• Adherence to antiretroviral therapy: supervision or support?

      Mills, Edward J; Lester, Richard; Ford, Nathan; Faculty of Health Sciences, University of Ottawa, Ottawa, Canada; Department of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, Canada; Médecins Sans Frontiers, Geneva, Switzerland; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa (Elsevier, 2012-02)
      We are entering a new phase in the strategic use of antiretroviral drugs. In addition to dramatically reducing HIV/AIDS-related morbidity and mortality, these drugs have recently shown an important effect in reducing HIV incidence and transmission.
    • AIDS: patent rights versus patient's rights.

      Chirac, P; von Schoen-Angerer, T; Kasper, T; Ford, N; Médecins Sans Frontières, Paris, France. (Elsevier, 2000-08-05)
    • Challenges associated with providing diabetes care in humanitarian settings

      Boulle, P; Kehlenbrink, S; Smith, J; Beran, D; Jobanputra, K (Elsevier, 2019-03-13)
      The humanitarian health landscape is gradually changing, partly as a result of the shift in global epidemiological trends and the rise of non-communicable diseases, including diabetes. Humanitarian actors are progressively incorporating care for diabetes into emergency medical response, but challenges abound. This Series paper discusses contemporary practical challenges associated with diabetes care in humanitarian contexts in low-income and middle-income countries, using the six building blocks of health systems described by WHO (information and research, service delivery, health workforce, medical products and technologies, governance, and financing) as a framework. Challenges include the scarcity of evidence on the management of diabetes and clinical guidelines adapted to humanitarian contexts; unavailability of core indicators for surveillance and monitoring systems; and restricted access to the medicines and diagnostics necessary for adequate clinical care. Policy and system frameworks do not routinely include diabetes and little funding is allocated for diabetes care in humanitarian crises. Humanitarian organisations are increasingly gaining experience delivering diabetes care, and interagency collaboration to coordinate, improve data collection, and analyse available programmes is in progress. However, the needs around all six WHO health system building blocks are immense, and much work needs to be done to improve diabetes care for crisis-affected populations.
    • Community support is associated with better antiretroviral treatment outcomes in a resource-limited rural district in Malawi.

      Zachariah, R; Teck, R; Buhendwa, L; Fitzgerald, M; Labana, S; Chinji, C; Humblet, P; Harries, A D; Médecins Sans Frontières, Medical Department (Operational Research), Brussels Operational Center, 68 Rue de Gasperich, L-1617, Luxembourg, Belgium. zachariah@internet.lu (Elsevier, 2007-01)
      A study was carried in a rural district in Malawi among HIV-positive individuals placed on antiretroviral treatment (ART) in order to verify if community support influences ART outcomes. Standardized ART outcomes in areas of the district with and without community support were compared. Between April 2003 (when ART was started) and December 2004 a total of 1634 individuals had been placed on ART. Eight hundred and ninety-five (55%) individuals were offered community support, while 739 received no such support. For all patients placed on ART with and without community support, those who were alive and continuing ART were 96 and 76%, respectively (P<0.001); death was 3.5 and 15.5% (P<0.001); loss to follow-up was 0.1 and 5.2% (P<0.001); and stopped ART was 0.8 and 3.3% (P<0.001). The relative risks (with 95% CI) for alive and on ART [1.26 (1.21-1.32)], death [0.22 (0.15-0.33)], loss to follow-up [0.02 (0-0.12)] and stopped ART [0.23 (0.08-0.54)] were all significantly better in those offered community support (P<0.001). Community support is associated with a considerably lower death rate and better overall ART outcomes. The community might be an unrecognized and largely 'unexploited resource' that could play an important contributory role in countries desperately trying to scale up ART with limited resources.
    • Early Antiretroviral Therapy initiation: Access and Equity of Viral Load Testing for HIV Treatment Monitoring

