Articles tagged as "India"

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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What works to link people living with HIV to care - a review

Facilitators and barriers in HIV linkage to care interventions: a qualitative evidence review.

Tso LS, Best J, Beanland R, Doherty M, Lackey M, Ma Q, Hall BJ, Yang B, Tucker JD. AIDS. 2016 Apr 6. [Epub ahead of print]

Objective: To synthesize qualitative evidence on linkage to care interventions for people living with HIV.

Design: Systematic literature review.

Methods: We searched nineteen databases for studies reporting qualitative evidence on linkage interventions. Data extraction and thematic analysis were used to synthesize findings. Quality was assessed using the CASP tool and certainty of evidence was evaluated using the CERQual approach.

Results: Twenty-five studies from eleven countries focused on adults (24 studies), adolescents (8 studies), and pregnant women (4 Facilitators included community-level factors (i.e. task-shifting, mobile outreach, integrated HIV and primary services, supportive cessation programs for substance users, active referrals, and dedicated case management teams) and individual-level factors (encouragement of peers/family and positive interactions with healthcare providers in transitioning into care). One key barrier for people living with HIV was perceived inability of providers to ensure confidentiality as part of linkage to care interventions. Providers reported difficulties navigating procedures across disparate facilities and having limited resources for linkage to care interventions.

Conclusions: Our findings extend the literature by highlighting the importance of task-shifting, mobile outreach, and integrated HIV and primary services. Both community and individual level factors may increase the feasibility and acceptability of HIV linkage to care interventions. These findings may inform policies to increase the reach of HIV services available in communities.

Abstract access  

Editor’s notes: As the authors of this paper observe, most evaluations of linkage to care programmes have focused on quantitative assessment. This useful paper provides a thorough overview of the findings from 25 studies which used qualitative methods for assessment. Linkage-to- care programmes feasible in different country settings were identified in this review.  The authors also highlight gaps, most notably a lack of information on linkage-to-care programmes for men. They also note the need for longitudinal assessments that look at changes over time.

This paper is a useful synthesis of findings. But it is also an excellent example of how to carry out a systematic review of qualitative research. The description of the qualitative meta-synthesis the authors performed adds additional value to this paper. 

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What works to link people living with HIV to care - a review

Facilitators and barriers in HIV linkage to care interventions: a qualitative evidence review.

Tso LS, Best J, Beanland R, Doherty M, Lackey M, Ma Q, Hall BJ, Yang B, Tucker JD. AIDS. 2016 Apr 6. [Epub ahead of print]

Objective: To synthesize qualitative evidence on linkage to care interventions for people living with HIV.

Design: Systematic literature review.

Methods: We searched nineteen databases for studies reporting qualitative evidence on linkage interventions. Data extraction and thematic analysis were used to synthesize findings. Quality was assessed using the CASP tool and certainty of evidence was evaluated using the CERQual approach.

Results: Twenty-five studies from eleven countries focused on adults (24 studies), adolescents (8 studies), and pregnant women (4 Facilitators included community-level factors (i.e. task-shifting, mobile outreach, integrated HIV and primary services, supportive cessation programs for substance users, active referrals, and dedicated case management teams) and individual-level factors (encouragement of peers/family and positive interactions with healthcare providers in transitioning into care). One key barrier for people living with HIV was perceived inability of providers to ensure confidentiality as part of linkage to care interventions. Providers reported difficulties navigating procedures across disparate facilities and having limited resources for linkage to care interventions.

Conclusions: Our findings extend the literature by highlighting the importance of task-shifting, mobile outreach, and integrated HIV and primary services. Both community and individual level factors may increase the feasibility and acceptability of HIV linkage to care interventions. These findings may inform policies to increase the reach of HIV services available in communities.

Abstract access  

Editor’s notes: As the authors of this paper observe, most evaluations of linkage to care programmes have focused on quantitative assessment. This useful paper provides a thorough overview of the findings from 25 studies which used qualitative methods for assessment. Linkage-to- care programmes feasible in different country settings were identified in this review.  The authors also highlight gaps, most notably a lack of information on linkage-to-care programmes for men. They also note the need for longitudinal assessments that look at changes over time.

This paper is a useful synthesis of findings. But it is also an excellent example of how to carry out a systematic review of qualitative research. The description of the qualitative meta-synthesis the authors performed adds additional value to this paper. 

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Comparing the performance of different community-based measures of viral load as correlates for HIV incidence

Community viral load, antiretroviral therapy coverage, and HIV incidence in India: a cross-sectional, comparative study.

