2 days off) in young people with chronic human immunodeficiency virus infection: an open, randomised, parallel-group Phase II/III trial.

Butler K, Inshaw J, Ford D, Bernays S, Scott K, Kenny J, Klein N, Turkova A, Harper L, Nastouli E, Paparini S, Choudhury R, Rhodes T, Babiker A, Gibb D. Health Technol Assess. 2016 Jun;20(49):1-108. doi: 10.3310/hta20490.

Background: For human immunodeficiency virus (HIV)-infected adolescents facing lifelong antiretroviral therapy (ART), short-cycle therapy (SCT) with long-acting agents offers the potential for drug-free weekends, less toxicity, better adherence and cost savings.

Objectives: To determine whether or not efavirenz (EFV)-based ART in short cycles of 5 days on and 2 days off is as efficacious (in maintaining virological suppression) as continuous EFV-based ART (continuous therapy; CT). Secondary objectives included the occurrence of new clinical HIV events or death, changes in immunological status, emergence of HIV drug resistance, drug toxicity and changes in therapy.

Design: Open, randomised, non-inferiority trial.

Setting: Europe, Thailand, Uganda, Argentina and the USA.

Participants: Young people (aged 8-24 years) on EFV plus two nucleoside reverse transcriptase inhibitors and with a HIV-1 ribonucleic acid level [viral load (VL)] of < 50 copies/ml for > 12 months.

Interventions: Young people were randomised to continue daily ART (CT) or change to SCT (5 days on, 2 days off ART).

Main outcome measures: Follow-up was for a minimum of 48 weeks (0, 4 and 12 weeks and then 12-weekly visits). The primary outcome was the difference between arms in the proportion with VL > 50 copies/ml (confirmed) by 48 weeks, estimated using the Kaplan-Meier method (12% non-inferiority margin) adjusted for region and age.

Results: In total, 199 young people (11 countries) were randomised (n = 99 SCT group, n = 100 CT group) and followed for a median of 86 weeks. Overall, 53% were male; the median age was 14 years (21% ≥ 18 years); 13% were from the UK, 56% were black, 19% were Asian and 21% were Caucasian; and the median CD4% and CD4 count were 34% and 735 cells/mm3, respectively. By week 48, only one participant (CT) was lost to follow-up. The SCT arm had a 27% decreased drug exposure as measured by the adherence questionnaire and a MEMSCap Medication Event Monitoring System (MEMSCap Inc., Durham, NC, USA) substudy (median cap openings per week: SCT group, n = 5; CT group, n = 7). By 48 weeks, six participants in the SCT group and seven in the CT group had a confirmed VL > 50 copies/ml [difference -1.2%, 90% confidence interval (CI) -7.3% to 4.9%] and two in the SCT group and four in the CT group had a confirmed VL > 400 copies/ml (difference -2.1%, 90% CI -6.2% to 1.9%). All six participants in the SCT group with a VL > 50 copies/ml resumed daily ART, of whom five were resuppressed, three were on the same regimen and two with a switch; two others on SCT resumed daily ART for other reasons. Overall, three participants in the SCT group and nine in the CT group (p = 0.1) changed ART regimen, five because of toxicity, four for simplification reasons, two because of compliance issues and one because of VL failure. Seven young people (SCT group, n = 2; CT group, n = 5) had major non-nucleoside reverse transcriptase inhibitor mutations at VL failure, of whom two (n = 1 SCT group, n = 1 CT group) had the M184V mutation. Two young people had new Centers for Disease Control B events (SCT group, n = 1; CT group, n = 1). There were no significant differences between SCT and CT in grade 3/4 adverse events (13 vs. 14) or in serious adverse events (7 vs. 6); there were fewer ART-related adverse events in the SCT arm (2 vs. 14; p = 0.02). At week 48 there was no evidence that SCT led to increased inflammation using an extensive panel of markers. Young people expressed a strong preference for SCT in a qualitative substudy and in pre- and post-trial questionnaires. In total, 98% of the young people are taking part in a 2-year follow-up extension of the trial.