      Peter, T; Ellenberger, D; Kim, AA; Boeras, D; Messele, T; Roberts, T; Stevens, W; Jani, I; Abimiku, A; Ford, N; et al. (Elsevier, 2016-10-20)
      Scaling up access to HIV viral load testing for individuals undergoing antiretroviral therapy in low-resource settings is a global health priority, as emphasised by research showing the benefits of suppressed viral load for the individual and the whole population. Historically, large-scale diagnostic test implementation has been slow and incomplete because of service delivery and other challenges. Building on lessons from the past, in this Personal View we propose a new framework to accelerate viral load scale-up and ensure equitable access to this essential test. The framework includes the following steps: (1) ensuring adequate financial investment in scaling up this test; (2) achieving pricing agreements and consolidating procurement to lower prices of the test; (3) strengthening functional tiered laboratory networks and systems to expand access to reliable, high-quality testing across countries; (4) strengthening national leadership, with prioritisation of laboratory services; and (5) demand creation and uptake of test results by clinicians, nurses, and patients, which will be vital in ensuring viral load tests are appropriately used to improve the quality of care. The use of dried blood spots to stabilise and ship samples from clinics to laboratories, and the use of point-of-care diagnostic tests, will also be important for ensuring access, especially in settings with reduced laboratory capacity. For countries that have just started to scale up viral load testing, lessons can be learnt from countries such as Botswana, Brazil, South Africa, and Thailand, which have already established viral load programmes. This framework might be useful for guiding the implementation of viral load with the aim of achieving the new global HIV 90-90-90 goals by 2020.
    • Exploring HIV infection and susceptibility to measles among older children and adults in Malawi: a facility-based study

      Polonsky, Jonathan A; Singh, Beverley; Masiku, Charlie; Langendorf, Céline; Kagoli, Matthew; Hurtado, Northan; Berthelot, Mathilde; Heinzelmann, Annette; Puren, Adrian; Grais, Rebecca F (Elsevier, 2014-12-11)
      Background HIV infection increases measles susceptibility in infants, but little is known about this relationship among older children and adults. We conducted a facility-based study to explore whether HIV status and/or CD4 count were associated with either measles seroprotection and/or measles antibody concentration. Methods We conveniently sampled HIV-infected patients presenting for follow-up care, and HIV-uninfected individuals presenting for HIV testing at Chiradzulu District Hospital, Malawi, from January to September 2012. We recorded age, sex and reported measles vaccination and infection history. Blood samples were taken to determine CD4 count and measles antibody concentration. Results 1935 (1434 HIV-infected; 501 HIV-uninfected) participants were recruited. The majority of adults, and approximately half the children, were measles seroprotected, with lower odds among HIV-infected children (adjusted OR=0.27, 95% CI: 0.10-0.69, p=0.006), but not adults. Among HIV-infected participants, neither CD4 count (p=0.16) nor time on antiretroviral therapy (p=0.25) were associated with measles antibody concentration, while older age (p<0.001) and female sex (p<0.001) were independently associated with this measure. Conclusions We found no evidence that HIV infection contributes to the risk for measles infection among adults, but HIV-infected children (including at ages older than previously reported), were less likely to be seroprotected in this sample.
    • First-line and second-line antiretroviral therapy.

      Calmy, A; Pascual, F; Ford, N (Elsevier, 2004)
    • The future role of CD4 cell count for monitoring antiretroviral therapy

      Ford, Nathan; Meintjes, Graeme; Pozniak, Anton; Bygrave, Helen; Hill, Andrew; Peter, Trevor; Davies, Mary-Ann; Grinsztejn, Beatriz; Calmy, Alexandra; Kumarasamy, N; et al. (Elsevier, 2014-11-19)
      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.
    • Hepatitis C seroprevalence and HIV co-infection in sub-Saharan Africa: a systematic review and meta-analysis

      Rao, V Bhargavi; Johari, Nur; du Cros, Philipp; Messina, Janey; Ford, Nathan; Cooke, Graham S (Elsevier, 2015-05-05)
      An estimated 150 million people worldwide are infected with hepatitis C virus (HCV). HIV co-infection accelerates the progression of HCV and represents a major public health challenge. We aimed to determine the epidemiology of HCV and the prevalence of HIV co-infection in sub-Saharan Africa.
    • High prevalence of lipoatrophy among patients on stavudine-containing first-line antiretroviral therapy regimens in Rwanda.

