Articles tagged as "Botswana"

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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Improved delivery of isoniazid preventive therapy with integrated HIV and TB services

Interventions to improve delivery of isoniazid preventive therapy: an overview of systematic reviews

Adams LV, Talbot EA, Odato K, Blunt H, Steingart KR. BMC Infect Dis. 2014 May 21;14(1):281. doi: 10.1186/1471-2334-14-281.

Background: Uptake of isoniazid preventive therapy (IPT) to prevent tuberculosis has been poor, particularly in the highest risk populations. Interventions to improve IPT delivery could promote implementation. The large number of existing systematic reviews on treatment adherence has made drawing conclusions a challenge. To provide decision makers with the evidence they need, we performed an overview of systematic reviews to compare different organizational interventions to improve IPT delivery as measured by treatment completion among those at highest risk for the development of TB disease, namely child contacts or HIV-infected individuals.

Methods: We searched the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (DARE), and MEDLINE up to August 15, 2012. Two authors used a standardized data extraction form and the AMSTAR instrument to independently assess each review.

Results: Six reviews met inclusion criteria. Interventions included changes in the setting/site of IPT delivery, use of quality monitoring mechanisms (e.g., directly observed therapy), IPT delivery integration into other healthcare services, and use of lay health workers. Most reviews reported a combination of outcomes related to IPT adherence and treatment completion rate but without a baseline or comparison rate. Generally, we found limited evidence to demonstrate that the studied interventions improved treatment completion.

Conclusions: While most of the interventions were not shown to improve IPT completion, integration of tuberculosis and HIV services yielded high treatment completion rates in some settings. The lack of data from high burden TB settings limits applicability. Further research to assess different IPT delivery interventions, including those that address barriers to care in at-risk populations, is urgently needed to identify the most effective practices for IPT delivery and TB control in high TB burden settings.

Abstract  Full-text [free] access

Editor’s notes: Isoniazid preventive therapy (IPT) is a key component of the “3 Is” strategy to reduce tuberculosis among people living with HIV. Despite evidence of efficacy, initiation of IPT among eligible people in HIV care programmes has been disappointing. When IPT has been delivered as a stand-alone activity, treatment completion has often been poor. This overview of systematic reviews brings together evidence concerning organisational programmes to improve IPT delivery, using treatment completion as the main outcome. Three of the six included reviews, specifically included HIV-positive people.

When IPT delivery was integrated into other services, such as HIV care, good IPT completion rates were reported. A common weakness in the studies reviewed, was the lack of a suitable comparison group. This made it difficult to be sure that the good outcomes were due to the service integration. HIV This Month reported in June 2014 a trial from South Africa, showing that IPT reduces TB incidence among people taking antiretroviral therapy. Viewed together, these studies provide additional evidence supporting IPT delivery as part of the package of care for people in HIV care. More research is needed to guide implementers on how to deliver TB preventive therapy most effectively for people living with HIV.

Avoid TB deaths
Africa, Asia, Europe, Northern 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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Fewer clinical events with early antiretroviral therapy in a trial among serodiscordant couples

Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial.

Grinsztejn B, Hosseinipour MC, Ribaudo HJ, Swindells S, Eron J, Chen YQ, Wang L, Ou SS, Anderson M, McCauley M, Gamble T, Kumarasamy N, Hakim JG, Kumwenda J, Pilotto JH, Godbole SV, Chariyalertsak S, de Melo MG, Mayer KH, Eshleman SH, Piwowar-Manning E, Makhema J, Mills LA, Panchia R, Sanne I, Gallant J, Hoffman I, Taha TE, Nielsen-Saines K, Celentano D, Essex M, Havlir D, Cohen MS, HPTN 052-ACTG Study Team. Lancet Infect Dis. 2014 Apr;14(4):281-90. doi: 10.1016/S1473-3099(13)70692-3. Epub 2014 Mar 4.

