Nathan Ford

University of Cape Town, Kaapstad, Western Cape, South Africa

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Publications (273)2849.58 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Efavirenz (EFV) is widely used for the treatment of antiretroviral-naïve HIV-positive individuals, but there are concerns about the risk of adverse neuropsychiatric events. We systematically reviewed the safety of efavirenz in first-line therapy. 4 databases were searched up to October 2014 for randomized trials comparing efavirenz against non-efavirenz based-regimens for the treatment of antiretroviral-naïve HIV-positive adults and children. The primary outcome was drug discontinuation as a result of any adverse event. Relative risks and proportions were pooled using random effects meta-analysis. 42 trials were included for review. A lower relative and absolute risk of discontinuations due to adverse drug reactions was seen with efavirenz compared to nevirapine. The relative and absolute risk of discontinuation was greater for efavirenz compared to low dose efavirenz, rilpivirine, tenofovir, atazanavir, and maraviroc. The relative risk of discontinuation was greater for efavirenz compared to dolutegravir and raltegravir but absolute risks were not significantly different. There was no difference in the risk of any severe clinical adverse events for any comparison. With the exception of dizziness, fewer than 10% of patients exposed to efavirenz experienced any other specific type of neuropsychniatric event. No suicides were reported. This review found that over 90% of patients remained on an EFV-based first-line regimen after an average follow up time of 78 weeks. The relative risk of discontinuations due to adverse events was higher for efavirenz compared to most other first-line options but absolute differences were less than 5% for all comparisons.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2015; DOI:10.1097/QAI.0000000000000606 · 4.39 Impact Factor
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    ABSTRACT: Rwanda has achieved substantial progress in scaling up of antiretroviral therapy. We aimed to assess the effect of increased access to antiretroviral therapy on life expectancy among HIV-positive patients in two distinct periods of lower and higher antiretroviral therapy coverage (1997-2007 and 2008-11). In a retrospective observational cohort study, we collected clinical and demographic data for all HIV-positive patients enrolled in care at 110 health facilities across all five provinces of Rwanda. We included patients aged 15 years or older with a known enrolment date between 1997 and 2014. We constructed abridged life tables from age-specific mortality rates and life expectancy stratified by sex, CD4 cell count, and WHO disease stage at enrolment in care and initiation of antiretroviral therapy. We included 72 061 patients in this study, contributing 213 983 person-years of follow-up. The crude mortality rate was 33·4 deaths per 1000 person-years (95% CI 32·7-34·2). Life expectancy for the overall cohort was 25·6 additional years (95% CI 25·1-26·1) at 20 years of age and 23·3 additional years (95% CI 22·9-23·7) at 35 years of age. Life expectancy at 20 years of age in the period of 1997-2007 was 20·4 additional years (95% CI 19·5-21·3); for the period of 2008-11, life expectancy had increased to 25·6 additional years (95% CI 24·8-26·4). Individuals enrolling in care with CD4 cell counts of 500 cells per μL or more, and with WHO disease stage I, had the highest life expectancies. This study adds to the growing body of evidence showing the benefit to HIV-positive patients of early enrolment in care and initiation of antiretroviral therapy. Bill & Melinda Gates Foundation. Copyright © 2015 Nsanzimana et al. Open Access article distributed under the terms of CC BY-NC-SA. Published by .. All rights reserved.
