Articles tagged as "United States of America"

Updated evidence that DMPA increases HIV risk among women

Update on hormonal contraceptive methods and risk of HIV acquisition in women: a systematic review of epidemiological evidence, 2016.

Polis CB, Curtis KM, Hannaford PC, Phillips SJ, Chipato T, Kiarie JN, Westreich DJ, Steyn PS. AIDS. 2016 Aug 5. [Epub ahead of print]

Objective and design: Some studies suggest that specific hormonal contraceptive (HC) methods (particularly depot medroxyprogesterone acetate [DMPA]) may increase women's HIV acquisition risk. We updated a systematic review to incorporate recent epidemiological data.

Methods: We searched for articles published between 1/15/2014-1/15/2016, and hand-searched reference lists. We identified longitudinal studies comparing users of a specific HC method against either (1) non-users of HC, or (2) users of another specific HC method. We added newly identified studies to those in the previous review, assessed study quality, created forest plots to display results, and conducted a meta-analysis for data on DMPA versus no HC.

Results: We identified ten new reports: five were considered "unlikely to inform the primary question". We focus on the other five reports, along with 9 from the previous review, considered "informative but with important limitations". The preponderance of data for oral contraceptive pills, injectable norethisterone enanthate (NET-EN), and levonorgestrel implants do not suggest an association with HIV acquisition, though data for implants are limited. The new, higher-quality studies on DMPA (or non-disaggregated injectables), which had mixed results in terms of statistical significance, had hazard ratios (HR) between 1.2 and 1.7, consistent with our meta-analytic estimate for all higher-quality studies of HR 1.4.

Conclusions: While confounding in these observational data cannot be excluded, new information increases concerns about DMPA and HIV acquisition risk in women. If the association is causal, the magnitude of effect is likely ≤HR 1.5. Data for other hormonal contraceptive methods, including NET-EN, are largely reassuring.

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Editor’s notes: For several years there has been debate about whether the risk of HIV acquisition in women may be increased by the use of hormonal contraception. A systematic review published in 2014 included a meta-analysis of data from 22 studies, and this paper adds 10 new studies to the analysis. While these new papers carried some of the previous review’s limitations which cannot be ignored, the new data also lends further strength to the evidence and renewed analysis. The authors found some encouraging results which suggest that there is no significant increased risk of HIV with the use of oral contraceptives and the NET-EN injectable. However, this analysis does suggest that there is an increased risk of 1.4-1.5 of HIV with the use of DMPA. This is particularly concerning given the widespread use of this product throughout the world, and especially in areas where high rates of new HIV infections continue to persist, such as sub-Saharan Africa. Studies continue to explore this association of risk, and will hopefully produce evidence in the near future to definitively provide guidance as to how clinicians should direct the use of DMPA in women at risk of HIV. 

Africa, Northern America
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Young people living with HIV, stigma and its mental health effects

HIV-related stigma, shame, and avoidant coping: risk factors for internalizing symptoms among youth living with HIV?

Bennett DS, Hersh J, Herres J, Foster J. Child Psychiatry Hum Dev. 2016 Aug;47(4):657-64. doi: 10.1007/s10578-015-0599-y.

Youth living with HIV (YLH) are at elevated risk of internalizing symptoms, although there is substantial individual variability in adjustment. We examined perceived HIV-related stigma, shame-proneness, and avoidant coping as risk factors of internalizing symptoms among YLH. Participants (N = 88; ages 12-24) completed self-report measures of these potential risk factors and three domains of internalizing symptoms (depressive, anxiety, and PTSD) during a regularly scheduled HIV clinic visit. Hierarchical regressions were conducted for each internalizing symptoms domain, examining the effects of age, gender, and maternal education (step 1), HIV-related stigma (step 2), shame- and guilt-proneness (step 3), and avoidant coping (step 4). HIV-related stigma, shame-proneness, and avoidant coping were each correlated with greater depressive, anxiety, and PTSD symptoms. Specificity was observed in that shame-proneness, but not guilt-proneness, was associated with greater internalizing symptoms. In multivariable analyses, HIV-related stigma and shame-proneness were each related to greater depressive and PTSD symptoms. Controlling for the effects of HIV-related stigma and shame-proneness, avoidant coping was associated with PTSD symptoms. The current findings highlight the potential importance of HIV-related stigma, shame, and avoidant coping on the adjustment of YLH, as interventions addressing these risk factors could lead to decreased internalizing symptoms among YLH.

