Articles tagged as "Viet Nam"

Model estimates large global burden of childhood tuberculosis infection and potentially preventable future tuberculosis disease

Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study.

Dodd PJ, Gardiner E, Coghlan R, Seddon JA. Lancet Glob Health. 2014 Aug;2(8):e453-9. doi: 10.1016/S2214-109X(14)70245-1. Epub 2014 Jul 8.

Background: Confirmation of a diagnosis of tuberculosis in children (aged <15 years) is challenging; under-reporting can result even when children do present to health services. Direct incidence estimates are unavailable, and WHO estimates build on paediatric notifications, with adjustment for incomplete surveillance by the same factor as adult notifications. We aimed to estimate the incidence of infection and disease in children, the prevalence of infection, and household exposure in the 22 countries with a high burden of the disease.

Methods: Within a mechanistic mathematical model, we combined estimates of adult tuberculosis prevalence in 2010, with aspects of the natural history of paediatric tuberculosis. In a household model, we estimated household exposure and infection. We accounted for the effects of age, BCG vaccination, and HIV infection. Additionally, we tested sensitivity to key structural assumptions by repeating all analyses without variation in BCG efficacy by latitude.

Findings: The median number of children estimated to be sharing a household with an individual with infectious tuberculosis in 2010 was 15 319 701 (IQR 13 766 297-17 061 821). In 2010, the median number of Mycobacterium tuberculosis infections in children was 7 591 759 (5 800 053-9 969 780), and 650 977 children (424 871-983 118) developed disease. Cumulative exposure meant that the median number of children with latent infection in 2010 was 53 234 854 (41 111 669-68 959 804). The model suggests that 35% (23-54) of paediatric cases of tuberculosis in the 15 countries reporting notifications by age in 2010 were detected. India is predicted to account for 27% (22-33) of the total burden of paediatric tuberculosis in the 22 countries. The predicted proportion of tuberculosis burden in children for each country correlated with incidence, varying between 4% and 21%.

Interpretation: Our model has shown that the incidence of paediatric tuberculosis is higher than the number of notifications, particularly in young children. Estimates of current household exposure and cumulative infection suggest an enormous opportunity for preventive treatment.

Abstract  Full-text [free] access 

Editor’s notes: Estimating the burden of childhood tuberculosis has been largely neglected until recently. Children with tuberculosis rarely transmit and therefore from a control perspective, childhood tuberculosis does not notably contribute to the continuation of the tuberculosis epidemic. This modelling paper attempts to estimate the global burden of childhood tuberculosis infection and disease. Incidence estimates are made by using adult tuberculosis prevalence data to tackle the known limitations of using paediatric notification data. A second model estimates the prevalence of infection in children and household exposure, ignoring exposure outside of the household.  As with all mathematical model predictions, precision of estimates are dependent on the data used as inputs in the model. Despite these limitations, the paper draws attention to the fact that the burden of childhood tuberculosis infection and disease is significant and reflects failure of tuberculosis control in the 22 high-burden countries. The paper also highlights the fact that household contact tracing and preventive therapy in tuberculosis-exposed children could substantially reduce future tuberculosis-related morbidity.

Avoid TB deaths
Comorbidity, Epidemiology
Africa, Asia, Latin America
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Integrating HIV, malaria and diarrhoea prevention is far more efficient than vertical programmes

Scaling up integrated prevention campaigns for global health: costs and cost-effectiveness in 70 countries. 

Marseille E, Jiwani A, Raut A, Verguet S, Walson J, Kahn JG. BMJ Open. 2014 Jun 26;4(6):e003987. doi: 10.1136/bmjopen-2013-003987.

Objective: This study estimated the health impact, cost and cost-effectiveness of an integrated prevention campaign (IPC) focused on diarrhoea, malaria and HIV in 70 countries ranked by per capita disability-adjusted life-year (DALY) burden for the three diseases.

