Virological Failure, HIV-1 Drug Resistance and Early Mortality in Adults Admitted to Hospital in Malawi: A Nested Observational Cohort Study

Ankur Gupta-Wright; Katherine Fielding; Joep J. van Oosterhout; Melanie Alufandika; Daniel J. Grint; Elizabeth Chimbayo; Judith Heaney; Matthew Byott; Eleni Nastouli; Henry Mwandumba; Elizabeth L. Corbett; Ravindra K. Gupta

doi:10.1016/s2352-3018(20)30172-7

Virological Failure, HIV-1 Drug Resistance and Early Mortality in Adults Admitted to Hospital in Malawi: A Nested Observational Cohort Study

Ankur Gupta-Wright, Katherine Fielding, Joep J. van Oosterhout, Melanie Alufandika, Daniel J. Grint, Elizabeth Chimbayo, Judith Heaney, Matthew Byott, Eleni Nastouli, Henry Mwandumba, Elizabeth L. Corbett, Ravindra K. Gupta

Clinical Sciences

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Abstract

Background: Antiretroviral therapy (ART) scale-up in sub-Saharan Africa (SSA) combined with weak routine virological monitoring has driven increasing HIV drug resistance. We investigated ART failure, drug resistance and early mortality among hospital inpatients in Malawi.

Methods: An observational cohort study nested in a trial of urine-based TB screening in unselected HIV-positive adults followed up for 2 months. Patients taking ART for ≥6 months at hospital admission had frozen plasma samples tested for HIV-1 viral load. Those with HIV-1 RNA ≥1000 copies/ml had drug resistance testing by ultra-deep sequencing, with drug resistance defined as intermediate or high-level resistance using the Stanford HIVDR Algorithm

Findings: Of 1316 patients recruited in the Malawi trial site between October 2015 and September 2017, 786 had taken ART for ≥6 months of whom 252/786 (32.1%) patients had viral load ≥1000 copies/ml (virological failure). Mean age was 38 years, 61.5% were female and median CD4 count was 60 cells/µL. Of 237 (94.0%) patients with HIV drug resistance results available, 195 (82.3%) had resistance to lamivudine, 128 (54.0%) to tenofovir and 219 (92.4%) to efavirenz. Resistance to at least 2 drugs was common (196/237, 82.7%) and this was associated with increased 2-month mortality (adjusted hazard ratio 1.7, 95% CI 1.2-2.4, p=0.004).

Interpretation: HIV virological failure and HIV multidrug resistance were common in HIV-positive inpatients, and associated with increased early mortality. Targeted interventions including adherence support, rapid viral load testing and routine access to drug resistance testing are urgently needed. Enabling prompt diagnosis and switching to alternative ART could reduce early mortality among HIV-positive inpatients.

Original language	English
Pages (from-to)	e620-e628
Journal	The Lancet HIV
Volume	7
Issue number	9
DOIs	https://doi.org/10.1016/s2352-3018(20)30172-7
Publication status	Published - 2 Sept 2020

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STAMP HIV DR paper - HMwandumbaAccepted author manuscript, 664 KBLicence: CC BY

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Gupta-Wright, A., Fielding, K., van Oosterhout, J. J., Alufandika, M., Grint, D. J., Chimbayo, E., Heaney, J., Byott, M., Nastouli, E., Mwandumba, H., Corbett, E. L., & Gupta, R. K. (2020). Virological Failure, HIV-1 Drug Resistance and Early Mortality in Adults Admitted to Hospital in Malawi: A Nested Observational Cohort Study. The Lancet HIV, 7(9), e620-e628. https://doi.org/10.1016/s2352-3018(20)30172-7

@article{a4e206fec1c847a7a8933ad1db214947,

title = "Virological Failure, HIV-1 Drug Resistance and Early Mortality in Adults Admitted to Hospital in Malawi: A Nested Observational Cohort Study",

abstract = "Background: Antiretroviral therapy (ART) scale-up in sub-Saharan Africa (SSA) combined with weak routine virological monitoring has driven increasing HIV drug resistance. We investigated ART failure, drug resistance and early mortality among hospital inpatients in Malawi.Methods: An observational cohort study nested in a trial of urine-based TB screening in unselected HIV-positive adults followed up for 2 months. Patients taking ART for ≥6 months at hospital admission had frozen plasma samples tested for HIV-1 viral load. Those with HIV-1 RNA ≥1000 copies/ml had drug resistance testing by ultra-deep sequencing, with drug resistance defined as intermediate or high-level resistance using the Stanford HIVDR AlgorithmFindings: Of 1316 patients recruited in the Malawi trial site between October 2015 and September 2017, 786 had taken ART for ≥6 months of whom 252/786 (32.1\%) patients had viral load ≥1000 copies/ml (virological failure). Mean age was 38 years, 61.5\% were female and median CD4 count was 60 cells/µL. Of 237 (94.0\%) patients with HIV drug resistance results available, 195 (82.3\%) had resistance to lamivudine, 128 (54.0\%) to tenofovir and 219 (92.4\%) to efavirenz. Resistance to at least 2 drugs was common (196/237, 82.7\%) and this was associated with increased 2-month mortality (adjusted hazard ratio 1.7, 95\% CI 1.2-2.4, p=0.004).Interpretation: HIV virological failure and HIV multidrug resistance were common in HIV-positive inpatients, and associated with increased early mortality. Targeted interventions including adherence support, rapid viral load testing and routine access to drug resistance testing are urgently needed. Enabling prompt diagnosis and switching to alternative ART could reduce early mortality among HIV-positive inpatients.",

author = "Ankur Gupta-Wright and Katherine Fielding and \{van Oosterhout\}, \{Joep J.\} and Melanie Alufandika and Grint, \{Daniel J.\} and Elizabeth Chimbayo and Judith Heaney and Matthew Byott and Eleni Nastouli and Henry Mwandumba and Corbett, \{Elizabeth L.\} and Gupta, \{Ravindra K.\}",