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Editor’s notes: This study examined the relationship between stigma, shame and avoidant coping strategies and the development of internalizing symptoms, such as anxiety and depression, in young people living with HIV. It is based on researcher-administered questionnaires with 88 young people living with HIV attending an HIV clinic in Philadelphia, USA. The questionnaire included multiple scales to assess. These included young people’s self-reported issues with HIV stigma; tendency to feel shame; tendency to feel guilt; avoidant coping strategies; depressive symptoms; anxiety symptoms; and post-traumatic stress disorder symptoms. Multiple statistical analyses were performed, controlling for the effects of gender, age and maternal education. The study found that HIV-associated stigma, shame and avoidant strategies are risk-factors for the development of depression, anxiety and post-traumatic stress disorder in young people living with HIV. The study provides evidence for the development of psychosocial support that focuses on shame reduction as a way to mediate the impact of stigma on mental health outcomes for young people living with HIV.

Northern America
United States of America
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Challenges in assessing quality in HIV outpatient care

Structure and quality of outpatient care for people living with an HIV infection.

Engelhard EA, Smit C, Nieuwkerk PT, Reiss P, Kroon FP, Brinkman K, Geerlings SE. AIDS Care. 2016 Aug;28(8):1062-72. doi: 10.1080/09540121.2016.1153590. Epub 2016 Mar 13.

Policy-makers and clinicians are faced with a gap of evidence to guide policy on standards for HIV outpatient care. Ongoing debates include which settings of care improve health outcomes, and how many HIV-infected patients a health-care provider should treat to gain and maintain expertise. In this article, we evaluate the studies that link health-care facility and care provider characteristics (i.e., structural factors) to health outcomes in HIV-infected patients. We searched the electronic databases MEDLINE, PUBMED, and EMBASE from inception until 1 January 2015. We included a total of 28 observational studies that were conducted after the introduction of combination antiretroviral therapy in 1996. Three aspects of the available research linking the structure to quality of HIV outpatient care were evaluated: (1) assessed structural characteristics (i.e., health-care facility and care provider characteristics); (2) measures of quality of HIV outpatient care; and (3) reported associations between structural characteristics and quality of care. Rather than scarcity of data, it is the diversity in methodology in the identified studies and the inconsistency of their results that led us to the conclusion that the scientific evidence is too weak to guide policy in HIV outpatient care. We provide recommendations on how to address this heterogeneity in future studies and offer specific suggestions for further reading that could be of interest for clinicians and researchers.

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Editor’s notes: The availability of antiretroviral therapy has resulted in remarkable decreases in HIV-associated mortality.  Complexity in the management of HIV infection has however grown along with these advances in treatment. Health-care providers are confronted with challenges associated with antiretroviral therapy including toxicities; drug-drug interactions and drug resistance; and comorbidities and aging among the population living with HIV. In order to achieve optimal health outcomes, care for people living with HIV should be provided at health-care facilities and by care providers with sufficient expertise. A variety of different delivery models have been attempted to achieve this. There are a growing number of studies assessing care delivery models and programmes in outpatient HIV care.  In this article the authors provide an overview of the scientific literature linking health-care facility and care provider characteristics to the quality of HIV outpatient care.

The authors conducted a systematic review of articles that reported an original observational research study with an adult population living with HIV, were conducted after 1996, and that did not focus exclusively on interventions.

The authors acknowledge the limitations of their research. These included a disproportionate number of studies based in the USA and sub-Saharan Africa (thus limited generalisability); diversity in the definition of structural variables; a wide scope of measures of quality of care used in studies; and limited inclusion of peoples’ healthcare experiences. The authors summarise two main implications of their research.  First, they note that their findings suggest that health-care provider experience improves outcomes among people living with HIV although they are unable to make recommendations regarding facility volume requirements for outpatient care. Second, they advocate for the need for research to extend to regions outside the USA and sub-Saharan Africa.  They also note the need for researchers to align their methods of measuring quality including by going beyond HIV-associated morbidity in the evaluation of health outcomes.  Peoples’ preferences and retention in care should also play an important role in the evaluation of the quality of care.

