• Coadministration of lopinavir/ritonavir and rifampicin in HIV and tuberculosis co-infected adults in South Africa

      Murphy, R A; Marconi, V C; Gandhi, R T; Kuritzkes, D R; Sunpath, H; Medical Unit, Médecins Sans Frontières/Doctors Without Borders, New York, New York, United States of America (Public Library of Science, 2012-09-28)
      In HIV-infected patients receiving rifampicin-based treatment for tuberculosis (TB), the dosage of lopinavir/ritonavir (LPV/r) is adjusted to prevent sub-therapeutic lopinavir concentrations. In this setting, South African clinicians were advised to administer super-boosted LPV/r (400 mg/400 mg) twice daily, instead of standard dosed LPV/r (400 mg/100 mg) twice daily. We sought to determine--in routine practice--the tolerability and HIV treatment outcomes associated with super-boosted LPV/r compared to unadjusted LPV/r in combination with rifampicin-based TB treatment.
    • 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.
    • Low uptake of antiretroviral therapy after admission with human immunodeficiency virus and tuberculosis in KwaZulu-Natal, South Africa.

      Murphy, R A; Sunpath, H; Taha, B; Kappagoda, S; Maphasa, K T M; Kuritzkes, D R; Smeaton, L; Doctors Without Borders USA, New York, USA; McCord Hospital, South Africa; Harvard Medical School, Massachusetts, USA; Division of Infectious Disease and Geographic Medicine, California, USA; Zoe-Life, South Africa; Section of Retroviral Therapeutics, Massachusetts, USA; Centre for Biostatistics in AIDS Research, Massachusetts, USA (2010-07-01)
      A prospective cohort study was conducted among human immunodeficiency virus (HIV) infected in-patients with tuberculosis (TB) or other opportunistic infections (OIs) in South Africa to estimate subsequent antiretroviral therapy (ART) uptake and survival.
    • 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.