Articles tagged as "Cameroon"

Hepatitis B virus co-infection: a challenge to successful ART in sub-Saharan Africa?

Prevalence of HIV and hepatitis B virus co-infection in sub-Saharan Africa and the potential impact and program feasibility of hepatitis B surface antigen screening in resource-limited settings.

Stabinski L, OʼConnor S, Barnhart M, Kahn RJ, Hamm TE. J Acquir Immune Defic Syndr. 2015 Apr 15;68 Suppl 3:S274-85. doi: 10.1097/QAI.0000000000000496.

Background: Screening people living with HIV for hepatitis B virus (HBV) co-infection is recommended in resource-rich settings to optimize HIV antiretroviral therapy (ART) and mitigate HBV-related liver disease. This review examines the need, feasibility, and impact of screening for HBV in resource-limited settings (RLS).

Methods: We searched 6 databases to identify peer-reviewed publications between 2007 and 2013 addressing (1) HIV/HBV co-infection frequency in sub-Saharan Africa (SSA); (2) performance of hepatitis B surface antigen (HBsAg) rapid strip assays (RSAs) in RLS; (3) impact of HBV co-infection on morbidity, mortality, or liver disease progression; and/or (4) impact of HBV-suppressive antiretroviral medications as part of ART on at least one of 5 outcomes (mortality, morbidity, HIV transmission, retention in HIV care, or quality of life). We rated the quality of individual articles and summarized the body of evidence and expected impact of each intervention per outcome addressed.

Results: Of 3940 identified studies, 85 were included in the review: 55 addressed HIV/HBV co-infection frequency; 6 described HBsAg RSA performance; and 24 addressed the impact of HIV/HBV co-infection and ART. HIV/HBV frequency in sub-Saharan Africa varied from 0% to >28.4%. RSA performance in RLS showed good, although variable, sensitivity and specificity. Quality of studies ranged from strong to weak. Overall quality of evidence for the impact of HIV/HBV co-infection and ART on morbidity and mortality was fair and good to fair, respectively.

Conclusions: Combined, the body of evidence reviewed suggests that HBsAg screening among people living with HIV could have substantial impact on preventing morbidity and mortality among HIV/HBV co-infected individuals in RLS.

Abstract access 

Editor’s notes: The routes of transmission for hepatitis B virus (HBV) and HIV are the same, and they frequently co-infect individuals in high HIV prevalence settings. HIV has also been shown to accelerate the progression of HBV. This has important implications for ART programmes, given also the potential for hepatotoxicity of ART. The response of both infections to certain antivirals gives an opportunity to treat both infections simultaneously, but also the potential to engender resistant strains of virus if treatment is optimised for one and not the other.

This paper reviews the evidence that might support inclusion of HBV screening as part of HIV care programmes. No clinical trials have been done in this area, so the review is based on observational studies. The data are incomplete and geographically patchy, largely from Nigeria and South Africa. However, this does not prevent the authors from concluding that the co-infection risk is sufficiently high and the consequences of lack of treatment sufficiently severe to consider allocation of scarce resources to identify and manage HBV co-infection in HIV programmes. Appropriate validated screening tools - rapid tests for hepatitis B surface antigen - are available. The potential benefit warrants consideration of this issue in sub-Saharan Africa, and inclusion of HBV surveillance alongside HIV to resolve the paucity of data in most countries. This should be rapidly followed by further consideration of the cost- and risk-benefit of introduction of an HBV screening and treatment programme.

Interested readers might also refer to a review by Matthews et al. (J Clin Virol 2014;6:20-33) which considers similar questions and also discusses hepatitis C co-infection.

Avoid TB deaths
Africa
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Hepatitis B virus co-infection: a challenge to successful ART in sub-Saharan Africa?

Prevalence of HIV and hepatitis B virus co-infection in sub-Saharan Africa and the potential impact and program feasibility of hepatitis B surface antigen screening in resource-limited settings.

Stabinski L, OʼConnor S, Barnhart M, Kahn RJ, Hamm TE. J Acquir Immune Defic Syndr. 2015 Apr 15;68 Suppl 3:S274-85. doi: 10.1097/QAI.0000000000000496.

