Wagman J.A.,University of California at San Diego |
Campbell J.C.,Johns Hopkins University |
Thoma M.,Family and Reproductive Health |
Ndyanabo A.,Uganda Virus Research Institute |
And 6 more authors.
The Lancet Global Health | Year: 2015
Background: Intimate partner violence (IPV) is associated with HIV infection. We aimed to assess whether provision of a combination of IPV prevention and HIV services would reduce IPV and HIV incidence in individuals enrolled in the Rakai Community Cohort Study (RCCS), Rakai, Uganda. Methods: We used pre-existing clusters of communities randomised as part of a previous family planning trial in this cohort. Four intervention group clusters from the previous trial were provided standard of care HIV services plus a community-level mobilisation intervention to change attitudes, social norms, and behaviours related to IPV, and a screening and brief intervention to promote safe HIV disclosure and risk reduction in women seeking HIV counselling and testing services (the Safe Homes and Respect for Everyone [SHARE] Project). Seven control group clusters (including two intervention groups from the original trial) received only standard of care HIV services. Investigators for the RCCS did a baseline survey between February, 2005, and June, 2006, and two follow-up surveys between August, 2006, and April, 2008, and June, 2008, and December, 2009. Our primary endpoints were self-reported experience and perpetration of past year IPV (emotional, physical, and sexual) and laboratory-based diagnosis of HIV incidence in the study population. We used Poisson multivariable regression to estimate adjusted prevalence risk ratios (aPRR) of IPV, and adjusted incidence rate ratios (aIRR) of HIV acquisition. This study was registered with ClinicalTrials.gov, number NCT02050763. Findings: Between Feb 15, 2005, and June 30, 2006, we enrolled 11 448 individuals aged 15-49 years. 5337 individuals (in four intervention clusters) were allocated into the SHARE plus HIV services group and 6111 individuals (in seven control clusters) were allocated into the HIV services only group. Compared with control groups, individuals in the SHARE intervention groups had fewer self-reports of past-year physical IPV (346 [16%] of 2127 responders in control groups vs 217 [12%] of 1812 responders in intervention groups; aPRR 0·79, 95% CI 0·67-0·92) and sexual IPV (261 [13%] of 2038 vs 167 [10%] of 1737; 0·80, 0·67-0·97). Incidence of emotional IPV did not differ (409 [20%] of 2039 vs 311 [18%] of 1737; 0·91, 0·79-1·04). SHARE had no effect on male-reported IPV perpetration. At follow-up 2 (after about 35 months) the intervention was associated with a reduction in HIV incidence (1·15 cases per 100 person-years in control vs 0·87 cases per 100 person-years in intervention group; aIRR 0·67, 95% CI 0·46-0·97, p=0·0362). Interpretation: SHARE could reduce some forms of IPV towards women and overall HIV incidence, possibly through a reduction in forced sex and increased disclosure of HIV results. Findings from this study should inform future work toward HIV prevention, treatment, and care, and SHARE's ecological approach could be adopted, at least partly, as a standard of care for other HIV programmes in sub-Saharan Africa. Funding: Bill & Melinda Gates Foundation, US National Institutes of Health, WHO, President's Emergency Plan for AIDS Relief, Fogarty International Center. © 2015 Wagman et al. Open Access article distributed under the terms of CC BY-NC-ND.
