Articles tagged as "Dominican Republic"

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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Violence experience of women living with HIV: a global study

Violence. Enough already: findings from a global participatory survey among women living with HIV.

Orza L, Bewley S, Chung C, Crone ET, Nagadya H, Vazquez M, Welbourn A. J Int AIDS Soc. 2015 Dec 1;18(6 Suppl 5):20285. doi: 10.7448/IAS.18.6.20285. eCollection 2015.

Introduction: Women living with HIV are vulnerable to gender-based violence (GBV) before and after diagnosis, in multiple settings. This study's aim was to explore how GBV is experienced by women living with HIV, how this affects women's sexual and reproductive health (SRH) and human rights (HR), and the implications for policymakers.

Methods: A community-based, participatory, user-led, mixed-methods study was conducted, with women living with HIV from key affected populations. Simple descriptive frequencies were used for quantitative data. Thematic coding of open qualitative responses was performed and validated with key respondents.

Results: In total, 945 women living with HIV from 94 countries participated in the study. Eighty-nine percent of 480 respondents to an optional section on GBV reported having experienced or feared violence, either before, since and/or because of their HIV diagnosis. GBV reporting was higher after HIV diagnosis (intimate partner, family/neighbours, community and health settings). Women described a complex and iterative relationship between GBV and HIV occurring throughout their lives, including breaches of confidentiality and lack of SRH choice in healthcare settings, forced/coerced treatments, HR abuses, moralistic and judgemental attitudes (including towards women from key populations), and fear of losing child custody. Respondents recommended healthcare practitioners and policymakers address stigma and discrimination, training, awareness-raising, and HR abuses in healthcare settings.

Conclusions: Respondents reported increased GBV with partners and in families, communities and healthcare settings after their HIV diagnosis and across the life-cycle. Measures of GBV must be sought and monitored, particularly within healthcare settings that should be safe. Respondents offered policymakers a comprehensive range of recommendations to achieve their SRH and HR goals. Global guidance documents and policies are more likely to succeed for the end-users if lived experiences are used.

Abstract  Full-text [free] access

Editor’s notes: Violence against women who are living with HIV is common globally. This paper reports on a study of 832 women living with HIV from 94 countries who participated in an online survey, recruited through a non-random snowball sampling model. The survey comprised quantitative and qualitative (free text) components. Participants included women who had ever or were currently using injection drugs (14%), who had ever or were currently selling sex (14%), and who had ever or were currently homeless (14%). Lifetime experience of violence among respondents was high (86%). Perpetrators included: intimate partner (59%), family member / neighbour (45%), community member (53%), health care workers (53%) and police, military, prison or detention services (17%). Findings suggest that violence is not a one off occurrence and cannot easily be packaged as a cause or a consequence of HIV. Instead violence occurs throughout women’s lives, takes multiple forms, and has a complex and iterative relationship with HIV.

The study population did not represent all women living with HIV, and was biased towards women with internet access who have an activist interest. Nonetheless, the study provides further evidence of the breadth and frequency of gender based violence experienced by women living with HIV. Key recommendations for policy makers include training of health care workers working in sexual and reproductive services to offer non-discriminatory services to women living with HIV and to effectively respond to disclosures of gender based violence (such as intimate partner violence) as part of the package of care.

Algeria, Angola, Argentina, Armenia, Australia, Austria, Azerbaijan, Belarus, Belgium, Belize, Bolivarian Republic of Venezuela, Bolivia, Botswana, Burkina Faso, Burundi, Cambodia, Cameroon, Canada, Chile, China, Colombia, Costa Rica, Côte d'Ivoire, Czech Republic, Democratic Republic of the Congo, Denmark, Dominican Republic, Ecuador, El Salvador, Estonia, Ethiopia, France, Gabon, Germany, Ghana, Greece, Guatemala, Honduras, Hungary, India, Indonesia, Ireland, Italy, Jamaica, Kazakhstan, Kenya, Kyrgyzstan, Lesotho, Malawi, Mali, Mexico, Moldova, Morocco, Mozambique, Myanmar, Namibia, Nepal, Netherlands, New Zealand, Nicaragua, Nigeria, Norway, Panama, Paraguay, Peru, Poland, Republic of the Congo, Romania, Russian Federation, Rwanda, Serbia, South Africa, Spain, Sri Lanka, Sudan, Swaziland, Switzerland, Tajikistan, Togo, Transdniestria, Turkey, Uganda, Ukraine, United Kingdom, United Republic of Tanzania, United States of America, Uruguay, Uzbekistan, Viet Nam, Zambia, Zimbabwe
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Expanding ART access: increasing costs

The HIV treatment gap: estimates of the financial resources needed versus available for scale-up of antiretroviral therapy in 97 countries from 2015 to 2020.

Dutta A, Barker C, Kallarakal A. PLoS Med. 2015 Nov 24;12(11):e1001907. doi: 10.1371/journal.pmed.1001907. eCollection 2015.