Methods: We constructed a deterministic cost-effectiveness model portraying an IPC combining counselling and testing, cotrimoxazole prophylaxis, referral to treatment and condom distribution for HIV prevention; bed nets for malaria prevention; and provision of household water filters for diarrhoea prevention. We developed a mix of empirical and modelled cost and health impact estimates applied to all 70 countries. One-way, multiway and scenario sensitivity analyses were conducted to document the strength of our findings. We used a healthcare payer's perspective, discounted costs and DALYs at 3% per year and denominated cost in 2012 US dollars.

Primary and secondary outcomes: The primary outcome was cost-effectiveness expressed as net cost per DALY averted. Other outcomes included cost of the IPC; net IPC costs adjusted for averted and additional medical costs and DALYs averted.

Results: Implementation of the IPC in the 10 most cost-effective countries at 15% population coverage would cost US$583 million over 3 years (adjusted costs of US$398 million), averting 8.0 million DALYs. Extending IPC programmes to all 70 of the identified high-burden countries at 15% coverage would cost an adjusted US$51.3 billion and avert 78.7 million DALYs. Incremental cost-effectiveness ranged from US$49 per DALY averted for the 10 countries with the most favourable cost-effectiveness to US$119, US$181, US$335, US$1 692 and US$8 340 per DALY averted as each successive group of 10 countries is added ordered by decreasing cost-effectiveness.

Conclusions: IPC appears cost-effective in many settings, and has the potential to substantially reduce the burden of disease in resource-poor countries. This study increases confidence that IPC can be an important new approach for enhancing global health.

Abstract  Full-text [free] access

Editor’s notes: Increasingly governments and policy makers are seeking to identify how to invest resources most effectively, to achieve multiple health and development outcomes. This paper presents a cost-effectiveness analysis of an integrated campaign to prevent diarrhoea, malaria and HIV.  

They developed a model to estimate the cost per disability adjusted life year (DALY) averted by this intervention, across 70 countries with high disease burden, assuming 15% coverage. The authors categorise countries by income level and their opportunity index (i.e. the opportunity to avert DALYs by having a high disease burden). The findings suggest that an integrated prevention campaign (IPC) could cost as little as US$7 per DALY averted in Guinea-Bissau, a low income, high opportunity country. As would be expected, the contribution of the different IPC components varied by country, depending on their relative disease burdens. This suggests that further focusing of activities within countries may further improve efficiency.

The model was also used to consider potential roll out strategies across counties. For this, countries were grouped into blocks of 10, and ordered with increasing incremental-cost effectiveness. The authors suggest that reaching the top 40 countries with IPC, even at just 15% coverage, could achieve far greater health benefits, with a substantially lower budget, than requested under PEPFAR for antiretroviral therapy alone.

This paper provides further evidence of the need for a more integrated approach to improve population health across disease areas.

Africa, Asia, Europe, Latin America
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Meta-analysis finds partial support for elevated HIV prevalence among the military

Systematic review and meta-analysis of HIV prevalence among men in militaries in low income and middle income countries. 

Lloyd J, Papworth E, Grant L, Beyrer C, Baral S. Sex Transm Infect. 2014 Apr 7. doi: 10.1136/sextrans-2013-051463. [Epub ahead of print]

Objectives: To determine whether the current HIV prevalence in militaries of low-income and middle-income countries is higher, the same, or lower than the HIV prevalence in the adult male population of those countries.

Methods: HIV prevalence data from low-income and middle-income countries' military men were systematically reviewed during 2000-2012 from peer reviewed journals, clearing-house databases and the internet. Standardised data abstraction forms were used to collect information on HIV prevalence, military branch and sample size. Random effects meta-analyses were completed with the Mantel-Haenszel method comparing HIV prevalence among military populations with other men in each country.

