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ABSTRACT: Following its recognition in 1981, the HIV/AIDS epidemic has evolved to become the greatest challenge in global health, with some 34 million persons living with HIV worldwide. Early epidemiologic studies identified the major transmission routes of the virus before it was discovered, and enabled the implementation of prevention strategies. Although the first identified cases were in MSM in the United States and western Europe, the greatest impact of the epidemic has been in sub-Saharan Africa, where most of the transmission occurs between heterosexuals. Nine countries in southern Africa account for less than 2% of the world's population but now they represent about one third of global HIV infections. Where broadly implemented, HIV screening of donated blood and antiretroviral treatment (ART) of pregnant women have been highly effective in preventing transfusion-associated and perinatally acquired HIV, respectively. Access to sterile equipment has also been a successful intervention for injection drug users. Prevention of sexual transmission has been more difficult. Perhaps the greatest challenge in terms of prevention has been in the global community of MSM in which HIV remains endemic at high prevalence. The most promising interventions are male circumcision for prevention of female-to-male transmission and use of ART to reduce infectiousness, but the extent to which these interventions can be brought to scale will determine their population-level impact.
AIDS (London, England) 06/2012; 26(10):1205-13. · 4.91 Impact Factor
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The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 05/2012; 16(5):569-70. · 2.73 Impact Factor
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ABSTRACT: Peter Bloland and colleagues from the US CDC lay out the agency's priorities for health systems strengthening efforts.
PLoS Medicine 04/2012; 9(4):e1001199. · 16.27 Impact Factor
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ABSTRACT: June 2011 marks the 30th anniversary of the first description of what became known as HIV/AIDS, now one of history's worst pandemics. The basic public health tools of surveillance and epidemiologic investigation helped define the epidemic and led to initial prevention recommendations. Features of the epidemic, including the zoonotic origin of HIV and its spread through global travel, are central to the concept of emerging infectious diseases. As the epidemic expanded into developing countries, new models of global health and new global partnerships developed. Advocacy groups played a major role in mobilizing the response to the epidemic, having human rights as a central theme. Through the commitments of governments and private donors, modern HIV treatment has become available throughout the developing world. Although the end of the epidemic is not yet in sight and many challenges remain, the response has been remarkable and global health has changed for the better.
Emerging Infectious Diseases 06/2011; 17(6):1044-8. · 6.79 Impact Factor
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Timothy K Thomas,
Rose Masaba,
Craig B Borkowf,
Richard Ndivo,
Clement Zeh,
Ambrose Misore,
Juliana Otieno,
Denise Jamieson,
Michael C Thigpen,
Marc Bulterys,
Laurence Slutsker, Kevin M De Cock,
Pauli N Amornkul,
Alan E Greenberg,
Mary Glenn Fowler
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ABSTRACT: Effective strategies are needed for the prevention of mother-to-child HIV transmission (PMTCT) in resource-limited settings. The Kisumu Breastfeeding Study was a single-arm open label trial conducted between July 2003 and February 2009. The overall aim was to investigate whether a maternal triple-antiretroviral regimen that was designed to maximally suppress viral load in late pregnancy and the first 6 mo of lactation was a safe, well-tolerated, and effective PMTCT intervention.
HIV-infected pregnant women took zidovudine, lamivudine, and either nevirapine or nelfinavir from 34-36 weeks' gestation to 6 mo post partum. Infants received single-dose nevirapine at birth. Women were advised to breastfeed exclusively and wean rapidly just before 6 mo. Using Kaplan-Meier methods we estimated HIV-transmission and death rates from delivery to 24 mo. We compared HIV-transmission rates among subgroups defined by maternal risk factors, including baseline CD4 cell count and viral load. Among 487 live-born, singleton, or first-born infants, cumulative HIV-transmission rates at birth, 6 weeks, and 6, 12, and 24 mo were 2.5%, 4.2%, 5.0%, 5.7%, and 7.0%, respectively. The 24-mo HIV-transmission rates stratified by baseline maternal CD4 cell count <500 and ≥500 cells/mm(3) were 8.4% (95% confidence interval [CI] 5.8%-12.0%) and 4.1% (1.8%-8.8%), respectively (p = 0.06); the corresponding rates stratified by baseline maternal viral load <10,000 and ≥10,000 copies/ml were 3.0% (1.1%-7.8%) and 8.7% (6.1%-12.3%), respectively (p = 0.01). None of the 12 maternal and 51 infant deaths (including two second-born infants) were attributed to antiretrovirals. The cumulative HIV-transmission or death rate at 24 mo was 15.7% (95% CI 12.7%-19.4%).
This trial shows that a maternal triple-antiretroviral regimen from late pregnancy through 6 months of breastfeeding for PMTCT is safe and feasible in a resource-limited setting. These findings are consistent with those from other trials using maternal triple-antiretroviral regimens during breastfeeding in comparable settings.