    03/2015; 6(3). DOI:10.1016/S2214-109X(14)70364-X
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    ABSTRACT: Background & Aims: Combinations of direct-acting antivirals can cure hepatitis C virus in the majority of treatment-naïve patients. Mass treatment programmes to cure hepatitis C virus in developing countries are only feasible if the costs of treatment and laboratory diagnostics are very low. This analysis aimed to estimate minimum costs of direct acting antiviral treatment and associated diagnostic monitoring. Methods: Clinical trials of hepatitis C virus direct-acting antivirals were reviewed to identify combinations with consistently high rates of sustained virological response across hepatitis C genotypes. For each direct-acting antiviral, molecular structures, doses, treatment duration and components of retro-synthesis were used to estimate costs of large-scale, generic production. Manufacturing costs per gram of direct-acting antiviral were based upon treating at least 5 million patients/year and a 40% margin for formulation. Costs of diagnostic support were estimated based on published minimum prices of genotyping, hepatitis C virus antigen tests plus full blood count/clinical chemistry. Results: Predicted minimum costs for 12-week courses of combination direct-acting antivirals with the most consistent efficacy results were: US$122 per person for sofosbuvir+daclatasvir, US$152 for sofosbuvir+ribavirin, US$192 for sofosbuvir+ledipasvir and US$115 for MK-8742+MK-5172. Diagnostic testing costs were estimated at US$90 for genotyping US$34 for two hepatitis C virus antigen tests and US$22 for two full blood count/clinical chemistry. Conclusions: Minimum costs of treatment and diagnostics to cure hepatitis C virus infection were estimated at US$171-360 per-person without genotyping or US$261-450 per-person with genotyping. These cost estimates assume that existing large-scale treatment programmes can be established. This article is protected by copyright. All rights reserved. © 2014 by the American Association for the Study of Liver Diseases.
    Hepatology 02/2015; 61(4). DOI:10.1002/hep.27641 · 11.19 Impact Factor
  • The Lancet HIV 01/2015; DOI:10.1016/S2352-3018(14)00039-3
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    ABSTRACT: Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration. Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/μl over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts <350 cells/μl, bias ranged from -35.2 to +13.1 cells/μl while at counts >350 cells/μl, bias ranged from -70.7 to +47 cells/μl, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/μl ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained. A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed.
    PLoS ONE 01/2015; 10(3):e0115019. DOI:10.1371/journal.pone.0115019 · 3.53 Impact Factor
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    Clinical Infectious Diseases 12/2014; DOI:10.1093/cid/ciu1138 · 9.42 Impact Factor
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    ABSTRACT: This study assesses the extent to which the strength of a recommendation in a World Health Organization (WHO) guideline affects uptake of the recommendation in national guidelines.
    Journal of Clinical Epidemiology 12/2014; DOI:10.1016/j.jclinepi.2014.11.006 · 5.48 Impact Factor
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    ABSTRACT: We evaluated variations in completion rates for HIV postexposure prophylaxis (PEP) according to the exposure type (occupational, nonoccupational, and sexual assault), patient, and programme characteristics. Four major databases were searched together with conference abstract databases from inception to 1 December 2013, updated in PubMed on 1 June 2014. Randomized and nonrandomized studies reporting completion rates for PEP were included regardless of exposure type, age, or geographical location and data pooled using random-effects meta-analysis. Ninety-seven studies, reporting outcomes on 21 462 PEP initiations, were reviewed. Nonoccupational exposure to HIV was the main reason for PEP in 34 studies (n = 11 840), occupational exposure in 22 studies (n = 3058), sexual assault in 26 studies (n = 3093), and the remainder of studies (15 studies, n = 3471) reported outcomes for mixed exposures. Overall, 56.6% [95% confidence (CI) 50.9-62.2%; τ 0.25] of people considered eligible for PEP completed the full standard 28-day course. Compared with the overall estimate of PEP completion, rates were highest for studies reporting PEP for nonoccupational exposures (65.6%, 95% CI 55.6-75.6%) and lowest for sexual assault (40.2%, 95% CI 31.2-49.2%); higher rates of PEP completion were also reported for MSM (67.2%, 95% CI 59.5-74.9%). Completion rates appeared to be lower for adolescents (36.6%, 95% CI 4.0-69.2%) compared with adults (59.1%, 95% CI 53.9-64.2%) or children (64.0%, 95% CI 41.2-86.8%). Adherence to a full 28-day course of antiretroviral drugs prescribed for PEP is poor. Efforts should be made to simplify guidelines for prescribers and support adherence for people taking PEP, with particular attention needed for adolescents and victims of sexual assault.
