Nathan Ford

Johns Hopkins University, Baltimore, Maryland, United States

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Publications (246)2644.14 Total impact

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    ABSTRACT: Improved access to anti-retroviral therapy increases the need for affordable monitoring using assays such as CD4 and/or viral load in resource-limited settings. Barriers to accessing treatment, high rates of loss to initiation and poor retention in care are prompting the need to find alternatives to conventional centralized laboratory testing in certain countries. Strong advocacy has led to a rapidly expanding repertoire of point-of-care tests for HIV. point-of-care testing is not without its challenges: poor regulatory control, lack of guidelines, absence of quality monitoring and lack of industry standards for connectivity, to name a few. The management of HIV increasingly requires a multidisciplinary testing approach involving hematology, chemistry, and tests associated with the management of non-communicable diseases, thus added expertise is needed. This is further complicated by additional human resource requirements and the need for continuous training, a sustainable supply chain, and reimbursement strategies. It is clear that to ensure appropriate national implementation either in a tiered laboratory model or a total decentralized model, clear country-specific assessments need to be conducted.
    BMC medicine. 09/2014; 12(1):173.
  • AIDS (London, England) 08/2014; · 4.91 Impact Factor
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    ABSTRACT: HIV self-testing (HIVST), a process in which an individual performs a HIV rapid diagnostic test and interprets the result in private, is an emerging approach that is well accepted, potentially cost-effective and empowering for those who may not otherwise test. To further explore the potential of HIVST, the Liverpool School of Tropical Medicine and World Health Organization held the first global symposium on the legal, ethical, gender, human rights and public health implications of HIVST. The meeting highlighted the potential of HIVST to increase access to and uptake of HIV testing, and emphasized the need to further develop evidence around the quality of HIVST and linkage to post-test services, and to assess the risks and the benefits associated with scale-up. This special issue of AIDS and Behavior links directly to the symposium and presents some of the latest research and thinking on the scale-up of HIV self-testing.
    AIDS and Behavior 07/2014; · 3.49 Impact Factor
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    ABSTRACT: Buruli Ulcer (BU)-HIV co-infection is an important emerging management challenge for BU disease. Limited by paucity of scientific studies, guidance for management of this co-infection has been lacking.
    Tropical Medicine & International Health 06/2014; · 2.94 Impact Factor
  • AIDS (London, England) 06/2014; 28(10):1542-1543. · 4.91 Impact Factor
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    ABSTRACT: Further scale-up of antiretroviral therapy (ART) to those in need while supporting the growing patient cohort on ART requires continuous adaptation of healthcare delivery models. We describe several approaches to manage stable patients on ART developed by Médecins Sans Frontières together with Ministries of Health in four countries in sub-Saharan Africa.
    Tropical Medicine & International Health 05/2014; · 2.94 Impact Factor
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    ABSTRACT: Cotrimoxazole is widely prescribed to treat a range of infections and for HIV-infected individuals it is administered as prophylaxis to protect against opportunistic infections. Some reports suggest that fetuses exposed to cotrimoxazole during early pregnancy may have an increased risk of congenital anomalies. We carried out this systematic review in order to update the evidence of cotrimoxazole safety in pregnancy.