News Article | October 20, 2016
Adair wasn’t the only person asking these questions. As recently as July, researchers and activists at the International AIDS conference in Durban, South Africa, pointed out that life-saving antiretroviral treatment to suppress HIV reached sub-Saharan Africa years after the drugs were available in developed countries and worried that the same thing could happen with a future cure. “HIV cure research is still in its infancy. For now, it’s mainly restricted to the North and high-income countries,” says Dr. Paula Munderi of the Medical Research Council/Uganda Virus Research Institute at a symposium on global HIV cure research. “My appeal today is that low-income countries — Africa in particular, which has the bulk of the patients — not be left out of the research agenda.” Adair had heard other gene therapy researchers dismissing questions about accessibility by saying, “First we have to show gene therapy works, and then we’ll worry about that.” “Why not now?” she remembered thinking. “Is there a way we could do this, in a simplified fashion?” With Kiem’s encouragement, when Adair became head of her own lab in 2014, she used her Fred Hutch start-up funding to work on finding a way to make these still experimental therapies available and affordable wherever they are needed. In the brain cancer clinical trial, Adair used a first-generation device made by Miltenyi Biotec to separate the stem cells from other blood cells. It involved adding specialized metal beads to bone marrow removed from patients, then using a magnet to pull out the stem cells. But when she started working on a clinical trial for Fanconi anemia, a rare genetic disorder that leads to bone marrow failure, she needed something faster. Such patients have a tiny number of stem cells to begin with, and those are very susceptible to damage from exposure to ambient oxygen. To limit their exposure time, Adair had to find a way to speed up the process of separating and modifying the cells. Serendipitously, Miltenyi had just sent over a demonstration model of a second-generation machine that automated and sped up the bead and magnet process and also happened to be capable of processing the exact volumes of bone marrow Adair needed for the trial. Working with Miltenyi’s Tim Waters, Adair directed reprogramming of the device to see if it could meet her timetable. When initial tests worked, the Hutch bought the new machine and got federal approval to use it in the Fanconi anemia trial, treating the first patient in 2014. The whole time she was thinking, “I want to make this device do everything.” The Miltenyi machine, called the CliniMACS Prodigy, was small enough. It was a closed system, meaning no exposure to ambient air. It could be automated. Its interface was similar to an apheresis machine, another clinical device that separates blood into its components and which hospital staffs in many developing countries already are trained to use. Adair shared her grand vision with Waters, who is a co-author on the Nature Communications paper. It called for reconfiguring and reprogramming the device to do all of the steps, including the cleanroom jobs of adding the viral vector and removing residual reagents, then developing components specific to each disease that would be available in “kits” and kept in pharmacy freezers. Included in each kit would be disposable tubing to carry the patient’s blood cells from a sterile bag into the machine. A nurse would attach the bag to the machine, add chemical reagents from the kit to pull out the stem cells, nutrients to support the growth of those cells and the viral vector engineered to do the gene transfer for that disease. Additional disposable tubing would carry the modified cells to a second sterile bag that would go right into the patient’s IV. Reconfiguring the device meant tedious calculations, mechanical tests and relearning physics principles she’d forgotten from college — things she hadn’t imagined ever doing, says Adair. “Once I found this particular project,” she says, “I was so motivated by the problem that it’s tackling — specifically, distribution to places in the world that don’t have any access to this type of therapy now — it made me excited. And that in turn made other people excited.” The “box” itself costs about $150,000 to purchase — a one-time investment that would be used for thousands of patients. Each individual kit would cost about $26,000, Adair says. Though not inexpensive, the cost of what could be a one-time treatment compares favorably to lifetime care for many diseases. Take HIV, for example: lifetime treatment with antiretroviral drugs to suppress the virus is estimated to cost about $600,000. Gene therapy in a box also costs less than what cell-based gene therapy treatment costs research institutions now – between $38,000 and $55,000, according to Adair, in addition to the cleanroom and other infrastructure costs. But the one-step box could also be used here in the United States or in Europe, Adair says, which could help drive down costs because it requires less infrastructure and staffing. Adair and her team, which includes other Fred Hutch researchers and scientists at Washington State University, spent the last 18 months developing the device, comparing the products produced to those manufactured in cleanrooms and testing the modified cells in animal models, key prerequisites to obtaining U.S. Food and Drug Administration consent to test the products in humans. She is hoping to send a box to a clinic that is not in a high-tech research center to test its ease of use. “There are probably 1,000 modifications that could improve how efficient it is,” she says. “But by making a platform that doesn’t require you to be at one of the expert academic institutions for gene therapy, we’re facilitating more people being able to explore these processes and potentially incorporate their own changes.”