Background: The World Health Organization (WHO) released revised guidelines in 2015 recommending that all people living with HIV, regardless of CD4 count, initiate antiretroviral therapy (ART) upon diagnosis. However, few studies have projected the global resources needed for rapid scale-up of ART. Under the Health Policy Project, we conducted modeling analyses for 97 countries to estimate eligibility for and numbers on ART from 2015 to 2020, along with the facility-level financial resources required. We compared the estimated financial requirements to estimated funding available.

Methods and findings: Current coverage levels and future need for treatment were based on country-specific epidemiological and demographic data. Simulated annual numbers of individuals on treatment were derived from three scenarios: (1) continuation of countries' current policies of eligibility for ART, (2) universal adoption of aspects of the WHO 2013 eligibility guidelines, and (3) expanded eligibility as per the WHO 2015 guidelines and meeting the Joint United Nations Programme on HIV/AIDS "90-90-90" ART targets. We modeled uncertainty in the annual resource requirements for antiretroviral drugs, laboratory tests, and facility-level personnel and overhead.

We estimate that 25.7 (95% CI 25.5, 26.0) million adults and 1.57 (95% CI 1.55, 1.60) million children could receive ART by 2020 if countries maintain current eligibility plans and increase coverage based on historical rates, which may be ambitious. If countries uniformly adopt aspects of the WHO 2013 guidelines, 26.5 (95% CI 26.0 27.0) million adults and 1.53 (95% CI 1.52, 1.55) million children could be on ART by 2020. Under the 90-90-90 scenario, 30.4 (95% CI 30.1, 30.7) million adults and 1.68 (95% CI 1.63, 1.73) million children could receive treatment by 2020. The facility-level financial resources needed for scaling up ART in these countries from 2015 to 2020 are estimated to be US$45.8 (95% CI 45.4, 46.2) billion under the current scenario, US$48.7 (95% CI 47.8, 49.6) billion under the WHO 2013 scenario, and US$52.5 (95% CI 51.4, 53.6) billion under the 90-90-90 scenario. After projecting recent external and domestic funding trends, the estimated 6-y financing gap ranges from US$19.8 billion to US$25.0 billion, depending on the costing scenario and the U.S. President's Emergency Plan for AIDS Relief contribution level, with the gap for ART commodities alone ranging from US$14.0 to US$16.8 billion. The study is limited by excluding above-facility and other costs essential to ART service delivery and by the availability and quality of country- and region-specific data.

Conclusions: The projected number of people receiving ART across three scenarios suggests that countries are unlikely to meet the 90-90-90 treatment target (81% of people living with HIV on ART by 2020) unless they adopt a test-and-offer approach and increase ART coverage. Our results suggest that future resource needs for ART scale-up are smaller than stated elsewhere but still significantly threaten the sustainability of the global HIV response without additional resource mobilization from domestic or innovative financing sources or efficiency gains. As the world moves towards adopting the WHO 2015 guidelines, advances in technology, including the introduction of lower-cost, highly effective antiretroviral regimens, whose value are assessed here, may prove to be "game changers" that allow more people to be on ART with the resources available.

Abstract Full-text [free] access

Editor’s notes: This is a complex and important paper that seeks to understand the financial requirements necessary to: a) continue countries’ current policies of eligibility for ART, b) roll out universal adoption of certain aspects of WHO 2013 eligibility guidelines, and c) expand eligibility as per WHO 2015 guidelines and meeting the Joint United Nations Programme on HIV/AIDS ‘90-90-90’ targets.

The authors estimated the number of adults and children eligible for and receiving HIV treatment, as well as the cost of providing ART in 97 countries across six regions, covering different income levels. They estimated that 25.7 million adults and 1.57 million children could receive ART by 2020 if countries maintain the current eligibility strategies. If countries adopted WHO 2013 eligibility guidelines, 26.5 million adults and 1.53 million children would be on ART by 2020, and if they adopted the 90-90-90 scenario, 30.4 million adults and 1.68 million children could receive treatment by then. The financial resources necessary for this scale up are estimated to be US$ 45.8 billion under current eligibility, US$ 48.7 billion under WHO 2013 scenario and US$ 52.5 billion under the 90-90-90 scenario. The estimated funding gap for the six year period ranges between US$ 20 and US$ 25 billion. In this study, the costs of commodities were taken directly from data collated by other organisations.  No empirical cost estimates of service delivery were made.  Nor was there an attempt to understand the cost implications of the development synergies and social and programme enablers that may be needed to increase the number of people living with HIV knowing their status.  The new WHO recommendations need to be actively pursued if we are to meet targets, rather than passively continuing with “business as usual”. 

Nonetheless, the findings of this study highlight the gap between guidelines written by WHO and very real programmatic obstacles on the ground. There is evidence to suggest that universal test-and-treat strategies could lead to substantially improved health outcomes at the population level, as well as potentially being cost-saving in the long-term. However, as the authors have illustrated, it would require increased levels of funding. What needs to be explored further now is how to overcome the logistical hurdles of rolling out such an initiative. Changing systems and practices is costly and takes time. Health workers will have to be retrained, data collection strategies will have to be revised. Expanding treatment may also mean increasing the number of health staff working on this initiative, which has an opportunity cost that may reverberate in other parts of the health system. Substantially altering health service provision, particularly in weak health systems, may have knock-on effects with unexpected and unintended consequences.