Results: 2 214 studies were retrieved, of which 18 studies representing nearly 150 000 military men across 11 countries and 4 regions were included. Military male HIV prevalence across the studies ranged from 0.06% (n=22 666) in India to 13.8% (n=2 733) in Tanzania with a pooled prevalence of 1.1% (n=147 591). HIV prevalence in male military populations in sub-Saharan Africa was significantly higher when compared with reproductive age (15-49 years) adult men (OR: 2.8, 95% CI 1.01 to 7.81). HIV prevalence in longer-serving male military populations compared with reproductive age adult men was significantly higher (OR: 2.68, 95% CI 1.65 to 4.35).

Conclusions: Our data reveals that across the different settings, the burden of HIV among militaries may be higher or lower than the civilian male populations. In this study, male military populations in sub-Saharan Africa, low-income countries and longer-serving men have significantly higher HIV prevalence. Given the national security implications of the increased burden of HIV, interventions targeting military personnel in these populations should be scaled up where appropriate.

Abstract access 

Editor’s notes: Men in military service are considered a key population because they spend protracted periods away from home and may engage in casual or other high-risk sex. This is not just a health concern for the armed forces themselves, but countries have in the past refused the assistance of peacekeeping forces because they were deemed a source of new infections. This systematic review concludes that HIV infection rates in the military are not universally higher than among men of reproductive age in the general population. However, significantly elevated prevalence was detected in studies from sub-Saharan Africa and among military who have been in service for over one year. The latter suggests that the relatively high prevalence results from increased exposure during service rather than the disproportional recruitment of men with HIV into service. On the contrary, the prevalence among new recruits is lower than in the general population. Prevention efforts, including HIV testing and counselling, and condom distribution, need to be increased during deployment in settings where exposure to HIV is high.

Epidemiology
Africa, Asia, Latin America
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Masking diversity – the problems with labels for key populations

'Mobile men with money': HIV prevention and the erasure of difference.

Aggleton P, Bell SA, Kelly-Hanku A. Glob Public Health. 2014;9(3):257-70. doi: 10.1080/17441692.2014.889736. Epub 2014 Mar 4.

Mobile Men with Money is one of the latest risk categories to enter into HIV prevention discourse. Used in countries in Asia, the Pacific and Africa, it refers to diverse groups of men (e.g. businessmen, miners and itinerant wage labourers) who, in contexts of high population movement and economic disparity, find themselves at heightened risk of HIV as members of a 'most-at-risk population', or render others vulnerable to infection. How adequate is such a description? Does it make sense to develop HIV prevention programmes from such understandings? The history of the epidemic points to major weaknesses in the use of terminologies such as 'sex worker' and 'men who have sex with men' when characterising often diverse populations. Each of these terms carries negative connotations, portraying the individuals concerned as being apart from the 'general population', and posing a threat to it. This paper examines the diversity of men classified as mobile men with money, pointing to significant variations in mobility, wealth and sexual networking conducive to HIV transmission. It highlights the patriarchal, heteronormative and gendered assumptions frequently underpinning use of the category and suggests more useful ways of understanding men, masculinity, population movement, relative wealth in relation to HIV vulnerability and risk.

Abstract access 

Editor’s notes: Criticism of the use of labels to identify groups of people considered to be at high risk of HIV infection is not new, but this paper serves as a timely reminder of the dangers of such labels and abbreviations. The authors explain why a term that has entered common usage in recent years ‘mobile men with money’, is inappropriate. They argue that the label plays to stereotypes of men as powerful risk takers and, usually, women as their vulnerable victims. The use of the term hides the diversity of men who move around because of their work and other activities, who may be in very different professions and circumstances. It also suggests that mobility is a negative activity, overlooking the great economic and other benefits of migration. They argue that the term is not helpful for HIV programming or activities.  It is unhelpful because it fails to take account of the structural factors that influence and shape the risks many men and women, face. It is often tempting to make use of abbreviations and catchy phrases in our work. This paper helps to remind us why we need to think carefully about terminology and labelling.

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Stigma from health care professionals inhibits HIV testing among men who have sex with men in Viet Nam

'Never testing for HIV' among men who have sex with men in Viet Nam: results from an internet-based cross-sectional survey.