Kamali A.,Uganda Virus Research Institute
Tropical Medicine and International Health | Year: 2010
Summary HIV epidemic has had greatest impact in sub-Saharan Africa (SSA) and mainly in East and Southern Africa with HIV prevalence in some parts going up to 30%. In the recent years, considerable HIV research on prevention, treatment and care, and vaccine has been conducted in many developing countries and provided evidence-based knowledge to control the epidemic. However, there have also been disappointing results in HIV prevention trials such as in HIV vaccine and microbicide trials. Despite these outcomes, important lessons have been learnt that help in designing future trials. This article examines the recent advances in HIV research in developing countries. The most recent HIV prevention research has demonstrated the effect of male circumcision on HIV acquisition, and lack of impact of HSV-2 treatment on HIV transmission and acquisition. Use of HIV antiretroviral drugs (ARVs) for HIV prevention is a new area that has attracted interest and a number of trials are examining the effect of oral Pre-Exposure Prophylaxis on HIV acquisition and also looking at the potential of ARVs in reducing infectiousness. Progress has been made in HIV treatment, monitoring treatment efficacy and toxicity as well as evaluation of different models of ART delivery. HIV vaccine research has, however, faced most challenges despite many efforts that have been put in. Looking into the future, there are ongoing trials that will hopefully generate important information to strengthen HIV policies in the next few years. There are, however, many other gaps in HIV research that need to be urgently addressed. © 2010 Blackwell Publishing Ltd.
Fidler S.,Imperial College London |
Porter K.,Medical Research Council Clinical Trials Unit |
Ewings F.,Medical Research Council Clinical Trials Unit |
Frater J.,University of Oxford |
And 16 more authors.
New England Journal of Medicine | Year: 2013
BACKGROUND: Short-course antiretroviral therapy (ART) in primary human immunodeficiency virus (HIV) infection may delay disease progression but has not been adequately evaluated. METHODS: We randomly assigned adults with primary HIV infection to ART for 48 weeks, ART for 12 weeks, or no ART (standard of care), with treatment initiated within 6 months after seroconversion. The primary end point was a CD4+ count of less than 350 cells per cubic millimeter or long-term ART initiation. RESULTS: A total of 366 participants (60% men) underwent randomization to 48-week ART (123 participants), 12-week ART (120), or standard care (123), with an average follow-up of 4.2 years. The primary end point was reached in 50% of the 48-week ART group, as compared with 61% in each of the 12-week ART and standard-care groups. The average hazard ratio was 0.63 (95% confidence interval [CI], 0.45 to 0.90; P = 0.01) for 48-week ART as compared with standard care and was 0.93 (95% CI, 0.67 to 1.29; P = 0.67) for 12-week ART as compared with standard care. The proportion of participants who had a CD4+ count of less than 350 cells per cubic millimeter was 28% in the 48-week ART group, 40% in the 12-week group, and 40% in the standard-care group. Corresponding values for long-term ART initiation were 22%, 21%, and 22%. The median time to the primary end point was 65 weeks (95% CI, 17 to 114) longer with 48-week ART than with standard care. Post hoc analysis identified a trend toward a greater interval between ART initiation and the primary end point the closer that ART was initiated to estimated seroconversion (P = 0.09), and 48-week ART conferred a reduction in the HIV RNA level of 0.44 log10 copies per milliliter (95% CI, 0.25 to 0.64) 36 weeks after the completion of short-course therapy. There were no significant between-group differences in the incidence of the acquired immunodeficiency syndrome, death, or serious adverse events. CONCLUSIONS: A 48-week course of ART in patients with primary HIV infection delayed disease progression, although not significantly longer than the duration of the treatment. There was no evidence of adverse effects of ART interruption on the clinical outcome. (Funded by the Wellcome Trust; SPARTAC Controlled-Trials.com number, ISRCTN76742797, and EudraCT number, 2004-000446-20.) Copyright © 2013 Massachusetts Medical Society.