    Journal of acquired immune deficiency syndromes (1999). 05/2014;
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    ABSTRACT: Pediatric antiretroviral treatment coverage in resource-limited settings continues to lag behind adults. Task shifting is an effective approach broadly used for adults, which some countries have also adopted for children, but implementation is limited by lack of confidence and skills among nonspecialist staff. A systematic review was conducted by combining key terms for task shifting, antiretroviral therapy (ART), and children. Five databases and two conferences were searched from inception till August 01, 2013. Eight observational studies provided outcome data for 11,828 children who received ART from nonphysician providers across 10 countries in sub-Saharan Africa. The cumulative pooled proportion of deaths was 3.2% [95% confidence interval (CI): 2.0 to 4.5] at 6 months, 4.6% (95% CI: 2.1 to 7.1) at 12 months, 6.2% (95% CI: 3.7 to 8.8) at 24 months, and 5.9% (95% CI: 3.5 to 8.3) at 36 months. Mortality and loss to follow-up in task-shifting programs were comparable to those reported by programs providing doctor- or specialist-led care. Our review suggests that task shifting of ART care can result in outcomes comparable to routine physician care, and this approach should be considered as part of a strategy to scale-up pediatric treatment. Specialist care will remain important for management of sick patients and complicated cases. Further qualitative research is needed to inform optimal implementation of task shifting for pediatric patients.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2014; 65(4):414-22. · 4.65 Impact Factor
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    ABSTRACT: To compare the advantages to patients and to programmes between fixed-dose combination (FDC) antiretroviral therapy and separate tablet regimens. Three electronic databases and two conference abstract sites were searched from inception to 01 March 2013 without geographical, language or date limits. Studies were included if they reported data on clinical outcomes, patient-reported outcomes and programme-related outcomes that could be related to pill burden for adult and adolescent patients on ART. For the primary outcomes of adherence and virological suppression, relative risks and 95% confidence intervals were calculated, and these were pooled using random effects meta-analysis. Twenty-one studies including information on 27 230 subjects were reviewed. Data from randomised trials showed better adherence among patients receiving FDCs than among patients who did not (relative risk 1.10, 95%CI 0.98-1.22); these findings were consistent with data from observational cohorts (RR 1.17, 95% CI 1.07-1.28). There was also a tendency towards greater virological suppression among patients receiving FDCs in randomised trials (RR 1.04, 95%CI 0.99-1.10) and observational cohort studies (RR 1.07, 95% CI 0.97-1.18). In all studies reporting patient preference, FDCs were preferred. The overall quality of the evidence was rated as low. Fixed-dose combinations appear to offer multiple advantages for programmes and patients, particularly with respect to treatment adherence.
    Tropical Medicine & International Health 03/2014; · 2.94 Impact Factor
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    ABSTRACT: Primate studies and some observational human data have raised concern regarding an association of first-trimester efavirenz exposure with central nervous system congenital anomalies. The objective of this review is to update evidence on efavirenz safety in HIV-infected pregnant women to inform revision of the 2013 WHO guidelines for antiretroviral therapy in low and middle-income countries.
    AIDS (London, England) 03/2014; 28 Suppl 2:S123-31. · 4.91 Impact Factor
  • Clinical Infectious Diseases 02/2014; · 9.37 Impact Factor
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    ABSTRACT: Introduction: Point-of-care testing for CD4 cell count is considered a promising way of reducing the time to eligibility assessment for antiretroviral therapy (ART) and of increasing retention in care prior to treatment initiation. In this review, we assess the available evidence on the patient and programme impact of point-of-care CD4 testing. Methods: We searched nine databases and two conference sites (up until 26 October 2013) for studies reporting patient and programme outcomes following the introduction of point-of-care CD4 testing. Where appropriate, results were pooled using random-effects methods. Results: Fifteen studies, mainly from sub-Saharan Africa, were included for review, providing evidence for adults, adolescents, children and pregnant women. Compared to conventional laboratory-based testing, point-of-care CD4 testing increased the likelihood of having CD4 measured [odds ratio (OR) 4.1, 95% CI 3.5-4.9, n=2] and receiving a CD4 result (OR 2.8, 95% CI 1.5-5.6, n=6). Time to being tested was significantly reduced, by a median of nine days; time from CD4 testing to receiving the result was reduced by as much as 17 days. Evidence for increased treatment initiation was mixed. Discussion: The results of this review suggest that point-of-care CD4 testing can increase retention in care prior to starting treatment and can also reduce time to eligibility assessment, which may result in more eligible patients being initiated on ART.