Conclusions: Non-inferiority of VL suppression in young people on EFV-based first-line ART with a VL of < 50 copies/ml was demonstrated for SCT compared with CT, with similar resistance, safety and inflammatory marker profiles. The SCT group had fewer ART-related adverse events. Further evaluation of the immunological and virological impact of SCT is ongoing. A limitation of the trial is that the results cannot be generalised to settings where VL monitoring is either not available or infrequent, nor to use of low-dose EFV. Two-year extended follow-up of the trial is ongoing to confirm the durability of the SCT strategy. Further trials of SCT in settings with infrequent VL monitoring and with other antiretroviral drugs such as tenofovir alafenamide, which has a long intracellular half-life, and/or dolutegravir, which has a higher barrier to resistance, are planned.

Trial registration: Current Controlled Trials ISRCTN97755073; EUDRACT 2009-012947-40; and CTA 27505/0005/001-0001.

Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (projects 08/53/25 and 11/136/108), the European Commission through EuroCoord (FP7/2007/2015), the Economic and Social Research Council, the PENTA Foundation, the Medical Research Council and INSERM SC10-US19, France, and will be published in full in Health Technology Assessment; Vol. 20, No. 49. See the NIHR Journals Library website for further project information.

Abstract  Full-text [free] access 

Editor’s notes: Adherence to ART has been shown to deteriorate in adolescence, with missed doses occurring particularly at weekends. Pharmacokinetic properties of some ART drugs, such as efavirenz, allow for a break in pill taking without a break in effective treatment. Non-inferiority trials evaluating five days on, two days off in adults have shown continuous ART to be non-inferior with low rates of virologic rebound.  This formed the rationale for this global, randomised Phase II/III trial in young people.

In the BREATHER trial, non-inferiority of viral suppression in adolescents on efavirenz-based first-line ART was shown for short-cycle treatment compared with continuous treatment. Overall 93% of adolescents remained virally suppressed. Findings from the two-year long-term follow-up phase will confirm if short-cycle treatment is effective and safe in this population.  Further studies are required to confirm the applicability of this strategy in real-life settings where viral load monitoring is likely to be less frequent than in a trial setting.

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Demand-side activities are essential for achieving population level impact of HIV prevention tools

Interventions to strengthen the HIV prevention cascade: a systematic review of reviews.

Krishnaratne S, Hensen B, Cordes J, Enstone J, Hargreaves JR. Lancet HIV. 2016 Jul;3(7):e307-17. doi: 10.1016/S2352-3018(16)30038-8.

Background: Much progress has been made in interventions to prevent HIV infection. However, development of evidence-informed prevention programmes that translate the efficacy of these strategies into population effect remain a challenge. In this systematic review, we map current evidence for HIV prevention against a new classification system, the HIV prevention cascade.

Methods: We searched for systematic reviews on the effectiveness of HIV prevention interventions published in English from Jan 1, 1995, to July, 2015. From eligible reviews, we identified primary studies that assessed at least one of: HIV incidence, HIV prevalence, condom use, and uptake of HIV testing. We categorised interventions as those seeking to increase demand for HIV prevention, improve supply of HIV prevention methods, support adherence to prevention behaviours, or directly prevent HIV. For each specific intervention, we assigned a rating based on the number of randomised trials and the strength of evidence.

Findings: From 88 eligible reviews, we identified 1964 primary studies, of which 292 were eligible for inclusion. Primary studies of direct prevention mechanisms showed strong evidence for the efficacy of pre-exposure prophylaxis (PrEP) and voluntary medical male circumcision. Evidence suggests that interventions to increase supply of prevention methods such as condoms or clean needles can be effective. Evidence arising from demand-side interventions and interventions to promote use of or adherence to prevention tools was less clear, with some strategies likely to be effective and others showing no effect. The quality of the evidence varied across categories.

Interpretation: There is growing evidence to support a number of efficacious HIV prevention behaviours, products, and procedures. Translating this evidence into population impact will require interventions that strengthen demand for HIV prevention, supply of HIV prevention technologies, and use of and adherence to HIV prevention methods.

