Antiretroviral Adherence, Elevated Viral Load, and Drug Resistance Mutations in Human Immunodeficiency Virus-infected Women Initiating Treatment in Pregnancy: A Nested Case-control Study

Landon Myer, Andrew D. Redd, Elton Mukonda, Briana A. Lynch, Tamsin K. Phillips, Anna Eisenberg, Nei Yuan Hsiao, Adam Capoferri, Alison Zerbe, William Clarke, Maia Lesosky, Autumn Breaud, James McIntyre, Daniel Bruno, Craig Martens, Elaine J. Abrams, Steven J. Reynolds

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Elevated viral load (VL) early after antiretroviral therapy (ART) initiation appears frequently in pregnant and postpartum women living with human immunodeficiency virus; however the relative contributions of pre-ART drug resistance mutations (DRMs) vs nonadherence in the etiology of elevated VL are unknown. METHODS: Within a cohort of women initiating ART during pregnancy in Cape Town, South Africa, we compared women with elevated VL after initial suppression (cases, n = 80) incidence-density matched to women who maintained suppression over time (controls, n = 87). Groups were compared on pre-ART DRMs and detection of antiretrovirals in stored plasma. RESULTS: The prevalence of pre-ART DRMs was 10% in cases and 5% in controls (adjusted odds ratio [aOR], 1.53 [95% confidence interval {CI}, .4-5.9]); all mutations were to nonnucleoside reverse transcriptase inhibitors. At the time of elevated VL, 19% of cases had antiretrovirals detected in plasma, compared with 87% of controls who were suppressed at a matched time point (aOR, 131.43 [95% CI, 32.8-527.4]). Based on these findings, we estimate that <10% of all elevated VL in the cohort may be attributable to pre-ART DRMs vs >90% attributable to ART nonadherence. CONCLUSIONS: DRMs account for a small proportion of all elevated VL among women occurring in the 12 months after ART initiation during pregnancy in this setting, with nonadherence appearing to drive most episodes of elevated VL. Alongside the drive for access to more robust antiretroviral agents in resource-limited settings, there is an ongoing need for effective strategies to support ART adherence in this patient population.

Original languageEnglish (US)
Pages (from-to)501-508
Number of pages8
JournalClinical infectious diseases : an official publication of the Infectious Diseases Society of America
Volume70
Issue number3
DOIs
StatePublished - Jan 16 2020

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Viral Drug Resistance
Viral Load
Case-Control Studies
HIV
Pregnancy
Mutation
Drug Resistance
Therapeutics
Odds Ratio
Confidence Intervals
Anti-Retroviral Agents
Reverse Transcriptase Inhibitors
Patient Compliance
South Africa
Postpartum Period
Pregnant Women

Keywords

  • adherence
  • antiretroviral therapy
  • drug resistance
  • postpartum
  • pregnancy

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Antiretroviral Adherence, Elevated Viral Load, and Drug Resistance Mutations in Human Immunodeficiency Virus-infected Women Initiating Treatment in Pregnancy : A Nested Case-control Study. / Myer, Landon; Redd, Andrew D.; Mukonda, Elton; Lynch, Briana A.; Phillips, Tamsin K.; Eisenberg, Anna; Hsiao, Nei Yuan; Capoferri, Adam; Zerbe, Alison; Clarke, William; Lesosky, Maia; Breaud, Autumn; McIntyre, James; Bruno, Daniel; Martens, Craig; Abrams, Elaine J.; Reynolds, Steven J.

In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Vol. 70, No. 3, 16.01.2020, p. 501-508.

Research output: Contribution to journalArticle

Myer, Landon ; Redd, Andrew D. ; Mukonda, Elton ; Lynch, Briana A. ; Phillips, Tamsin K. ; Eisenberg, Anna ; Hsiao, Nei Yuan ; Capoferri, Adam ; Zerbe, Alison ; Clarke, William ; Lesosky, Maia ; Breaud, Autumn ; McIntyre, James ; Bruno, Daniel ; Martens, Craig ; Abrams, Elaine J. ; Reynolds, Steven J. / Antiretroviral Adherence, Elevated Viral Load, and Drug Resistance Mutations in Human Immunodeficiency Virus-infected Women Initiating Treatment in Pregnancy : A Nested Case-control Study. In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2020 ; Vol. 70, No. 3. pp. 501-508.
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abstract = "BACKGROUND: Elevated viral load (VL) early after antiretroviral therapy (ART) initiation appears frequently in pregnant and postpartum women living with human immunodeficiency virus; however the relative contributions of pre-ART drug resistance mutations (DRMs) vs nonadherence in the etiology of elevated VL are unknown. METHODS: Within a cohort of women initiating ART during pregnancy in Cape Town, South Africa, we compared women with elevated VL after initial suppression (cases, n = 80) incidence-density matched to women who maintained suppression over time (controls, n = 87). Groups were compared on pre-ART DRMs and detection of antiretrovirals in stored plasma. RESULTS: The prevalence of pre-ART DRMs was 10{\%} in cases and 5{\%} in controls (adjusted odds ratio [aOR], 1.53 [95{\%} confidence interval {CI}, .4-5.9]); all mutations were to nonnucleoside reverse transcriptase inhibitors. At the time of elevated VL, 19{\%} of cases had antiretrovirals detected in plasma, compared with 87{\%} of controls who were suppressed at a matched time point (aOR, 131.43 [95{\%} CI, 32.8-527.4]). Based on these findings, we estimate that <10{\%} of all elevated VL in the cohort may be attributable to pre-ART DRMs vs >90{\%} attributable to ART nonadherence. CONCLUSIONS: DRMs account for a small proportion of all elevated VL among women occurring in the 12 months after ART initiation during pregnancy in this setting, with nonadherence appearing to drive most episodes of elevated VL. Alongside the drive for access to more robust antiretroviral agents in resource-limited settings, there is an ongoing need for effective strategies to support ART adherence in this patient population.",
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T2 - A Nested Case-control Study