PLoS Medicine 03/2011; 8(3):e1001015. · 16.27 Impact Factor
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ABSTRACT: The incidence of tuberculosis has increased among South African gold miners despite comprehensive control programmes, including a radiological screening programme. No data are available as to the optimal frequency of screening. The aim of this study was to compare 6-monthly and 12-monthly radiological screening for active tuberculosis case-finding.
Employees of a gold mining company were randomly assigned to the control arm (screening at baseline, 12 and 24 months) or the intervention arm (additional 'intervention' radiographs at 6 and 18 months after baseline). Study outcomes included proportion of tuberculosis cases detected by screening, proportion smear-positive, extent of disease and mortality.
22,634 miners were randomised. Compared with 12-monthly screening, 6-monthly screening detected more tuberculosis suspects but not more cases, partly due to greater attrition between screening and further investigation after 'intervention' compared with routine radiographs. Tuberculosis cases detected in the 6-monthly versus the 12-monthly screening arm had less extensive disease (p=0.05) and a lower tuberculosis-specific mortality (death on tuberculosis treatment) (2.1 and 2.8 per 1000 person-years respectively, HR 0.73, 95% CI 0.50 to 1.08, p=0.1), which was most marked in the first 2 months of treatment (HR 0.48, 95% CI 0.23 to 0.98, p=0.04) when death from tuberculosis is most likely.
In settings with a high prevalence of HIV and tuberculosis despite standard tuberculosis control measures, more frequent case-finding may reduce the extent of disease, tuberculosis mortality and tuberculosis transmission through earlier detection of active tuberculosis cases. To be effective, however, all tuberculosis suspects identified through screening must be investigated for tuberculosis.
Thorax 02/2011; 66(2):134-9. · 6.84 Impact Factor
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ABSTRACT: HIV has increased the incidence of tuberculosis (TB) by up to sevenfold in African countries, but antiretroviral therapy (ART) reduces the incidence of AIDS-related TB. We use a mathematical model to investigate the short-term and long-term impacts of ART on the incidence of TB, assuming that people are tested for HIV once a year, on average, and start ART at a fixed time after HIV seroconversion or at a fixed CD4(+) cell count. We fit the model to trend data on HIV prevalence and TB incidence in nine countries in sub-Saharan Africa. If HIV-positive people start ART within 5 y of seroconversion, the incidence of AIDS-related TB in 2015 will be reduced by 48% (range: 37-55%). Long-term reductions depend sensitively on the delay to starting ART. If treatment is started 5, 2, or 1 y after HIV seroconversion, or as soon as people test positive, the incidence in 2050 will be reduced by 66% (range: 57-80%), 95% (range: 93-96%), 97.7% (range: 96.9-98.2%) and 98.4% (range: 97.8-98.9%), respectively. In the countries considered here, early ART could avert 0.71 ± 0.36 [95% confidence interval (CI)] million of 3.4 million cases of TB between 2010 and 2015 and 5.8 ± 2.9 (95% CI) million of 15 million cases between 2015 and 2050. As more countries provide ART at higher CD4(+) cell counts, the impact on TB should be investigated to test the predictions of this model.
Proceedings of the National Academy of Sciences 10/2010; 107(45):19485-9. · 9.68 Impact Factor
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ABSTRACT: Antiretroviral therapy and isoniazid preventive therapy (IPT) are both effective interventions to prevent HIV-associated tuberculosis, but work via different mechanisms. We propose that these two interventions might best be used as complementary strategies at different stages of HIV progression. At relatively high CD4-cell counts, IPT reduces tuberculosis risk by 64% (95% CI 39-78%) in patients with positive tuberculin skin tests, and is the key tuberculosis preventive intervention before patients are eligible for antiretroviral therapy. However, at low CD4-cell counts, reliable exclusion of active tuberculosis is difficult, fewer patients are eligible for IPT, and waning immune function might limit the durability of its effect. In such patients, antiretroviral therapy is the primary intervention needed, reducing tuberculosis incidence by 67% (95% CI 61-73%). However, tuberculosis risk during long-term antiretroviral therapy remains several times higher than background, especially in those with poor immune recovery. Patients might therefore derive additional benefit from combined use of IPT and antiretroviral therapy to simultaneously treat mycobacterial infection and restore tuberculosis-specific immune function. For those first presenting with advanced immunodeficiency, we propose that concurrent IPT might best be delayed until completion of the first few months of antiretroviral therapy, when active tuberculosis can be more reliably excluded. Data from randomised controlled trials are needed to underpin further development of public-health policy.