WHO guidelines serve a vital purpose of giving us a goal to aim for. But studies like this one help us know if and how we can get there. 

Africa, Asia, Europe, Latin America, Oceania
Algeria, Angola, Armenia, Azerbaijan, Bahamas, Bangladesh, Barbados, Belarus, Belize, Benin, Bhutan, Bolivia, Botswana, Bulgaria, Burkina Faso, Burundi, Cambodia, Cameroon, Central African Republic, Chad, China, Comoros, Côte d'Ivoire, Cuba, Democratic Republic of the Congo, Djibouti, Dominican Republic, Egypt, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Gambia, Georgia, Ghana, Guatemala, Guinea, Guinea-Bissau, Guyana, Haiti, Honduras, India, Indonesia, Iran (Islamic Republic of), Jamaica, Kazakhstan, Kenya, Kyrgyzstan, Lao People's Democratic Republic, Lesotho, Liberia, Madagascar, Malawi, Malaysia, Mali, Mauritania, Mauritius, Moldova, Mongolia, Morocco, Mozambique, Myanmar, Namibia, Nepal, Nicaragua, Niger, Nigeria, Pakistan, Papua New Guinea, Philippines, Republic of the Congo, Romania, Russia, Rwanda, Senegal, Serbia and Montenegro, Sierra Leone, Somalia, South Africa, Sri Lanka, Sudan, Suriname, Swaziland, Tajikistan, Thailand, Togo, Trinidad and Tobago, Tunisia, Uganda, Ukraine, United Republic of Tanzania, Uzbekistan, Viet Nam, Yemen, Zambia, Zimbabwe
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Better integration of programmes against alcohol use necessary at every step of the HIV treatment cascade

The impact of alcohol use and related disorders on the HIV continuum of care: a systematic review: alcohol and the HIV continuum of care.

Vagenas P, Azar MM, Copenhaver MM, Springer SA, Molina PE, Altice FL. Curr HIV/AIDS Rep. 2015 Sep 28. [Epub ahead of print]

Alcohol use is highly prevalent globally with numerous negative consequences to human health, including HIV progression, in people living with HIV (PLH). The HIV continuum of care, or treatment cascade, represents a sequence of targets for intervention that can result in viral suppression, which ultimately benefits individuals and society. The extent to which alcohol impacts each step in the cascade, however, has not been systematically examined. International targets for HIV treatment as prevention aim for 90% of PLH to be diagnosed, 90% of them to be prescribed with antiretroviral therapy (ART), and 90% to achieve viral suppression; currently, only 20% of PLH are virally suppressed. This systematic review, from 2010 through May 2015, found 53 clinical research papers examining the impact of alcohol use on each step of the HIV treatment cascade. These studies were mostly cross-sectional or cohort studies and from all income settings. Most (77 %) found a negative association between alcohol consumption on one or more stages of the treatment cascade. Lack of consistency in measurement, however, reduced the ability to draw consistent conclusions. Nonetheless, the strong negative correlations suggest that problematic alcohol consumption should be targeted, preferably using evidence-based behavioral and pharmacological interventions, to indirectly increase the proportion of PLH achieving viral suppression, to achieve treatment as prevention mandates, and to reduce HIV transmission.

Abstract access 

Editor’s notes: This systematic review examined the impact of alcohol consumption on each step of the HIV treatment cascade. This covered HIV diagnosis, linkage to care, retention in care, ART initiation and adherence, and sustained virologic suppression. Overall, there was an association between alcohol consumption and negative consequences on various steps of the treatment cascade. The majority of studies focused on the effect of alcohol use disorders and ART adherence, and on viral suppression. There was fairly consistent evidence of reduced adherence among people with alcohol use disorders. Key findings of this review include the lack of consistency in studies of alcohol consumption. Many studies are not using standardised, validated, measures such as the AUDIT, and there is the lack of studies on the association of alcohol use with earlier stages of the cascade, including testing uptake and linkage to care. Further studies in this area would be useful, to identify whether programmes focused on problematic alcohol use are necessary at HIV testing centres.

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TAF: a new, safer version of tenofovir?

Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials.

Sax PE, Wohl D, Yin MT, Post F, DeJesus E, Saag M, Pozniak A, Thompson M, Podzamczer D, Molina JM, Oka S, Koenig E, Trottier B, Andrade-Villanueva J, Crofoot G, Custodio JM, Plummer A, Zhong L, Cao H, Martin H, Callebaut C, Cheng AK, Fordyce MW, McCallister S, GS-US-292-0104/0111 Study Team. Lancet. 2015 Jun 27;385(9987):2606-15. doi: 10.1016/S0140-6736(15)60616-X. Epub 2015 Apr 15.

