The relative contributions of HIV drug resistance, nonadherence and low-level viremia to viremic episodes on antiretroviral therapy in sub-Saharan Africa

Seth C Inzaule; Silvia Bertagnolio; Cissy M Kityo; Margaret Siwale; Sulaimon Akanmu; Maureen Wellington; Marleen de Jager; Prudence Ive; Kishor Mandaliya; Wendy Stevens; Tamara S Boender; Pascale Ondoa; Kim C E Sigaloff; Tobias F Rinke de Wit; Raph L Hamers

doi:10.1097/QAD.0000000000002588

The relative contributions of HIV drug resistance, nonadherence and low-level viremia to viremic episodes on antiretroviral therapy in sub-Saharan Africa

Seth C Inzaule
, Silvia Bertagnolio
, Cissy M Kityo
, Margaret Siwale
, Sulaimon Akanmu
, Maureen Wellington
, Marleen de Jager
, Prudence Ive
, Kishor Mandaliya
, Wendy Stevens
, Tamara S Boender
, Pascale Ondoa
, Kim C E Sigaloff
, Tobias F Rinke de Wit
, Raph L Hamers

Health Sciences

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

INTRODUCTION: To achieve viral suppression among more than 90% of people on antiretroviral therapy (ART), improved understanding is warranted of the modifiable causes of HIV viremic episodes. We assessed the relative contributions of drug-resistance, nonadherence and low-level viremia (LLV) (viral load 50-999 cps/ml) on viremic episodes in sub-Saharan Africa.

METHODS: In a multicountry adult cohort initiating nonnucleoside reverse transcriptase inhibitor-based first-line ART, viremic episodes (viral load ≥1000 cps/ml) were classified as first, viral nonsuppression at 12 months; second, virological rebound at 24 months (after initial viral suppression at 12 months); third, failure to achieve viral resuppression at 24 months (after viremic episode at 12 months). We used adjusted odds ratios from multivariable logistic regression to estimate attributable fractions for each risk factor.

RESULTS: Of 2737 cohort participants, 1935 had data on pretreatment drug resistance (PDR) and at least 1 viral load outcome. Viral nonsuppression episodes [173/1935 (8.9%)] were attributable to nonadherence in 30% (35% in men vs. 24% in women) and to PDR to nonnucleoside reverse transcriptase inhibitors in 10% (15% in women vs. 6% in men). Notably, at contemporary PDR prevalences of 10-25%, PDR would explain 13-30% of viral nonsuppression. Virological rebound episodes [96/1515 (6.3%)] were mostly attributable to LLV (29%) and nonadherence (14%), and only rarely to PDR (1.1%). Failures to achieve viral resuppression [66/81 (81.5%)] were mostly attributable to the presence of acquired drug resistance (34%) and only rarely to nonadherence (2.4%).

CONCLUSION: Effective adherence interventions could substantially reduce viral nonsuppression (especially in men) and virological rebound (especially during LLV), but would have limited effect on improving viral resuppression. Alternative ART regimens could circumvent PDR and acquired resistance.

Original language	English
Pages (from-to)	1559-1566
Number of pages	8
Journal	AIDS
Volume	34
Issue number	10
DOIs	https://doi.org/10.1097/QAD.0000000000002588
Publication status	Published - 1 Aug 2020

Funding

The Pan-African Studies to Evaluate Resistance (PASER) is an initiative of the Amsterdam Institute for Global Health and Development, with major support provided by the Ministry of Foreign Affairs of The Netherlands through a partnership with Stichting Aids Fonds (grant no. 12454) and The Netherlands Organization for Scientific Research (NWO-WOTRO grant no. W07.10.101 and W07.10.106), and additional support provided by De Grote Onderneming, The Embassy of the Kingdom of the Netherlands, Heineken Africa Foundation and Jura Foundation.

Funders	Funder number
De Grote Onderneming
Jura Foundation
The Embassy of the Kingdom of the Netherlands, Heineken Africa Foundation
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	W07.10.101, W07.10.106
Ministerie van Buitenlandse Zaken	12454

Keywords

Adult
Africa South of the Sahara
Anti-HIV Agents/therapeutic use
Drug Resistance, Viral
Female
HIV Infections/drug therapy
Humans
Male
Medication Adherence
Viral Load
Viremia/complications

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10.1097/QAD.0000000000002588

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Inzaule, S. C., Bertagnolio, S., Kityo, C. M., Siwale, M., Akanmu, S., Wellington, M., de Jager, M., Ive, P., Mandaliya, K., Stevens, W., Boender, T. S., Ondoa, P., Sigaloff, K. C. E., Rinke de Wit, T. F., & Hamers, R. L. (2020). The relative contributions of HIV drug resistance, nonadherence and low-level viremia to viremic episodes on antiretroviral therapy in sub-Saharan Africa. AIDS, 34(10), 1559-1566. https://doi.org/10.1097/QAD.0000000000002588

