Nathan Ford

World Health Organization WHO, Genève, Geneva, Switzerland

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Publications (308)3491.62 Total impact

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    ABSTRACT: Introduction: Despite significant progress in improving access to antiretroviral therapy over the past decade, substantial numbers of people living with HIV (PLHIV) in all regions continue to experience severe illness and require hospitalization. We undertook a global review assessing the proportion of hospitalizations and in-hospital deaths because of tuberculosis (TB) in PLHIV. Methods: Seven databases were searched to identify studies reporting causes of hospitalizations among PLHIV from 1 January 2007 to 31 January 2015 irrespective of age, geographical region or language. The proportion of hospitalizations and in-hospital mortality attributable to TB was estimated using random effects meta-analysis. Results: From an initial screen of 9049 records, 66 studies were identified, providing data on 35,845 adults and 2792 children across 42 countries. Overall, 17.7% (95% CI 16.0 to 20.2%) of all adult hospitalizations were because of TB, making it the leading cause of hospitalization overall; the proportion of adult hospitalizations because of TB exceeded 10% in all regions except the European region. Of all paediatric hospitalizations, 10.8% (95% CI 7.6 to 13.9%) were because of TB. There was insufficient data among children for analysis by region. In-hospital mortality attributable to TB was 24.9% (95% CI 19.0 to 30.8%) among adults and 30.1% (95% CI 11.2 to 48.9%) among children. Discussion: TB remains a leading cause of hospitalization and in-hospital death among adults and children living with HIV worldwide.
    No preview · Article · Jan 2016 · Journal of the International AIDS Society
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    ABSTRACT: Introduction: An increasing proportion of adult patients initiating antiretroviral therapy (ART) in resource-limited settings are aged >50 years. Older populations on ART appear to have heightened risk of death, but little is known about factors influencing mortality in this population. Methods: We performed a retrospective observational multisite cohort study including all adult patients (>= 15 years) initiating ART between 2003 and 2013 in programmes supported by Medecins Sans Frontieres across 12 countries in Asia, Africa and Europe. Patients were stratified into two age groups, >50 years and 15 to 50 years. A Cox proportional hazards model was used to explore factors associated with mortality. Results: The study included 41,088 patients: 2591 (6.3%) were aged >50 years and 38,497 (93.7%) were aged 15 to 50 years. The mortality rate was significantly higher in the age group >50 years [367 (14.2%) deaths; mortality rate 7.67 deaths per 100 person-years (95% confidence interval, CI: 6.93 to 8.50)] compared to the age group 15 to 50 years [3788 (9.8%) deaths; mortality rate 4.18 deaths per 100 person-years (95% CI: 4.05 to 4.31)], p<0.0001. Higher CD4 levels at baseline were associated with significantly reduced mortality rates in the 15 to 50 age group but this association was not seen in the >50 age group. WHO Stage 4 conditions were more strongly associated with increased mortality rates in the 15 to 50 age group compared to populations >50 years. WHO Stage 3 conditions were associated with an increased mortality rate in the 15 to 50 age group but not in the >50 age group. Programme region did not affect mortality rates in the >50 age group; however being in an Asian programme was associated with a 36% reduced mortality rate in populations aged 15 to 50 years compared to being in an African programme. There was a higher overall incidence of Stage 3 WHO conditions in people >50 years (12.8/100 person-years) compared to those 15 to 50 years (8.1/100 person-years) (p<0.01). The rate of Stage 4 WHO conditions was similar (5.8/100 versus 6.1/100 respectively, p=0.52). Mortality rates on ART associated with the majority of specific WHO conditions were similar between the 15 to 50 and >50 age groups. Conclusions: Older patients on ART in resource-limited settings have increased mortality rates, but compared to younger populations this appears to be less influenced by baseline CD4 count and WHO clinical stage. HIV treatment programmes in resource-limited settings need to consider risk factors associated with mortality on ART in older populations, which may differ to those related to younger adults.
    No preview · Article · Jan 2016 · Journal of the International AIDS Society
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    ABSTRACT: Objective: This systematic review was carried out to determine the effectiveness of continuous isoniazid (given for at least 36 months) for the treatment of latent tuberculosis infection (LTBI) in people living with HIV (PLHIV). Methods: Six databases and HIV and tuberculosis (TB) conference abstract books were searched for randomized controlled trials that compared the effectiveness of continuous isoniazid treatment with 6 months of isoniazid application. Outcomes of interest were TB incidence, mortality, adverse events and risk of drug resistance. Data were pooled using fixed-effects meta-analysis. Results: Three studies were included, from Botswana, South Africa and India. The risk of active TB was 38% lower among patients receiving continuous isoniazid compared with isoniazid regimen for 6 months [relative risk (RR) 0.62, 95% confidence interval (CI): 0.42-0.89; I = 0%], and 49% lower for those with a positive tuberculin skin test (TST) (RR 0.51, 95% CI: 0.30-0.86; I = 7%). Similarly, individuals with positive TST had a 50% lower chance of death (RR 0.50, 95% CI: 0.27-0.91; I = 3%). Two studies found no evidence of an increase in adverse events in the continuous isoniazid group, whereas a third study, that used a different definition for adverse events, found strong evidence of increase. There was no evidence of increased drug resistance when continuous isoniazid was given. Conclusion: For PLHIV in settings with high TB and HIV prevalence and transmission, continuous isoniazid for at least 36 months is beneficial and probably outweighs the risk of increased adverse events compared with isoniazid regimen for 6 months.
    No preview · Article · Jan 2016 · AIDS (London, England)
  • Nathan Ford · Haileyesus Getahun