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Antiretroviral therapy dramatically reduces transmission of HIV to sexual partners

Antiretroviral therapy for the prevention of HIV-1 transmission.

Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Cottle L, Zhang XC, Makhema J, Mills LA, Panchia R, Faesen S, Eron J, Gallant J, Havlir D, Swindells S, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano DD, Essex M, Hudelson SE, Redd AD, Fleming TR. N Engl J Med. 2016 Jul 18. [Epub ahead of print]

Background: An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission.

Methods: We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis.

Results: Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant.

Conclusions: The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 ClinicalTrials.gov number, NCT00074581.).

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Editor’s notes: The HPTN 052 trial has been a landmark study in establishing antiretroviral therapy as a strategy for preventing onward transmission of HIV. It was a study of more than 800 couples. More than half of the couples were in African countries. In each couple, one sexual partner was HIV positive and the other HIV negative.  The participants living with HIV were randomised either to receive immediate antiretroviral therapy or to delay until their CD4 count fell to 350, an approved approach at that time. The HIV negative partners were then monitored for acquisition of HIV.  When new HIV infections occurred, the virus was studied for genetic similarity to the virus of the known positive partner. The interim analysis was published in 2011.  It illustrated the programme to be so effective that the randomisation was ended and all the participants living with HIV were offered antiretroviral therapy. 

This article presents data after five years of follow-up, and if anything the results are even more remarkable. In more than 10 000 person-years of follow up, there were only eight transmissions of genetically linked virus from participants receiving antiretroviral therapy. Of these transmissions, four occurred early in treatment when the viral load would not be expected to be suppressed.  The other four occurred after treatment failure. In this enormous study, there were therefore no linked transmissions from participants who were stable on treatment without detectable viraemia. The study provides powerful support for the UNAIDS 90-90-90 treatment target.  The widest possible effective use of antiretroviral therapy will not only improve the health of people treated but could have a dramatic effect on new HIV infections.

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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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Patient navigators and financial incentives have no effect on HIV viral suppression in people with substance use disorders

Effect of patient navigation with or without financial incentives on viral suppression among hospitalized patients with HIV infection and substance use: a randomized clinical trial.  

Metsch LR, Feaster DJ, Gooden L, Matheson T, Stitzer M, Das M, Jain MK, Rodriguez AE, Armstrong WS, Lucas GM, Nijhawan AE, Drainoni ML, Herrera P, Vergara-Rodriguez P, Jacobson JM, Mugavero MJ, Sullivan M, Daar ES, McMahon DK, Ferris DC, Lindblad R, VanVeldhuisen P, Oden N, Castellon PC, Tross S, Haynes LF, Douaihy A, Sorensen JL, Metzger DS, Mandler RN, Colfax GN, del Rio C. JAMA. 2016 Jul 12;316(2):156-70. doi: 10.1001/jama.2016.8914.

Importance: Substance use is a major driver of the HIV epidemic and is associated with poor HIV care outcomes. Patient navigation (care coordination with case management) and the use of financial incentives for achieving predetermined outcomes are interventions increasingly promoted to engage patients in substance use disorders treatment and HIV care, but there is little evidence for their efficacy in improving HIV-1 viral suppression rates.

Objective: To assess the effect of a structured patient navigation intervention with or without financial incentives to improve HIV-1 viral suppression rates among patients with elevated HIV-1 viral loads and substance use recruited as hospital inpatients.

Design, setting, and participants: From July 2012 through January 2014, 801 patients with HIV infection and substance use from 11 hospitals across the United States were randomly assigned to receive patient navigation alone (n = 266), patient navigation plus financial incentives (n = 271), or treatment as usual (n = 264). HIV-1 plasma viral load was measured at baseline and at 6 and 12 months.