Solomon SS, Mehta SH, McFall AM, Srikrishnan AK, Saravanan S, Laeyendecker O, Balakrishnan P, Celentano DD, Solomon S, Lucas GM. Lancet HIV. 2016 Apr;3(4):e183-90. doi: 10.1016/S2352-3018(16)00019-9. Epub 2016 Mar 11.

Background: HIV incidence is the best measure of treatment-programme effectiveness, but its measurement is difficult and expensive. The concept of community viral load as a modifiable driver of new HIV infections has attracted substantial attention. We set out to compare several measures of community viral load and antiretroviral therapy (ART) coverage as correlates of HIV incidence in high-risk populations.

Methods: We analysed data from a sample of people who inject drugs and men who have sex with men, who were participants of the baseline assessment of a cluster-randomised trial in progress across 22 cities in India (ClinicalTrials.gov number NCT01686750). We recruited the study population by use of respondent-driven sampling and did the baseline assessment at 27 community-based sites (12 for men who have sex with men and 15 for people who inject drugs). We estimated HIV incidence with a multiassay algorithm and calculated five community-based measures of HIV control: mean log10 HIV RNA in participants with HIV in a community either engaged in care (in-care viral load), aware of their status but not necessarily in care (aware viral load), or all HIV-positive individuals whether they were aware, in care, or not (population viral load); participants with HIV in a community with HIV RNA more than 150 copies per mL (prevalence of viraemia); and the proportion of participants with HIV who self-reported ART use in the previous 30 days (population ART coverage). All participants were tested for HIV, with additional testing in HIV-positive individuals. We assessed correlations between the measures and HIV incidence with Spearman correlation coefficients and linear regression analysis.

Findings: Between Oct 1, 2012, and Dec 19, 2013, we recruited 26 503 participants, 12 022 men who have sex with men and 14 481 people who inject drugs. Median incidence of HIV was 0.87% (IQR 0.40-1.17) in men who have sex with men and 1.43% (0.60-4.00) in people who inject drugs. Prevalence of viraemia was more strongly correlated with HIV incidence (correlation 0.81, 95% CI 0.62-0.91; p<0.0001) than all other measures, although correlation was significant with aware viral load (0.59, 0.27-0.79; p=0.001), population viral load (0.51, 0.16-0.74; p=0.007), and population ART coverage (-0.54, -0.76 to -0.20; p=0.004). In-care viral load was not correlated with HIV incidence (0.29, -0.10 to 0.60; p=0.14). With regression analysis, we estimated that to reduce HIV incidence by 1 percentage point in a community, prevalence of viraemia would need to be reduced by 4.34%, and ART use in HIV-positive individuals would need to increase by 19.5%.

Interpretation: Prevalence of viraemia had the strongest correlation with HIV incidence in this sample and might be a useful measure of the effectiveness of a treatment programme.

Abstract access    

Editor’s notes: The ideal metric of impact for a programme looking at the prevention benefits of treatment would be the reduction in HIV incidence in the target population. Incidence is however very difficult to measure. ‘Community viral load’ has been proposed as an alternative. However its estimation using data collected either in a routine clinical setting or from a cohort study can suffer from bias, due to the population included not being representative of the wider population of people living with HIV.

This paper describes a study among gay men and other men who have sex with men and people who inject drugs carried out at 27 sites in India. Participants were recruited using respondent-driven sampling (in which respondents recruit their peers to produce a generally representative sample of hard-to-reach populations). At each site incidence was estimated using a multi-assay algorithm designed to identify seroconversion occurring approximately within the last six months. Five community-based measures of viral load were measured at each site. Of these, the prevalence of HIV viraemia (i.e. the proportion of the population with a viral load greater than 150 copies per mL), was most strongly associated with HIV incidence, while mean viral load among people in-care was not associated. This latter finding is important if a case-based surveillance approach using only data collected at clinics is to be used to estimate incidence. Population ART coverage, a measure of the proportion of the site participants on ART was also strongly correlated with incidence. As this can be measured through a simple questionnaire, rather than lab-based assays, it could be an easily and cheaply obtainable correlate for incidence, albeit one potentially prone to response bias.

Asia
India
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HPV prevalent in a key population in India – potential for vaccination

Prevalence of anal HPV infection among HIV-positive men who have sex with men in India.

Hernandez AL, Karthik R, Sivasubramanian M, Raghavendran A, Gnanamony M, Lensing S, Lee JY, Kannangai R, Abraham P, Mathai D, Palefsky JM. J Acquir Immune Defic Syndr. 2016 Apr 1;71(4):437-43. doi: 10.1097/QAI.0000000000000855.