@article{e5844db1c0ef46a0a47963bbba8ad5db,

title = "The relative contributions of HIV drug resistance, nonadherence and low-level viremia to viremic episodes on antiretroviral therapy in sub-Saharan Africa",

abstract = "INTRODUCTION: To achieve viral suppression among more than 90\% of people on antiretroviral therapy (ART), improved understanding is warranted of the modifiable causes of HIV viremic episodes. We assessed the relative contributions of drug-resistance, nonadherence and low-level viremia (LLV) (viral load 50-999 cps/ml) on viremic episodes in sub-Saharan Africa.METHODS: In a multicountry adult cohort initiating nonnucleoside reverse transcriptase inhibitor-based first-line ART, viremic episodes (viral load ≥1000 cps/ml) were classified as first, viral nonsuppression at 12 months; second, virological rebound at 24 months (after initial viral suppression at 12 months); third, failure to achieve viral resuppression at 24 months (after viremic episode at 12 months). We used adjusted odds ratios from multivariable logistic regression to estimate attributable fractions for each risk factor.RESULTS: Of 2737 cohort participants, 1935 had data on pretreatment drug resistance (PDR) and at least 1 viral load outcome. Viral nonsuppression episodes [173/1935 (8.9\%)] were attributable to nonadherence in 30\% (35\% in men vs. 24\% in women) and to PDR to nonnucleoside reverse transcriptase inhibitors in 10\% (15\% in women vs. 6\% in men). Notably, at contemporary PDR prevalences of 10-25\%, PDR would explain 13-30\% of viral nonsuppression. Virological rebound episodes [96/1515 (6.3\%)] were mostly attributable to LLV (29\%) and nonadherence (14\%), and only rarely to PDR (1.1\%). Failures to achieve viral resuppression [66/81 (81.5\%)] were mostly attributable to the presence of acquired drug resistance (34\%) and only rarely to nonadherence (2.4\%).CONCLUSION: Effective adherence interventions could substantially reduce viral nonsuppression (especially in men) and virological rebound (especially during LLV), but would have limited effect on improving viral resuppression. Alternative ART regimens could circumvent PDR and acquired resistance.",

keywords = "Adult, Africa South of the Sahara, Anti-HIV Agents/therapeutic use, Drug Resistance, Viral, Female, HIV Infections/drug therapy, Humans, Male, Medication Adherence, Viral Load, Viremia/complications",

author = "Inzaule, \{Seth C\} and Silvia Bertagnolio and Kityo, \{Cissy M\} and Margaret Siwale and Sulaimon Akanmu and Maureen Wellington and \{de Jager\}, Marleen and Prudence Ive and Kishor Mandaliya and Wendy Stevens and Boender, \{Tamara S\} and Pascale Ondoa and Sigaloff, \{Kim C E\} and \{Rinke de Wit\}, \{Tobias F\} and Hamers, \{Raph L\}",

year = "2020",

month = aug,

day = "1",

doi = "10.1097/QAD.0000000000002588",

language = "English",

volume = "34",

pages = "1559--1566",

journal = "AIDS",

issn = "0269-9370",

publisher = "Lippincott Williams and Wilkins",

number = "10",

}

Inzaule, SC, Bertagnolio, S, Kityo, CM, Siwale, M, Akanmu, S, Wellington, M, de Jager, M, Ive, P, Mandaliya, K, Stevens, W, Boender, TS, Ondoa, P, Sigaloff, KCE, Rinke de Wit, TF & Hamers, RL 2020, 'The relative contributions of HIV drug resistance, nonadherence and low-level viremia to viremic episodes on antiretroviral therapy in sub-Saharan Africa', AIDS, vol. 34, no. 10, pp. 1559-1566. https://doi.org/10.1097/QAD.0000000000002588

TY - JOUR

T1 - The relative contributions of HIV drug resistance, nonadherence and low-level viremia to viremic episodes on antiretroviral therapy in sub-Saharan Africa

