• 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.
    • Diagnosis and management of antiretroviral-therapy failure in resource-limited settings in sub-Saharan Africa: challenges and perspectives.

      Harries, Anthony D; Zachariah, Rony; van Oosterhout, Joep J; Reid, Steven D; Hosseinipour, Mina C; Arendt, Vic; Chirwa, Zengani; Jahn, Andreas; Schouten, Erik J; Kamoto, Kelita; et al. (2010-01)
      Despite the enormous progress made in scaling up antiretroviral therapy (ART) in sub-Saharan Africa, many challenges remain, not least of which are the identification and management of patients who have failed first-line therapy. Less than 3% of patients are receiving second-line treatment at present, whereas 15-25% of patients have detectable viral loads 12 months or more into treatment, of whom a substantial proportion might have virological failure. We discuss the reasons why virological ART failure is likely to be under-diagnosed in the routine health system, and address the current difficulties with standard recommended second-line ART regimens. The development of new diagnostic tools for ART failure, in particular a point-of-care HIV viral-load test, combined with simple and inexpensive second-line therapy, such as boosted protease-inhibitor monotherapy, could revolutionise the management of ART failure in resource-limited settings.
    • Ending deaths from HIV-related cryptococcal meningitis by 2030

      Shroufi, A; Chiller, T; Jordan, A; Denning, DW; Harrison, TS; Govender, NP; Loyse, A; Baptiste, S; Rajasingham, R; Boulware, DR; et al. (Elsevier, 2021-01-01)
      The UNAIDS target to reduce HIV-related death to fewer than 500 000 deaths per year by 2020 will not be met. 1 This statement might not be headline grabbing as this target was never as prominent as the 90-90-90 targets, 2 the achievement of which is a necessary but not sufficient step towards ending AIDS mortality.
    • 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.
    • HIV and cytomegalovirus in Thailand.

      Chua, A; Wilson, D; Ford, N (Elsevier, 2005-06)
    • Nevirapine versus Efavirenz for patients co-infected with HIV and Tuberculosis: A Randomised Non-Inferiority Trial

      Bonnet, Maryline; Bhatt, Nilesh; Baudin, Elisabeth; Silva, Carlota; Michon, Christophe; Taburet, Anne-Marie; Ciaffi, Laura; Sobry, Agnès; Bastos, Rui; Nunes, Elizabete; et al. (2013-02-19)
      BACKGROUND: In countries with a high incidence of HIV and tuberculosis co-infection, nevirapine and efavirenz are widely used as antiretroviral therapy but both interact with antituberculosis drugs. We aimed to compare efficacy and safety of a nevirapine-based antiretroviral therapy (started at full dose) with an efavirenz-based regimen in co-infected patients. METHODS: We did a multicentre, open-label, randomised, non-inferiority trial at three health centres in Maputo, Mozambique. We enrolled adults (≥18 years) with tuberculosis and previously untreated HIV infection (CD4 cell counts <250 cells per μL) and alanine aminotransferase and total bilirubin concentrations of less than five times the upper limit of normal. 4-6 weeks after the start of tuberculosis treatment, we randomly allocated patients (1:1) with central randomisation, block sizes of two to six, and stratified by site and CD4 cell count to nevirapine (200 mg twice daily) or efavirenz (600 mg once daily), plus lamivudine and stavudine. The primary endpoint was virological suppression at 48 weeks (HIV-1 RNA <50 copies per mL) in all patients who received at least one dose of study drug (intention-to-treat population); death and loss to follow-up were recorded as treatment failure. The non-inferiority margin for the difference of efficacy was 10%. We assessed efficacy in intention-to-treat and per-protocol populations and safety in all patients who received study drug. This study is registered with ClinicalTrials.gov, number NCT00495326. FINDINGS: Between October, 2007, and March, 2010, we enrolled 285 patients into each group. 242 (85%) patients in the nevirapine group and 233 (82%) patients in the efavirenz group completed follow-up. In the intention-to-treat population, 184 patients (64·6%, 95% CI 58·7-70·1) allocated nevirapine achieved virological suppression at week 48, as did 199 patients (69·8%, 64·1-75·1) allocated efavirenz (one-sided 95% CI of the difference of efficacy 11·7%). In the per-protocol population, 170 (70·0%, 63·8-75·7) of 243 patients allocated nevirapine achieved virological suppression at week 48, as did 194 (78·9%, 73·2-83·8) of 246 patients allocated efavirenz (one-sided 95% CI 15·4%). The median CD4 cell count at randomisation was 89 cells per μL. 15 patients substituted nevirapine with efavirenz and six patients substituted efavirenz with nevirapine. 20 patients allocated nevirapine (7%) had grade 3-4 increase of alanine aminotransferase compared with 17 patients allocated efavirenz (6%). Three patients had severe rash after receipt of nevirapine (1%) but no patients did after receipt of efavirenz. 18 patients in the nevirapine group died, as did 17 patients in the efavirenz group. INTERPRETATION: Although non-inferiority of the nevirapine-regimen was not shown, nevirapine at full dose could be a safe, acceptable alternative for patients unable to tolerate efavirenz. FUNDING: French Research Agency for HIV/AIDS and hepatitis (ANRS).
    • Scaling-up co-trimoxazole prophylaxis in HIV-exposed and HIV-infected children in high HIV-prevalence countries.

      Zachariah, R; Harries, A D; Luo, C; Bachman, G; Graham, S M; Médecins Sans Frontières, Medical department (Operational Research), Brussels Operational Center, Brussels, Belgium. zachariah@internet.lu (Elsevier, 2007-10)
      Co-trimoxazole (trimethoprim-sulfamethoxazole) is a widely available antibiotic that substantially reduces HIV-related morbidity and mortality in both adults and children. Prophylaxis with co-trimoxazole is a recommended intervention of proven benefit that could serve not only as an initial step towards improving paediatric care in young children with limited access to antiretroviral treatment, but also as an important complement to antiretroviral therapy in resource-limited settings. Despite co-trimoxazole's known clinical benefits, the potential operational benefits, and favourable recommendations by WHO, UNAIDS, and UNICEF, its routine use in developing countries--particularly sub-Saharan Africa--has remained limited. Out of an estimated 4 million children in need of co-trimoxazole prophylaxis (HIV-exposed and HIV-infected), only 4% are currently receiving this intervention. We discuss some of the major barriers preventing the scale-up of co-trimoxazole prophylaxis for children in countries with a high prevalence of HIV and propose specific actions required to tackle these challenges.