Background: Screening people living with HIV for hepatitis B virus (HBV) co-infection is recommended in resource-rich settings to optimize HIV antiretroviral therapy (ART) and mitigate HBV-related liver disease. This review examines the need, feasibility, and impact of screening for HBV in resource-limited settings (RLS).

Methods: We searched 6 databases to identify peer-reviewed publications between 2007 and 2013 addressing (1) HIV/HBV co-infection frequency in sub-Saharan Africa (SSA); (2) performance of hepatitis B surface antigen (HBsAg) rapid strip assays (RSAs) in RLS; (3) impact of HBV co-infection on morbidity, mortality, or liver disease progression; and/or (4) impact of HBV-suppressive antiretroviral medications as part of ART on at least one of 5 outcomes (mortality, morbidity, HIV transmission, retention in HIV care, or quality of life). We rated the quality of individual articles and summarized the body of evidence and expected impact of each intervention per outcome addressed.

Results: Of 3940 identified studies, 85 were included in the review: 55 addressed HIV/HBV co-infection frequency; 6 described HBsAg RSA performance; and 24 addressed the impact of HIV/HBV co-infection and ART. HIV/HBV frequency in sub-Saharan Africa varied from 0% to >28.4%. RSA performance in RLS showed good, although variable, sensitivity and specificity. Quality of studies ranged from strong to weak. Overall quality of evidence for the impact of HIV/HBV co-infection and ART on morbidity and mortality was fair and good to fair, respectively.

Conclusions: Combined, the body of evidence reviewed suggests that HBsAg screening among people living with HIV could have substantial impact on preventing morbidity and mortality among HIV/HBV co-infected individuals in RLS.

Abstract access 

Editor’s notes: The routes of transmission for hepatitis B virus (HBV) and HIV are the same, and they frequently co-infect individuals in high HIV prevalence settings. HIV has also been shown to accelerate the progression of HBV. This has important implications for ART programmes, given also the potential for hepatotoxicity of ART. The response of both infections to certain antivirals gives an opportunity to treat both infections simultaneously, but also the potential to engender resistant strains of virus if treatment is optimised for one and not the other.

This paper reviews the evidence that might support inclusion of HBV screening as part of HIV care programmes. No clinical trials have been done in this area, so the review is based on observational studies. The data are incomplete and geographically patchy, largely from Nigeria and South Africa. However, this does not prevent the authors to conclude that the co-infection risk is sufficiently high and the consequences of lack of treatment sufficiently severe to consider allocation of scarce resources to identify and manage HBV co-infection in HIV programmes. Appropriate validated screening tools such as rapid tests for hepatitis B surface antigen are available. The potential benefit warrants consideration of this issue in sub-Saharan Africa, and inclusion of HBV surveillance alongside HIV to resolve the paucity of data in most countries. This should be rapidly followed by further consideration of the cost- and risk-benefit of introduction of an HBV screening and treatment programme.

Interested readers might also refer to a review by Matthews et al. (J Clin Virol 2014;6:20-33) which considers similar questions and also discusses hepatitis C co-infection.

Avoid TB deaths
Africa
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Need for further water, sanitation and hygiene programmes among people living with HIV

The impact of water, sanitation, and hygiene interventions on the health and well-being of people living with HIV: a systematic review.

Yates T, Lantagne D, Mintz E, Quick R. J Acquir Immune Defic Syndr. 2015 Apr 15;68 Suppl 3:S318-30. doi: 10.1097/QAI.0000000000000487.

Background: Access to improved water supply and sanitation is poor in low-income and middle-income countries. Persons living with HIV/AIDS (PLHIV) experience more severe diarrhea, hospitalizations, and deaths from diarrhea because of waterborne pathogens than immunocompetent populations, even when on antiretroviral therapy (ART).

Methods: We examined the existing literature on the impact of water, sanitation, and hygiene (WASH) interventions on PLHIV for these outcomes: (1) mortality, (2) morbidity, (3) retention in HIV care, (4) quality of life, and (5) prevention of ongoing HIV transmission. Cost-effectiveness was also assessed. Relevant abstracts and articles were gathered, reviewed, and prioritized by thematic outcomes of interest. Articles meeting inclusion criteria were summarized in a grid for comparison.