Background: Use of antiretroviral treatment for HIV-1 infection has decreased AIDS-related morbidity and mortality and prevents sexual transmission of HIV-1. However, the best time to initiate antiretroviral treatment to reduce progression of HIV-1 infection or non-AIDS clinical events is unknown. We reported previously that early antiretroviral treatment reduced HIV-1 transmission by 96%. We aimed to compare the effects of early and delayed initiation of antiretroviral treatment on clinical outcomes.

Methods: The HPTN 052 trial is a randomised controlled trial done at 13 sites in nine countries. We enrolled HIV-1-serodiscordant couples to the study and randomly allocated them to either early or delayed antiretroviral treatment by use of permuted block randomisation, stratified by site. Random assignment was unblinded. The HIV-1-infected member of every couple initiated antiretroviral treatment either on entry into the study (early treatment group) or after a decline in CD4 count or with onset of an AIDS-related illness (delayed treatment group). Primary events were AIDS clinical events (WHO stage 4 HIV-1 disease, tuberculosis, and severe bacterial infections) and the following serious medical conditions unrelated to AIDS: serious cardiovascular or vascular disease, serious liver disease, end-stage renal disease, new-onset diabetes mellitus, and non-AIDS malignant disease. Analysis was by intention-to-treat.

Findings: 1 763 people with HIV-1 infection and a serodiscordant partner were enrolled in the study; 886 were assigned early antiretroviral treatment and 877 to the delayed treatment group (two individuals were excluded from this group after randomisation). Median CD4 counts at randomisation were 442 (IQR 373-522) cells per μL in patients assigned to the early treatment group and 428 (357-522) cells per μL in those allocated delayed antiretroviral treatment. In the delayed group, antiretroviral treatment was initiated at a median CD4 count of 230 (IQR 197-249) cells per μL. Primary clinical events were reported in 57 individuals assigned to early treatment initiation versus 77 people allocated to delayed antiretroviral treatment (hazard ratio 0.73, 95% CI 0.52-1.03; p=0.074). New-onset AIDS events were recorded in 40 participants assigned to early antiretroviral treatment versus 61 allocated delayed initiation (0.64, 0.43-0.96; p=0.031), tuberculosis developed in 17 versus 34 patients, respectively (0.49, 0.28-0.89, p=0.018), and primary non-AIDS events were rare (12 in the early group vs nine with delayed treatment). In total, 498 primary and secondary outcomes occurred in the early treatment group (incidence 24.9 per 100 person-years, 95% CI 22.5-27.5) versus 585 in the delayed treatment group (29.2 per 100 person-years, 26.5-32.1; p=0.025). 26 people died, 11 who were allocated to early antiretroviral treatment and 15 who were assigned to the delayed treatment group.

Interpretation: Early initiation of antiretroviral treatment delayed the time to AIDS events and decreased the incidence of primary and secondary outcomes. The clinical benefits recorded, combined with the striking reduction in HIV-1 transmission risk previously reported, provides strong support for earlier initiation of antiretroviral treatment.

Abstract access 

Editor’s notes: The HPTN 052 trial has received wide attention for its main result. This shows a large reduction in HIV transmission risk among HIV-serodiscordant couples where HIV-positive partners with CD4 counts between 350 and 550 started immediate antiretroviral therapy (ART). This was compared to deferring treatment until the CD4 count fell below 250 or an AIDS-defining illness occurred. This analysis reports on clinical events in the trial. Despite the trial population having relatively high CD4 counts at baseline, new AIDS-defining events, excluding tuberculosis, were the most common outcome. These were reduced in the early ART arm. Tuberculosis incidence was reduced by half. Non-AIDS events were rare.

For these trial results to translate into population level benefits, more people need to know their HIV status at an early stage, before they develop symptomatic disease. People with positive test results then need to link to care successfully so that treatment can be initiated. Stigma remains a key barrier to testing and accessing care in many settings. Virologic suppression among people in the intervention arm of this trial was very high, implying very good adherence to treatment. Strategies to support excellent adherence and retention are needed as ART programmes expand and include people starting ART earlier.

Comorbidity, HIV Treatment
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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Pervasive geographic and transportation-related barriers to HIV services use in sub-Saharan Africa

Impact of geographic and transportation-related barriers on HIV outcomes in sub-Saharan Africa: a systematic review.

