• CD4 count slope and mortality in HIV-infected patients on antiretroviral therapy: multicohort analysis from South Africa

      Hoffmann, Christopher J; Schomaker, Michael; Fox, Matthew P; Mutevedzi, Portia; Giddy, Janet; Prozesky, Hans; Wood, Robin; Garone, Daniela B; Egger, Matthias; Boulle, Andrew; Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. choffmann@jhmi.edu (Lippincott Williams & Wilkins, 2013-05-01)
      In many resource-limited settings monitoring of combination antiretroviral therapy (cART) is based on the current CD4 count, with limited access to HIV RNA tests or laboratory diagnostics. We examined whether the CD4 count slope over 6 months could provide additional prognostic information.
    • Development of dual-class antiretroviral drug resistance in a child coinfected with HIV and tuberculosis: a case report from KwaZulu-Natal, South Africa.

      Murphy, R A; France, H; Sunpath, H; Gordon, M L; Marconi, V; Kuritzkes, D R; McIntosh, K; Massachusetts General Hospital, and Brigham and Women's Hospital, Boston, MA, USA. richard.murphy@newyork.msf.org (Published by Oxford University Press, 2009-02)
      The treatment of concurrent HIV and tuberculosis (TB) in children <3 years of age has not been well-studied and is complicated by potential drug-drug interactions. The recommended antiretroviral therapy (ART) in coinfected children in South Africa consists of full-strength ritonavir, lamivudine and stavudine. We report on a child initiated on this regimen, during concurrent TB treatment, who promptly developed an adverse reaction, virologic failure and dual-class antiretroviral drug resistance, compromising subsequent salvage ART.
    • 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; International Union against Tuberculosis and Lung Disease, Paris, France. adharries@theunion.org (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.
    • Immunovirological response to combined antiretroviral therapy and drug resistance patterns in children: 1- and 2-year outcomes in rural Uganda.

      Ahoua, Laurence; Guenther, Gunar; Rouzioux, Christine; Pinoges, Loretxu; Anguzu, Paul; Taburet, Anne-Marie; Balkan, Suna; Olson, David M; Olaro, Charles; Pujades-Rodríguez, Mar; Clinical Research Department, Epicentre, Paris, France; Laboratory of Virology, Necker Hospital, Paris, France; Department of Operations, Médecins Sans Frontières, Arua, Uganda; Laboratory of Clinical Pharmacology, Bicêtre Hospital, Kremlin Bicêtre, France; Medical Department, Médecins Sans Frontières, Paris, France; Medical Department, Médecins Sans Frontières, New York, USA; Medical and Administrative Hospital Direction, Arua Regional Referral Hospital, Arua, Uganda (BioMed Central, 2011-07-26)
      Children living with HIV continue to be in urgent need of combined antiretroviral therapy (ART). Strategies to scale up and improve pediatric HIV care in resource-poor regions, especially in sub-Saharan Africa, require further research from these settings. We describe treatment outcomes in children treated in rural Uganda after 1 and 2 years of ART start.
    • Low lopinavir plasma or hair concentrations explain second-line protease inhibitor failures in a resource-limited setting.

      van Zyl, Gert Uves; van Mens, Thijs E; McIlleron, Helen; Zeier, Michele; Nachega, Jean B; Decloedt, Eric; Malavazzi, Carolina; Smith, Peter; Huang, Yong; van der Merwe, Lize; Gandhi, Monica; Maartens, Gary; Division of Medical Virology, Department of Pathology, NHLS Tygerberg and Stellenbosch University, Tygerberg, South Africa. guvz@sun.ac.za (2011-04)
      In resource-limited settings, many patients, with no prior protease inhibitor (PI) treatment on a second-line, high genetic barrier, ritonavir-boosted PI-containing regimen have virologic failure.
    • Mean CD4 cell count changes in patients failing a first-line antiretroviral therapy in resource-limited settings.

      Calmy, Alexandra; Balestre, Eric; Bonnet, Fabrice; Boulle, Andrew; Sprinz, Eduardo; Wood, Robin; Delaporte, Eric; Messou, Eugène; McIntyre, James; El Filali, Kamal Marhoum; Schechter, Mauro; Kumarasamy, N; Bangsberg, David; McPhail, Patrick; Van Der Borght, Stefaan; Zala, Carlos; Egger, Matthias; Thiébaut, Rodolphe; Dabis, François; HIV Unit, Geneva University Hospital, Geneva, Switzerland. acalmy@gmail.com (BMC, 2012-12)
      Changes in CD4 cell counts are poorly documented in individuals with low or moderate-level viremia while on antiretroviral treatment (ART) in resource-limited settings. We assessed the impact of on-going HIV-RNA replication on CD4 cell count slopes in patients treated with a first-line combination ART.
    • Weight gain at 3 months of antiretroviral therapy is strongly associated with survival: evidence from two developing countries

      Madec, Yoann; Szumilin, Elisabeth; Genevier, Christine; Ferradini, Laurent; Balkan, Suna; Pujades, Mar; Fontanet, Arnaud; Unité d'Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris, France; Medecins Sans Frontieres, Paris, France; Medecins Sans Frontieres, Nairobi, Kenya; Infectious Diseases Department, Khmero-Soviet Friendship Hospital, Phnom Penh, Cambodia; Epicentre, Paris, France (2009-04-27)
      BACKGROUND: In developing countries, access to laboratory tests remains limited, and the use of simple tools such as weight to monitor HIV-infected patients treated with antiretroviral therapy should be evaluated. METHODS: Cohort study of 2451 Cambodian and 2618 Kenyan adults who initiated antiretroviral therapy between 2001 and 2007. The prognostic value of weight gain at 3 months of antiretroviral therapy on 3-6 months mortality, and at 6 months on 6-12 months mortality, was investigated using Poisson regression. RESULTS: Mortality rates [95% confidence interval (CI)] between 3 and 6 months of antiretroviral therapy were 9.9 (7.6-12.7) and 13.5 (11.0-16.7) per 100 person-years in Cambodia and Kenya, respectively. At 3 months, among patients with initial body mass index less than or equal to 18.5 kg/m (43% of the study population), mortality rate ratios (95% CI) were 6.3 (3.0-13.1) and 3.4 (1.4-8.3) for those with weight gain less than or equal to 5 and 5-10%, respectively, compared with those with weight gain of more than 10%. At 6 months, weight gain was also predictive of subsequent mortality: mortality rate ratio (95% CI) was 7.3 (4.0-13.3) for those with weight gain less than or equal to 5% compared with those with weight gain of more than 10%. CONCLUSION: Weight gain at 3 months is strongly associated with survival. Poor compliance or undiagnosed opportunistic infections should be investigated in patients with initial body mass index less than or equal to 18.5 and achieving weight gain less than or equal to 10%.