    AIDS (London, England) 11/2014; 28(18):2721-2727. DOI:10.1097/QAD.0000000000000505 · 6.56 Impact Factor
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    ABSTRACT: For more than two decades, CD4 cell count measurements have been central to understanding HIV disease progression, making important clinical decisions, and monitoring the response to antiretroviral therapy (ART). In well resourced settings, the monitoring of patients on ART has been supported by routine virological monitoring. Viral load monitoring was recommended by WHO in 2013 guidelines as the preferred way to monitor people on ART, and efforts are underway to scale up access in resource-limited settings. Recent studies suggest that in situations where viral load is available and patients are virologically suppressed, long-term CD4 monitoring adds little value and stopping CD4 monitoring will have major cost savings. CD4 cell counts will continue to play an important part in initial decisions around ART initiation and clinical management, particularly for patients presenting late to care, and for treatment monitoring where viral load monitoring is restricted. However, in settings where both CD4 cell counts and viral load testing are routinely available, countries should consider reducing the frequency of CD4 cell counts or not doing routine CD4 monitoring for patients who are stable on ART. Copyright © 2014 Elsevier Ltd. All rights reserved.
    The Lancet Infectious Diseases 11/2014; DOI:10.1016/S1473-3099(14)70896-5 · 19.45 Impact Factor
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    ABSTRACT: Introduction Antiretrovirals are available at low prices in sub-Saharan Africa, but these prices may not be consistently available for middle-income countries in other regions with large HIV epidemics. Over 30% of HIV infected people live in countries outside sub-Saharan Africa. Several key antiretrovirals are still on patent, with generic production restricted. We assessed price variations for key antiretroviral drugs inside versus outside sub-Saharan Africa. Methods HIV drug prices used in national programmes (2010–2014) were extracted from the WHO Global Price Reporting Mechanism database for all reporting middle-income countries as classified by the World Bank. Treatment costs (branded and generic) were compared for countries inside sub-Saharan Africa versus those outside. Five key second-line antiretrovirals were analysed: abacavir, atazanavir, darunavir, lopinavir/ritonavir, raltegravir. Results Prices of branded antiretrovirals were significantly higher outside sub-Saharan Africa (p<0.001, adjusted for year of purchase) (see Table 1). For example, the median (interquartile range) price of darunavir from Janssen was $732 (IQR $732-806) per person-year in sub-Saharan Africa versus $4689 (IQR $4075-5717) in non-African middle-income countries, an increase of 541%. However, when supplied by generic companies, most antiretrovirals were similarly priced between countries in sub-Saharan Africa and other regions. Conclusions Pharmaceutical companies are selling antiretrovirals to non-African middle-income countries at prices 74–541% higher than African countries with similar gross national incomes. However, generic companies are selling most of these drugs at similar prices across regions. Mechanisms to ensure fair pricing for patented antiretrovirals across both African and non-African middle-income countries need to be improved, to ensure sustainable treatment access.
    Journal of the International AIDS Society 11/2014; 17(4(Suppl 3)):19604. DOI:10.7448/IAS.17.4.19604 · 4.21 Impact Factor
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    ABSTRACT: Currently, access to treatment for HCV is limited, with treatment rates lowest in the more resource-limited countries, including those countries with the highest prevalence. The use of oral DAAs has the potential to provide treatment at scale by offering opportunities to simplify drug regimens, laboratory requirements, and service delivery models. Key desirable characteristics of future HCV treatment regimens include high efficacy, tolerability, pan-genotype activity, short treatment duration, oral therapy, affordability, and availability as fixed-dose combination. Using such a regimen, HCV treatment delivery could be greatly simplified. Treatment could be initiated following confirmation of the presence of viraemia, with an initial assessment of the stage of liver disease. A combination DAA therapy that is safe and effective across genotypes could remove the need for genotyping and intermediary viral load assessments for response-guided therapy and reduce the need for adverse event monitoring. Simpler, safer, shorter therapy will also facilitate simplified service delivery, including task shifting, decentralization, and integration of treatment and care. The opportunity to scale up HCV treatment using such delivery approaches will depend on efforts needed to guarantee that the new DAAs are affordable in low-income settings. This will require the engagement of all stakeholders, ranging from the companies developing these new treatments, WHO and other international organizations, including procurement and funding mechanisms, governments and civil society.