Munderi P.,Uganda Virus Research Institute
Current Opinion in HIV and AIDS | Year: 2010
Purpose of review: To review data related to the outcomes of antiretroviral therapy (ART) and the current operational experiences of ART programmes in low-income and middle-income countries (LMICs), concentrating on the implications and feasibility of changing ART initiation practice. Recent findings: ART initiation practice inhigh-income country settings has been modified in favour of starting ART earlier, basing on early evidence that HIV-associated morbidity and mortality are significantly reduced, and because there are increasingly more potent less toxic antiretroviral drug options available.In LMICs, ART initiation continues to follow conservative practice. At the same time, reports from ART programmes in low-income settings continue to demonstrate great benefits in terms of survival for people with HIV. However, compared with high-income country settings, the clinical outcomes of ART in LMICs are less favourable. The enormous HIV disease burden coupled with weaker health service capability is a key challenge to expanding ART effectively, although, as ART programmes mature, there are early indications that patient outcomes may be improving. Summary: In the immediate term, whether it is feasible to move to wide-scale earlier initiation of ART in LMICs remains in question; the priority for many countries is still equity and meeting the unmet needs for treatment. However, the possibility that early ART could reduce the risk of HIV transmission presents a particularly compelling incentive for earlier treatment in the high-burden settings of LMICs and further evidence on this rationale is anticipated from ongoing and planned studies. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Farine D.R.,University of Oxford |
Downing C.P.,Uganda Virus Research Institute |
Downing P.A.,University of Oxford
Behavioral Ecology | Year: 2014
Despite widespread research on the interaction rules that drive group-living behavior in animals, little is known about the spatial self-organization of individuals in heterospecific groups. This has led to significant challenges in teasing apart the various mechanisms thought to underpin multispecies groups. One potentially useful approach for gaining an understanding of this process is to identify the rules that best predict the observed distribution of individuals across these groups. In order to gain an insight into the decision-making process that might generate patterns of heterospecific associations, we collected data on the number and distribution of nests in breeding colonies that contained 3 species of weaverbird. We found no evidence of segregation by species, either within or between colonies. Using agent-based simulations of males applying different rules of attraction and repulsion to conspecifics or heterospecifics, we found that the best-fitting rule contained no heterospecific attraction. In this rule, individuals picked colonies based on an optimal distribution of conspecific nests. Given that nests are an important sexual signal in weavers, our findings suggest that this rule is biologically relevant: Males are seeking an optimal trade-off between attracting females via lekking and competing for mates if too many conspecific nests are present. © The Author 2014.
Munderi P.,Uganda Virus Research Institute |
Grosskurth H.,Uganda Virus Research Institute |
Grosskurth H.,London School of Hygiene and Tropical Medicine |
Droti B.,Uganda Virus Research Institute |
Ross D.A.,London School of Hygiene and Tropical Medicine
AIDS | Year: 2012
OBJECTIVES: To review and summarize the essential components of HIV treatment and care services in low and middle-income countries (LMICs). METHODS: Literature review and reflection on programmatic experience. FINDINGS: There is increasing recognition that the essential 'package' of HIV care must include early identification of HIV-positive people in need of care, appropriate initial and continued counselling, assessment of HIV disease stage, treatment with HAART for those who need it, monitoring while on treatment for efficacy, adherence and side-effects, detection and management of other complications of HIV infection, provision of sexual and reproductive health services as well as careful record-keeping.The impressive scale-up of HIV treatment and care services has required decentralization of service provision linked to task-shifting. But the future holds even greater challenges, as the number of people in need of HIV care continues to rise at a time when many traditional donors and governments in the most-affected regions have reduced budgets. CONCLUSION: In the long-term, the increased demand for HIV-care services can only be satisfied through increased decentralisation to peripheral health units, with the role of each type of unit being appropriate to the human and material resources available to it.HIV-care services can also naturally integrate with the care of chronic noncommunicable diseases and with closely related services like mother and child health, and thus should promote a shift from vertical to integrated programming. Staff training and support around a set of evidence-based policies and guidelines and a reliable supply of essential medicines and supplies are further essential components for a successful programme. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Dye T.V.,New York University |
Apondi R.,Uganda Virus Research Institute |
Lugada E.,CHF International
PLoS ONE | Year: 2011
Background: Many countries face severe scale-up barriers toward achievement of MDGs. We ascertained motivational and experiential dimensions of participation in a novel, rapid, ''diagonal'' Integrated Prevention Campaign (IPC) in rural Kenya that provided prevention goods and services to 47,000 people within one week, aimed at rapidly moving the region toward MDG achievement. Specifically, the IPC provided interventions and commodities targeting disease burden reduction in HIV/ AIDS, malaria, and water-borne illness. Methods: Qualitative in-depth interviews (IDI) were conducted with 34 people (18 living with HIV/AIDS and 16 not HIVinfected) randomly selected from IPC attendees consenting to participate. Interviews were examined for themes and patterns to elucidate participant experience and motivation with IPC. Findings: Participants report being primarily motivated to attend IPC to learn of their HIV status (through voluntary counseling and testing), and with receipt of prevention commodities (bednets, water filters, and condoms) providing further incentive. Participants reported that they were satisfied with the IPC experience and offered suggestions to improve future campaigns. Interpretation: Learning their HIV status motivated participants along with the incentive of a wider set of commodities that were rapidly deployed through IPC in this challenging region. The critical role of wanting to know their HIV status combined with commodity incentives may offer a new model for rapid scaled-up of prevention strategies that are wider in scope in rural Africa. © 2011 Dye et al.