Interventions: Patient navigation included up to 11 sessions of care coordination with case management and motivational interviewing techniques over 6 months. Financial incentives (up to $1160) were provided for achieving targeted behaviors aimed at reducing substance use, increasing engagement in HIV care, and improving HIV outcomes. Treatment as usual was the standard practice at each hospital for linking hospitalized patients to outpatient HIV care and substance use disorders treatment.

Main outcomes and measures: The primary outcome was HIV viral suppression (200 copies/mL) relative to viral nonsuppression or death at the 12-month follow-up.

Results: Of 801 patients randomized, 261 (32.6%) were women (mean [SD] age, 44.6 years [10.0 years]). There were no differences in rates of HIV viral suppression versus nonsuppression or death among the 3 groups at 12 months. Eighty-five of 249 patients (34.1%) in the usual-treatment group experienced treatment success compared with 89 of 249 patients (35.7%) in the navigation-only group for a treatment difference of 1.6% (95% CI, -6.8% to 10.0%; P = .80) and compared with 98 of 254 patients (38.6%) in the navigation-plus-incentives group for a treatment difference of 4.5% (95% CI -4.0% to 12.8%; P = .68). The treatment difference between the navigation-only and the navigation-plus-incentives group was -2.8% (95% CI, -11.3% to 5.6%; P = .68).

Conclusions and relevance: Among hospitalized patients with HIV infection and substance use, patient navigation with or without financial incentives did not have a beneficial effect on HIV viral suppression relative to nonsuppression or death at 12 months vs treatment as usual. These findings do not support these interventions in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01612169.

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Editor’s notes: Substance use in people living with HIV has consistently been shown to be associated with poor clinical outcomes. Within this population, management often requires a combination of treatment for both HIV and substance use disorders. It is evident that it is the poor engagement in one or both of these treatment approaches that contributes significantly to poor clinical outcomes. The author’s group aimed to fill a gap in current evidence and explore whether two activities, patient navigation and financial incentives, could potentially motivate engagement with both treatment approaches and ultimately improve HIV viral suppression.

This study tested, among people living with HIV in hospital,  with substance use disorders, six months of patient navigation alone (care co-ordination and case management), or six months of patient navigation alongside a financial incentive plan. While overall uptake and retention to the programme schedules were high, no differences in HIV-1 viral suppression rates (which were generally poor) or death by 12 months were noted.

One factor that must be highlighted is that the participation in actual substance use treatment programmes post hospital discharge was low across all groups (average 24.8%), primarily due to a lack of available services in the regions. It may be that the programme may have been more effective in a different population of people already established in substance use treatment programmes, or if treatment had been more easily accessible.

The study serves as a reminder that such key populations are extremely vulnerable with a number of comorbidities and competing priorities. While not supporting health care navigation or financial incentives in their defined setting, the study findings emphasise a need to develop and tailor, cost-effective activities to improve health outcomes in this group.

Northern America
United States of 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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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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Does place of sex change risk behaviours among men who have sex with men?

Is location of sex associated with sexual risk behaviour in men who have sex with men? Systematic review of within-subjects studies.

Melendez-Torres GJ, Nye E, Bonell C. AIDS Behav. 2016 Jun;20(6):1219-27. doi: 10.1007/s10461-015-1093-z.

To understand associations between location of sex and sexual risk, it is most helpful to compare sexual encounters within persons. We systematically reviewed within-subjects comparisons of sexual encounters reported by men who have sex with men (MSM) with respect to location of sex. Within-subjects comparisons of sexual risk and location of sex were eligible if they collected data post-1996 from samples of MSM. We independently screened results and full-text records in duplicate. Of 6336 de-duplicated records, we assessed 138 full-text studies and included six, most of which compared unprotected anal intercourse against other anal intercourse. This small, but high quality, body of evidence suggests that associations between attendance at sex-on-premises venues and person-level sexual risk may be due to overall propensity towards unprotected sex. However, there may be some location factors that promote or are associated with serononconcordant unprotected anal intercourse. Health promoters may wish to focus on person-level characteristics.