The Lancet Infectious Diseases 07/2010; 10(7):489-98. · 17.39 Impact Factor
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ABSTRACT: Despite policies, strategies, and guidelines, the epidemic of HIV-associated tuberculosis continues to rage, particularly in southern Africa. We focus our attention on the regions with the greatest burden of disease, especially sub-Saharan Africa, and concentrate on prevention of tuberculosis in people with HIV infection, a challenge that has been greatly neglected. We argue for a much more aggressive approach to early diagnosis and treatment of HIV infection in affected communities, and propose urgent assessment of frequent testing for HIV and early start of antiretroviral treatment (ART). This approach should result in short-term and long-term declines in tuberculosis incidence through individual immune reconstitution and reduced HIV transmission. Implementation of the 3Is policy (intensified tuberculosis case finding, infection control, and isoniazid preventive therapy) for prevention of HIV-associated tuberculosis, combined with earlier start of ART, will reduce the burden of tuberculosis in people with HIV infection and provide a safe clinical environment for delivery of ART. Some progress is being made in provision of HIV care to HIV-infected patients with tuberculosis, but too few receive co-trimoxazole prophylaxis and ART. We make practical recommendations about how to improve this situation. Early HIV diagnosis and treatment, the 3Is, and a comprehensive package of HIV care, in association with directly observed therapy, short-course (DOTS) for tuberculosis, form the basis of prevention and control of HIV-associated tuberculosis. This call to action recommends that both HIV and tuberculosis programmes exhort implementation of strategies that are known to be effective, and test innovative strategies that could work. The continuing HIV-associated tuberculosis epidemic needs bold but responsible action, without which the future will simply mirror the past.
The Lancet 05/2010; 375(9729):1906-19. · 38.28 Impact Factor
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ABSTRACT: In 2007 an estimated 33 million people were living with HIV; 67% resided in sub-Saharan Africa, with 35% in eight countries alone. In 2007, there were about 1.4 million HIV-positive tuberculosis cases. Globally, approximately 4 million people had been given highly active antiretroviral therapy (HAART) by the end of 2008, but in 2007, an estimated 6.7 million were still in need of HAART and 2.7 million more became infected with HIV.Although there has been unprecedented investment in confronting HIV/AIDS - the Joint United Nations Programme on HIV/AIDS estimates $13.8 billion was spent in 2008 - a key challenge is how to address the HIV/AIDS epidemic given limited and potentially shrinking resources. Economic disparities may further exacerbate human rights issues and widen the increasingly divergent approaches to HIV prevention, care and treatment.HIV transmission only occurs from people with HIV, and viral load is the single greatest risk factor for all modes of transmission. HAART can lower viral load to nearly undetectable levels. Prevention of mother to child transmission offers proof of the concept of HAART interrupting transmission, and observational studies and previous modelling work support using HAART for prevention. Although knowing one's HIV status is key for prevention efforts, it is not known with certainty when to start HAART.Building on previous modelling work, we used an HIV/AIDS epidemic of South African intensity to explore the impact of testing all adults annually and starting persons on HAART immediately after they are diagnosed as HIV positive. This theoretical strategy would reduce annual HIV incidence and mortality to less than one case per 1000 people within 10 years and it would reduce the prevalence of HIV to less than 1% within 50 years. To explore HAART as a prevention strategy, we recommend further discussions to explore human rights and ethical considerations, clarify research priorities and review feasibility and acceptability issues.
Journal of the International AIDS Society 01/2010; 13:1. · 3.26 Impact Factor
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The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 09/2009; 13(8):925-6. · 2.73 Impact Factor
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Bulletin of the World Health Organisation 08/2009; 87(7):488-488A. · 4.64 Impact Factor
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ABSTRACT: HIV/AIDS, tuberculosis, and malaria are 3 major global public health threats and cause substantial morbidity, mortality, negative socioeconomic impact, and human suffering. Despite the significant increase in financial support and recent progress in addressing these 3 diseases, important obstacles and unmet priorities remain. Disease-specific interventions have had a considerable impact on improving health systems. However, despite considerable investment, weak health systems, inadequate human resources, and poor laboratory infrastructure continue to be major obstacles to expanding health services. Health system strengthening should be addressed in an integrated approach that includes HIV-, tuberculosis-, and malaria-specific interventions. Investment in strategic information and public health laboratory network capacity strengthening are key actions to expand services to successfully address those diseases in heavily impacted countries.
American Journal of Clinical Pathology 07/2009; 131(6):844-8. · 2.60 Impact Factor
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Pauli N Amornkul,
Hilde Vandenhoudt,
Peter Nasokho,
Frank Odhiambo,
Dufton Mwaengo,
Allen Hightower,
Anne Buvé,
Ambrose Misore,
John Vulule,
Charles Vitek,
Judith Glynn,
Alan Greenberg,
Laurence Slutsker, Kevin M De Cock
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ABSTRACT: To estimate HIV prevalence and characterize risk factors among young adults in Asembo, rural western Kenya.
Community-based cross-sectional survey.