Mbonye A.K.,Makerere University |
Birungi J.,Uganda Virus Research Institute |
Yanow S.,Provincial Laboratory for Public Health |
Magnussen P.,Copenhagen University
BMC Infectious Diseases | Year: 2013
Background: Malaria is a public health problem in Uganda; affecting mainly women and children. Effective treatment has been hampered by over-diagnosis and over-treatment with anti-malarial drugs among patients presenting with fever. In order to understand the effect of drug pressure on sulfadoxine-pyrimethamine (SP) resistance in pregnancy, a sample of pregnant women presenting with fever in out-patient clinics was studied. The main objective was to assess prescription patterns and drug use in pregnancy especially SP; and draw implications on the efficacy of SP for intermittent preventive treatment of malaria in pregnancy (IPTp).Methods: A total of 998 pregnant women with a history of fever were interviewed and blood samples taken for diagnosis of malaria and HIV infections. Data were captured on the drugs prescribed for the current febrile episode and previous use of drugs especially SP, anti-retroviral drugs (ARVs) and cotrimoxazole.Results: Few pregnant women, 128 (12.8%) were parasitaemic for P.falciparum; and of these, 72 (56.3%) received first-line treatment with Artemether-lumefantrine (Coartem®) 14 (10.9%) SP and 33 (25.8%) quinine. Of the parasite negative patients (non-malarial fevers), 186 (21.4%) received Coartem, 423 (48.6%) SP and 19 (2.1%) cotrimoxazole. Overall, malaria was appropriately treated in 35.5% of cases. Almost all febrile pregnant women, 91.1%, were sleeping under a mosquito net. The majority of them, 911 (91.3%), accepted to have an HIV test done and 92 (9.2%) were HIV positive. Of the HIV positive women, 23 (25.0%) were on ARVs, 10 (10.9%) on cotrimoxazole and 30 (32.6%) on SP. A significant proportion of women, 40 (43.5%), were on both SP and cotrimoxazole. Age and occupation were associated with diagnosis and treatment of malaria and HIV infections.Conclusion: There is inappropriate treatment of malaria and non-malarial fevers among pregnant women in these facilities. This is due to non-adherence to the guidelines. Over-prescription and use of anti-malarial drugs, especially SP may have implications on resistance against SP for malaria prevention in pregnancy. The policy implications of these findings are to evaluate SP efficacy as IPTp; and the need to enforce adherence to the current clinical treatment guidelines. © 2013 Mbonye et al.; licensee BioMed Central Ltd.
Bechange S.,Uganda Management Institute UMI |
Bechange S.,Uganda Virus Research Institute
International Journal of Health Planning and Management | Year: 2010
The aim of the study was to identify the main determinants of grassroots project success among HIV/AIDS NGOs operating in Rakai, Uganda. It was a cross-sectional study using face-to-face interviews in a mixed-methods approach among community members and NGOs involved in providing HIV/AIDS and related health services. The study found that the success of grassroots projects of HIV/AIDS NGOs essentially relies on adequate financial resources, competent human resources, strong organizational leadership, and NGO networking. These data suggest that to increase grassroots project success, HIVand AIDS NGOs in Rakai need to improve not only the budget base and human capacities but as well decision-making processes, organizational vision, mission and strategies, gender allocation in staffing, and beneficiary involvement. Copyright © 2010 John Wiley & Sons, Ltd.