Results: We reviewed 3355 citations, evaluated 132 abstracts, and read 33 articles. The majority of the 16 included articles focused on morbidity, with less emphasis on mortality. Contaminated water, lack of sanitation, and poor hygienic practices in homes of PLHIV increase the risk of diarrhea, which can result in increased viral load, decreased CD4 counts, and reduced absorption of nutrients and antiretroviral medication. We found WASH programming, particularly water supply, household water treatment, and hygiene interventions, reduced morbidity. Data were inconclusive on mortality. Research gaps remain in retention in care, quality of life, and prevention of ongoing HIV transmission. Compared with the standard threshold of 3 times GDP per capita, WASH interventions were cost-effective, particularly when incorporated into complementary programs.

Conclusions: Although research is required to address behavioral aspects, evidence supports that WASH programming is beneficial for PLHIV.

Abstract access 

Editor’s notes: Researchers, implementers, and policy makers have been examining how to better integrate programmes with overlapping burdens of morbidity and mortality. This paper illustrates how access to clean water and good sanitation practices, or lack thereof, can impact the health of people living with HIV. Water, sanitation, and hygiene (WASH) programmes can improve the negative effects poor water quality and bad sanitation have on people living with HIV. They reduce or even eliminate diarrheal infections, which allow for better absorption of HIV treatment medication that leads to a reduction in viral load and increased CD4 counts. While this systematic review revealed evidence on the reduced burden of morbidity that WASH programmes can confer, little has been done in the way of research linking WASH programmes to mortality in people living with HIV, nor how they may affect adherence or retention in care. Side effects of HIV treatment is a common reason why people stop taking medications, and common side effects are nausea and diarrhoea. It is possible that intestinal issues caused by unsafe drinking water could exacerbate the impact of side effects on people already experiencing them, therefore reducing motivation to continue taking their ARVs. This paper also suggests that synergies in cost sharing and increasing cost effectiveness could be achieved by integrating programmes. However further research is necessary to fully understand the logistical and cost implications.

 

Africa, Asia
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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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Co-enrolling family members improves retention of women on antiretroviral therapy

Family matters: co-enrollment of family members into care is associated with improved outcomes for HIV-infected women initiating antiretroviral therapy.

Myer L, Abrams EJ, Zhang Y, Duong J, El-Sadr WM, Carter RJ. J Acquir Immune Defic Syndr. 2014 Dec 1;67 Suppl 4:S243-9. doi: 10.1097/QAI.0000000000000379.

Background: Although there is widespread interest in understanding how models of care for delivering antiretroviral therapy (ART) may influence patient outcomes, family-focused approaches have received little attention. In particular, there have been few investigations of whether the co-enrollment of HIV-infected family members may improve adult ART outcomes over time.

Methods: We examined the association between co-enrollment of HIV-infected family members into care and outcomes of women initiating ART in 12 HIV care and treatment programs across sub-Saharan Africa. Using data from the mother-to-child transmission (MTCT) Plus Initiative, women starting ART were categorized according to the co-enrollment of an HIV-infected partner and/or HIV-infected child within the same program. Mortality and loss to follow-up were assessed for up to 5 years after women's ART initiation.

Results: Of the 2877 women initiating ART included in the analysis, 31% (n = 880) had at least 1 HIV-infected family member enrolled into care at the same program, including 24% (n = 689) who had an HIV-infected male partner, and 10% (n = 295) who had an HIV-infected child co-enrolled. There was no significant difference in the risk of death of women by family co-enrollment status (P = 0.286). However, the risk of loss to follow-up was greatest among women who did not have an HIV-infected family member co-enrolled (19% after 36 months on ART) compared with women who had an HIV-infected family member co-enrolled (3%-8% after 36 months on ART) (P < 0.001). These associations persisted after adjustment for demographic and clinical covariates and were consistent across countries and care programs.

Discussion: These data provide novel evidence for the association between adult outcomes on ART and co-enrollment of HIV-infected family members into care at the same program. Interventions that build on women's family contexts warrant further consideration in both research and policies to promote retention in ART services across sub-Saharan Africa.