Abstract  Full-text [free] access

Editor’s notes: Demand, supply and use of programmes are crucial for the uptake and effective use of HIV prevention strategies. This paper presents an impressive undertaking in which the authors conducted a review of systematic reviews on the evidence for the effectiveness of HIV prevention programmes across the multiple steps in an HIV prevention cascade. This particular prevention cascade allocates programmes into demand-side, supply-side, adherence, and direct HIV prevention technologies. This was published in a separate paper in conjunction with this review. The review found that there is strong evidence with regards to which direct HIV prevention technologies are efficacious, as well as maps where adherence and supply-side programmes have been effective. A primary gap was noted on the demand-side of the cascade (e.g. information, education and communication, and peer-based activities to increase demand for medical male circumcision) where studies have not resulted in reducing HIV incidence or prevalence. There remains a need to understand why, despite supply, there is low uptake of some HIV prevention strategies, and for evaluation of novel activities to increase demand.  

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Negative police activity a structural determinant of HIV

Policing practices as a structural determinant for HIV among sex workers: a systematic review of empirical findings.

Footer KH, Silberzahn BE, Tormohlen KN, Sherman SG. J Int AIDS Soc. 2016 Jul 18;19(4 Suppl 3):20883. doi: 10.7448/IAS.19.4.20883. eCollection 2016.

Introduction: Sex workers are disproportionately infected with HIV worldwide. Significant focus has been placed on understanding the structural determinants of HIV and designing related interventions. Although there is growing international evidence that policing is an important structural HIV determinant among sex workers, the evidence has not been systematically reviewed.

Methods: We conducted a systematic review of quantitative studies to examine the effects of policing on HIV and STI infection and HIV-related outcomes (condom use; syringe use; number of clients; HIV/STI testing and access) among cis and trans women sex workers. Databases included PubMed, Embase, Scopus, Sociological Abstracts, Popline, Global Health (OVID), Web of Science, IBSS, IndMed and WHOLIS. We searched for studies that included police practices as an exposure for HIV or STI infection or HIV-related outcomes.

Results: Of the 137 peer-reviewed articles identified for full text review, 14 were included, representing sex workers' experiences with police across five settings. Arrest was the most commonly explored measure with between 6 and 45% of sex workers reporting having ever been arrested. Sexual coercion was observed between 3 and 37% of the time and police extortion between 12 and 28% across studies. Half the studies used a single measure to capture police behaviours. Studies predominantly focused on "extra-legal policing practices," with insufficient attention to the role of "legal enforcement activities". All studies found an association between police behaviours and HIV or STI infection, or a related risk behaviour.

Conclusions: The review points to a small body of evidence that confirms policing practices as an important structural HIV determinant for sex workers, but studies lack generalizability with respect to identifying those police behaviours most relevant to women's HIV risk environment.

Abstract  Full-text [free] access 

Editor’s notes: The paper reports on a systematic review, which explored how quantitative research to date has operationalized the measurement of law enforcement practices as a structural determinant of HIV for female (including transgender) sex workers. The authors reviewed 14 quantitative studies using policing practices as a micro-structural determinant for HIV risk among sex workers. They found substantial heterogeneity in both the police measures and the health outcomes considered by the different studies. Overall, the studies found that police measures were regularly reported by sex workers, with an average of 34% of sex workers experiencing at least one police measure. They found that arrest was the most commonly explored measure in the studies. Following this, sexual coercion and then police extortion were important.

The studies reported that these police measures were consistently, positively, associated with either HIV infection or STI symptoms or with inconsistent condom use. Having ever been arrested, sexual coercion, police extortion, and syringe confiscation was associated with an increased risk of acquiring an HIV infection or an STI. These measures, and displacement by the police, were also associated with inconsistent condom use. Intervening on interactions between sex workers and the police reduced HIV risk over the time of the programme.