Background: India has a large population of HIV-positive individuals, including men who have sex with men (MSM), and the incidence of human papillomavirus (HPV)-related cancers is high. In developed countries, HIV-positive MSM exhibit the highest prevalence of anal HPV infection and incidence of anal cancer. Little is known about anal HPV infection in HIV-positive Indian MSM.

Methods: We evaluated 300 HIV-positive MSM from 2 cities in India. Men were tested for anal HPV infection using L1-HPV DNA polymerase chain reaction with probes specific for 29 types and a mixture of 10 additional types. CD4 level and plasma HIV viral load were measured. Participants completed an interviewer-administered questionnaire including a sexual history.

Results: The prevalence of anal HPV was 95% (95% confidence interval: 91% to 97%). The 3 most common types were HPV 35 (20%), HPV 16 (13%), and HPV 6/11 (13%). History of taking antiretroviral medications decreased risk of anal HPV 16 infection [relative risk (RR): 0.6 (0.4-1.0)]. Having an increased number of vaginal sex partners lowered risk of any anal HPV infection. Ever having receptive sex increased risk of any anal HPV [RR: 1.2 (1.1-1.4)] and anal HPV 16 [RR: 6.5 (1.8-107)].

Conclusions: Almost all Indian HIV-positive MSM had anal HPV infection. The prevalence of HPV 16 was lower and the prevalence of other oncogenic HPV types was higher than in similar populations in North America and Europe. Vaccine-based prevention strategies for HPV infection in India should consider potential differences in HPV type distribution among HIV-infected MSM when designing interventions.

Abstract access  

Editor’s notes: This is the first report of anal human papilloma virus (HPV) prevalence and associated risk factors among HIV-positive gay men and other men who have sex with men in India. The incidence of HPV-associated anogenital disease is high in Indian men and women. Given that Indian men who are HIV-positive have an increased risk of anal cancer compared to HIV negative men, data on HPV infection in this population is warranted.

The authors report a high prevalence of any HPV type (95%) and any oncogenic HPV type (49%), similar to reports among other HIV-positive gay men and other men who have sex with men in northern America and Europe. An important distinction within this cohort is that many of these men self-identify as bisexual. Just under half (47%) reported being married and two-thirds (62%) reported having at least one female sex partner in their lifetime. This finding has important implications for HPV transmission between gay men and other men who have sex with men and female partners, given the high HPV prevalence in this population. HPV vaccination of key populations has the potential to reduce this transmission.

HPV vaccination in HIV-negative men and women with evidence of prior infection has been shown to confer protection against infection from other HPV types. Men in this cohort had an average of 1.7 oncogenic HPV infections, and so a broader spectrum vaccine such as the 9-valent vaccine which targets seven of the oncogenic HPV types (16/18/31/33/45/52/58) could still protect against acquisition of other vaccine types. Notably, the most common oncogenic type detected was HPV35 which, although not targeted by any of the currently available vaccines, is implicated in cervical cancer. While HPV16 and 18 are the types most commonly found in anal cancer in the general population and in cervical cancer among HIV-positive and negative women, little is known about the association of HPV types with anal disease in people living with HIV. Additional studies are necessary to firstly determine the incidence of anal cancer among HIV-positive gay men and other men who have sex with men in India, and secondly to evaluate which HPV types are linked to anal disease in order to estimate the fraction of disease that could be prevented through vaccination. Further, HPV vaccination of gay men and other men who have sex with men in India could confer additional protection to their female partners through a reduction in transmission of oncogenic HPV types, resulting in a consequent reduction in cervical disease attributed to these HPV types.   

Comorbidity, Epidemiology
Asia
India
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Profound effect of ART on mortality through reduction of opportunistic infections

Incidence of opportunistic infections and the impact of antiretroviral therapy among HIV-infected adults in low and middle income countries: a systematic review and meta-analysis. 

Low A, Gavriilidis G, Larke N, Lajoie MR, Drouin O, Stover J, Muhe L, Easterbrook P. Clin Infect Dis. 2016 Mar 6. pii: ciw125. [Epub ahead of print]

Background: To understand regional burdens and inform delivery of health services, we conducted a systematic review and meta-analysis to evaluate the effect of antiretroviral therapy (ART) on incidence of key opportunistic infections (OIs) in HIV-infected adults in low and middle-income countries (LMIC).