    Journal of the International AIDS Society 01/2014; 17(1):18809. · 3.94 Impact Factor
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    ABSTRACT: Background. Several combinations of two or three Direct Acting Antivirals (DAAs) can cure HCV in the majority of treatment-naïve patients. DAAs for HCV infection have similar mechanisms of action and chemical structures to antiretrovirals for HIV infection. Generic antiretrovirals are currently manufactured at very low prices, to treat 10 million people with HIV/AIDS in developing countries. Methods. Four HCV DAAs, currently either in Phase III development or recent approval (daclatasvir, sofosbuvir, simeprevir, faldaprevir) and ribavirin were classified by chemical structure, molecular weight, total daily dose and complexity of synthesis. The likely range of manufacturing costs per gram of DAA were then projected as formulated product cost, based upon treating a minimum of one million patients annually (to arrive at volume demand) combined with an analysis of the complexity of synthesis and a 40% margin for formulation. Projections were then compared with actual costs of antiretrovirals with similar structures. Results. Minimum manufacturing costs of antiretrovirals were US$0.2-2.1/g. The complexity of chemical synthesis for HCV DAAs was ranked from lowest to highest: ribavirin, daclatasvir, sofosbuvir, faldaprevir and simeprevir. Predicted manufacturing costs for 12-week courses of HCV DAAs were: US$21-63 for ribavirin, US$10-30 for daclatasvir, US$68-136 for sofosbuvir, US$100-210 for faldaprevir, and US$130-270 for simeprevir. Conclusions. Within the next 15 years, large-scale manufacture of two or three drug combinations of HCV DAAs is feasible, with minimum target prices of US$100-250 per 12 week treatment course. These low prices could make widespread access to HCV treatment in low and middle income countries a realistic goal.
    Clinical Infectious Diseases 01/2014; · 9.37 Impact Factor
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    ABSTRACT: Viral load (VL) monitoring is the standard of care in developing country settings for detecting HIV treatment failure. Since 2010 the World Health Organization has recommended a phase-in approach to VL monitoring in resource-limited settings. We conducted a systematic review of the accuracy and precision of HIV VL technologies for treatment monitoring. A search of Medline and Embase was conducted for studies evaluating the accuracy or reproducibility of commercially available HIV VL assays. 37 studies were included for review including evaluations of the Amplicor Monitor HIV-1 v1.5 (n = 25), Cobas TaqMan v2.0 (n = 11), Abbott RealTime HIV-1 (n = 23), Versant HIV-1 RNA bDNA 3.0 (n = 15), Versant HIV-1 RNA kPCR 1.0 (n = 2), ExaVir Load v3 (n = 2), and NucliSens EasyQ v2.0 (n = 1). All currently available HIV VL assays are of sufficient sensitivity to detect plasma virus levels at a lower detection limit of 1,000 copies/mL. Bias data comparing the Abbott RealTime HIV-1, TaqMan v2.0 to the Amplicor Monitor v1.5 showed a tendency of the Abbott RealTime HIV-1 to under-estimate results while the TaqMan v2.0 overestimated VL counts. Compared to the Amplicor Monitor v1.5, 2-26% and 9-70% of results from the Versant bDNA 3.0 and Abbott RealTime HIV-1 differed by greater than 0.5log10. The average intra and inter-assay variation of the Abbott RealTime HIV-1 were 2.95% (range 2.0-5.1%) and 5.44% (range 1.17-30.00%) across the range of VL counts (2log10-7log10). This review found that all currently available HIV VL assays are of sufficient sensitivity to detect plasma VL of 1,000 copies/mL as a threshold to initiate investigations of treatment adherence or possible treatment failure. Sources of variability between VL assays include differences in technology platform, plasma input volume, and ability to detect HIV-1 subtypes. Monitoring of individual patients should be performed on the same technology platform to ensure appropriate interpretation of changes in VL. Prospero registration # CD42013003603.
    PLoS ONE 01/2014; 9(2):e85869. · 3.73 Impact Factor
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    Tom Decroo, Nathan Ford, Marie Laga
    The Lancet Global Health. 01/2014; 2(5):e262–e263.