    No preview · Article · Dec 2015
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    ABSTRACT: There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future.
    Full-text · Article · Dec 2015 · Nature
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    ABSTRACT: Introduction: As the global community makes progress towards the 90-90-90 targets by 2020, a key challenge is ensuring that antiretroviral drugs for children and adolescents are suitable to the context of resource-limited settings. Drug optimization aims to support the expanded use of more simplified, less toxic drug regimens with high barriers to drug resistance that require minimal clinical monitoring while maintaining therapeutic efficacy. This manuscript summarizes the progress made and outlines further critical steps required to ensure that the right drugs are available to start children and adolescents on treatment and to keep them virologically suppressed. Discussion: Building upon previous work in drug optimization, several important steps were taken in 2014 to ensure alignment between WHO dosing recommendations and the requirements of regulatory bodies, to accelerate drug development, to reduce intellectual property barriers to generic production of combined formulations and rationalize drug selection in countries. The priority for the future is to improve access to antiretroviral therapy (ART) at the two ends of the paediatric age spectrum infants and adolescents where the treatment gap is greatest, and optimize drug sequencing with better use of available medicines for second-and third-line ART. Future efforts in this area will require continuous collaboration and coordination, and the promotion of innovative approaches to accelerate access to new drugs and formulations. Conclusions: While significant progress has been made, additional efforts are needed to ensure that treatment targets are reached by 2020.
    No preview · Article · Dec 2015 · Journal of the International AIDS Society
  • Nathan Ford · Zara Shubber

    No preview · Article · Nov 2015 · Clinical Infectious Diseases
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    Full-text · Article · Nov 2015 · PLoS Neglected Tropical Diseases
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    ABSTRACT: In recent years children and adolescents have emerged as a priority for HIV prevention and care services. We conducted a systematic review to investigate the acceptability, yield and prevalence of HIV testing and counselling (HTC) strategies in children and adolescents (5 to 19 years) in sub-Saharan Africa. An electronic search was conducted in MEDLINE, EMBASE, Global Health and conference abstract databases. Studies reporting on HTC acceptability, yield and prevalence and published between January 2004 and September 2014 were included. Pooled proportions for these three outcomes were estimated using a random effects model. A quality assessment was conducted on included studies. A total of 16,380 potential citations were identified, of which 21 studies (23 entries) were included. Most studies were conducted in Kenya (n=5) and Uganda (n=5) and judged to provide moderate (n=15) to low quality (n=7) evidence, with data not disaggregated by age. Seven studies reported on provider-initiated testing and counselling (PITC), with the remainder reporting on family-centred (n=5), home-based (n=5), outreach (n=5) and school-linked HTC among primary schoolchildren (n=1). PITC among inpatients had the highest acceptability (86.3%; 95% confidence interval [CI]: 65.5 to 100%), yield (12.2%; 95% CI: 6.1 to 18.3%) and prevalence (15.4%; 95% CI: 5.0 to 25.7%). Family-centred HTC had lower acceptance compared to home-based HTC (51.7%; 95% CI: 10.4 to 92.9% vs. 84.9%; 95% CI: 74.4 to 95.4%) yet higher prevalence (8.4%; 95% CI: 3.4 to 13.5% vs. 3.0%; 95% CI: 1.0 to 4.9%). School-linked HTC showed poor acceptance and low prevalence. While PITC may have high test acceptability priority should be given to evaluating strategies beyond healthcare settings (e.g. home-based HTC among families) to identify individuals earlier in their disease progression. Data on linkage to care and cost-effectiveness of HTC strategies are needed to strengthen policies.
    No preview · Article · Oct 2015 · Journal of the International AIDS Society
  • Nathan Ford · Andrew Boulle · Matthias Egger