    Journal of Hepatology 11/2014; 61(1). DOI:10.1016/j.jhep.2014.09.019 · 10.40 Impact Factor
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    ABSTRACT: Objective To ascertain estimates of adult patients, recorded as lost to follow-up (LTFU) within antiretroviral treatment (ART) programmes, who have self-transferred care, died or truly stopped ART in low- and middle-income countries.Methods PubMed, EMBASE, Web of Science, Science Direct, LILACS, IndMed and AIM databases (2003-2013) and IAS/AIDS conference abstracts (2011-2013) were searched for tracing studies reporting the proportion of traced patients found to have self-transferred, died or stopped ART. These estimates were then combined using random-effects meta-analysis. Risk of bias was assessed through subgroup and sensitivity analyses.Results28 studies were eligible for inclusion, reporting true outcomes for 10,806 traced patients attending approximately 258 ART facilities. None were from outside sub-Saharan Africa. 23 studies reported 4.5-54.4% traced LTFU patients self-transferring care, providing a pooled estimate of 18.6% (95% CI 15.8-22.0%). A significant positive association was found between rates of self-transfer and LTFU in the ART cohort. The pooled estimates for unreported deaths was 38.8% (95% CI 30.8-46.8%; 27 studies), and 28.6% (95% CI 21.9-36.0%; 20 studies) for patients stopping ART. A significant decrease in unreported deaths from 50.0% (95% CI 41.5-58.4%) to 30.0% (95% CI 21.1-38.9%) was found comparing study periods before and after 31/12/2007.Conclusions Substantial unaccounted for transfers and deaths among patients LTFU confirms that retention and mortality is underestimated where the true outcomes of LTFU patients are not ascertained.This article is protected by copyright. All rights reserved.
    Tropical Medicine & International Health 11/2014; 20(3). DOI:10.1111/tmi.12434 · 2.30 Impact Factor
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    ABSTRACT: Voluntary medical male circumcision has been conclusively demonstrated to reduce the lifetime risk of male acquisition of HIV. The strategy has been adopted as a component of a comprehensive strategy towards achieving an AIDS-free generation. A number of countries in which prevalence of HIV is high and circumcision is low have been identified as a priority, where innovative approaches to scale-up are currently being explored. Rwanda, as one of the priority countries, has faced a number of challenges to successful scale-up. We discuss here how simplifications in the procedure, addressing a lack of healthcare infrastructure and mobilizing resources, and engaging communities of both men and women have permitted Rwanda to move forward with more optimism in its scale-up tactics. Examples from Rwanda are used to highlight how these barriers can and should be addressed.
    BMC Medicine 10/2014; 12(1):184. DOI:10.1186/s12916-014-0184-4 · 7.28 Impact Factor
  • Clinical Infectious Diseases 10/2014; DOI:10.1093/cid/ciu767 · 9.42 Impact Factor
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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. DOI:10.1186/s12916-014-0173-7 · 7.28 Impact Factor
  • AIDS (London, England) 08/2014; 28(14). DOI:10.1097/QAD.0000000000000406 · 6.56 Impact Factor
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    ABSTRACT: IntroductionSeveral approaches have been taken to reduce pre-antiretroviral therapy (ART) losses between HIV testing and ART initiation in low- and middle-income countries, but a systematic assessment of the evidence has not yet been undertaken. The aim of this systematic review is to assess the potential for interventions to improve or facilitate linkage to or retention in pre-ART care and initiation of ART in low- and middle-income settings.MethodsAn electronic search was conducted on Medline, Embase, Global Health, Web of Science and conference databases to identify studies describing interventions aimed at improving linkage to or retention in pre-ART care or initiation of ART. Additional searches were conducted to identify on-going trials on this topic, and experts in the field were contacted. An assessment of the risk of bias was conducted. Interventions were categorized according to key domains in the existing literature. ResultsA total of 11,129 potentially relevant citations were identified, of which 24 were eligible for inclusion, with the majority (n=21) from sub-Saharan Africa. In addition, 15 on-going trials were identified. The most common interventions described under key domains included: health system interventions (i.e. integration in the setting of antenatal care); patient convenience and accessibility (i.e. point-of-care CD4 count (POC) testing with immediate results, home-based ART initiation); behaviour interventions and peer support (i.e. improved communication, patient referral and education) and incentives (i.e. food support). Several interventions showed favourable outcomes: integration of care and peer supporters increased enrolment into HIV care, medical incentives increased pre-ART retention, POC CD4 testing and food incentives increased completion of ART eligibility screening and ART initiation. Most studies focused on the general adult patient population or pregnant women. The majority of published studies were observational cohort studies, subject to an unclear risk of bias.ConclusionsFindings suggest that streamlining services to minimize patient visits, providing adequate medical and peer support, and providing incentives may decrease attrition, but the quality of the current evidence base is low. Few studies have investigated combined interventions, or assessed the impact of interventions across the HIV cascade. Results from on-going trials investigating POC CD4 count testing, patient navigation, rapid ART initiation and mobile phone technology may fill the quality of evidence gap. Further high-quality studies on key population groups are required, with interventions informed by previously reported barriers to care.