Background: Tenofovir disoproxil fumarate can cause renal and bone toxic effects related to high plasma tenofovir concentrations. Tenofovir alafenamide is a novel tenofovir prodrug with a 90% reduction in plasma tenofovir concentrations. Tenofovir alafenamide-containing regimens can have improved renal and bone safety compared with tenofovir disoproxil fumarate-containing regimens.

Methods: In these two controlled, double-blind phase 3 studies, we recruited treatment-naive HIV-infected patients with an estimated creatinine clearance of 50 mL per min or higher from 178 outpatient centres in 16 countries. Patients were randomly assigned (1:1) to receive once-daily oral tablets containing 150 mg elvitegravir, 150 mg cobicistat, 200 mg emtricitabine, and 10 mg tenofovir alafenamide (E/C/F/tenofovir alafenamide) or 300 mg tenofovir disoproxil fumarate (E/C/F/tenofovir disoproxil fumarate) with matching placebo. Randomisation was done by a computer-generated allocation sequence (block size 4) and was stratified by HIV-1 RNA, CD4 count, and region (USA or ex-USA). Investigators, patients, study staff, and those assessing outcomes were masked to treatment group. All participants who received one dose of study drug were included in the primary intention-to-treat efficacy and safety analyses. The main outcomes were the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL at week 48 as defined by the US Food and Drug Administration (FDA) snapshot algorithm (pre-specified non-inferiority margin of 12%) and pre-specified renal and bone endpoints at 48 weeks. These studies are registered with ClinicalTrials.gov, numbers NCT01780506 and NCT01797445.

Findings: We recruited patients from Jan 22, 2013, to Nov 4, 2013 (2175 screened and 1744 randomly assigned), and gave treatment to 1733 patients (866 given E/C/F/tenofovir alafenamide and 867 given E/C/F/tenofovir disoproxil fumarate). E/C/F/tenofovir alafenamide was non-inferior to E/C/F/tenofovir disoproxil fumarate, with 800 (92%) of 866 patients in the tenofovir alafenamide group and 784 (90%) of 867 patients in the tenofovir disoproxil fumarate group having plasma HIV-1 RNA less than 50 copies per mL (adjusted difference 2.0%, 95% CI -0.7 to 4.7). Patients given E/C/F/tenofovir alafenamide had significantly smaller mean serum creatinine increases than those given E/C/F/tenofovir disoproxil fumarate (0.08 vs 0.12 mg/dL; p<0.0001), significantly less proteinuria (median % change -3 vs 20; p<0.0001), and a significantly smaller decrease in bone mineral density at spine (mean % change -1.30 vs -2.86; p<0.0001) and hip (-0.66 vs -2.95; p<0.0001) at 48 weeks.

Interpretation: Through 48 weeks, more than 90% of patients given E/C/F/tenofovir alafenamide or E/C/F/tenofovir disoproxil fumarate had virological success. Renal and bone effects were significantly reduced in patients given E/C/F/tenofovir alafenamide. Although these studies do not have the power to assess clinical safety events such as renal failure and fractures, our data suggest that E/C/F/tenofovir alafenamide will have a favourable long-term renal and bone safety profile.

Abstract access 

Editor’s notes: Tenofovir alafenamide fumarate (TAF) is a new antiretroviral agent developed by Gilead Sciences and is closely related to tenofovir disoproxil fumarate (TDF).  TDF is widely used, highly potent, and safe in the majority of people but long-term use has been associated with small risks of decreased kidney function, chronic kidney disease, and decreased bone mineral density.  Both TAF and TDF are prodrugs of tenofovir but TAF achieves highly potent concentrations of tenofovir inside HIV-relevant immune cells with much lower plasma concentrations than TDF.  The lower plasma concentration of tenofovir associated with TAF is hypothesised to reduce the toxic effects with regards to kidney and bone health. TAF is also effective at the lower dose of 10-25 mg, compared with the standard TDF dose of 300mg per day.  This may translate into lower drug costs if the lower dose required means lower manufacturing costs.

The authors report the combined results of two phase III, non-inferiority studies comparing the safety and effectiveness of TAF with TDF, funded by Gilead Sciences. In both studies, TAF was co-formulated into one, once-a-day tablet with elvitegravir, cobicistat and emtricitabine. There was a high rate of virologic suppression with the TAF-containing regimen, which was non-inferior to the TDF regimen. Compared to TDF, TAF had significantly more favourable effects on renal and bone parameters, with smaller decreases in creatinine clearance and bone mineral density and smaller increases in proteinuria. The real-world clinical significance of these findings remains to be seen but TAF-containing regimens may offer meaningful safety and cost benefits over TDF regimens in the long-term. The favourable characteristics of TAF have also led to the development of a sustained-release subcutaneous TAF implant, which has recently been evaluated in dogs. A long-acting TAF implant could have translational potential as a candidate for HIV prophylaxis in vulnerable populations.

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Increasing transmitted resistance to antiretroviral therapy in low/middle-income countries - highest prevalence in MSM

Global burden of transmitted HIV drug resistance and HIV-exposure categories: a systematic review and meta-analysis.