García MC, Duong QL, Mercer LE, Meyer SB, Ward PR. BMC Public Health. 2013 Dec 28;13(1):1236. doi: 10.1186/1471-2458-13-1236.

Background: Men who have sex with men in Viet Nam have been under-studied as a high-risk group for HIV infection, and this population's percentage and determinants of HIV testing have not been comprehensively investigated.

Methods: A national Internet-based survey of self-reported sexual and health seeking behaviours was conducted between August and October 2011 with 2 077 Vietnamese men who had sex with men in the last twelve months to identify the frequency of 'never testing for HIV' among Internet-using MSM living in Viet Nam, as well as the factors associated with this HIV-related high-risk behavior. Logistic regression analyses were conducted to assess the demographic characteristics and behaviours predicting never testing for HIV.

Results: A total of 76.5% of men who have sex with men who were surveyed reported never having been voluntarily tested for HIV. Predictors of never being tested included having a monthly income less than VND 5 Million, being a student, using the Internet less than 15 hour per week, and not participating in a behavioural HIV intervention.

Conclusions: Never testing for HIV is common among Internet-using men who have sex with men in Viet Nam. Given the dangerously high prevalence of this high-risk behaviour, our findings underscore the urgent need for segmented and targeted HIV prevention, care and treatment strategies, focusing on drastically reducing the number of men who have sex with men never testing for HIV in Viet Nam.

Abstract  Full-text [free] access

Editor’s notes: There is growing concern about new and resurging epidemics among men who have sex with men (MSM) globally. Previous data from Viet Nam have estimated HIV prevalence of around 20%. The low rate of HIV-testing found in this fairly large study of men who reported having sex with men in the past 12 months, is therefore quite alarming. The most common reasons for not having tested were an assumption of being HIV-negative, stigma (from health professionals), fear associated with testing and lack of knowledge about where to go to be tested. This study highlights the critical gaps in HIV testing in this setting and the urgent need to focus sexual health resources on the provision of sexual health services for MSM free from stigma and discrimination. The study also highlights the need for increasing awareness of the availability and importance of HIV testing among sexually active MSM.

Asia
Viet Nam
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Linking cervical cancer prevention into infrastructure for HIV services in sub-Saharan Africa

Infrastructure requirements for human papillomavirus vaccination and cervical cancer screening in sub-Saharan Africa.

Sankaranarayanan R, Anorlu R, Sangwa-Lugoma G, Denny LA. Vaccine. 2013 Dec 29;31 Suppl 5:F47-52. doi: 10.1016/j.vaccine.2012.06.066.

The availability of both human papillomavirus (HPV) vaccination and alternative screening tests has greatly improved the prospects of cervical cancer prevention in sub-Saharan African (SSA) countries. The inclusion of HPV vaccine in the portfolio of new vaccines offered by the Global Alliance for Vaccines and Immunization (GAVI) to GAVI-eligible countries has vastly improved the chances of introducing HPV vaccination. Further investments to improve vaccine storage, distribution and delivery infrastructure and human resources of the Extended Programme of Immunization will substantially contribute to the faster introduction of HPV vaccination in SSA countries through both school- and campaign-based approaches. Alternative methods to cytology for the prevention of cervical cancer through the early detection and treatment of cervical cancer precursors have been extensively evaluated in the past 15 years, in Africa as well as in other low-resource settings. Visual inspection with 3-5% dilute acetic acid (VIA) and HPV testing are the two alternative screening methods that have been most studied, in both cross-sectional and randomised clinical trials. VIA is particularly suitable to low-resource settings; however, its efficacy in reducing cervical cancer is likely to be significantly lower than HPV testing. The introduction of VIA screening programmes will help develop the infrastructure that will, in turn, facilitate the introduction of affordable HPV testing in future. Links with the existing HIV/AIDS control programmes is another strategy to improve the infrastructure and screening services in SSA. Infrastructural requirements for an integrated approach aiming to vaccinate single-year cohorts of girls in the 9-13 years age-range and to screen women over 30 years of age using VIA or affordable rapid HPV tests are outlined in this manuscript.