The authors argue that these findings point to the potentially pivotal role that the police have as a structural determinant for HIV in vulnerable populations. However, they argue that nearly all the papers identified in this review fail to take account of the complexities of the risk environment in which law enforcement occurs. The authors thus suggest a need for better measures for legal and extra-legal enforcement practices as mechanisms through which sex workers’ HIV risk is mediated.

Africa, Asia, Europe, Latin America
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The negative health impacts of HIV-associated stigma

Examining the associations between HIV-related stigma and health outcomes in people living with HIV/AIDS: a series of meta-analyses.

Rueda S, Mitra S, Chen S, Gogolishvili D, Globerman J, Chambers L, Wilson M, Logie CH, Shi Q, Morassaei S, Rourke SB. BMJ Open. 2016 Jul 13;6(7):e011453. doi: 10.1136/bmjopen-2016-011453.

Objective: To conduct a systematic review and series of meta-analyses on the association between HIV-related stigma and health among people living with HIV.

Data sources: A structured search was conducted on 6 electronic databases for journal articles reporting associations between HIV-related stigma and health-related outcomes published between 1996 and 2013.

Study eligibility criteria: Controlled studies, cohort studies, case-control studies and cross-sectional studies in people living with HIV were considered for inclusion.

Outcome measures: Mental health (depressive symptoms, emotional and mental distress, anxiety), quality of life, physical health, social support, adherence to antiretroviral therapy, access to and usage of health/social services and risk behaviours.

Results: 64 studies were included in our meta-analyses. We found significant associations between HIV-related stigma and higher rates of depression, lower social support and lower levels of adherence to antiretroviral medications and access to and usage of health and social services. Weaker relationships were observed between HIV-related stigma and anxiety, quality of life, physical health, emotional and mental distress and sexual risk practices. While risk of bias assessments revealed overall good quality related to how HIV stigma and health outcomes were measured on the included studies, high risk of bias among individual studies was observed in terms of appropriate control for potential confounders. Additional research should focus on elucidating the mechanisms behind the negative relationship between stigma and health to better inform interventions to reduce the impact of stigma on the health and well-being of people with HIV.

Conclusions: This systematic review and series of meta-analyses support the notion that HIV-related stigma has a detrimental impact on a variety of health-related outcomes in people with HIV. This review can inform the development of multifaceted, intersectoral interventions to reduce the impact of HIV-related stigma on the health and well-being of people living with HIV.

Abstract  Full-text [free] access 

Editor’s notes: There is a growing body of research documenting the negative impact of stigma and discrimination on the health of people living with HIV. Stigma is associated with poorer mental health, including emotional distress, depression and reduced psychological functioning. It has also been linked to intermediate health outcomes such as seeking healthcare and adherence to antiretroviral therapy. This paper reports a comprehensive systematic review and meta-analyses summarising the published evidence on the relationship between HIV-associated stigma and a wide range of health outcomes, including intermediate health outcomes. Results illustrate associations between HIV-associated stigma and depressive symptoms, lower levels of social support, ART adherence and use of health services. However, the majority of studies in the review were cross-sectional and longitudinal studies are necessary to explore the complex relationship between these factors, including the role of moderating factors, such as coping strategies. In addition, more research is necessary from low- and middle-income countries given that much of the published research is from North America. Further, there is also a need to better understand the intersection of HIV-associated stigma with other types of stigma experienced by people living with HIV, including homophobia, racism and gender discrimination. 

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Accurate country-level data necessary to inform HIV incidence estimates

Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015: the Global Burden of Disease Study 2015.