Abstract  Full-text [free] access

Editor’s notes: With the dramatic increase in the number of people on antiretroviral therapy (ART) over the last decade, further understanding of the impact of different service delivery models on treatment outcomes (including death and retention-in-care) is needed. Previous studies have compared health systems approaches such as primary care versus hospital delivery, task-shifting to nurses and community-based approaches. This study is one of the first to focus on the impact of family-focused approaches on adult outcomes. In this large multi-country study of women enrolled in prevention of mother-to-child transmission programmes, co-enrolment of a family member living with HIV was not associated with mortality among women, but co-enrollment was associated with an approximate halving of the risk of being lost to follow up. This association was consistent across different sub-groups of age, parity, partner status and location. The strength and consistency of the finding highlights the central role that family and social support can play in shaping health-seeking behaviours among people living with HIV. Further research would include the effect of co-enrolment on treatment outcomes among men, and exploration of specific aspects of co-enrolment, such as disclosure. 

Africa
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Which activities promote adherence to antiretroviral therapy?

Interventions to promote adherence to antiretroviral therapy in Africa: a network meta-analysis.

Mills EJ, Lester R, Thorlund K, Lorenzi M, Muldoon K, Kanters S, Linnemayr S, Gross R, Calderon Y, Amico KR, Thirumurthy H, Pearson C, Remien RH, Mbuagbaw L, Thabane L, Chung MH, Wilson IB, Liu A, Uthman OA, Simoni J, Bangsberg D, Yaya S, Bärnighausen T, Ford N, Nachega JB, Lancet HIV 2014; 1: e104–11 doi:10.1016/S2352-3018(14)00003-4.

Background: Adherence to antiretroviral therapy (ART) is necessary for the improvement of the health of patients and for public health. We sought to determine the comparative effectiveness of different interventions for improving ART adherence in HIV-infected people living in Africa.

Methods: We searched for randomised trials of interventions to promote antiretroviral adherence within adults in Africa. We searched AMED, CINAHL, Embase, Medline (via PubMed), and ClinicalTrials.gov from inception to Oct 31, 2014, with the terms “HIV”, “ART”, “adherence”, and “Africa”. We created a network of the interventions by pooling the published and individual patients' data for comparable treatments and comparing them across the individual interventions with Bayesian network meta-analyses. The primary outcome was adherence defined as the proportion of patients meeting trial defined criteria; the secondary endpoint was viral suppression.

Findings: We obtained data for 14 randomised controlled trials, with 7110 patients. Interventions included daily and weekly short message service (SMS; text message) messaging, calendars, peer supporters, alarms, counselling, and basic and enhanced standard of care (SOC). Compared with SOC, we found distinguishable improvement in self-reported adherence with enhanced SOC (odds ratio [OR] 1·46, 95% credibility interval [CrI] 1·06–1·98), weekly SMS messages (1·65, 1·25–2·18), counselling and SMS combined (2·07, 1·22–3·53), and treatment supporters (1·83, 1·36–2·45). We found no compelling evidence for the remaining interventions.

Results: were similar when using viral suppression as an outcome, although the network contained less evidence than that for adherence. Treatment supporters with enhanced SOC (1·46, 1·09–1·97) and weekly SMS messages (1·55, 1·01–2·38) were significantly better than basic SOC.

Interpretation: Several recommendations for improving adherence are unsupported by the available evidence. These findings can inform future intervention choices for improving ART adherence in low-income settings.

Abstract access 

Editor’s notes: To maximise the impact of antiretroviral therapy (ART), people living with HIV should be diagnosed early, enrolled and retained in pre-ART care, initiated on ART and retained in ART care. Long-term adherence to achieve and maintain viral load suppression is the last step in the continuum of HIV care. Engagement along the complete treatment cascade will determine the long-term success of the global response to HIV.

A large number of potential programmes aimed at the improvement of engagement with care are available. While there is an urgent need for research on these programmes and on the effect of combined programmes, there is also the reality of a resource constrained environment. Network meta-analysis is a method to synthesise the evidence of programmes. The meta-analysis uses common comparators when these activities have not been compared head-to-head (resulting in indirect evidence), combined with evidence from head-to-head comparisons (direct evidence).