Lankowski AJ, Siedner MJ, Bangsberg DR, Tsai AC. AIDS Behav. 2014 Feb 23. [Epub ahead of print]

Difficulty obtaining reliable transportation to clinic is frequently cited as a barrier to HIV care in sub-Saharan Africa (SSA). Numerous studies have sought to characterize the impact of geographic and transportation-related barriers on HIV outcomes in SSA, but to date there has been no systematic attempt to summarize these findings. In this systematic review, we summarized this body of literature. We searched for studies conducted in SSA examining the following outcomes in the HIV care continuum: (1) voluntary counseling and testing, (2) pre-antiretroviral therapy (ART) linkage to care, (3) loss to follow-up and mortality, and (4) ART adherence and/or viral suppression. We identified 34 studies containing 52 unique estimates of association between a geographic or transportation-related barrier and an HIV outcome. There was an inverse effect in 23 estimates (44 %), a null association in 26 (50 %), and a paradoxical beneficial impact in 3 (6 %). We conclude that geographic and transportation-related barriers are associated with poor outcomes across the continuum of HIV care.

Abstract

Editor’s notes: This systematic review focuses on the importance of structural barriers to uptake of HIV treatment and care. Specifically, these are the association between geographic and transportation-related barriers and poor outcomes among HIV positive persons. Most of the quantitative and qualitative evidence reviewed in this paper (from 66 studies in sub-Saharan Africa) support the authors’ hypothesis that geographic and transportation-related barriers contribute to poor outcomes in HIV-positive individuals at all points along the continuum of HIV care. These were indexed in terms of voluntary counselling and testing, pre- antiretroviral therapy linkage to care, loss to follow-up, and adherence and/or viral suppression. A lack of association between these barriers and HIV services use was more common in studies where the study had clear limitations. For example, the use of self-reported as opposed to objective measures of exposures, small sample sizes, and the lack of control for confounding variables. The study has important policy implications related to the decentralisation of HIV treatment and care services, point-of-care services delivery, the provision of transportation stipends, the simplification of management protocols, and the reduction in the frequency of follow up visits.

Africa
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CD4 counts at antiretroviral therapy start rising globally, but could do better!

Immunodeficiency at the start of combination antiretroviral therapy in low-,  middle-, and high-income countries.

The IeDEA and ART Cohort Collaborations. J Acquir Immune Defic Syndr 2014 Jan 1;65(1):e8-e16. doi: 10.1097/QAI.0b013e3182a39979.

Objective: To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC), and high-income (HIC) countries.

Methods: Patients aged 16 years or older starting cART in a clinic participating in a multicohort collaboration spanning 6 continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multilevel linear regression models were adjusted for age, gender, and calendar year; missing CD4 counts were imputed.

Results: In total, 379 865 patients from 9 LIC, 4 LMIC, 4 UMIC, and 6 HIC were included. In LIC, the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/µL between 2002 and 2009. Corresponding increases in LMIC, UMIC, and HIC were from 87 to 155 cells/µL (76% increase), 88 to 135 cells/µL (53%), and 209 to 274 cells/µL (31%). In 2009, compared with LIC, median counts were 13 cells/µL [95% confidence interval (CI): -56 to +30] lower in LMIC, 22 cells/µL (-62 to +18) lower in UMIC, and 112 cells/µL (+75 to +149) higher in HIC. They were 23 cells/µL (95% CI: +18 to +28 cells/µL) higher in women than men. Median counts were 88 cells/µL (95% CI: +35 to +141 cells/µL) higher in countries with an estimated national cART coverage >80%, compared with countries with <40% coverage.

Conclusions: Median CD4 cell counts at the start of cART increased 2000-2009 but remained below 200 cells/µL in LIC and MIC and below 300 cells/µL in HIC. Earlier start of cART will require substantial efforts and resources globally.