Wang H, Wolock TM, Carter A, Nguyen G, Kyu HH, Gakidou E, Hay SI, Mills EJ, Trickey A, Msemburi W, Coates MM, Mooney MD, Fraser MS, Sligar A, Salomon J, Larson HJ, Friedman J, Abajobir AA, Abate KH, Abbas KM, Razek MM, Abd-Allah F, Abdulle AM, Abera SF, Abubakar I, Abu-Raddad LJ, Abu-Rmeileh NM, Abyu GY, Adebiyi AO, Adedeji IA, Adelekan AL, Adofo K, Adou AK, Ajala ON, Akinyemiju TF, Akseer N, Lami FH, Al-Aly Z, Alam K, Alam NK, Alasfoor D, Aldhahri SF, Aldridge RW, Alegretti MA, Aleman AV, Alemu ZA, Alfonso-Cristancho R, Ali R, Alkerwi A, Alla F, Mohammad R, Al-Raddadi S, Alsharif U, Alvarez E, Alvis-Guzman N, Amare AT, Amberbir A, Amegah AK, Ammar W, Amrock SM, Antonio CA, Anwari P, Arnlov J, Artaman A, Asayesh H, Asghar RJ, Assadi R, Atique S, Atkins LS, Avokpaho EF, Awasthi A, Quintanilla BP, Bacha U, Badawi A, Barac A, Barnighausen T, Basu A, Bayou TA, Bayou YT, Bazargan-Hejazi S, Beardsley J, Bedi N, Bennett DA, Bensenor IM, Betsu BD, Beyene AS, Bhatia E, Bhutta ZA, Biadgilign S, Bikbov B, Birlik SM, Bisanzio D, Brainin M, Brazinova A, Breitborde NJ, Brown A, Burch M, Butt ZA, Campuzano JC, Cardenas R, Carrero JJ, Castaneda-Orjuela CA, Rivas JC, Catala-Lopez F, Chang HY, Chang JC, Chavan L, Chen W, Chiang PP, Chibalabala M, Chisumpa VH, Choi JY, Christopher DJ, Ciobanu LG, Cooper C, Dahiru T, Damtew SA, Dandona L, Dandona R, das Neves J, de Jager P, De Leo D, Degenhardt L, Dellavalle RP, Deribe K, Deribew A, Des Jarlais DC, Dharmaratne SD, Ding EL, Doshi PP, Driscoll TR, Dubey M, Elshrek YM, Elyazar I, Endries AY, Ermakov SP, Eshrati B, Esteghamati A, Faghmous ID, Farinha CS, Faro A, Farvid MS, Farzadfar F, Fereshtehnejad SM, Fernandes JC, Fischer F, Fitchett JR, Foigt N, Fullman N, Furst T, Gankpe FG, Gebre T, Gebremedhin AT, Gebru AA, Geleijnse JM, Gessner BD, Gething PW, Ghiwot TT, Giroud M, Gishu MD, Glaser E, Goenka S, Goodridge A, Gopalani SV, Goto A, Gugnani HC, Guimaraes MD, Gupta R, Gupta R, Gupta V, Haagsma J, Hafezi-Nejad N, Hagan H, Hailu GB, Hamadeh RR, Hamidi S, Hammami M, Hankey GJ, Hao Y, Harb HL, Harikrishnan S, Haro JM, Harun KM, Havmoeller R, Hedayati MT, Heredia-Pi IB, Hoek HW, Horino M, Horita N, Hosgood HD, Hoy DG, Hsairi M, Hu G, Huang H, Huang JJ, Iburg KM, Idrisov BT, Innos K, Iyer VJ, Jacobsen KH, Jahanmehr N, Jakovljevic MB, Javanbakht M, Jayatilleke AU, Jeemon P, Jha V, Jiang G, Jiang Y, Jibat T, Jonas JB, Kabir Z, Kamal R, Kan H, Karch A, Karema CK, Karletsos D, Kasaeian A, Kaul A, Kawakami N, Kayibanda JF, Keiyoro PN, Kemp AH, Kengne AP, Kesavachandran CN, Khader YS, Khalil I, Khan AR, Khan EA, Khang YH, Khubchandani J, Kim YJ, Kinfu Y, Kivipelto M, Kokubo Y, Kosen S, Koul PA, Koyanagi A, Defo BK, Bicer BK, Kulkarni VS, Kumar GA, Lal DK, Lam H, Lam JO, Langan SM, Lansingh VC, Larsson A, Leigh J, Leung R, Li Y, Lim SS, Lipshultz SE, Liu S, Lloyd BK, Logroscino G, Lotufo PA, Lunevicius R, Razek HM, Mahdavi M, Majdan M, Majeed A, Makhlouf C, Malekzadeh R, Mapoma CC, Marcenes W, Martinez-Raga J, Marzan MB, Masiye F, Mason-Jones AJ, Mayosi BM, McKee M, Meaney PA, Mehndiratta MM, Mekonnen AB, Melaku YA, Memiah P, Memish ZA, Mendoza W, Meretoja A, Meretoja TJ, Mhimbira FA, Miller TR, Mikesell J, Mirarefin M, Mohammad KA, Mohammed S, Mokdad AH, Monasta L, Moradi-Lakeh M, Mori R, Mueller UO, Murimira B, Murthy GV, Naheed A, Naldi L, Nangia V, Nash D, Nawaz H, Nejjari C, Ngalesoni FN, de Dieu Ngirabega J, Nguyen QL, Nisar MI, Norheim OF, Norman RE, Nyakarahuka L, Ogbo FA, Oh IH, Ojelabi FA, Olusanya BO, Olusanya JO, Opio JN, Oren E, Ota E, Padukudru MA, Park HY, Park JH, Patil ST, Patten SB, Paul VK, Pearson K, Peprah EK, Pereira CC, Perico N, Pesudovs K, Petzold M, Phillips MR, Pillay JD, Plass D, Polinder S, Pourmalek F, Prokop DM, Qorbani M, Rafay A, Rahimi K, Rahimi-Movaghar V, Rahman M, Rahman MH, Rahman SU, Rai RK, Rajsic S, Ram U, Rana SM, Rao PV, Remuzzi G, Rojas-Rueda D, Ronfani L, Roshandel G, Roy A, Ruhago GM, Saeedi MY, Sagar R, Saleh MM, Sanabria JR, Santos IS, Sarmiento-Suarez R, Sartorius B, Sawhney M, Schutte AE, Schwebel DC, Seedat S, Sepanlou SG, Servan-Mori EE, Shaikh. Lancet HIV. 2016 Aug;3(8):e361-87. doi: 10.1016/S2352-3018(16)30087-X. Epub 2016 Jul 19.