    No preview · Article · Oct 2015 · AIDS
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    ABSTRACT: Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3-4 month isoniazid plus rifampicin; or 3-4 month rifampicin alone.
    Full-text · Article · Sep 2015 · European Respiratory Journal
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    Helen Cox · Nathan Ford

    Full-text · Article · Sep 2015
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    ABSTRACT: Background: Ongoing CD4 monitoring in patients on antiretroviral therapy (ART) with viral suppression has been questioned. We evaluated the probability of CD4 decline in children with viral suppression and CD4 recovery after 1 year on ART. Methods: We included children from 8 South African cohorts with routine HIV-RNA monitoring if: (1) they were "responders" (HIV-RNA <400 copies/ml and no severe immunosuppression after >1 year on ART [time 0]) and (2) >1 HIV-RNA and CD4 measurement within 15 months of time 0. We determined the probability of CD4 decline to WHO-defined severe immunosuppression for 3 years after time 0 if viral suppression was maintained. Follow-up was censored at the first of: day before first HIV-RNA measurement >400 copies/ml; day before a >15 month gap in testing; date of death, loss to follow-up, transfer out or database closure. Results: Among 5984 children (median age at time 0: 5.8 years [IQR:3.1-9.0]), 270 experienced a single CD4 decline to severe immunosuppression within 3 years of time 0 with probability of 6.6% (95%CI:5.8-7.4). A subsequent CD4 measurement within 15 months of the first low measurement was available for 63% of children with CD4 decline and 86% showed CD4 recovery. The probability of CD4 decline was lowest (2.8%) in children >2 years with no/mild immunosuppression and on ART for <18 months at time 0. This group comprised 40% of children. Conclusion: This finding suggests that it may be safe to stop routine CD4 monitoring in children aged ≥2 years and rely on virologic monitoring alone.
    Full-text · Article · Sep 2015 · The Pediatric Infectious Disease Journal
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    ABSTRACT: Background: Ototoxicity is a severe side effect of aminoglycoside antibiotics. Aminoglycosides are recommended for the treatment of multidrug-resistant TB (MDR-TB). N-Acetylcysteine (NAC) appears to protect against drug- and noise-induced hearing loss. This review aimed to determine if coadministering NAC with aminoglycoside affected ototoxicity development, and to assess the safety and tolerability of prolonged NAC administration. Methods: Eligible studies reported on the efficacy of concomitant NAC and aminoglycoside administration for ototoxicity prevention or long-term (≥6 weeks) administration of NAC regardless of indication. Pooled estimates were calculated using a fixed-effects model. Heterogeneity was assessed using the I(2) statistic. Results: Three studies reported that NAC reduced ototoxicity in 146 patients with end-stage renal failure receiving aminoglycosides. Pooled relative risk for otoprotection at 4-6 weeks was 0.14 (95% CI 0.05 to 0.45), and the risk difference was -33.3% (95% CI 45.5% to 21.2%). Eighty-three studies (N=9988) described the administration of NAC for >6 weeks. Abdominal pain, nausea and vomiting, diarrhoea and arthralgia were increased 1.4-2.2 times. Discussion: This review provides evidence for the safety and otoprotective effect of NAC when coadministered with aminoglycoside. It represents a strong justification for a clinical trial to investigate the effect of concomitant NAC treatment in patients receiving aminoglycosides as part of MDR-TB treatment.
    No preview · Article · Sep 2015 · Thorax
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    ABSTRACT: Background Continued debate exists about whether initiation of antiretroviral therapy (ART) in symptom-free patients at higher baseline CD4 cell counts results in important clinical benefi ts. We aimed to examine to what extent baseline CD4 cell count at linkage to HIV care and at ART initiation predicts mortality in adults with HIV in Rwanda.
    Full-text · Article · Sep 2015 · The Lancet HIV
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    Full-text · Dataset · Aug 2015
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    ABSTRACT: The effectiveness of antiretroviral therapy (ART) is assessed by measuring CD4 cell counts and viral load. Recent studies have questioned the added value of routine CD4 cell count measures in patients who are virologically suppressed. We systematically searched three databases and two conference sites up to 31 October 2014 for studies reporting CD4 changes among patients who were on ART and virologically suppressed. No geographic, language or age restrictions were applied. We identified 12 published and 1 unpublished study reporting CD4 changes among 20,297 virologically suppressed patients. The pooled proportion of patients who experienced an unexplained, confirmed CD4 decline was 0.4% (95% CI 0.2-0.6%). Results were not influenced by duration of follow-up, age, study design or region of economic development. No studies described clinical adverse events among virologically suppressed patients who experienced CD4 declines. The findings of this review support reducing or stopping routine CD4 monitoring for patients who are immunologically stable on ART in settings where routine viral load monitoring is provided.
    Full-text · Article · Aug 2015 · Journal of the International AIDS Society