Using a network meta-analysis of randomized trials of programmes to improve ART adherence in Africa, the authors simultaneously compared eight groups of activities against standard care and against each other. The authors found that standard care augmented with intensified adherence counselling, or enhanced standard care, improved adherence to ART. Also weekly SMS messages, enhanced standard care combined with SMS, and enhanced standard care combined with having a treatment supporter were superior to standard care, with regards to self-reported adherence and viral suppression. The authors speculate that combinations of cognitive and behavioural programmes maximise the activity efficacy. Interestingly, their study found a large benefit for weekly but not for daily SMS messages. However the heterogeneity in the published treatment effects could be attributed to heterogeneity of the implemented programmes, especially of behavioural interventions. For example, the authors point out that there is a wide variability in the definition of standard care, and in the definition of treatment supporters.

The authors also note that several recommendations for improving adherence are unsupported by the evidence they examined using network meta-analysis.

Health care delivery
Africa
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More, older people living with HIV, but how many more?

Increasing trends in HIV prevalence among people aged 50 years and older: evidence from estimates and survey data.

Mahy M, Autenrieth CS, Stanecki K, Wynd S. AIDS. 2014 Sep 12. [Epub ahead of print]

Objective: To present the most recent 2013 UNAIDS estimates of HIV prevalence among people aged 50 years and older, and to validate these estimates using data from national household surveys.

Design: Modelled estimates of HIV prevalence were validated against nationally representative household survey measures of HIV prevalence.

Methods: The UNAIDS 2013 HIV estimates were used to compute HIV prevalence and number of people living with HIV aged 50 years and older. Sex-specific HIV-prevalence rates by 5-year age groups were calculated from nationally representative household surveys conducted between 2003 and 2013, and were compared to prevalence rates from the modelled estimates. The ratios of the prevalence rates from the two sources were analysed.

Results: In 2013, an estimated 4.2 million (4.0-4.5 million) people aged 50 years and older were living with HIV. The global HIV prevalence among older individuals more than doubled in almost all the 5-year age groups since 1995. There was a relatively good agreement between the modelled HIV-prevalence rates and the survey-based rates among men and women aged 50-54 years (0.90 and 0.98 median ratio, respectively), whereas for 55-59-year-olds, the differences were more notable (ratios of 0.63 for men and 0.9 for women).

Conclusion: Both data sources suggest HIV-prevalence rates among people aged over 50 have increased steadily in recent years. Care and treatment services need to address the specific needs of older people living with HIV. Action is needed to incorporate older age groups into HIV surveillance systems.

Abstract access 

Editor’s notes: According to the most recent estimates, the global number of people above age 50 years and living with HIV, has more than doubled since the mid-1990s. In southern Africa, it has more than tripled. These numbers are expected to increase further as treatment programmes continue to expand. This study by the UNAIDS secretariat, underscores the numeric importance of this population subgroup. Above all, it highlights how little we know about the epidemic in older adults. The authors compare UNAIDS (modelled) HIV prevalence estimates with those from nationally representative surveys. They find good correspondence among 50-54 year-old men and women. The discrepancy between the two sources are more pronounced above age 54 years where the UNAIDS figures tend to fall short of the empirical estimates. This is particularly the case for men. HIV prevalence estimates among older women are rather scarce as surveys and data collection at antenatal clinics typically focus on women of reproductive age. Longer than expected survival of people living with HIV and higher than anticipated HIV incidence at older ages, could explain the discrepancy between the estimates. But we need more and better data about these age groups to be in a position to adjudicate between these explanations.

Epidemiology
Africa
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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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No evidence that antiretroviral therapy increases risk taking behaviour

Effects of HIV antiretroviral therapy on sexual and injecting risk-taking behaviour: a systematic review and meta-analysis.

Doyle JS, Degenhardt L, Pedrana AE, McBryde ES, Guy R, Stoove MA, Weaver E, Grulich AE, Lo YR, Hellard ME. Clin Infect Dis. 2014 Aug 4. pii: ciu602. [Epub ahead of print]

Background:  Increased global access and use of HIV antiretroviral therapy (ART) has been postulated to undermine HIV prevention efforts by changing individual risk-taking behaviour. This review aims to determine whether ART use is associated with changes in sexual or injecting risk-taking behaviour or diagnosis of sexually transmitted infections (STIs).