Methods: Eligible studies describing the cumulative incidence of OIs and proportion on ART from 1990 to November 2013 were identified using multiple databases. Summary incident risks for the ART-naive period, and during and after the first year of ART, were calculated using random effects meta-analyses. Summary estimates from ART subgroups were compared using meta-regression. The number of OI cases and associated costs averted if ART was initiated at CD4 ≥200 cells/µl was estimated using UNAIDS country estimates and global average OI treatment cost per case.

Results: We identified 7965 citations, and included 126 studies describing 491 608 HIV-infected persons. In ART-naive patients, summary risk was highest (>5%) for oral candidiasis, tuberculosis, herpes zoster, and bacterial pneumonia. The reduction in incidence was greatest for all OIs during the first 12 months of ART (range 57-91%) except for tuberculosis, and was largest for oral candidiasis, PCP and toxoplasmosis. Earlier ART was estimated to have averted 857 828 cases in 2013 (95% confidence interval [CI], 828 032-874 853), with cost savings of $46.7 million (95% CI, 43.8-49.4).

Conclusions: There was a major reduction in risk for most OIs with ART use in LMICs, with the greatest effect seen in the first year of treatment. ART has resulted in substantial cost savings from OIs averted.

Abstract  Full-text [free] access

Editor’s notes: Opportunistic infections (OIs) remain the major cause of HIV-associated mortality. OIs account for substantially higher mortality in low and middle income countries (LMICs) compared to high income countries (HICs).

This paper describes the results of a systematic review and meta-analysis including about 500 000 people on ART in LMICs across three regions (sub-Saharan Africa, Asia, and Latin America). These large numbers enabled the investigators to look at the effect of ART on the incidence of key OIs during and after the first year of treatment.

Not surprisingly they found that the effect of ART reduced the risk of all OIs during the first year after ART initiation, although the reduction was less for tuberculosis. The authors attribute this to the occurrence of tuberculosis across a wide range of CD4 cell counts, a smaller effect of early immune restoration and the contribution of TB as a manifestation of immune reconstitution syndrome during the first months after ART initiation. Beyond one year after ART initiation, the reduction in tuberculosis was greater.

They conclude that the effect of ART on the incidence of most HIV-associated OIs is the key reason for the global decline in HIV-associated mortality. However, a significant proportion of HIV-positive persons still continue to present with advanced disease. Besides timely ART initiation, additional measures such as CTX prophylaxis, screening for TB and cryptococcal disease, and the use of isoniazid and fluconazole prophylaxis should be considered for late presenters. 

Africa, Asia, Latin America
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Empirical TB treatment no better than isoniazid among people with low CD4 counts and negative TB tests

Empirical tuberculosis therapy versus isoniazid in adult outpatients with advanced HIV initiating antiretroviral therapy (REMEMBER): a multicountry open-label randomised controlled trial. 

Hosseinipour MC, Bisson GP, Miyahara S, Sun X, Moses A, Riviere C, Kirui FK, Badal-Faesen S, Lagat D, Nyirenda M, Naidoo K, Hakim J, Mugyenyi P, Henostroza G, Leger PD, Lama JR, Mohapi L, Alave J, Mave V, Veloso VG, Pillay S, Kumarasamy N, Bao J, Hogg E, Jones L, Zolopa A, Kumwenda J, Gupta A, Adult ACTGAST. Lancet. 2016 Mar 19;387(10024):1198-209. doi: 10.1016/S0140-6736(16)00546-8.

Background: Mortality within the first 6 months after initiating antiretroviral therapy is common in resource-limited settings and is often due to tuberculosis in patients with advanced HIV disease. Isoniazid preventive therapy is recommended in HIV-positive adults, but subclinical tuberculosis can be difficult to diagnose. We aimed to assess whether empirical tuberculosis treatment would reduce early mortality compared with isoniazid preventive therapy in high-burden settings.

Methods: We did a multicountry open-label randomised clinical trial comparing empirical tuberculosis therapy with isoniazid preventive therapy in HIV-positive outpatients initiating antiretroviral therapy with CD4 cell counts of less than 50 cells per µL. Participants were recruited from 18 outpatient research clinics in ten countries (Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda). Individuals were screened for tuberculosis using a symptom screen, locally available diagnostics, and the GeneXpert® MTB/RIF assay when available before inclusion. Study candidates with confirmed or suspected tuberculosis were excluded. Inclusion criteria were liver function tests 2.5 times the upper limit of normal or less, a creatinine clearance of at least 30 mL/min, and a Karnofsky score of at least 30. Participants were randomly assigned (1:1) to either the empirical group (antiretroviral therapy and empirical tuberculosis therapy) or the isoniazid preventive therapy group (antiretroviral therapy and isoniazid preventive therapy). The primary endpoint was survival (death or unknown status) at 24 weeks after randomisation assessed in the intention-to-treat population. Kaplan-Meier estimates of the primary endpoint across groups were compared by the z-test. All participants were included in the safety analysis of antiretroviral therapy and tuberculosis treatment. This trial is registered with ClinicalTrials.gov, number NCT01380080.