AU - Myer, Landon

AU - Redd, Andrew D.

AU - Mukonda, Elton

AU - Lynch, Briana A.

AU - Phillips, Tamsin K.

AU - Eisenberg, Anna

AU - Hsiao, Nei Yuan

AU - Capoferri, Adam

AU - Zerbe, Alison

AU - Clarke, William

AU - Lesosky, Maia

AU - Breaud, Autumn

AU - McIntyre, James

AU - Bruno, Daniel

AU - Martens, Craig

AU - Abrams, Elaine J.

AU - Reynolds, Steven J.

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N2 - BACKGROUND: Elevated viral load (VL) early after antiretroviral therapy (ART) initiation appears frequently in pregnant and postpartum women living with human immunodeficiency virus; however the relative contributions of pre-ART drug resistance mutations (DRMs) vs nonadherence in the etiology of elevated VL are unknown. METHODS: Within a cohort of women initiating ART during pregnancy in Cape Town, South Africa, we compared women with elevated VL after initial suppression (cases, n = 80) incidence-density matched to women who maintained suppression over time (controls, n = 87). Groups were compared on pre-ART DRMs and detection of antiretrovirals in stored plasma. RESULTS: The prevalence of pre-ART DRMs was 10% in cases and 5% in controls (adjusted odds ratio [aOR], 1.53 [95% confidence interval {CI}, .4-5.9]); all mutations were to nonnucleoside reverse transcriptase inhibitors. At the time of elevated VL, 19% of cases had antiretrovirals detected in plasma, compared with 87% of controls who were suppressed at a matched time point (aOR, 131.43 [95% CI, 32.8-527.4]). Based on these findings, we estimate that <10% of all elevated VL in the cohort may be attributable to pre-ART DRMs vs >90% attributable to ART nonadherence. CONCLUSIONS: DRMs account for a small proportion of all elevated VL among women occurring in the 12 months after ART initiation during pregnancy in this setting, with nonadherence appearing to drive most episodes of elevated VL. Alongside the drive for access to more robust antiretroviral agents in resource-limited settings, there is an ongoing need for effective strategies to support ART adherence in this patient population.

AB - BACKGROUND: Elevated viral load (VL) early after antiretroviral therapy (ART) initiation appears frequently in pregnant and postpartum women living with human immunodeficiency virus; however the relative contributions of pre-ART drug resistance mutations (DRMs) vs nonadherence in the etiology of elevated VL are unknown. METHODS: Within a cohort of women initiating ART during pregnancy in Cape Town, South Africa, we compared women with elevated VL after initial suppression (cases, n = 80) incidence-density matched to women who maintained suppression over time (controls, n = 87). Groups were compared on pre-ART DRMs and detection of antiretrovirals in stored plasma. RESULTS: The prevalence of pre-ART DRMs was 10% in cases and 5% in controls (adjusted odds ratio [aOR], 1.53 [95% confidence interval {CI}, .4-5.9]); all mutations were to nonnucleoside reverse transcriptase inhibitors. At the time of elevated VL, 19% of cases had antiretrovirals detected in plasma, compared with 87% of controls who were suppressed at a matched time point (aOR, 131.43 [95% CI, 32.8-527.4]). Based on these findings, we estimate that <10% of all elevated VL in the cohort may be attributable to pre-ART DRMs vs >90% attributable to ART nonadherence. CONCLUSIONS: DRMs account for a small proportion of all elevated VL among women occurring in the 12 months after ART initiation during pregnancy in this setting, with nonadherence appearing to drive most episodes of elevated VL. Alongside the drive for access to more robust antiretroviral agents in resource-limited settings, there is an ongoing need for effective strategies to support ART adherence in this patient population.

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