    Journal of the International AIDS Society 08/2014; 17(1):19032. DOI:10.7448/IAS.17.1.19032 · 4.21 Impact Factor
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    Wendy Susan Stevens, Nathan Ford
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    ABSTRACT: Access to antiretroviral therapy (ART) is expanding at a rapid rate in resource-limited settings, with ambitious goals such as having 90% of infected individuals on ART by 2020. With the expansion of ART, there will be the need to expand assays for both HIV diagnosis and monitoring. To achieve these goals, clinical and diagnostic algorithms need to undergo constant review to ensure that they remain relevant and have the desired impact. While all assays used in HIV care need to be considered, this opinion focuses on the changes that could be made to CD4+ testing algorithms, resulting in reduced use allowing funds to be diverted to the current gold standard assay for measuring treatment success, the HIV viral load.
    South African Medical Journal 08/2014; 104(8):559-60. DOI:10.7196/samj.8299
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    Journal of the International AIDS Society 07/2014; 17(1):19323. DOI:10.7448/IAS.17.1.19323 · 4.21 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; 18(S4). DOI:10.1007/s10461-014-0832-x · 3.49 Impact Factor

Publication Stats

5k Citations
2,849.58 Total Impact Points


  • 2009–2015
    • University of Cape Town
      • • Centre of Infectious Disease Epidemiology & Research
      • • School of Public Health and Family Medicine
      Kaapstad, Western Cape, South Africa
  • 2014
    • University of Liverpool
      Liverpool, England, United Kingdom
  • 2012–2014
    • Imperial College London
      • Division of Infectious Diseases
      Londinium, England, United Kingdom
    • University of British Columbia - Vancouver
      • British Colombia Centre for Excellence in HIV/AIDS
      Vancouver, British Columbia, Canada
    • University of Ottawa
      • Faculty of Health Sciences
      Ottawa, Ontario, Canada
    • Stanford University
      • Division of General Medical Disciplines
      Palo Alto, CA, United States
  • 2002–2014
    • Médecins Sans Frontières
      Bruxelles, Brussels Capital Region, Belgium
    • London School of Hygiene and Tropical Medicine
      Londinium, England, United Kingdom
  • 2013
    • Stellenbosch University
      Stellenbosch, Western Cape, South Africa
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 1999–2013
    • Doctors Without Borders
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • University of Washington Seattle
      • School of Public Health
      Seattle, Washington, United States
  • 2008–2011
    • Simon Fraser University
      • Faculty of Health Sciences
      Burnaby, British Columbia, Canada
    • Groote Schuur Hospital
      Kaapstad, Western Cape, South Africa
  • 2010
    • Johns Hopkins Medicine
      • Department of Surgery
      Baltimore, MD, United States
  • 2004
    • Veterinarians Without Borders Switzerland
      Geneva, Switzerland
  • 2001
    • University of Toronto
      Toronto, Ontario, Canada
  • 2000
    • Utrecht University
      Utrecht, Utrecht, Netherlands