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Gupta-Wright, A, Fielding, K, van Oosterhout, JJ, Alufandika, M, Grint, DJ, Chimbayo, E, Heaney, J, Byott, M, Nastouli, E, Mwandumba, H, Corbett, EL & Gupta, RK 2020, 'Virological Failure, HIV-1 Drug Resistance and Early Mortality in Adults Admitted to Hospital in Malawi: A Nested Observational Cohort Study', The Lancet HIV, vol. 7, no. 9, pp. e620-e628. https://doi.org/10.1016/s2352-3018(20)30172-7

TY - JOUR

T1 - Virological Failure, HIV-1 Drug Resistance and Early Mortality in Adults Admitted to Hospital in Malawi: A Nested Observational Cohort Study

AU - Gupta-Wright, Ankur

AU - Fielding, Katherine

AU - van Oosterhout, Joep J.

AU - Alufandika, Melanie

AU - Grint, Daniel J.

AU - Chimbayo, Elizabeth

AU - Heaney, Judith

AU - Byott, Matthew

AU - Nastouli, Eleni

AU - Mwandumba, Henry

AU - Corbett, Elizabeth L.

AU - Gupta, Ravindra K.

PY - 2020/9/2

Y1 - 2020/9/2

N2 - Background: Antiretroviral therapy (ART) scale-up in sub-Saharan Africa (SSA) combined with weak routine virological monitoring has driven increasing HIV drug resistance. We investigated ART failure, drug resistance and early mortality among hospital inpatients in Malawi.Methods: An observational cohort study nested in a trial of urine-based TB screening in unselected HIV-positive adults followed up for 2 months. Patients taking ART for ≥6 months at hospital admission had frozen plasma samples tested for HIV-1 viral load. Those with HIV-1 RNA ≥1000 copies/ml had drug resistance testing by ultra-deep sequencing, with drug resistance defined as intermediate or high-level resistance using the Stanford HIVDR AlgorithmFindings: Of 1316 patients recruited in the Malawi trial site between October 2015 and September 2017, 786 had taken ART for ≥6 months of whom 252/786 (32.1%) patients had viral load ≥1000 copies/ml (virological failure). Mean age was 38 years, 61.5% were female and median CD4 count was 60 cells/µL. Of 237 (94.0%) patients with HIV drug resistance results available, 195 (82.3%) had resistance to lamivudine, 128 (54.0%) to tenofovir and 219 (92.4%) to efavirenz. Resistance to at least 2 drugs was common (196/237, 82.7%) and this was associated with increased 2-month mortality (adjusted hazard ratio 1.7, 95% CI 1.2-2.4, p=0.004).Interpretation: HIV virological failure and HIV multidrug resistance were common in HIV-positive inpatients, and associated with increased early mortality. Targeted interventions including adherence support, rapid viral load testing and routine access to drug resistance testing are urgently needed. Enabling prompt diagnosis and switching to alternative ART could reduce early mortality among HIV-positive inpatients.

AB - Background: Antiretroviral therapy (ART) scale-up in sub-Saharan Africa (SSA) combined with weak routine virological monitoring has driven increasing HIV drug resistance. We investigated ART failure, drug resistance and early mortality among hospital inpatients in Malawi.Methods: An observational cohort study nested in a trial of urine-based TB screening in unselected HIV-positive adults followed up for 2 months. Patients taking ART for ≥6 months at hospital admission had frozen plasma samples tested for HIV-1 viral load. Those with HIV-1 RNA ≥1000 copies/ml had drug resistance testing by ultra-deep sequencing, with drug resistance defined as intermediate or high-level resistance using the Stanford HIVDR AlgorithmFindings: Of 1316 patients recruited in the Malawi trial site between October 2015 and September 2017, 786 had taken ART for ≥6 months of whom 252/786 (32.1%) patients had viral load ≥1000 copies/ml (virological failure). Mean age was 38 years, 61.5% were female and median CD4 count was 60 cells/µL. Of 237 (94.0%) patients with HIV drug resistance results available, 195 (82.3%) had resistance to lamivudine, 128 (54.0%) to tenofovir and 219 (92.4%) to efavirenz. Resistance to at least 2 drugs was common (196/237, 82.7%) and this was associated with increased 2-month mortality (adjusted hazard ratio 1.7, 95% CI 1.2-2.4, p=0.004).Interpretation: HIV virological failure and HIV multidrug resistance were common in HIV-positive inpatients, and associated with increased early mortality. Targeted interventions including adherence support, rapid viral load testing and routine access to drug resistance testing are urgently needed. Enabling prompt diagnosis and switching to alternative ART could reduce early mortality among HIV-positive inpatients.

U2 - 10.1016/s2352-3018(20)30172-7

DO - 10.1016/s2352-3018(20)30172-7

M3 - Article

SN - 2405-4704

VL - 7

SP - e620-e628

JO - The Lancet HIV

JF - The Lancet HIV

IS - 9

ER -

Virological Failure, HIV-1 Drug Resistance and Early Mortality in Adults Admitted to Hospital in Malawi: A Nested Observational Cohort Study

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