Background: Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.

Methods: For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification.

Findings: Global HIV incidence reached its peak in 1997, at 3.3 million new infections (95% uncertainty interval [UI] 3.1-3.4 million). Annual incidence has stayed relatively constant at about 2.6 million per year (range 2.5-2.8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38.8 million (95% UI 37.6-40.4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1.8 million deaths (95% UI 1.7-1.9 million) in 2005, to 1.2 million deaths (1.1-1.3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections.

Interpretation: Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030.

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Editor’s notes: The global estimates for HIV incidence, prevalence, and deaths produced by the Global Burden of Disease (GBD) mathematical modelling approach for 2015 are somewhat higher than those published by UNAIDS in June 2016 prior to the International Conference on AIDS held in Durban in July. Both GBD and UNAIDS agree that as the scale-up of antiretroviral treatment (ART) continues, HIV-associated mortality is declining with the result that HIV prevalence is rising as the number of people living with HIV continues to grow. The metric of critical interest to policy makers and programme planners is HIV incidence, the number of new infections. Each new infection means ART for life, starting from HIV diagnosis now rather than later in disease progression. Both GBD and UNAIDS estimates suggest that globally annual HIV incidence stopped declining after 2005 and has remained persistently high at 2.5 million (2.2-2.7 million) according to GDB and 2.1 million (1.8-2.4 million) according to UNAIDS. Where the estimates differ is at country level, precisely where they can make the most difference to decision making. GBD estimates for HIV incidence for countries in the regions of northern America, Europe, Australasia, and central Asia are significantly lower than the reported numbers of newly diagnosed cases (see the comparison table in the Lancet commentary by Supervie and Costagliola. For example, 85 252 people were newly diagnosed with HIV in the Russian federation in 2014 whereas the GBD estimate for people newly acquiring HIV in 2015 was only 57 340, albeit with a wide range of uncertainly. For the United States of America, the uncertainly bounds around the GBD estimate of 23 040 do not include 44,073, the number of newly diagnosed cases. Furthermore, new diagnoses likely underestimate actual HIV incidence as they include people who acquired HIV in previous years. Estimates for some high prevalence countries are significantly higher than those produced by those countries with UNAIDS support. For example, http://aidsinfo.unaids.org/ illustrates South Africa as having 380 000 (330 000-430 000) new infections while GBD estimates 529 670 (440 940 to 630 390). Modelling estimates are simply estimates but they cannot be confirmatory or even complementary when they are so different. UNAIDS and IHME (GBD) are already working to understand the differences in the two mathematical modelling approaches - their methodologies, parameters, and assumptions - in order to explain important discrepancies at country level. More importantly, improved data collection by countries of the numbers of HIV diagnoses, people accessing and staying on ART, and the proportion of people living with HIV who achieve viral suppression is necessary to monitor progress towards the UNAIDS 90-90-90 treatment target. Enhanced clinical and epidemiological surveillance systems are also key to the creation of more accurate estimates of country HIV incidence, the metric that reflects HIV prevention programme progress and informs budget allocations and programme planning for HIV treatment. 