Abstract access 

Editor’s notes: In this multi-cohort analysis spanning six continents, median CD4 counts at initiation of combination antiretroviral therapy were substantially higher in high-income compared to low- or middle-income countries. Median CD4 counts at initiation increased between 2002 and 2009 in most countries studied, but these increases were greater in low- and middle-income than high-income countries and were greater among men than women. Baseline CD4 counts in low- and middle-income countries were higher among countries with national antiretroviral therapy coverage of 80% or above. Nevertheless, despite the massive scale-up of antiretroviral therapy in low-income countries since 2002, the increases in median CD4 count at the start of antiretroviral therapy have been modest. Substantial efforts and resources are needed to achieve earlier implementation of antiretroviral therapy globally.

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A multi-assay algorithm approach enables accurate estimation of HIV incidence from cross-sectional data

Development of Methods for Cross-Sectional HIV Incidence Estimation in a Large, Community Randomized Trial.

Laeyendecker O, Kulich M, Donnell D, Komárek A, Omelka M, Mullis CE, Szekeres G, Piwowar-Manning E, Fiamma A, Gray RH, Lutalo T, Morrison CS, Salata RA, Chipato T, Celum C, Kahle EM, Taha TE, Kumwenda NI, Karim QA, Naranbhai V, Lingappa JR, Sweat MD, Coates T, Eshleman SH. PLoS One. 2013 Nov 13;8(11):e78818. doi: 10.1371/journal.pone.0078818.

Background: Accurate methods of HIV incidence determination are critically needed to monitor the epidemic and determine the population level impact of prevention trials. One such trial, Project Accept, a Phase III, community-randomized trial, evaluated the impact of enhanced, community-based voluntary counseling and testing on population-level HIV incidence. The primary endpoint of the trial was based on a single, cross-sectional, post-intervention HIV incidence assessment.

Methods and findings: Test performance of HIV incidence determination was evaluated for 403 multi-assay algorithms [MAAs] that included the BED capture immunoassay [BED-CEIA] alone, an avidity assay alone, and combinations of these assays at different cutoff values with and without CD4 and viral load testing on samples from seven African cohorts (5,325 samples from 3,436 individuals with known duration of HIV infection [1 month to >10 years]). The mean window period (average time individuals appear positive for a given algorithm) and performance in estimating an incidence estimate (in terms of bias and variance) of these MAAs were evaluated in three simulated epidemic scenarios (stable, emerging and waning). The power of different test methods to detect a 35% reduction in incidence in the matched communities of Project Accept was also assessed. A MAA was identified that included BED-CEIA, the avidity assay, CD4 cell count, and viral load that had a window period of 259 days, accurately estimated HIV incidence in all three epidemic settings and provided sufficient power to detect an intervention effect in Project Accept.

Conclusions: In a Southern African setting, HIV incidence estimates and intervention effects can be accurately estimated from cross-sectional surveys using a MAA. The improved accuracy in cross-sectional incidence testing that a MAA provides is a powerful tool for HIV surveillance and program evaluation.

Abstract  Full-text [free] access

Editor’s notes: This study explores a cross-sectional method to determine occurrence of new HIV infections in a population. This was done as an alternative to longitudinal follow-up of individuals which is onerous; or using changes in estimates of existing infections as an indication of rates of new infections, which is potentially less accurate. The methods described here could be invaluable for monitoring the HIV epidemic and in evaluating prevention initiatives. Challenges in estimating HIV incidence include finding a suitable window period i.e., long enough in order to detect recent infection from a given sample, but not so long that chronic infections are also detected; and the impact of HIV viral load, treatment duration and other factors on serological assays. The investigators examined multiple approaches to combine existing tools in simulated epidemic scenarios. They validated their findings using samples with known duration of infection and available CD4 count blood samples, from a number of established HIV prevention trials. Testing algorithms that included multiple assays were superior to single serologic assays; the incidence estimates obtained using multiple assays had lower bias and better precision. The optimal method was a 4-assay multi-assay algorithm (MAA) which could detect the ratio between incidence in the intervention and control communities of Project Accept more accurately than would have been obtained with 6 monthly follow-up of a cohort of participants. The main limitation of note was that sub-type D infections were frequently misclassified. The authors recommend that further research for subtype D endemic areas is required. 