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Editor’s notes: Infection with human papillomavirus (HPV) can lead to cervical cancer. HIV-positive women are more likely to acquire and have persistent HPV, so the high burden of HIV in sub-Saharan Africa (SSA) contributes to the burden of cervical cancer. This review article discusses the options for the prevention of cervical cancer in SSA. While this article is primarily focused on cervical cancer, it highlights the potential linkages of prevention activities with HIV/AIDS services with an emphasis on infrastructure to improve access to these services for women in SSA. The options for cervical cancer prevention in SSA include HPV vaccination, visual inspection tests, HPV DNA tests and cytology screening. These options and the infrastructure required for each are described in detail, and some of the barriers to delivery are highlighted. Treatment options are also described, including cryotherapy following visual inspection. 

Africa, Asia
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An integrated investment approach for women’s and children’s health

Advancing social and economic development by investing in women's and children's health: a new Global Investment Framework.

Stenberg K, Axelson H, Sheehan P, Anderson I, Gülmezoglu AM, Temmerman M, Mason E, Friedman HS, Bhutta ZA, Lawn JE, Sweeny K, Tulloch J, Hansen P, Chopra M, Gupta A, Vogel JP, Ostergren M, Rasmussen B, Levin C, Boyle C, Kuruvilla S, Koblinsky M, Walker N, de Francisco A, Novcic N, Presern C, Jamison D, Bustreo F; on behalf of the Study Group for the Global Investment Framework for Women's Children's Health. Lancet. 2013 Nov 18. doi: S0140-6736(13)62231-X. pii: 10.1016/S0140-6736(13)62231-X. [Epub ahead of print]

A new Global Investment Framework for Women's and Children's Health demonstrates how investment in women's and children's health will secure high health, social, and economic returns. We costed health systems strengthening and six investment packages for: maternal and newborn health, child health, immunisation, family planning, HIV/AIDS, and malaria. Nutrition is a cross-cutting theme. We then used simulation modelling to estimate the health and socioeconomic returns of these investments. Increasing health expenditure by just $5 per person per year up to 2035 in 74 high-burden countries could yield up to nine times that value in economic and social benefits. These returns include greater gross domestic product (GDP) growth through improved productivity, and prevention of the needless deaths of 147 million children, 32 million stillbirths, and 5 million women by 2035. These gains could be achieved by an additional investment of $30 billion per year, equivalent to a 2% increase above current spending.

Abstract access 

Editor’s notes: Over the past 20 years there have been substantial gains in maternal and child health (MCH). However, much still needs to be done – assuming a continuation of current rates of progress, there would nevertheless be shortfalls in the achievement of MDG 4 and 5 targets. Especially in sub-Saharan Africa, HIV is an important underlying cause of maternal and child ill health. This paper models the costs and benefits of an accelerated action on MCH, including for HIV, the prevention of mother to child HIV transmission; first line treatment for pregnant women; cotrimoxazole for children, and the provision of paediatric antiretroviral therapy (ART). These HIV services are complemented by health systems strengthening; increased family planning provision; and packages for malaria, immunisation, and child health. The paper is interesting for many reasons, including both the breadth of its intervention focus, and the detailed modelling of the likely health, social and economic benefits of such investments.

Although the direct HIV related benefits are not described in detail in the main paper, it is likely that these result both from increased contraceptive use (prong 2 for preventing vertical HIV transmission), as well as ART and cotrimoxazole provision. It also illustrates the potential value of developing a cross-disease investment approach, as a means to ensure that services effectively respond to the breadth of women’s and children’s health needs. This more ‘joined up’, integrated perspective on strategies for health investment can support core investments in health systems strengthening. It can also potentially achieve important cross-disease synergies, e.g., ensuring that a child who has not acquired HIV at birth does not then die from malaria. 