Pham QD, Wilson DP, Law MG, Kelleher AD, Zhang L. AIDS. 2014 Nov 28;28(18):2751-62. doi: 10.1097/QAD.0000000000000494.

Objectives: Our aim was to review the global disparities of transmitted HIV drug resistance (TDR) in antiretroviral-naive MSM, people who inject drugs (PWID) and heterosexual populations in both high-income and low/middle-income countries.

Design/methods: We undertook a systematic review of the peer-reviewed English literature on TDR (1999-2013). Random-effects meta-analyses were performed to pool TDR prevalence and compare the odds of TDR across at-risk groups.

Results: A total of 212 studies were included in this review. Areas with greatest TDR prevalence were North America (MSM: 13.7%, PWID: 9.1%, heterosexuals: 10.5%); followed by western Europe (MSM: 11.0%, PWID: 5.7%, heterosexuals: 6.9%) and South America (MSM: 8.3%, PWID: 13.5%, heterosexuals: 7.5%). Our data indicated disproportionately high TDR burdens in MSM in Oceania (Australia 15.5%), eastern Europe/central Asia (10.2%) and east Asia (7.8%). TDR epidemics have stabilized in high-income countries, with a higher prevalence (range 10.9-12.6%) in MSM than in PWID (5.2-8.3%) and heterosexuals (6.4-9.0%) over 1999-2013. In low/middle-income countries, TDR prevalence in all at-risk groups in 2009-2013 almost doubled than that in 2004-2008 (MSM: 7.8 vs. 4.2%, P = 0.011; heterosexuals: 4.1 vs. 2.6%, P < 0.001; PWID: 4.8 vs. 2.4%, P = 0.265, respectively). The risk of TDR infection was significantly greater in MSM than that in heterosexuals and PWID. We observed increasing trends of resistance to non-nucleoside reverse transcriptase and protease inhibitors among MSM.

Conclusion: TDR prevalence is stabilizing in high-income countries, but increasing in low/middle-income countries. This is likely due to the low, but increasing, coverage of antiretroviral therapy in these settings. Transmission of TDR is most prevalent among MSM worldwide.

Abstract access 

Editor’s notes: HIV mutates very rapidly, and many early antiretroviral agents had a low genetic barrier to the development of resistance. Thus the emergence of virus resistant to antiretroviral agents, particularly to early drug classes, was inevitable. Surveillance for drug-resistant virus among people with no prior history of taking antiretroviral drugs (transmitted drug resistance) is essential to monitor the spread of drug resistance at population level.

This systematic review aimed to compare transmitted drug resistance in different geographical regions and between subpopulations of HIV-positive people by likely route of transmission. Transmitted resistance was most prevalent in high income settings. This is not surprising given wide use of suboptimal drug regimens before effective triple therapy was available. Reassuringly, the prevalence of transmitted resistance seems to have stabilised in high-income settings. The increase in transmitted resistance in low and middle income countries is of more concern. It is not surprising, given that first-line regimens comprising two nucleoside reverse transcriptase inhibitors and a non-nucleoside reverse transcriptase inhibitor are vulnerable to the development of resistance if the drug supply is interrupted or adherence is suboptimal. In addition, if viral load monitoring is not available, people remain on failing drug regimens for longer, and thus have more risk of transmitting resistant virus.

Within the subpopulations examined in this review, transmitted resistance was consistently higher in men who have sex with men, suggesting that resistance testing prior to treatment is particularly valuable for this population.

Limitations of the review include exclusion of studies that did not compare transmitted resistance between the specified subpopulations, and small sample size in many subgroups.

Continued surveillance for transmitted drug resistance is critical. This is most important in settings where individualised resistance testing is not available. This will ensure that people starting antiretroviral therapy receive treatment that will suppress their viral load effectively. Wider use of viral load monitoring, combined with access to effective second and third line regimens, will also help limit spread of drug resistance.

HIV Treatment
Angola, Argentina, Australia, Austria, Belgium, Benin, Botswana, Brazil, Burkina Faso, Cambodia, Cameroon, Canada, Central African Republic, Chad, China, Côte d'Ivoire, Croatia, Cuba, Cyprus, Denmark, Dominican Republic, El Salvador, Estonia, Ethiopia, France, Gabon, Georgia, Germany, Greece, Guatemala, Honduras, Hong Kong Special Administrative Region of China, Hungary, India, Indonesia, Ireland, Israel, Italy, Japan, Kazakhstan, Kenya, Latvia, Malawi, Malaysia, Moldova, Mozambique, Netherlands, Peru, Philippines, Poland, Portugal, Republic of Korea, Romania, Russia, Rwanda, Slovenia, South Africa, Spain, Swaziland, Sweden, Switzerland, Taiwan, Thailand, Uganda, United Kingdom of Great Britain and Northern Ireland, United Republic of Tanzania, United States of America, Viet Nam, Zambia, Zimbabwe
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Counting and classifying global deaths

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

Murray CJ, Ortblad KF, Guinovart C, et al. Lancet. 2014 Sep 13;384(9947):1005-70. doi: 10.1016/S0140-6736(14)60844-8. Epub 2014 Jul 22.