Epidemiology, HIV testing
Africa
Botswana, Kenya, Malawi, South Africa, Uganda, Zimbabwe
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Micronutrients delay immunological progression in treatment-naive patients

Effect of micronutrient supplementation on disease progression in asymptomatic, antiretroviral-naive, HIV-infected adults in Botswana: a randomized clinical trial.

Baum MK, Campa A, Lai S, Sales Martinez S, Tsalaile L, Burns P, Farahani M, Li Y, van Widenfelt E, Page JB, Bussmann H, Fawzi WW, Moyo S, Makhema J, Thior I,Essex M, Marlink R. JAMA. 2013 Nov 27;310(20):2154-63. doi: 10.1001/jama.2013.280923.

Importance: Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive.

Objective: To investigate whether long-term micronutrient supplementation is effective and safe in delaying disease progression when implemented early in adults infected with HIV subtype C who are ART-naive.

Design, setting, and participants: Randomized clinical trial of supplementation with either daily multivitamins (B vitamins and vitamins C and E), selenium alone, or multivitamins with selenium vs placebo in a factorial design for 24 months. The study was conducted in 878 patients infected with HIV subtype C with a CD4 cell count greater than 350/μL who were not receiving ART at Princess Marina Hospital in Gaborone, Botswana, between December 2004 and July 2009.

Interventions: Daily oral supplements of B vitamins and vitamins C and E, selenium alone, or multivitamins plus selenium, compared with placebo.

Main outcomes and measures: Reaching a CD4 cell count less than 200/μL until May 2008; after this date, reaching a CD4 cell count of 250/μL or less, consistent with the standard of care in Botswana for initiation of ART at the time of the study.

Results: There were 878 participants enrolled and randomized into the study. All participants were ART-naive throughout the study. In intent-to-treat analysis, participants receiving the combined supplement of multivitamins plus selenium had a significantly lower risk vs placebo of reaching CD4 cell count 250/μL or less (adjust ed hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01; absolute event rate [AER], 4.79/100 person-years; censoring rate, 0.92; 17 events; placebo AER, 9.22/100 person-years; censoring rate, 0.85; 32 events). Multivitamins plus selenium in a single supplement, vs placebo, also reduced the risk of secondary events of combined outcomes for disease progression (CD4 cell count ≤250/μL, AIDS-defining conditions, or AIDS-related death, whichever occurred earlier [adjusted HR, 0.56; 95% CI, 0.33-0.95; P = .03; AER, 6.48/100 person-years; censoring rate, 0.90; 23 events]). There was no effect of supplementation on HIV viral load. Multivitamins alone and selenium supplementation alone were not statistically different from placebo for any end point. Reported adverse events were adjudicated as unlikely to be related to the intervention, and there were no notable differences in incidence of HIV-related and health-related events among study groups.

Conclusions and relevance: In ART-naive HIV-infected adults, 24-month supplementation with a single supplement containing multivitamins and selenium was safe and significantly reduced the risk of immune decline and morbidity. Micronutrient supplementation may be effective when started in the early stages of HIV disease.

Abstract access 

Editor’s notes: Micronutrient deficiencies are prevalent in people living with HIV and have been shown to be associated with disease progression. Previous studies have shown that micronutrient supplementation can improve the markers of disease progression in patients with advanced HIV; however this is the first study to explore this question in patients with early-stage disease. To be eligible for entry into this 24 month, double-blind, placebo-controlled trial patients had to have a CD4 count >350 cells/mm3 i.e., higher than the recommended threshold for initiation of antiretroviral therapy (ART) in Botswana. When compared to placebo, micronutrient supplementation with multivitamins (B, C, E) plus selenium was found to approximately half the risk of immunological decline. Likewise, the risk of disease progression (earliest of CD4 ≤250 cell/ mm3, AIDS-defining condition or death) was significantly reduced. This low cost intervention could act as an incentive to engage patients in pre-ART care, a particularly challenging time period in terms of retention in care.

Africa
Botswana
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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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