Africa, Asia, Latin America, Oceania
Afghanistan, Angola, Azerbaijan, Bangladesh, Benin, Bolivia, Botswana, Brazil, Burkina Faso, Burundi, Cambodia, Cameroon, Central African Republic, Chad, China, Comoros, Congo, Côte d'Ivoire, Democratic People's Republic of Korea, Democratic Republic of the Congo, Djibouti, Egypt, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Gambia, Ghana, Guatemala, Guinea, Guinea-Bissau, Haiti, India, Indonesia, Iraq, Kenya, Kyrgyzstan, Lao People's Democratic Republic, Lesotho, Liberia, Madagascar, Malawi, Mali, Mauritania, Mexico, Morocco, Mozambique, Myanmar, Nepal, Niger, Nigeria, Pakistan, Papua New Guinea, Peru, Philippines, Rwanda, Sao Tome and Principe, Senegal, Sierra Leone, Solomon Islands, Somalia, South Africa, Sudan, Swaziland, Tajikistan, Togo, Turkmenistan, Uganda, United Republic of Tanzania, Uzbekistan, Viet Nam, Yemen, Zambia, Zimbabwe
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Highly variable virological outcomes in ART programmes in seven countries

Extraordinary Heterogeneity of Virological Outcomes in Patients Receiving Highly Antiretroviral Therapy and Monitored With the World Health Organization Public Health Approach in Sub-Saharan Africa and Southeast Asia.

Aghokeng AF, Monleau M, Eymard-Duvernay S, Dagnra A, Kania D, Ngo-Giang-Huong  N, Toni TD, Touré-Kane C, Truong LX, Delaporte E, Chaix ML, Peeters M, Ayouba A; for the ANRS 12186 Study Group. Clin Infect Dis. 2013 Oct 23. [Epub ahead of print]

Background:  The limited access to virological monitoring in developing countries is a major weakness of the current antiretroviral treatment (ART) strategy in these settings. We conducted a large cross-sectional study in Burkina Faso, Cameroon, Cote d'Ivoire, Senegal, Togo, Thailand, and Vietnam to assess virological failure and drug resistance mutations (DRMs) after 12 or 24 months of ART.

Methods:  Between 2009 and 2011, we recruited adults attending ART centers 10-14 months (the M12 group) or 22-26 months (M24 group) after initiating ART. Demographic and clinical data were collected on site, and viral load was measured. Samples with a viral load of ≥ 1 000 copies/mL, considered as the failure threshold, were genotyped for drug resistance assessment.

Results:  Overall, 3 935 patients were recruited (2 060 at M12 and 1 875 at M24). Median ages varied from 32 to 42 years. Median CD4+ T-cell counts at ART initiation were low (99-172 cells/µL). The main ART regimens included stavudine/zidovudine plus lamivudine plus nevirapine/efavirenz. Overall, virological failure frequency was 11.1% for M12 patients and 12.4% for M24 patients, and 71.0% to 86.1% of these patients, respectively, had drug-resistant virus. Across sites, virological failure varied from 2.9% to 20.6% in M12 patients and from 3.7% to 26.0% in M24 patients. Predominant DRMs were associated with ART regimens, but virus in several patients accumulated DRMs to drugs not received, such as abacavir, didanosine, tenofovir, etravirine, and rilpivirine.

Conclusions:  Our findings show heterogeneous virological failure and illustrate that, in addition to routine access to viral load, good management of ART programs is even more critical to improve treatment outcomes in resource-limited countries.