195 countries
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New evidence in support of opioid substitution therapy as a key HIV programme for people who inject drugs

Impact of opioid substitution therapy on antiretroviral therapy outcomes: a systematic review and meta-analysis.

Low AJ, Mburu G, Welton NJ, May MT, Davies CF, French C, Turner K, Looker KJ, Christensen H, McLean S, Rhodes T, Platt L, Hickman M, Guise A, Vickerman P. Clin Infect Dis. 2016 Jun 25. pii: ciw416. [Epub ahead of print]

Background: HIV-positive people who inject drugs (PWID) frequently encounter barriers accessing and remaining on antiretroviral treatment (ART). Some studies have suggested that opioid substitution therapy (OST) could facilitate PWID's engagement with HIV services. We conducted a systematic review and meta-analysis to evaluate the impact of concurrent OST use on ART-related outcomes among HIV-positive PWID.

Methods: We searched Medline, PsycInfo, Embase, Global Health, Cochrane, Web of Science, and Social Policy and Practice databases for studies between 1996 to November 2014 documenting the impact of OST, compared to no OST, on ART outcomes. Outcomes considered were: coverage and recruitment onto ART, adherence, viral suppression, attrition from ART, and mortality. Meta-analyses were conducted using random effects modelling, and heterogeneity assessed using Cochran's Q test and I2 statistic.

Results: We identified 4685 articles, and 32 studies conducted in North America, Europe, Indonesia and China were included. OST was associated with a 69% increase in recruitment onto ART (HR=1.69, 95% confidence interval (CI): 1.32-2.15), a 54% increase in ART coverage (OR=1.54; 95% CI: 1.17-2.03), a two-fold increase in adherence (OR=2.14, 95% CI: 1.41-3.26), and a 23% decrease in the odds of attrition (OR=0.77, 95% CI:0.63-0.95). OST was associated with a 45% increase in odds of viral suppression (OR=1.45, 95%CI:1.21-1.73), but there was limited evidence from six studies for OST decreasing mortality for PWID on ART (HR=0.91, 95% CI:0.65-1.25).

Conclusions: These findings support the use of OST, and its integration with HIV services, to improve the HIV treatment and care continuum amongst HIV-positive PWID.

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Editor’s notes: This is a very important study contributing new evidence on how opioid substitution therapy can help in the treatment and prevention of HIV among people who inject drugs. This review provides key evidence in support of opioid substitution therapy as a cornerstone HIV treatment and prevention programme. This evidence is essential given the growing number of HIV infections among people who inject drugs globally, particularly in eastern Europe and sub-Saharan Africa. There is a wealth of evidence from systematic reviews and mathematical modelling to illustrate how the use of opioid substitution therapy decreases risk of HIV acquisition at an individual-level.  It can also reduce HIV prevalence and incidence at the population level. This review is important in that it illustrates how opioid substitution therapy can facilitate HIV treatment.  Findings illustrate that opioid substitution therapy works by increasing adherence to HIV treatment, decreasing attrition from treatment and increasing odds of viral suppression reducing the odds of onwards HIV transmission. In addition to this important review, there is also a need to understand the role opioid substitution therapy might have in increasing uptake of HIV testing. This review does not address that question. It is notable that few studies on impact of opioid substitution therapy on HIV treatment outcomes and uptake included in the review were identified in low-income countries or eastern Europe where need is greatest. This partly reflects the lack of opioid substitution therapy programmes in that region, particularly the Russian Federation. This is also the case in sub-Saharan Africa where opioid substitution therapy programmes are newly established and yet to be evaluated. Future research is necessary to understand how opioid substitution therapy might work: (1) where transmission of HIV is predominantly sexual and (2) where injecting drug use occurs within very different social and economic contexts.