Background: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occurred since the Millennium Declaration.

Methods: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets.

Findings: Globally in 2013, there were 1.8 million new HIV infections (95% uncertainty interval 1.7 million to 2.1 million), 29.2 million prevalent HIV cases (28.1 to 31.7), and 1.3 million HIV deaths (1.3 to 1.5). At the peak of the epidemic in 2005, HIV caused 1.7 million deaths (1.6 million to 1.9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19.1 million life-years (16.6 million to 21.5 million) have been saved, 70.3% (65.4 to 76.1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$ 4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7.5 million (7.4 million to 7.7 million), prevalence was 11.9 million (11.6 million to 12.2 million), and number of deaths was 1.4 million (1.3 million to 1.5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7.1 million (6.9 million to 7.3 million), prevalence was 11.2 million (10.8 million to 11.6 million), and number of deaths was 1.3 million (1.2 million to 1.4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64.0% of cases (63.6 to 64.3) and 64.7% of deaths (60.8 to 70.3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1.2 million deaths (1.1 million to 1.4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31.5% (15.7 to 44.1). Outside of Africa, malaria mortality has been steadily decreasing since 1990.

Interpretation: Our estimates of the number of people living with HIV are 18.7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action.

Abstract  Full-text [free] access

Editor’s notes: The Global Burden of Disease (GBD) study uses standard methods to compare and track over time national distributions of deaths by cause, and the prevalence of disease and disability.  This detailed report focuses on HIV, TB and Malaria. It presents regional summaries of incidence, prevalence and mortality rates, and national estimates of the number of male and female deaths and new infections. Point estimates are shown for 2013, and annualised rates of change for 1990-2000 and 2000-2013. These highlight the contrasting trends in disease impact before and after the formulation of the Millennium Development Goal to combat these diseases.  The global peak of HIV mortality occurred in 2005, but regional annualised rates of change for 2000-2013 indicate that HIV deaths are still increasing significantly in east Asia, southern Africa, and most rapidly in eastern Europe.

The GBD 2013 global estimates of new infections and deaths agree closely with the corresponding estimates made by UNAIDS. But there are significant differences in the respective estimates of the number of people currently living with HIV (UNAIDS estimates are some 18% higher), and historical trends in AIDS deaths, with UNAIDS judging that the recent fall has been steeper. These differences are attributed primarily to methods used in the GBD study to ensure that the sum of deaths from specific causes fits the estimated all cause total, and to varying assumptions about historical survival patterns following HIV infection. 

It may be worthwhile to look at a comment by Michel Sidibé, Mark Dybul, and Deborah Birx in the Lancet on MDG 6 and beyond: from halting and reversing AIDS to ending the epidemic which refers to this study.

Epidemiology
Afghanistan, Albania, Algeria, Andorra, Angola, Antigua and Barbuda, Argentina, Australia, Austria, Bahamas, Bahrain, Bangladesh, Barbados, Belarus, Belgium, Belize, Benin, Bhutan, Bolivia, Bosnia and Herzegovina, Botswana, Brazil, Bulgaria, Burkina Faso, Burundi, Cambodia, Cameroon, Canada, Cape Verde, Central African Republic, Chad, Chile, China, Colombia, Comoros, Congo, Costa Rica, Côte d'Ivoire, Croatia, Cuba, Cyprus, Czech Republic, Democratic People's Republic of Korea, Democratic Republic of the Congo, Democratic Republic of Timor-Leste, Denmark, Djibouti, Dominica, Dominican Republic, Ecuador, Egypt, El Salvador, Equatorial Guinea, Eritrea, Estonia, Ethiopia, Fiji, Finland, France, Gabon, Gambia, Germany, Ghana, Greece, Grenada, Guatemala, Guinea, Guinea-Bissau, Guyana, Haiti, Honduras, Hungary, Iceland, India, Indonesia, Iran (Islamic Republic of), Iraq, Ireland, Israel, Italy, Jamaica, Jordan, Kazakhstan, Kenya, Kiribati, Kuwait, Kyrgyzstan, Lao People's Democratic Republic, Latvia, Lebanon, Lesotho, Liberia, Libyan Arab Jamahiriya, Lithuania, Luxembourg, Madagascar, Malawi, Malaysia, Maldives, Mali, Malta, Marshall Islands, Mauritania, Mauritius, Mexico, Micronesia (Federated States of), Monaco, Mongolia, Morocco, Mozambique, Myanmar, Namibia, Nepal, Netherlands, New Zealand, Nicaragua, Niger, Nigeria, Norway, Oman, Pakistan, Palestinian Territory, Occupied, Panama, Papua New Guinea, Paraguay, Peru, Philippines, Poland, Portugal, Qatar, Romania, Russian Federation, Rwanda, Saint Lucia, Saint Vincent and the Grenadines, Samoa, Sao Tome and Principe, Saudi Arabia, Senegal, Serbia and Montenegro, Seychelles, Sierra Leone, Slovakia, Slovenia, Solomon Islands, Somalia, South Africa, Spain, Sri Lanka, Sudan, Suriname, Swaziland, Sweden, Switzerland, Syrian Arab Republic, Taiwan, Tajikistan, Thailand, Togo, Tonga, Trinidad and Tobago, Tunisia, Turkey, Turkmenistan, Uganda, Ukraine, United States of America, Uruguay, Uzbekistan, Vanuatu, Venezuela, Viet Nam, Yemen, Zimbabwe
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More data needed from routine programme data on antiretroviral therapy cascade outcomes among female sex workers