Abstract access 

Editor’s notes: As the number of people taking antiretroviral therapy (ART) increases, more attention will be needed to sustaining programme quality and effectiveness. The proportion of people taking ART who have suppressed HIV viral load is a key measure of treatment success. This survey of ART programmes in seven countries found wide variation in the proportion of patients with HIV viral load ≥1 000 copies per ml. This illustrates the value of viral load monitoring as a measure of programme quality. Among individuals with HIV viral load ≥1 000 copies per ml, most but not all had drug-resistant virus. This illustrates the difficulty of rational management of “treatment failure” where resistance cannot be determined. Of more concern are few patients who had resistance to drugs they apparently had never taken. This underlines the importance of careful ART stewardship to maximize the benefits of ART at population level. 

Africa, Asia
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Combination antifungal therapy reduces mortality in HIV-associated cryptococcal meningitis

Combination Antifungal Therapy for Cryptococcal Meningitis

Day JN, Chau TTH, Wolbers M, Mai PP, Dung NT, Mai NH, et al. N Engl J Med 2013;368:1291-302.

Background: Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days.

Methods: We conducted a randomized, three-group, open-label trial of induction therapy for cryptococcal meningitis in patients with human immunodeficiency virus infection. All patients received amphotericin B at a dose of 1 mg per kilogram of body weight per day; patients in group 1 were treated for 4 weeks, and those in groups 2 and 3 for 2 weeks. Patients in group 2 concurrently received flucytosine at a dose of 100 mg per kilogram per day for 2 weeks, and those in group 3 concurrently received fluconazole at a dose of 400 mg twice daily for 2 weeks.

Results: A total of 299 patients were enrolled. Fewer deaths occurred by days 14 and 70 among patients receiving amphotericin B and flucytosine than among those receiving amphotericin B alone (15 vs. 25 deaths by day 14; hazard ratio, 0.57; 95% confidence interval [CI], 0.30 to 1.08; unadjusted P = 0.08; and 30 vs. 44 deaths by day 70; hazard ratio, 0.61; 95% CI, 0.39 to 0.97; unadjusted P = 0.04). Combination therapy with fluconazole had no significant effect on survival, as compared with monotherapy (hazard ratio for death by 14 days, 0.78; 95% CI, 0.44 to 1.41; P = 0.42; hazard ratio for death by 70 days, 0.71; 95% CI, 0.45 to 1.11; P = 0.13). Amphotericin B plus flucytosine was associated with significantly increased rates of yeast clearance from cerebrospinal fluid (−0.42 log10 colony-forming units [CFU] per milliliter per day vs. −0.31 and −0.32 log10 CFU per milliliter per day in groups 1 and 3, respectively; P<0.001 for both comparisons). Rates of adverse events were similar in all groups, although neutropenia was more frequent in patients receiving a combination therapy.

Conclusions: Amphotericin B plus flucytosine, as compared with amphotericin B alone, is associated with improved survival among patients with cryptococcal meningitis. A survival benefit of amphotericin B plus fluconazole was not found. (Funded by the Wellcome Trust and the British Infection Society; Controlled-Trials.com number, ISRCTN95123928.)

Abstract Full text [free] access 

Editor’s notes: Cryptococcal meningitis remains a leading cause of mortality in HIV-infected individuals in much of Africa and parts of South-East Asia, causing an estimated one million cases and 625,000 deaths every year. Previous studies have demonstrated that combination antifungal therapy with amphotericin B and flucytosine leads to more rapid clearance of cryptococci from the cerebrospinal fluid (CSF) of patients with cryptococcal meningitis than amphotericin B alone. This randomized controlled trial from Vietnam is the first to show improved clinical outcomes in patients receiving combination therapy. Amphotericin B plus flucytosine was associated with both faster rates of yeast clearance from the CSF and fewer deaths at two weeks and 10 weeks than monotherapy. The investigators also studied the combination of amphotericin with high dose fluconazole – a relatively inexpensive and widely available antifungal drug. Combination therapy with amphotericin B and high dose fluconazole did not lead to more rapid clearance of infection than amphotericin alone, or to substantial mortality reductions compared to monotherapy.

