The impact of short term Antiretroviral Therapy (ART) interruptions on longer term maternal health outcomes-A randomized clinical trial.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2020
Historique:
received: 20 09 2019
accepted: 03 01 2020
entrez: 31 1 2020
pubmed: 31 1 2020
medline: 15 4 2020
Statut: epublish

Résumé

Given well documented challenges faced by pregnant women living with HIV taking lifetime ART, it is critical to understand the impact of short-term ART exposure followed by treatment interruption on maternal health outcomes. HIV+ breastfeeding (BF) and Formula Feeding (FF) women with CD4 counts > 350 cells/mm3, enrolled in the 1077BF/1077FF PROMISE trial were followed to assess the effect of ART during pregnancy and breastfeeding respectively. The first analysis compared ART use limited to the antepartum period (AP-only) relative to women randomized to Zidovudine. The second analysis included women with no pregnancy combination ART exposure; and compared women randomized to either ART or no ART during postpartum (PP-only). Both analyses included follow-up time beyond breastfeeding period. The primary outcome was progression to AIDS and/or death. Secondary outcomes included adverse events and HIV-related events. 3490 and 1137 HIV+ women were enrolled from 14 sites in Africa and India from April 2011 through September 2014 in cohort AP-only and PP-only, respectively. Most were Black African (96%); median age was 27 years; 97% were WHO Clinical Stage I; and most had a screening CD4 count ≥500 cells/mm3 (78%). The rate of progression to AIDS and/or death was similar and low across all comparison arms (AP comparison, HR = 1.14, 95%CI (0.44, 2.96), p-value = 0.79). In the PP-only cohort, the rate of WHO stage 2-3 events was lower for women randomized to ART(HR = 0.65, 95% CI 0.42, 1.01, p-value = 0.05). The incidence of AIDS and/or death was low in pregnant/postpartum HIV+ women with highCD4 cell counts for all comparison arms. This provides some reassurance that there were limited consequences for short term ART interruption in this group of asymptomatic HIV+ women during up to 4 years of follow up; and underscores that even short term ART exposure postpartum may reduce the risk of WHO grade 2-3 disease progression.

Sections du résumé

BACKGROUND
Given well documented challenges faced by pregnant women living with HIV taking lifetime ART, it is critical to understand the impact of short-term ART exposure followed by treatment interruption on maternal health outcomes.
METHODS
HIV+ breastfeeding (BF) and Formula Feeding (FF) women with CD4 counts > 350 cells/mm3, enrolled in the 1077BF/1077FF PROMISE trial were followed to assess the effect of ART during pregnancy and breastfeeding respectively. The first analysis compared ART use limited to the antepartum period (AP-only) relative to women randomized to Zidovudine. The second analysis included women with no pregnancy combination ART exposure; and compared women randomized to either ART or no ART during postpartum (PP-only). Both analyses included follow-up time beyond breastfeeding period. The primary outcome was progression to AIDS and/or death. Secondary outcomes included adverse events and HIV-related events.
RESULTS
3490 and 1137 HIV+ women were enrolled from 14 sites in Africa and India from April 2011 through September 2014 in cohort AP-only and PP-only, respectively. Most were Black African (96%); median age was 27 years; 97% were WHO Clinical Stage I; and most had a screening CD4 count ≥500 cells/mm3 (78%). The rate of progression to AIDS and/or death was similar and low across all comparison arms (AP comparison, HR = 1.14, 95%CI (0.44, 2.96), p-value = 0.79). In the PP-only cohort, the rate of WHO stage 2-3 events was lower for women randomized to ART(HR = 0.65, 95% CI 0.42, 1.01, p-value = 0.05).
CONCLUSION
The incidence of AIDS and/or death was low in pregnant/postpartum HIV+ women with highCD4 cell counts for all comparison arms. This provides some reassurance that there were limited consequences for short term ART interruption in this group of asymptomatic HIV+ women during up to 4 years of follow up; and underscores that even short term ART exposure postpartum may reduce the risk of WHO grade 2-3 disease progression.

Identifiants

pubmed: 31999753
doi: 10.1371/journal.pone.0228003
pii: PONE-D-19-25671
pmc: PMC6992010
doi:

Types de publication

Journal Article Randomized Controlled Trial Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0228003

Subventions

Organisme : NIAID NIH HHS
ID : UM1 AI069423
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069424
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068632
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH083308
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069518
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069453
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI069424
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI106716
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069469
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069530
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069463
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068616
Pays : United States

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

Références

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pubmed: 29239901
N Engl J Med. 2006 Nov 30;355(22):2283-96
pubmed: 17135583
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pubmed: 26520926
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pubmed: 30890061
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pubmed: 28489856
N Engl J Med. 2016 Nov 3;375(18):1726-1737
pubmed: 27806243
AIDS. 2012 Oct 23;26(16):2039-52
pubmed: 22951634

Auteurs

Patience Atuhaire (P)

Makerere University -John Hopkins University Research Collaboration (MUJHU CARE LTD) CRS, Kampala, Uganda.

Sean S Brummel (S)

Harvard School of Public Health, Boston, Massachusetts, United States of America.

Blandina Theophil Mmbaga (BT)

Kilimanjaro Christian Medical Centre (KCMC), Moshi, Tanzania.

Konstantia Angelidou (K)

Harvard School of Public Health, Boston, Massachusetts, United States of America.

Lee Fairlie (L)

Wits RHI Shandukani Research Centre CRS, Johannesburg, South Africa.

Avy Violari (A)

Soweto IMPAACT CRS, Johannesburg, South Africa.

Gerhard Theron (G)

FAM-CRU CRS, Cape Town, South Africa.

Cornelius Mukuzunga (C)

Malawi CRS, Lilongwe, Malawi.

Sajeeda Mawlana (S)

Durban Paediatric HIV CRS, Durban, South Africa.

Mwangelwa Mubiana-Mbewe (M)

George CRS, Lusaka, Zambia.

Megeshinee Naidoo (M)

Umlazi CRS, Durban, South Africa.

Bonus Makanani (B)

Blantyre CRS, Blantyre, Malawi.

Patricia Mandima (P)

St Marys CRS, Harare, Zimbabwe.

Teacler Nematadzira (T)

Seke North CRS, Harare, Zimbabwe.

Nishi Suryavanshi (N)

Byramjee Jeejeebhoy Medical College (BJMC) CRS, Pune, India.

Tapiwa Mbengeranwa (T)

Harare Family Care CRS, Harare, Zimbabwe.

Amy Loftis (A)

UNC, Chapel Hill, North Carolina, United States of America.

Michael Basar (M)

Frontier Science, Amherst, Massachusetts, United States of America.

Katie McCarthy (K)

FHI 360, Durham, North Carolina, United States of America.

Judith S Currier (JS)

UCLA center for Clinical AIDS Research and Education, Los Angeles, California, United States of America.

Mary Glenn Fowler (MG)

Departments of Pathology and Epidemiology, Johns Hopkins University, Baltimore, Maryland, United States of America.

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