Antiretroviral therapy uptake, attrition, adherence and outcomes among HIV-infected female sex workers: a systematic review and meta-analysis.

Mountain E, Mishra S, Vickerman P, Pickles M, Gilks C, Boily MC. PLoS One. 2014 Sep 29;9(9):e105645. doi: 10.1371/journal.pone.0105645. eCollection 2014.

Purpose: We aimed to characterize the antiretroviral therapy (ART) cascade among female sex workers (FSWs) globally.

Methods: We systematically searched PubMed, Embase and MEDLINE in March 2014 to identify studies reporting on ART uptake, attrition, adherence, and outcomes (viral suppression or CD4 count improvements) among HIV-infected FSWs globally. When possible, available estimates were pooled using random effects meta-analyses (with heterogeneity assessed using Cochran's Q test and I2 statistic).

Results: 39 studies, reporting on 21 different FSW study populations in Asia, Africa, North America, South America, and Central America and the Caribbean, were included. Current ART use among HIV-infected FSWs was 38% (95% CI: 29%-48%, I2 = 96%, 15 studies), and estimates were similar between high-, and low- and middle-income countries. Ever ART use among HIV-infected FSWs was greater in high-income countries (80%; 95% CI: 48%-94%, I2 = 70%, 2 studies) compared to low- and middle-income countries (36%; 95% CI: 7%-81%, I2 = 99%, 3 studies). Loss to follow-up after ART initiation was 6% (95% CI: 3%-11%, I2 = 0%, 3 studies) and death after ART initiation was 6% (95% CI: 3%-11%, I2 = 0%, 3 studies). The fraction adherent to ≥95% of prescribed pills was 76% (95% CI: 68%-83%, I2 = 36%, 4 studies), and 57% (95% CI: 46%-68%, I2 = 82%, 4 studies) of FSWs on ART were virally suppressed. Median gains in CD4 count after 6 to 36 months on ART, ranged between 103 and 241 cells/mm3 (4 studies).

Conclusions: Despite global increases in ART coverage, there is a concerning lack of published data on HIV treatment for FSWs. Available data suggest that FSWs can achieve levels of ART uptake, retention, adherence, and treatment response comparable to that seen among women in the general population, but these data are from only a few research settings. More routine programme data on HIV treatment among FSWs across settings should be collected and disseminated.

Abstract  Full-text [free] access

Editor’s notes: Female sex workers remain a key population for HIV prevention, treatment and care. This is the first paper to systematically review and quantify the HIV treatment cascade among sex workers globally. The review highlights the scarcity of published data on HIV treatment among sex workers. For example, data were identified from only five countries in sub-Saharan Africa (Benin, Burkina Faso, Kenya, Rwanda and Zimbabwe) and a lack of data from routine (non research) settings. Further, most studies presented data on current antiretroviral therapy (ART) or CD4 count at initiation rather than follow-up data on attrition, adherence or viral suppression. The results suggest that research cohorts have been largely successful at enrolling and retaining female sex workers on ART, but there may be an issue with adherence. Adherence, in the few studies where it was measured (usually by self-report or pill counts) was high, and similar to estimates from the general population. But just over half of the participants initiating ART achieved viral suppression in the four studies which looked at this. This indicates scope for improvements in adherence (and adherence measurement) in these populations. This is possibly due to individual-level and structural-level barriers that sex workers face when receiving HIV treatment and care

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How can we improve the UNAIDS modes of transmission model?

The HIV modes of transmission model: a systematic review of its findings and adherence to guidelines.

Shubber Z, Mishra S, Vesga JF, Boily MC. J Int AIDS Soc. 2014 Jun 23;17:18928. doi: 10.7448/IAS.17.1.18928. eCollection 2014.

Introduction: The HIV Modes of Transmission (MOT) model estimates the annual fraction of new HIV infections (FNI) acquired by different risk groups. It was designed to guide country-specific HIV prevention policies. To determine if the MOT produced context-specific recommendations, we analyzed MOT Results by region and epidemic type, and explored the factors (e.g. data used to estimate parameter inputs, adherence to guidelines) influencing the differences.

Methods: We systematically searched MEDLINE, EMBASE and UNAIDS reports, and contacted UNAIDS country directors for published MOT Results from MOT inception (2003) to 25 September 2012.