Asia, Europe, Northern America
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Improved survival with lymphoma in the antiretroviral therapy era

Evolution of HIV-associated lymphoma over 3 decades.

Ramaswami R, Chia G, Dalla Pria A, Pinato DJ, Parker K, Nelson M, Bower M. J Acquir Immune Defic Syndr. 2016 Jun 1;72(2):177-83. doi: 10.1097/QAI.0000000000000946.

Introduction: The emergence of combined antiretroviral therapy (cART) and improvements in the management of opportunistic infections have altered the HIV epidemic over the last 30 years. We aimed to assess changes to the biology and outcomes of HIV-associated lymphomas over this period at the national center for HIV oncology in the United Kingdom.

Methods: Clinical characteristics at lymphoma diagnosis have been prospectively collected since 1986, along with details of lymphoma treatment and outcomes. The clinical features and outcomes were compared between 3 decades: pre-cART decade (1986-1995), early-cART decade (1996-2005), and late-cART decade (2006-2015).

Results: A total of 615 patients with HIV-associated lymphoma were included in the study: 158 patients in the pre-cART era, 200 patients in the early-cART era, and 257 patients in the late-cART era. In more recent decades, patients were older (P < 0.0001) and had higher CD4 cell counts (P < 0.0001) at lymphoma diagnosis. Over time, there has also been a shift in lymphoma histological subtypes, with an increase in lymphoma subtypes associated with moderate immunosuppression. The overall survival for patients with HIV-associated lymphoma has dramatically improved over the 3 decades (P < 0.0001).

Conclusion: Over the last 30 years, the clinical demographic of HIV-associated lymphomas has evolved, and the outcomes have improved.

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Editor’s notes: Lymphomas are the second most common malignancy after Kaposi’s sarcoma among people living with HIV in Europe, Australia and northern America. This study examined how the biology and rates of survival have changed since combination antiretroviral therapy (cART) became available.

People living with HIV and diagnosed with lymphoma over the past thirty years in a specialist oncology centre in the United Kingdom were included in the study. The mean age at diagnosis of lymphoma increased over time, most likely reflecting improvement in life expectancy with cART. As would be expected, the mean CD4 count and the proportion of people with a suppressed viral load at lymphoma diagnosis increased, while proportion with an AIDS-defining illness before lymphoma diagnosis declined significantly.  

This study demonstrated a shift of the histological subtypes of lymphoma that are associated with less severe immunosuppression, for example the proportion of primary CNS lymphoma (PCNSL) and diffuse large B-cell lymphoma (DLBCL), which are associated with severe immunosuppression, declined, while the proportion of Burkitt’s lymphoma and Hodgkin’s lymphoma (associated with less profound immunosuppression) increased.

A key finding of this study was the significantly improved overall survival of people with lymphoma. The improved survival is not explained by changes in histological subtypes of lymphoma over time, as improvement in prognosis was observed for each histological subtype. The substantial improvement in overall survival is attributable to a number of factors. They include the availability of cART, attention to opportunistic infection prophylaxis, improved supportive care for people undergoing lymphoma treatment as well as improved modalities of lymphoma treatment. Such modalities include efficacious drugs that can be safely co-administered with cART, e.g., rituximab, novel agents and use of autologous stem cell transplants.  

Europe
United Kingdom
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