Methods: A systematic review and meta-analysis was conducted of HIV-seropositive participants receiving ART compared to no ART use in experimental or observational studies. Primary outcomes included: (1) any unprotected sexual intercourse; (2) STI diagnoses; and (3) any unsafe injecting behaviour.

Results: Fifty-eight studies met the selection criteria. Fifty-six studies containing 32 857 participants reported unprotected sex; eleven studies containing 16 138 participants reported STI diagnoses; and four studies containing 1 600 participants reported unsafe injecting behaviour. All included studies were observational. Unprotected sex was lower in those receiving ART than those not receiving ART (odds ratio (OR) 0.73, 95%CI 0.64-0.83, p<0.001; heterogeneity I2=79%) in both high-income (n=38) and low-/middle-income country (n=18) settings, without any evidence of publication bias. STI diagnoses were also lower among individuals on ART (OR 0.58, 95%CI 0.33-1.01, p=0.053; I2=92%), however there was no difference in injecting risk-taking behaviour with antiretroviral use (OR 0.90, 95%CI 0.60-1.35, p=0.6; I2=0%).

Conclusions: Despite concerns that use of ART might increase sexual or injecting risk-taking, available research suggests unprotected sex is reduced among HIV-infected individuals on treatment. The reasons for this are not yet clear, though self-selection and mutually reinforcing effects of HIV treatment and prevention messages among people on ART are likely.

Abstract access 

Editor’s notes: Use of antiretroviral therapy (ART) may modify risk perception, leading to increases in risk-taking behaviour and HIV transmission. This has important implications for HIV prevention. In particular in low and middle-income countries, where the global burden of HIV is greatest and where access to, and use of, ART is rapidly increasing. This systematic review identified observational studies comparing risk-taking behaviour in people living with HIV using ART, compared with people not using ART. The review found that ART does not appear to increase reported unprotected anal or vaginal intercourse, newly diagnosed sexually transmitted infections, or unsafe injecting behaviour among people on treatment. The observation that reductions in unprotected sex are associated with ART use should be interpreted cautiously as limited data are available to accurately assess a causal relationship. The current practice of providing ART with counselling, education and ongoing clinical care probably offers the optimal strategy of ensuring that individuals on ART minimise risks associated with unsafe sex. 

Africa, Asia, Europe, Northern America, Oceania
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Hunger hinders antiretroviral therapy adherence

Does food insecurity undermine adherence to antiretroviral therapy? A systematic review.

Singer AW, Weiser SD, McCoy SI. AIDS Behav. 2014 Aug 6. [Epub ahead of print]

A growing body of research has identified food insecurity as a barrier to antiretroviral therapy (ART) adherence. We systematically reviewed and summarized the quantitative literature on food insecurity or food assistance and ART adherence. We identified nineteen analyses from eighteen distinct studies examining food insecurity and ART adherence. Of the thirteen studies that presented an adjusted effect estimate for the relationship between food insecurity and ART adherence, nine found a statistically significant association between food insecurity and sub-optimal ART adherence. Four studies examined the association between food assistance and ART adherence, and three found that ART adherence was significantly better among food assistance recipients than non-recipients. Across diverse populations, food insecurity is an important barrier to ART adherence, and food assistance appears to be a promising intervention strategy to improve ART adherence among persons living with HIV. Additional research is needed to determine the effectiveness and cost-effectiveness of food assistance in improving ART adherence and other clinical outcomes among people living with HIV in the era of widespread and long-term treatment.

Abstract access 

Editor’s notes: A number of qualitative studies have found that a lack of food is given as a reason for non-adherence to anti-retroviral therapy (ART). The authors wanted to see if quantitative studies on food security and adherence supported this view. As with many systematic reviews the number of quantitative studies included in the final analysis was small: fourteen. However, the majority of these studies did find an association between the availability of food and adherence. The authors very carefully describe the difference methods used to measure both food security and ART adherence.  These findings show both the wide range of methods used for measurement and definitions of adherence and food security, which made comparisons difficult. So, while the authors did find that food insecurity is a barrier to adherence, they could not say why. Given that food insecurity may be a threat to adherence for the some of the increasing numbers of people starting ART, further research is urgently needed. We need to understand more about the association between food and ART adherence. 

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