Findings: Between Oct 31, 2011, and June 9, 2014, we enrolled 850 participants. Of these, we randomly assigned 424 to receive empirical tuberculosis therapy and 426 to the isoniazid preventive therapy group. The median CD4 cell count at baseline was 18 cells per µL (IQR 9-32). At week 24, 22 (5%) participants from each group died or were of unknown status (95% CI 3.5-7.8) for empirical group and for isoniazid preventive therapy (95% CI 3.4-7.8); absolute risk difference of -0.06% (95% CI -3.05 to 2.94). Grade 3 or 4 signs or symptoms occurred in 50 (12%) participants in the empirical group and 46 (11%) participants in the isoniazid preventive therapy group. Grade 3 or 4 laboratory abnormalities occurred in 99 (23%) participants in the empirical group and 97 (23%) participants in the isoniazid preventive therapy group.

Interpretation: Empirical tuberculosis therapy did not reduce mortality at 24 weeks compared with isoniazid preventive therapy in outpatient adults with advanced HIV disease initiating antiretroviral therapy. The low mortality rate of the trial supports implementation of systematic tuberculosis screening and isoniazid preventive therapy in outpatients with advanced HIV disease.

Abstract access

Editor’s notes: Tuberculosis (TB) remains the leading cause of death among HIV-positive people worldwide. Existing diagnostic tests for TB lack sensitivity, particularly among HIV-positive people, and autopsy studies consistently illustrate that TB is common at death, but often not identified prior to death. This has led to questions about whether empirical TB treatment, meaning treatment for TB in the absence of bacteriological confirmation, should be more widely used among HIV-positive people.

This trial compared empirical TB treatment to isoniazid preventive therapy among adult outpatients with very low CD4 counts starting antiretroviral therapy (ART). People could be enrolled in the study if they did not have confirmed or suspected TB based on symptoms, locally-accessible diagnostic tests (including chest radiography and sputum smear) and, when available, testing with Xpert® MTB/RIF. There was no difference in mortality at six months between participants given empirical TB treatment compared to isoniazid preventive therapy. Mortality was remarkably low overall, particularly considering that participants had very low CD4 counts. It seems likely that the enrolment criteria excluded people at highest risk of death from participating in the study.

Screening for TB at the time of starting ART could reduce mortality if the tests are sufficiently sensitive, and if people identified to have TB receive effective treatment. However, this study was not designed to address how best to do this in resource-limited settings, where chest radiography and Xpert® MTB/RIF are often not accessible. This study does suggest that isoniazid preventive therapy can be given at the time of ART initiation among people who have been effectively screened for TB. The results of other studies of empirical TB treatment, with different designs in different populations, are awaited. Data from all these studies together may provide evidence to guide the optimal package of care for people presenting with advanced HIV disease. 

Comorbidity, HIV Treatment
Africa, Asia, Latin America
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Tenofovir resistance – need for caution but not panic

Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study.

TenoRes Study Group. Lancet Infect Dis. 2016 Jan 28. pii: S1473-3099(15)00536-8. doi: 10.1016/S1473-3099(15)00536-8. [Epub ahead of print]

Background: Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART.

Methods: The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene.

Findings: We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1.50, 95% CI 1.27-1.77 for CD4 cell count <100 cells per µL). Use of lamivudine versus emtricitabine increased the risk of tenofovir resistance across regions (OR 1.48, 95% CI 1.20-1.82). Of 700 individuals with tenofovir resistance, 578 (83%) had cytosine analogue resistance (M184V/I mutation), 543 (78%) had major NNRTI resistance, and 457 (65%) had both. The mean plasma viral load at virological failure was similar in individuals with and without tenofovir resistance (145 700 copies per mL [SE 12 480] versus 133 900 copies per mL [SE 16 650; p=0.626]).

Interpretation: We recorded drug resistance in a high proportion of patients after virological failure on a tenofovir-containing first-line regimen across low-income and middle-income regions. Effective surveillance for transmission of drug resistance is crucial.