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    ABSTRACT: Background Morbidity associated with HIV infection is poorly characterised, so we aimed to investigate the contribution of diff erent comorbidities to hospital admission and in-hospital mortality in adults and children living with HIV worldwide. Methods Using a broad search strategy combining terms for hospital admission and HIV infection, we searched MEDLINE via PubMed, Embase, Web of Science, LILACS, AIM, IMEMR and WPIMR from inception to Jan 31, 2015, to identify studies reporting cause of hospital admission in people living with HIV. We focused on data reported after 2007, the period in which access to antiretroviral therapy started to become widespread. We estimated pooled proportions of hospital admissions and deaths per disease category by use of random-eff ects models. We stratifi ed data by geographical region and age. Findings We obtained data from 106 cohorts, with reported causes of hospital admission for 313 006 adults and 6182 children living with HIV. For adults, AIDS-related illnesses (25 119 patients, 46%, 95% CI 40-53) and bacterial infections (14 034 patients, 31%, 20-42) were the leading causes of hospital admission. These two categories were the most common causes of hospital admission for adults in all geographical regions and the most common causes of mortality. Common region-specifi c causes of hospital admission included malnutrition and wasting, parasitic infections, and haematological disorders in the Africa region; respiratory disease, psychiatric disorders, renal disorders, cardiovascular disorders, and liver disease in Europe; haematological disorders in North America; and respiratory, neurological, digestive and liver-related conditions, viral infections, and drug toxicity in South and Central America. For children, AIDS-related illnesses (783 patients, 27%, 95% CI 19-34) and bacterial infections (1190 patients, 41%, 26-56) were the leading causes of hospital admission, followed by malnutrition and wasting, haematological disorders, and, in the African region, malaria. Mortality in individuals admitted to hospital was 20% (95% CI 18-23, 12 902 deaths) for adults and 14% (10-19, 643 deaths) for children. Interpretation This review shows the importance of prompt HIV diagnosis and treatment, and the need to reinforce existing recommendations to provide chemoprophylaxis and vaccination against major preventable infectious diseases to people living with HIV to reduce serious AIDS and non-AIDS morbidity. © 2015. World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved.
    Full-text · Article · Aug 2015 · The Lancet HIV
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    ABSTRACT: Background. More than 11.7 million people are currently receiving antiretroviral therapy (ART) in low- and middle-income countries (LMICs), and focused efforts are needed to ensure high levels of adherence and to min- imize treatment failure. Recently, international targets have emphasized the importance of long-term virological suppression as a key measure of program performance. Methods. We systematically reviewed publications and conference abstracts published between January 2006 and May 2013 that reported virological outcomes among human immunodeficiency virus type 1 (HIV-1)–infected adults receiving first-line ART for up to 5 years in LMICs. Summary estimates of virological suppression after 6, 12, 24, 36, 48, and 60 months of ART were analyzed using random-effects meta-analysis. Intention-to-treat (ITT) anal- ysis assumed all participants who were lost to follow-up, died, or stopped ART as having virological failure. Results. Summary estimates of virological suppression remained >80% for up to 60 months of ART for all 184 in- cluded cohorts. ITT analysis yielded 74.7% (95% confidence interval [CI], 72.2–77.2) suppression after 6 months and 61.8% (95% CI, 44.0–79.7) suppression after 48 months on ART. Switches to second-line ART were reported scarcely. Conclusions. Among individuals retained on ART, virological suppression rates during the first 5 years ofARTwere high (>80%) and stable. Suppression rates in ITT analysis declined during 4 years.
    Full-text · Article · Jul 2015 · Clinical Infectious Diseases
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    ABSTRACT: Background. More than 11.7 million people are currently receiving antiretroviral therapy (ART) in low- and middle-income countries (LMICs), and focused efforts are needed to ensure high levels of adherence and to minimize treatment failure. Recently, international targets have emphasized the importance of long-term virological suppression as a key measure of program performance. Methods. We systematically reviewed publications and conference abstracts published between January 2006 and May 2013 that reported virological outcomes among human immunodeficiency virus type 1 (HIV-1)–infected adults receiving first-line ART for up to 5 years in LMICs. Summary estimates of virological suppression after 6, 12, 24, 36, 48, and 60 months of ART were analyzed using random-effects meta-analysis. Intention-to-treat (ITT) analysis assumed all participants who were lost to follow-up, died, or stopped ART as having virological failure. Results. Summary estimates of virological suppression remained >80% for up to 60 months of ART for all 184 included cohorts. ITT analysis yielded 74.7% (95% confidence interval [CI], 72.2–77.2) suppression after 6 months and 61.8% (95% CI, 44.0–79.7) suppression after 48 months on ART. Switches to second-line ART were reported scarcely. Conclusions. Among individuals retained on ART, virological suppression rates during the first 5 years of ART were high (>80%) and stable. Suppression rates in ITT analysis declined during 4 years.
    Full-text · Article · Jul 2015 · Clinical Infectious Diseases