Results: We retrieved four journal articles and 20 UNAIDS reports covering 29 countries. In 13 countries, the largest FNI (range 26 to 63%) was acquired by the low-risk group and increased with low-risk population size. The FNI among female sex workers (FSWs) remained low (median 1.3%, range 0.04 to 14.4%), with little variability by region and epidemic type despite variability in sexual behaviour. In India and Thailand, where FSWs play an important role in transmission, the FNI among FSWs was 2 and 4%, respectively. In contrast, the FNI among men who have sex with men (MSM) varied across regions (range 0.1 to 89%) and increased with MSM population size. The FNI among people who inject drugs (PWID, range 0 to 82%) was largest in early-phase epidemics with low overall HIV prevalence. Most MOT studies were conducted and reported as per guidelines but data quality remains an issue.

Conclusions: Although countries are generally performing the MOT as per guidelines, there is little variation in the FNI (except among MSM and PWID) by region and epidemic type. Homogeneity in MOT FNI for FSWs, clients and low-risk groups may limit the utility of MOT for guiding country-specific interventions in heterosexual HIV epidemics.

 Abstract  Full-text [free] access

Editor’s notes: In 2002, the HIV Modes of Transmission model (MoT) was developed by UNAIDS to inform and focus, country-specific HIV prevention policies. The idea behind the model was to use simple mathematical modelling approaches, in combination with country specific data, to predict what the distribution of new HIV infection may look like. In this way, countries would be able to better focus their HIV response. Since its development and through 2012, the MoT has been applied in 29 countries, with the findings being used in many settings to shape priorities. In this study, the authors assess the degree to which the MoT produces different outputs in different epidemic contexts. They explore whether there are key parameters in the model that seem to drive similarities and/or differences in projections between countries. Surprisingly, across a broad range of epidemic settings, they found limited variability in the predicted annual fraction of new HIV infections (FNI) acquired by female sex workers (FSW) (0.04-14.4%). There were higher levels of variability between countries in the projected fraction of new HIV infections among men who have sex with men (0.01-89%) and people who inject drugs (0-82%).

The differences in the MoT projections were largely dependent on whether the country in question was categorised as having a concentrated / low-level epidemic, versus generalised epidemic, as defined by UNAIDS. Differences also arose depending upon whether ‘low risk groups’ were also included in the model. Indeed, for 22 of the 25 studies that included a low-risk group, this group was predicted to have a large annual fraction of new HIV infections (11.8-62.9%). This phenomenon arose, not because of high transmission rates in this group (in comparison to others such as MSM or PWIDs) but because these ‘low risk groups’ are large. They are one third of the total population. These findings may be misleading, as the projected high fraction of transmission is dependent on the assumption that everyone in this ‘low risk group’ does have some risk.

It appears that although the MoT was designed to address an important need, it is likely to have limited utility to guide programming in heterosexually driven epidemics.  To address this limitation, UNAIDS is supporting the HIV Modelling Consortium in their development of a revised MoT model that takes into better consideration risk categorization, data constraints and programmatic needs. The revised model is currently undergoing field testing and will be available for country use in 2015.

Africa, Asia, Europe, Latin America
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Renewed prevention efforts needed for key populations in Latin America and the Caribbean

Epidemiology of HIV in Latin America and the Caribbean.

De Boni R, Veloso VG, Grinsztejn B. Curr Opin HIV AIDS. 2014 Jan 3. [Epub ahead of print]

Purpose of review: The aim of the present review is to update HIV/AIDS Epidemiology in Latin America and the Caribbean highlighting the concentrated aspect of epidemic in the region.

Recent findings: Among general population, HIV prevalence in Latin America is at stable levels (0.2-0.7%). The Caribbean still has one of the highest HIV prevalence rates in the world (<0.1-3%), but incidences have declined around 49%. This is not the current situation for high-risk key populations; most incident cases occur among MSM. Available data on transgender women suggest that they are the most-at-risk group. Female sex workers still have a 12-fold chance of being HIV positive compared with other women. IDU prevalence was revised to 0.45%, but non-IDU has been suggested as a mediator between sexual risk and HIV.

Summary: The increase in treatment coverage (mean is at 63%) resulted in modifications of HIV/AIDS epidemiology. New strategies to seek, test and link key populations to care are urgently needed and targeted interventions to prevent HIV expansion among them must be adopted. These strategies should consider the particular situation regarding social inequalities, discrimination and violence that pervade the HIV epidemic among key populations.

Abstract access 

Editor’s notes: This review highlights recently published data on key populations in Latin America and the Caribbean, including men who have sex with men (MSM), transgender women, female sex workers and people who inject drugs. HIV remains a concentrated epidemic in Latin America and the Caribbean with MSM and transgender women being the most vulnerable populations. Although antiretroviral therapy (ART) coverage has increased to over 80% in several countries, a renewed focus on prevention, especially among key populations, is needed. It is estimated that prevention efforts currently only receive 15% of HIV public spending in this region. Culturally appropriate efforts are needed to identify and prevent HIV infection among key populations, and to better understand transmission dynamics of neglected groups such as transgender women. 

Latin America
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