Abstract  Full-text [free] access 

Editor’s notes: Global surveillance for tenofovir (TDF) resistance is important at a time of expanding use of TDF-containing regimens for treatment and prevention. This collaborative analysis used data collated from several small studies in different settings. Overall, around one in three people who had failed on TDF-containing treatment had evidence of TDF resistance, although this frequency varied between 20% in Europe to almost 60% in Africa. Mutations associated with NNRTIs and lamivudine/emtricitabine resistance were more common overall and were present in most people with TDF resistance.

The regional variation probably reflects differences in clinical practice and study inclusion criteria. All European studies involved cohorts with frequent viral load monitoring, whereas half of the African cohorts had no routine viral load monitoring. All European studies included people with virologic failure but with low-level viraemia (viral load <1000 copies/ml) whereas almost all African studies included only people with viral load >1000 copies/ml.

While these data provide useful estimates of the frequency of drug resistance mutations in people with virologic failure on first-line ART, there should be caution about extrapolating beyond this. Reports from cohort studies with an accurate denominator of all people starting TDF-containing first-line ART would be useful to give more reliable estimates of overall incidence of acquired TDF resistance. Moreover, there remains a need for representative population-based surveillance for acquired and transmitted drug resistance. So far, global surveillance has detected limited evidence of transmitted TDF-associated mutations, but this needs to be monitored closely, especially in high incidence settings.

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The effects of trauma follow people on the move

A systematic review of HIV risk behaviors and trauma among forced and unforced migrant populations from low and middle-income countries: state of the literature and future directions.

Michalopoulos LM, Aifah A, El-Bassel N. AIDS Behav. 2016 Feb;20(2):243-61. doi: 10.1007/s10461-015-1014-1.

The aim of the current systematic review is to examine the relationship between trauma and HIV risk behaviors among both forced and unforced migrant populations from low and middle income countries (LMIC). We conducted a review of studies published from 1995 to 2014. Data were extracted related to (1) the relationship between trauma and HIV risk behaviors, (2) methodological approach, (3) assessment methods, and (4) differences noted between forced and unforced migrants. A total of 340 records were retrieved with 24 studies meeting inclusion criteria. Our review demonstrated an overall relationship between trauma and HIV risk behaviors among migrant populations in LMIC, specifically with sexual violence and sexual risk behavior. However, findings from 10 studies were not in full support of the relationship. Findings from the review suggest that additional research using more rigorous methods is critically needed to understand the nature of the relationship experienced by this key-affected population.

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Editor’s notes: The number of forced and unforced migrants is growing globally. Refugees, asylum seekers, and internally displaced persons (IDP) are forced migrants who often migrate due to political violence or conflict. Labour migrants are seen as unforced migrants who choose to emigrate for economic reasons. About half of labour migrants worldwide are women who are increasingly migrating on their own being the sole income provider for their families. With respect to trauma exposure and HIV risk in settings of long-term political violence and conflict, the distinction between war migrant, non-war migrant, and long-term resident is blurred. This in-depth review of 24 studies related to low-and middle-income countries (LMIC), mostly from sub-Saharan Africa, found findings similar to those from non-migrant populations in high-income countries. These linked traumatic experiences among migrant populations with HIV risk behaviours. Sexual violence was consistently associated with HIV sexual risk behaviours and HIV infection across the studies. But there are big gaps in the scientific literature. For example, the relationship between trauma and HIV risks has been explored for female labour migrants who are sex workers but not among women who have other occupations. Most studies addressed sexual risk and alcohol dependence, but injecting drug risk behaviours and use of any illicit drugs were virtually ignored by most studies. Few studies examined a possible link for trauma that occurred pre-migration and post-migration. Three qualitative studies examined male migrants who have sex with men, finding that violent experiences and discrimination and stigma associated with homophobia, combined with other migrant-associated traumas, can compound their mental health outcomes and subsequent HIV risk behaviours – but all were only conducted in the last four years. No studies were found that focused on HIV prevention programmes to address trauma and HIV risks among migrant workers in LMIC. However, the studies do reveal important factors that prevention programmes would have to consider. For example, concerns among labour migrants about dangerous working conditions may take precedence over HIV risk perceptions and the need for safer sex. This systematic review presents a wealth of information while highlighting the need to improve the quality of scientific research examining the link between HIV and trauma among both forced and unforced migrants in LMIC. 

Africa, Asia, Europe, Latin America
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