This important trial confirms amphotericin plus flucytosine combination therapy as the gold standard for treatment of HIV-associated cryptococcal meningitis. Unfortunately flucytosine is not registered or available in the majority of countries in Africa and Asia where cryptococcal disease burden is highest. Efforts are now needed to secure access to both flucytosine and amphotericin B for cryptococcal meningitis treatment worldwide.

Avoid TB deaths
Asia
Viet Nam
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Good treatment outcomes in a drug-user centered national HIV treatment program

Outcomes of antiretroviral therapy in Vietnam: results from a national evaluation.

Nguyen DB, Do NT, Shiraishi RW, Le YN, Tran QH, Huu Nguyen H, Medland N, Nguyen LT, Struminger BB. PLoS One. 2013;8(2):e55750. doi: 10.1371/journal.pone.0055750. Epub 2013 Feb 15.

Vietnam has significantly scaled up its national antiretroviral therapy (ART) program since 2005. With the aim of improving Vietnam's national ART program, we conducted an outcome evaluation of the first five years of the program in this concentrated HIV epidemic where the majority of persons enrolled in HIV care and treatment services are people who inject drugs (PWID). The results of this evaluation may have relevance for other national ART programs with significant PWID populations. Retrospective cohort analysis of patients at 30 clinics randomly selected with probability proportional to size among 120 clinics with at least 50 patients on ART. Charts of patients whose ART initiation was at least 6 months prior to the study date were abstracted. Depending on clinic size, either all charts or a random sample of 300 charts were selected. Analyses were limited to treatment-naïve patients. Multiple imputations were used for missing data. Of 7,587 patient charts sampled, 6,875 were those of treatment-naïve patients (74.4% male, 95% confidence interval [CI]: 72.4-76.5, median age 30, interquartile range [IQR]: 26-34, 62.0% reported a history of intravenous drug use, CI: 58.6-65.3). Median baseline CD4 cell count was 78 cells/mm (IQR: 30-162) and 30.4% (CI: 25.8-35.1) of patients were at WHO stage IV. The majority of patients started d4T/3TC/NVP (74.3%) or d4T/3TC/EFV (18.6%). Retention rates after 6, 12, 24, and 36 months were 88.4% (CI: 86.8-89.9), 84.0% (CI: 81.8-86.0), 78.8% (CI: 75.7-81.6), and 74.6% (CI: 69.6-79.0). Median CD4 cell count gains after 6, 12, 24, and 36 months were 94 (IQR: 45-153), 142 (IQR: 78-217), 213 (IQR: 120-329), and 254 (IQR: 135-391) cells/mm. Patients who were PWID showed significantly poorer retention. The study showed good retention and immunological response to ART among a predominantly PWID group of patients despite advanced HIV infections at baseline.

Abstract access 

Editor’s notes: The HIV epidemic is concentrated among key populations, primarily among people who inject drugs, and less so among men who have sex with men, and sex workers. As of December 2011 an estimated 53% of those clinically or immunologically eligible. While concerns remain regarding the human rights of key populations in Vietnam, of note needle and syringe programs and methadone maintenance programs, key HIV prevention interventions, are available in most provinces. This study reviewed chart information on almost 7000 patients. 62% of patients on ART had a history of intravenous drug use and most patients started on ART at fairly advanced immunosuppression. Retention at 6 and 12 months was quite high for patients with and without a history of IV drug use- those with such a history began to have significantly lower retention by 2 years after treatment initiation. This study was not able to tease out the reasons for this later divergence in retention results.

People who use drugs remain a key population – well designed and managed programs can overcome previously raised concerns about the ability to engage and maintain drug users in HIV care. In addition to directly sensitizing the care and treatment programs to the specific needs of drugs users, syringe and needle exchange programs and provision of opioid substitution therapy have been demonstrated to have a HIV prevention impact. Given the relatively recent expansion of such services in Vietnam, hopefully more recent data will demonstrate a further narrowing of the retention differences between drug users and other populations on HIV treatment.

Asia
Viet Nam
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