Journal Article > ResearchAbstract
J Acquir Immune Defic Syndr. 22 January 2013; Volume 63 (Issue 1); DOI:10.1097/QAI.0b013e318287c1fe
Hoffman CJ, Schomaker M, Fox MP, Mutevedzi, Giddy J, et al.
J Acquir Immune Defic Syndr. 22 January 2013; Volume 63 (Issue 1); DOI:10.1097/QAI.0b013e318287c1fe
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.
Journal Article > ResearchFull Text
PLOS Med. 9 April 2013; Volume 10 (Issue 4); DOI:10.1371/journal.pmed.1001418
Johnson LF, Mossong J, Dorrington R, Schomaker M, Hoffman CJ, et al.
PLOS Med. 9 April 2013; Volume 10 (Issue 4); DOI:10.1371/journal.pmed.1001418
Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults.
Journal Article > ResearchFull Text
J Acquir Immune Defic Syndr. 7 July 2015; Volume 70 (Issue 3); DOI:10.1097/QAI.0000000000000748
Koller M, Fatti G, Chi BH, Keiser O, Hoffman CJ, et al.
J Acquir Immune Defic Syndr. 7 July 2015; Volume 70 (Issue 3); DOI:10.1097/QAI.0000000000000748
Journal Article > ResearchFull Text
EBioMedicine. 19 March 2017; Volume 18; 225-235.; DOI:10.1016/j.ebiom.2017.03.024
Rhee SY, Varghese B, Holmes SP, Van Zyl GU, Steegen K, et al.
EBioMedicine. 19 March 2017; Volume 18; 225-235.; DOI:10.1016/j.ebiom.2017.03.024
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.
Journal Article > ResearchFull Text
AIDS. 1 September 2013; Volume 27 (Issue 14); 2225-32.; DOI:10.1097/QAD.0b013e328362d887
Wandeler G, Gsponer T, Mulenga L, Garone DB, Wood R, et al.
AIDS. 1 September 2013; Volume 27 (Issue 14); 2225-32.; DOI:10.1097/QAD.0b013e328362d887
OBJECTIVES
Zidovudine (ZDV) is recommended for first-line antiretroviral therapy (ART) in resource-limited settings. ZDV may, however, lead to anemia and impaired immunological response. We compared CD4+ cell counts over 5 years between patients starting ART with and without ZDV in southern Africa.
DESIGN
Cohort study.
METHODS
Patients aged at least 16 years who started first-line ART in South Africa, Botswana, Zambia, or Lesotho were included. We used linear mixed-effect models to compare CD4+ cell count trajectories between patients on ZDV-containing regimens and patients on other regimens, censoring follow-up at first treatment change. Impaired immunological recovery, defined as a CD4+ cell count below 100 cells/μl at 1 year, was assessed in logistic regression. Analyses were adjusted for baseline CD4+ cell count and hemoglobin level, age, sex, type of regimen, viral load monitoring, and calendar year.
RESULTS
A total of 72,597 patients starting ART, including 19,758 (27.2%) on ZDV, were analyzed. Patients on ZDV had higher CD4+ cell counts (150 vs.128 cells/μl) and hemoglobin level (12.0 vs. 11.0 g/dl) at baseline, and were less likely to be women than those on other regimens. Adjusted differences in CD4+ cell counts between regimens containing and not containing ZDV were -16 cells/μl [95% confidence interval (CI) -18 to -14] at 1 year and -56 cells/μl (95% CI -59 to -52) at 5 years. Impaired immunological recovery was more likely with ZDV compared to other regimens (odds ratio 1.40, 95% CI 1.22-1.61).
CONCLUSION
In southern Africa, ZDV is associated with inferior immunological recovery compared to other backbones. Replacing ZDV with another nucleoside reverse transcriptase inhibitor could avoid unnecessary switches to second-line ART.
Zidovudine (ZDV) is recommended for first-line antiretroviral therapy (ART) in resource-limited settings. ZDV may, however, lead to anemia and impaired immunological response. We compared CD4+ cell counts over 5 years between patients starting ART with and without ZDV in southern Africa.
DESIGN
Cohort study.
METHODS
Patients aged at least 16 years who started first-line ART in South Africa, Botswana, Zambia, or Lesotho were included. We used linear mixed-effect models to compare CD4+ cell count trajectories between patients on ZDV-containing regimens and patients on other regimens, censoring follow-up at first treatment change. Impaired immunological recovery, defined as a CD4+ cell count below 100 cells/μl at 1 year, was assessed in logistic regression. Analyses were adjusted for baseline CD4+ cell count and hemoglobin level, age, sex, type of regimen, viral load monitoring, and calendar year.
RESULTS
A total of 72,597 patients starting ART, including 19,758 (27.2%) on ZDV, were analyzed. Patients on ZDV had higher CD4+ cell counts (150 vs.128 cells/μl) and hemoglobin level (12.0 vs. 11.0 g/dl) at baseline, and were less likely to be women than those on other regimens. Adjusted differences in CD4+ cell counts between regimens containing and not containing ZDV were -16 cells/μl [95% confidence interval (CI) -18 to -14] at 1 year and -56 cells/μl (95% CI -59 to -52) at 5 years. Impaired immunological recovery was more likely with ZDV compared to other regimens (odds ratio 1.40, 95% CI 1.22-1.61).
CONCLUSION
In southern Africa, ZDV is associated with inferior immunological recovery compared to other backbones. Replacing ZDV with another nucleoside reverse transcriptase inhibitor could avoid unnecessary switches to second-line ART.