      van Griensven, J; De Naeyer, L; Mushi, T; Ubarijoro, S; Gashumba, D; Gazille, C; Zachariah, R; Médecins Sans Frontières, Kimihurura, Kacyiru, 1361 Kigali, Rwanda. jvgrie@yahoo.com <jvgrie@yahoo.com> (Elsevier, 2007-08)
      This study was conducted among individuals placed on WHO-recommended first-line antiretroviral therapy (ART) at two urban health centres in Kigali, Rwanda, in order to determine (a) the overall prevalence of lipodystrophy and (b) the risk factors for lipoatropy. Consecutive individuals on ART for >1 year were systematically subjected to a standardised case definition-based questionnaire and clinical assessment. Of a total of 409 individuals, 370 (90%) were on an ART regimen containing stavudine (d4T), whilst the rest were receiving a zidovudine (AZT)-containing regimen. Lipodystrophy was apparent in 140 individuals (34%), of whom 40 (9.8%) had isolated lipoatrophy, 20 (4.9%) had isolated lipohypertrophy and 80 (19.6%) had mixed patterns. Fifty-six percent of patients reported the effects as disturbing. The prevalence of lipoatrophy was more than three times higher when taking d4T compared with AZT-containing regimens (31.4% vs. 10.3%). Being female, d4T-based ART, baseline body mass index >or=25 kg/m(2) or baseline CD4 count >or=150 cells/microl and increasing duration of ART were all significantly associated with lipoatrophy. Lipoatrophy appears to be an important long-term complication of WHO-recommended first-line ART regimens. These data highlight the urgent need for access to more affordable and less toxic ART regimens in resource-limited settings.
    • HIV and cytomegalovirus in Thailand.

      Chua, A; Wilson, D; Ford, N (Elsevier, 2005-06)
    • HIV and Tuberculosis in Prisons in Sub-Saharan Africa

      Telisinghe, L; Charalambous, S; Topp, SM; Herce, ME; Hoffmann, CJ; Barron, P; Schouten, EJ; Jahn, A; Zachariah, R; Harries, AD; et al. (Elsevier, 2016-07-14)
      Given the dual epidemics of HIV and tuberculosis in sub-Saharan Africa and evidence suggesting a disproportionate burden of these diseases among detainees in the region, we aimed to investigate the epidemiology of HIV and tuberculosis in prison populations, describe services available and challenges to service delivery, and identify priority areas for programmatically relevant research in sub-Saharan African prisons. To this end, we reviewed literature on HIV and tuberculosis in sub-Saharan African prisons published between 2011 and 2015, and identified data from only 24 of the 49 countries in the region. Where data were available, they were frequently of poor quality and rarely nationally representative. Prevalence of HIV infection ranged from 2·3% to 34·9%, and of tuberculosis from 0·4 to 16·3%; detainees nearly always had a higher prevalence of both diseases than did the non-incarcerated population in the same country. We identified barriers to prevention, treatment, and care services in published work and through five case studies of prison health policies and services in Zambia, South Africa, Malawi, Nigeria, and Benin. These barriers included severe financial and human-resource limitations and fragmented referral systems that prevent continuity of care when detainees cycle into and out of prison, or move between prisons. These challenges are set against the backdrop of weak health and criminal-justice systems, high rates of pre-trial detention, and overcrowding. A few examples of promising practices exist, including routine voluntary testing for HIV and screening for tuberculosis upon entry to South African and the largest Zambian prisons, reforms to pre-trial detention in South Africa, integration of mental health services into a health package in selected Malawian prisons, and task sharing to include detainees in care provision through peer-educator programmes in Rwanda, Zimbabwe, Zambia, and South Africa. However, substantial additional investments are required throughout sub-Saharan Africa to develop country-level policy guidance, build human-resource capacity, and strengthen prison health systems to ensure universal access to HIV and tuberculsosis prevention, treatment, and care of a standard that meets international goals and human rights obligations.
    • HIV/AIDS prevention and treatment.

      Goemaere, E; Ford, N; Benatar, S R (Elsevier, 2002-07-06)
    • How can the community contribute in the fight against HIV/AIDS and tuberculosis? An example from a rural district in Malawi.