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    ABSTRACT: Introduction: The World Health Organization (WHO) recommends that HIV-positive adults with CD4 count ≤500 cells/mm(3) initiate antiretroviral therapy (ART). In many countries of sub-Saharan Africa, CD4 count is not widely available or consistently used and instead the WHO clinical staging system is used to determine ART eligibility. However, concerns have been raised regarding its discriminatory ability to identify patients eligible to start ART. We therefore reviewed the accuracy of WHO stage 3 or 4 assessment in identifying ART eligibility according to CD4 count thresholds for ART initiation. Methods: We systematically searched PubMed and Global Health databases and conference abstracts using a comprehensive strategy for studies that compared the results of WHO clinical staging with CD4 count thresholds. Studies performed in sub-Saharan Africa and published in English between 1998 and 2013 were eligible for inclusion according to our predefined study protocol. Two authors independently extracted data and assessed methodological quality and risk of bias using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) tool. Summary estimates of sensitivity and specificity were derived for each CD4 count threshold and hierarchical summary receiver operator characteristic curves were plotted. Results: Fifteen studies met the inclusion criteria, including 25,032 participants from 14 countries. Most studies assessed individuals attending ART clinics prior to treatment initiation. WHO clinical stage 3 or 4 disease had a sensitivity of 60% (95% CI: 45-73%, Q=914.26, p<0.001) and specificity of 73% (95% CI: 60-83%, Q=1439.43, p<0.001) for a CD4 threshold of ≤200 cells/mm(3) (11 studies); sensitivity and specificity for a threshold of CD4 count ≤350 cells/mm(3) were 45% (95% CI: 26-66%, Q=1607.31, p<0.001) and 85% (95% CI: 69-93%, Q=896.70, p<0.001), respectively (six studies). For the threshold of CD4 count ≤500 cells/mm(3) sensitivity was 14% (95% CI: 13-15%) and specificity was 95% (95% CI: 94-96%) (one study). Conclusions: When used for individual treatment decisions, WHO clinical staging misses a high proportion of individuals who are ART eligible by CD4 count, with sensitivity falling as CD4 count criteria rises. Access to accurate, accessible, robust and affordable CD4 count testing methods will be a pressing need for as long as ART initiation decisions are based on criteria other than seropositivity.
    Journal of the International AIDS Society 01/2014; 17(1):18932. · 3.94 Impact Factor
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    ABSTRACT: Dried blood spots (DBS) have been used as alternative specimens to plasma to increase access to HIV viral load (VL) monitoring and early infant diagnosis (EID) in remote settings. We systematically reviewed evidence on the performance of DBS compared to plasma for VL monitoring and EID. Thirteen peer reviewed HIV VL publications and five HIV EID papers were included. Depending on the technology and the viral load distribution in the study population, the percentage of DBS samples that are within 0.5 log of VL in plasma ranged from 52-100%. Because the input sample volume is much smaller in a blood spot, there is a risk of false negatives with DBS. Sensitivity of DBS VL was found to be 78-100% compared to plasma at VL below 1000 copies/ml, but this increased to 100% at a threshold of 5000 copies/ml. Unlike a plasma VL test which measures only cell free HIV RNA, a DBS VL also measures proviral DNA as well as cell-associated RNA, potentially leading to false positive results when using DBS. The systematic review showed that specificity was close to 100% at DBS VL above 5000 copies/ml, and this threshold would be the most reliable for predicting true virologic failure using DBS. For early infant diagnosis, DBS has a sensitivity of 100% compared to fresh whole blood or plasma in all studies. Although limited data are available for EID, DBS offer a highly sensitive and specific sampling strategy to make viral load monitoring and early infant diagnosis more accessible in remote settings. A standardized approach for sampling, storing, and processing DBS samples would be essential to allow successful implementation. PROSPERO Registration #: CRD42013003621.