From a demographic surveillance system, we selected a random sample of residents aged 13-34 years, who were contacted at home and invited to a nearby mobile study site. Consent procedures for non-emancipated minors required assent and parental consent. From October 2003 - April 2004, consenting participants were interviewed on risk behavior and tested for HIV and HSV-2. HIV voluntary counseling and testing was offered.
Of 2606 eligible residents, 1822 (70%) enrolled. Primary reasons for refusal included not wanting blood taken, not wanting to learn HIV status, and partner/parental objection. Females comprised 53% of 1762 participants providing blood. Adjusted HIV prevalence was 15.4% overall: 20.5% among females and 10.2% among males. HIV prevalence was highest in women aged 25-29 years (36.5%) and men aged 30-34 years (41.1%). HSV-2 prevalence was 40.0% overall: 53% among females, 25.8% among males. In multivariate models stratified by gender and marital status, HIV infection was strongly associated with age, higher number of sex partners, widowhood, and HSV-2 seropositivity.
Asembo has extremely high HIV and HSV-2 prevalence, and probable high incidence, among young adults. Further research on circumstances around HIV acquisition in young women and novel prevention strategies (vaccines, microbicides, pre-exposure prophylaxis, HSV-2 prevention, etc.) are urgently needed.
PLoS ONE 02/2009; 4(7):e6470. · 4.09 Impact Factor
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The Lancet 12/2008; 373(9657):7-9. · 38.28 Impact Factor
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ABSTRACT: Roughly 3 million people worldwide were receiving antiretroviral therapy (ART) at the end of 2007, but an estimated 6.7 million were still in need of treatment and a further 2.7 million became infected with HIV in 2007. Prevention efforts might reduce HIV incidence but are unlikely to eliminate this disease. We investigated a theoretical strategy of universal voluntary HIV testing and immediate treatment with ART, and examined the conditions under which the HIV epidemic could be driven towards elimination.
We used mathematical models to explore the effect on the case reproduction number (stochastic model) and long-term dynamics of the HIV epidemic (deterministic transmission model) of testing all people in our test-case community (aged 15 years and older) for HIV every year and starting people on ART immediately after they are diagnosed HIV positive. We used data from South Africa as the test case for a generalised epidemic, and assumed that all HIV transmission was heterosexual.
The studied strategy could greatly accelerate the transition from the present endemic phase, in which most adults living with HIV are not receiving ART, to an elimination phase, in which most are on ART, within 5 years. It could reduce HIV incidence and mortality to less than one case per 1000 people per year by 2016, or within 10 years of full implementation of the strategy, and reduce the prevalence of HIV to less than 1% within 50 years. We estimate that in 2032, the yearly cost of the present strategy and the theoretical strategy would both be US$1.7 billion; however, after this time, the cost of the present strategy would continue to increase whereas that of the theoretical strategy would decrease.
Universal voluntary HIV testing and immediate ART, combined with present prevention approaches, could have a major effect on severe generalised HIV/AIDS epidemics. This approach merits further mathematical modelling, research, and broad consultation.
The Lancet 12/2008; 373(9657):48-57. · 38.28 Impact Factor
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The Lancet 07/2008; 371(9630):2068-70. · 38.28 Impact Factor
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New England Journal of Medicine 01/2008; 357(24):2510-4. · 53.30 Impact Factor
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JAMA The Journal of the American Medical Association 12/2007; 298(20):2412-4. · 30.03 Impact Factor
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Andrea A Kim,
Lucy Wanjiku,
Doris K Macharia,
Mary Wangai,
Anthony Isavwa,
Hussein Abdi,
Barbara J Marston,
Festus Ilako,
Mette Kjaer,
Kenneth Chebet, Kevin M De Cock,
Paul J Weidle
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ABSTRACT: Objective: This article describes toxicities to antiretroviral therapy (ART) among HIV-infected patients receiving care at a clinic in a large urban slum in Nairobi, Kenya. Methods: Patients were treated with nonnucleoside reverse transcriptase inhibitor-based ART and followed at scheduled intervals. Frequencies and cumulative probabilities of toxicities were calculated. Results: Among 283 patients starting ART, any and severe clinical toxicity were recorded as 65% and 6%, respectively. Cumulative probabilities for remaining free of any and severe clinical toxicities at 6, 12, and 18 months, were 0.47, 0.26, and 0.17, respectively and 0.98, 0.95, and 0.89, respectively. The probability of remaining free from elevated and grade 3 or 4 serum aminotransferase (AST) at 6, 12, and 18 months were 0.62, 0.42, and 0.21, respectively, and 0.99 at 6, 12, and 18 months. Conclusions: ART toxicities were frequent, but severe toxicities were less common. In resource-limited settings, ART toxicity should not represent a barrier to care.
Journal of the International Association of Physicians in AIDS Care (JIAPAC) 10/2007; 6(3):206-9.