      Zachariah, R; Teck, R; Buhendwa, L; Labana, S; Chinji, C; Humblet, P; Harries, A D; Médecins sans Frontières, Medical Department (Operational Research), Brussels Operational Center, Belgium. zachariah@internet.lu (Elsevier, 2006-02)
      This paper describes (a) the experience of initiating community involvement in HIV/AIDS and tuberculosis (TB) activities in a rural district in Malawi and (b) some of the different ways in which the community is contributing in the fight against these two diseases and the outcomes of their involvement. During a 2-year period, a total of 21,358 (41%) of 52,510 HIV tests performed at voluntary counselling and HIV testing (VCT) sites in the district were conducted by lay community counsellors. A team of 465 community volunteers, 1,362 trained family caregivers and 9 community nurses provided care and support to 5,106 HIV-positive individuals, of whom 2,006 (39%) were in WHO stage III or IV. All those in WHO stage III or IV were on co-trimoxazole prophylaxis and 895 (45%) of these were also on antiretroviral treatment. A total of 2,714 TB patients, of whom 1627 (60%) were HIV-positive, also received care and support. A total of 1,694 orphans were trained in vocational skills. Twelve vegetable gardens and three maize farms were set up, and pre-school activities were organised for 900 orphans. Communities can play an important contributory role in reducing the burden of HIV/AIDS and TB and in mitigating its impact. Despite this, community resources in most settings are often under-exploited and their role remains undefined.
    • (The Lancet)red: a missed opportunity.

      Calmy, A; Pascual, F; Shettle, S; de la Vega, F G; Ford, N (Elsevier, 2006-09-23)
    • Life in the Time of Antiretrovirals in South Africa

      Furin, J; Isaakidis, P (Elsevier, 2016-12-09)
    • Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration

      Rhee, SY; Varghese, V; Holmes, SP; Van Zyl, GU; Steegen, K; Boyd, MA; Cooper, DA; Nsanzimana, S; Saravanan, S; Charpentier, C; et al. (Elsevier, 2017-03-19)
      Tenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT) mutations selected in individuals with VF on such a regimen is not known. To identify TDF regimen-associated mutations (TRAMs), we compared the proportion of each RT mutation in 2873 individuals with VF on a WHO-recommended first-line TDF-containing regimen to its proportion in a cohort of 50,803 antiretroviral-naïve individuals. To identify TRAMs specifically associated with TDF-selection pressure, we compared the proportion of each TRAM to its proportion in a cohort of 5805 individuals with VF on a first-line thymidine analog-containing regimen. We identified 83 TRAMs including 33 NRTI-associated, 40 NNRTI-associated, and 10 uncommon mutations of uncertain provenance. Of the 33 NRTI-associated TRAMs, 12 - A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and Y115F - were more common among individuals receiving a first-line TDF-containing compared to a first-line thymidine analog-containing regimen. These 12 TDF-selected TRAMs will be important for monitoring TDF-associated transmitted drug-resistance and for determining the extent of reduced TDF susceptibility in individuals with VF on a TDF-containing regimen.
    • The Partec CyFlow Counter could provide an option for CD4+ T-cell monitoring in the context of scaling-up antiretroviral treatment at the district level in Malawi.

      Fryland, M; Chaillet, P; Zachariah, R; Barnaba, A; Bonte, L; Andereassen, R; Charrondière, S; Teck, R; Didakus, O; Médecins sans Frontières-Luxembourg, Thyolo District, Malawi. (Elsevier, 2006-10)
      A study was conducted in rural Malawi to verify (a) whether the Partec CyFlow Counter((R)) for CD4+ T-cell lymphocyte counting in HIV-positive individuals could be introduced into a district hospital laboratory and (b) whether it would produce CD4 counts of acceptable quality. CD4+ cell counting was performed using the Partec CyFlow Counter and the results were compared with a reference method (FACsCount). A total of 311 blood samples were analysed and the correlation coefficient for the CyFlow Counter was 0.92 (95% CI 0.89-0.95). Mean CD4 counts using the Partec and the reference methods were 308.2 cells/microl and 316.9 cells/microl, respectively. The mean difference in CD4 count values was -8.68 cells/microl (95% CI -18.8 to 1.4). Mean intra-run variation was -6.84 cells/microl (95% CI -12.9 to 0.79). In the district laboratory setting, the instrument could accommodate up to 75 blood samples per technician per day. After being trained, local laboratory staff found the CyFlow Counter procedures simple to run and the instrument easy to manipulate. The Partec CyFlow Counter produces sufficiently reliable results and the instrument appears robust under field conditions. It could provide a new option for introducing routine CD4+ cell monitoring at the district level in the context of scaling-up antiretroviral therapy in Malawi.