    PLoS ONE 01/2014; 9(3):e86461. · 3.73 Impact Factor
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    ABSTRACT: The provision of antiretroviral therapy (ART) in low and middle-income countries is a chronic disease intervention of unprecedented magnitude and is the dominant health systems challenge for high-burden countries, many of which rank among the poorest in the world. Substantial external investment, together with the requirement for service evolution to adapt to changing needs, including the constant shift to earlier ART initiation, makes outcome monitoring and reporting particularly important. However, there is growing concern at the inability of many high-burden countries to report on the outcomes of patients who have been in care for various durations, or even the number of patients in care at a particular point in time. In many instances, countries can only report on the number of patients ever started on ART. Despite paper register systems coming under increasing strain, the evolution from paper directly to complex electronic medical record solutions is not viable in many contexts. Implementing a bridging solution, such as a simple offline electronic version of the paper register, can be a pragmatic alternative. This paper describes and recommends a three-tiered monitoring approach in low- and middle-income countries based on the experience implementing such a system in the Western Cape province of South Africa. A three-tier approach allows Ministries of Health to strategically implement one of the tiers in each facility offering ART services. Each tier produces the same nationally required monthly enrolment and quarterly cohort reports so that outputs from the three tiers can be aggregated into a single database at any level of the health system. The choice of tier is based on context and resources at the time of implementation. As resources and infrastructure improve, more facilities will transition to the next highest and more technologically sophisticated tier. Implementing a three-tier monitoring system at country level for pre-antiretroviral wellness, ART, tuberculosis and mother and child health services can be an efficient approach to ensuring system-wide harmonization and accurate monitoring of services, including long term retention in care, during the scale-up of electronic monitoring solutions.
    Journal of the International AIDS Society 01/2014; 17(1):18908. · 3.94 Impact Factor
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    Journal of the International AIDS Society 01/2014; 17(1):19323. · 3.94 Impact Factor

Publication Stats

4k Citations
2,644.14 Total Impact Points

Institutions

  • 2013
    • Johns Hopkins University
      Baltimore, Maryland, United States
    • Stellenbosch University
      Stellenbosch, Western Cape, South Africa
    • World Health Organization WHO
      • Department of HIV/AIDS (HIV)
      Genève, Geneva, Switzerland
  • 2012–2013
    • University of Ottawa
      • Faculty of Health Sciences
      Ottawa, Ontario, Canada
    • Clinton Health Access Initiative
      Boston, Massachusetts, United States
    • Stanford University
      • Division of General Medical Disciplines
      Palo Alto, CA, United States
  • 2009–2013
    • University of Cape Town
      • • Centre of Infectious Disease Epidemiology & Research
      • • School of Public Health and Family Medicine
      Kaapstad, Western Cape, South Africa
  • 2008–2013
    • Simon Fraser University
      • Faculty of Health Sciences
      Burnaby, British Columbia, Canada
    • Groote Schuur Hospital
      Kaapstad, Western Cape, South Africa
  • 2001–2013
    • Doctors Without Borders
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • Mahidol University
      Krung Thep, Bangkok, Thailand
    • The Aids Support Organization
      Kampala, Central Region, Uganda
    • Burnet Institute
      Melbourne, Victoria, Australia
  • 2002–2011
    • Médecins Sans Frontières
      Bruxelles, Brussels Capital Region, Belgium
    • London School of Hygiene and Tropical Medicine
      • Department of Clinical Research
      London, ENG, United Kingdom
    • Centre Hospitalier Universitaire de Grenoble
      Grenoble, Rhône-Alpes, France
  • 2010
    • Johns Hopkins Medicine
      • Department of Surgery
      Baltimore, MD, United States
  • 2003–2009
    • University of Toronto
      • • Joint Centre for Bioethics
      • • Department of Medicine
      Toronto, Ontario, Canada
  • 2000
    • Utrecht University
      • Division of Clinical and Health Psychology
      Utrecht, Utrecht, Netherlands