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Editor’s notes: Venues where gay men and other men who have sex with men, have sex, fit broadly into three categories. These are: i) sex-on premises venues (indoor locations outside the home e.g. bathhouses, saunas, sex clubs, porn cinemas, public sex parties), ii) public sex environments (cruising locations / beats e.g. outdoor parks) and iii) homes of sexual partners. Men will usually have anonymous sexual encounters or sex with casual partners in the first two location categories. Use of specific locations for sex may be associated with specific sexual risk-taking at the person level. However, it is unclear if sexual risk is greater in certain venues compared to others. Is there a ‘location effect’ on sexual risk? Or put in a different way, does the same person behave differently (in terms of sexual risk), depending on the venue where they are having sex? To examine this, it is necessary to compare several sexual encounters within respondents at different sex locations. The authors of this paper systematically reviewed studies which reported within-subjects comparisons analysing the encounter-level association between location of sex and sexual risk behaviours among gay men and other men who have sex with men.

Six studies were included in the final review – four from the United States and two from Australia. It was not possible to conduct a meta-analysis due to differences in defining venue and sexual risk behaviours. Overall, the authors found little evidence of differences between condomless versus protected anal intercourse between public and private locations for sex. Additional studies are necessary, including how smartphone-mediated sex seeking is changing the locations and risk environment where gay men and other men will have sex with men. Research from other countries and contexts is also warranted.    

Northern America, Oceania
Australia, United States of America
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Perceived stigma may lead to increased experienced stigma among people living with HIV

A transactional approach to relationships over time between perceived HIV stigma and the psychological and physical well-being of people with HIV.

Miller CT, Solomon SE, Varni SE, Hodge JJ, Knapp FA, Bunn JY. Soc Sci Med. 2016 Jun 16;162:97-105. doi: 10.1016/j.socscimed.2016.06.025. [Epub ahead of print]

Rationale: Cross-sectional studies demonstrate that perceived discrimination is related to the psychological and physical well-being of stigmatized people. The theoretical and empirical foci of most of this research is on how racial discrimination undermines well-being. The present study takes a transactional approach to examine people with HIV, a potentially concealable stigma.

Hypothesis: The transactional approach posits that even as discrimination adversely affects the psychological well-being of people with HIV, psychological distress also makes them more sensitive to perceiving that they may be or have been stigmatized, and may increase the chances that other people actually do stigmatize them.

Methods: This hypothesis was tested in a longitudinal study in which 216 New England residents with HIV were recruited to complete measures of perceived HIV stigma and well-being across three time points, approximately 90 days apart. This study also expanded on past research by assessing anticipated and internalized stigma as well as perceived discrimination.

Results: Results indicated that all of these aspects of HIV stigma prospectively predicted psychological distress, thriving, and physical well-being. Equally important, psychological distress and thriving also prospectively predicted all three aspects of HIV stigma, but physical well-being did not.

Conclusion: These findings suggest that people with HIV are ensnared in a cycle in which experiences of stigma and reduced psychological well-being mutually reinforce each other.

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Editor’s notes: Stigma can act as a barrier to the delivery and uptake of HIV care. This study investigated the transactional approach to understanding stigma. The authors sought to determine whether psychological stress due to perceptions of discrimination causes people living with HIV to be more sensitive to perceiving stigma. Then in turn whether this makes it more likely that they will be stigmatized. The authors examined data from a longitudinal study of 216 participants in New England in the United States. The study was embedded within a larger study protocol that sought to answer a broad range of research questions. Participants responded to a questionnaire which asked questions about participants’ perceived stigma based on the HIV Stigma Scale developed by Berger and colleagues in 2001. The authors used three subscales to measure enacted, anticipated, and internalized stigma. Participants responded to questions on a 5-point subscale of strongly disagree (scored as 1) to strongly agree (scored as 5) to questions about the three different types of stigma. The authors analysed associations between perceived, internalized, and experienced stigma. The authors concluded that understanding the transactional relationship between HIV-associated stigma and psychological stress is important for developing and implementing effective HIV-associated stigma programmes. Perceptions of stigma may lead to increases in perceived and experienced stigma among people living with HIV. This study suggests that future programmes that seek to address HIV-associated stigma should incorporate an understanding of the transactional relationship between psychological stress and perceived and experienced stigma.

Northern America
United States of America
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