Publication Stats

7k Citations
3,491.62 Total Impact Points

Institutions

  • 2012-2015
    • World Health Organization WHO
      • Department of HIV/AIDS (HIV)
      Genève, Geneva, Switzerland
    • Imperial College London
      • Division of Infectious Diseases
      Londinium, England, United Kingdom
    • University of Ottawa
      • Faculty of Health Sciences
      Ottawa, Ontario, Canada
    • Stanford University
      • Division of General Medical Disciplines
      Palo Alto, CA, United States
  • 2002-2015
    • University of Cape Town
      • • School of Public Health and Family Medicine
      • • Centre of Infectious Disease Epidemiology & Research
      Kaapstad, Western Cape, South Africa
    • Drugs for Neglected Diseases Institute
      Genève, Geneva, Switzerland
    • London School of Hygiene and Tropical Medicine
      Londinium, England, United Kingdom
  • 2014
    • University of Liverpool
      Liverpool, England, United Kingdom
  • 2002-2014
    • Médecins Sans Frontières
      Bruxelles, Brussels Capital Region, Belgium
  • 2013
    • Johns Hopkins University
      Baltimore, Maryland, United States
    • Veterinarians Without Borders Switzerland
      Bernex GE, Geneva, Switzerland
  • 1999-2013
    • Doctors Without Borders
      Lutetia Parisorum, Île-de-France, France
    • Utrecht University
      • Division of Clinical and Health Psychology
      Utrecht, Utrecht, Netherlands
  • 2011
    • VU University Medical Center
      • Department of Medical Humanities
      Amsterdamo, North Holland, Netherlands
    • University of Washington Seattle
      Seattle, Washington, United States
  • 2008-2011
    • Simon Fraser University
      • Faculty of Health Sciences
      Burnaby, British Columbia, Canada
  • 2008-2010
    • College of Medicine of South Africa
      Kaapstad, Western Cape, South Africa