AU - Inzaule, Seth C

AU - Bertagnolio, Silvia

AU - Kityo, Cissy M

AU - Siwale, Margaret

AU - Akanmu, Sulaimon

AU - Wellington, Maureen

AU - de Jager, Marleen

AU - Ive, Prudence

AU - Mandaliya, Kishor

AU - Stevens, Wendy

AU - Boender, Tamara S

AU - Ondoa, Pascale

AU - Sigaloff, Kim C E

AU - Rinke de Wit, Tobias F

AU - Hamers, Raph L

PY - 2020/8/1

Y1 - 2020/8/1

N2 - INTRODUCTION: To achieve viral suppression among more than 90% of people on antiretroviral therapy (ART), improved understanding is warranted of the modifiable causes of HIV viremic episodes. We assessed the relative contributions of drug-resistance, nonadherence and low-level viremia (LLV) (viral load 50-999 cps/ml) on viremic episodes in sub-Saharan Africa.METHODS: In a multicountry adult cohort initiating nonnucleoside reverse transcriptase inhibitor-based first-line ART, viremic episodes (viral load ≥1000 cps/ml) were classified as first, viral nonsuppression at 12 months; second, virological rebound at 24 months (after initial viral suppression at 12 months); third, failure to achieve viral resuppression at 24 months (after viremic episode at 12 months). We used adjusted odds ratios from multivariable logistic regression to estimate attributable fractions for each risk factor.RESULTS: Of 2737 cohort participants, 1935 had data on pretreatment drug resistance (PDR) and at least 1 viral load outcome. Viral nonsuppression episodes [173/1935 (8.9%)] were attributable to nonadherence in 30% (35% in men vs. 24% in women) and to PDR to nonnucleoside reverse transcriptase inhibitors in 10% (15% in women vs. 6% in men). Notably, at contemporary PDR prevalences of 10-25%, PDR would explain 13-30% of viral nonsuppression. Virological rebound episodes [96/1515 (6.3%)] were mostly attributable to LLV (29%) and nonadherence (14%), and only rarely to PDR (1.1%). Failures to achieve viral resuppression [66/81 (81.5%)] were mostly attributable to the presence of acquired drug resistance (34%) and only rarely to nonadherence (2.4%).CONCLUSION: Effective adherence interventions could substantially reduce viral nonsuppression (especially in men) and virological rebound (especially during LLV), but would have limited effect on improving viral resuppression. Alternative ART regimens could circumvent PDR and acquired resistance.

AB - INTRODUCTION: To achieve viral suppression among more than 90% of people on antiretroviral therapy (ART), improved understanding is warranted of the modifiable causes of HIV viremic episodes. We assessed the relative contributions of drug-resistance, nonadherence and low-level viremia (LLV) (viral load 50-999 cps/ml) on viremic episodes in sub-Saharan Africa.METHODS: In a multicountry adult cohort initiating nonnucleoside reverse transcriptase inhibitor-based first-line ART, viremic episodes (viral load ≥1000 cps/ml) were classified as first, viral nonsuppression at 12 months; second, virological rebound at 24 months (after initial viral suppression at 12 months); third, failure to achieve viral resuppression at 24 months (after viremic episode at 12 months). We used adjusted odds ratios from multivariable logistic regression to estimate attributable fractions for each risk factor.RESULTS: Of 2737 cohort participants, 1935 had data on pretreatment drug resistance (PDR) and at least 1 viral load outcome. Viral nonsuppression episodes [173/1935 (8.9%)] were attributable to nonadherence in 30% (35% in men vs. 24% in women) and to PDR to nonnucleoside reverse transcriptase inhibitors in 10% (15% in women vs. 6% in men). Notably, at contemporary PDR prevalences of 10-25%, PDR would explain 13-30% of viral nonsuppression. Virological rebound episodes [96/1515 (6.3%)] were mostly attributable to LLV (29%) and nonadherence (14%), and only rarely to PDR (1.1%). Failures to achieve viral resuppression [66/81 (81.5%)] were mostly attributable to the presence of acquired drug resistance (34%) and only rarely to nonadherence (2.4%).CONCLUSION: Effective adherence interventions could substantially reduce viral nonsuppression (especially in men) and virological rebound (especially during LLV), but would have limited effect on improving viral resuppression. Alternative ART regimens could circumvent PDR and acquired resistance.

KW - Adult

KW - Africa South of the Sahara

KW - Anti-HIV Agents/therapeutic use

KW - Drug Resistance, Viral

KW - Female

KW - HIV Infections/drug therapy

KW - Humans

KW - Male

KW - Medication Adherence

KW - Viral Load

KW - Viremia/complications

U2 - 10.1097/QAD.0000000000002588

DO - 10.1097/QAD.0000000000002588

M3 - Article

C2 - 32675566

SN - 0269-9370

VL - 34

SP - 1559

EP - 1566

JO - AIDS

JF - AIDS

IS - 10

ER -

The relative contributions of HIV drug resistance, nonadherence and low-level viremia to viremic episodes on antiretroviral therapy in sub-Saharan Africa

Abstract

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Keywords

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