Maternal health outcomes among HIV-infected breastfeeding women with high CD4 counts: results of a treatment strategy trial

doi:10.1080/15284336.2018.1537327

Randomized Controlled Trial

. 2018 Dec;19(6):209-224.

doi: 10.1080/15284336.2018.1537327.

Maternal health outcomes among HIV-infected breastfeeding women with high CD4 counts: results of a treatment strategy trial

Risa M Hoffman¹, Konstantia Nadia Angelidou², Sean S Brummel², Friday Saidi³, Avy Violari⁴, Dingase Dula⁵, Vidya Mave^{6

7}, Lee Fairlie⁸, Gerhard Theron⁹, Moreen Kamateeka¹⁰, Tsungai Chipato¹¹, Benjamin H Chi¹², Lynda Stranix-Chibanda¹³, Teacler Nematadzira¹⁴, Dhayendre Moodley¹⁵, Debika Bhattacharya¹, Amita Gupta^{6

7}, Anne Coletti¹⁶, James A McIntyre^{17

18}, Karin L Klingman¹⁹, Nahida Chakhtoura²⁰, David E Shapiro², Mary Glenn Fowler²¹, Judith S Currier¹; IMPAACT PROMISE 1077BF/FF team

Affiliations

¹ a Division of Infectious Diseases, Department of Medicine , David Geffen School of Medicine at the University of California, Los Angeles , Los Angeles , CA , USA.
² b Center for Biostatistics in AIDS Research , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
³ c University of North Carolina Project-Malawi , Lilongwe , Malawi.
⁴ d Perinatal HIV Research Unit , Chris Hani Baragwanath Hospital , Soweto , South Africa.
⁵ e Malawi College of Medicine , Johns Hopkins Project , Chichiri , Malawi.
⁶ f BJGMC Clinical Trials Unit , Pune , India.
⁷ g Division of Infectious Diseases , Johns Hopkins School of Medicine , Baltimore , MD , USA.
⁸ h Wits Reproductive Health and HIV Institute , Johannesburg , South Africa.
⁹ i Stellenbosch University , Cape Town , South Africa.
¹⁰ j Makerere University, Johns Hopkins University Research Collaboration , Mulago Kampala , Uganda.
¹¹ k Department of Obstetrics and Gynecology , University of Zimbabwe , Harare , Zimbabwe.
¹² l Department of Obstetrics and Gynecology , University of North Carolina School of Medicine , Chapel Hill , NC , USA.
¹³ m University of Zimbabwe , Harare , Zimbabwe.
¹⁴ n University of Zimbabwe College of Health Sciences Clinical Trials Research Centre , Harare , Zimbabwe.
¹⁵ o Centre for the AIDS Programme of Research in South Africa and School of Clinical Medicine , University of KwaZulu Natal , Durban , South Africa.
¹⁶ p Family Health International 360 , Durham , NC , USA.
¹⁷ q Anova Health Institute , Johannesburg , South Africa.
¹⁸ r School of Public Health & Family Medicine , University of Cape Town , Cape Town , South Africa.
¹⁹ s Division of AIDS , National Institute of Allergy and Infectious Diseases National Institutes of Health , Bethesda , MD , USA.
²⁰ t Eunice Kennedy Shriver National Institute of Child Health and Human Development , National Institutes of Health , Bethesda , MD , USA.
²¹ u Department of Pathology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.

PMID: 30890061
PMCID: PMC6428202
DOI: 10.1080/15284336.2018.1537327

Randomized Controlled Trial

Maternal health outcomes among HIV-infected breastfeeding women with high CD4 counts: results of a treatment strategy trial

Risa M Hoffman et al. HIV Clin Trials. 2018 Dec.

. 2018 Dec;19(6):209-224.

doi: 10.1080/15284336.2018.1537327.

Authors

Affiliations

¹ a Division of Infectious Diseases, Department of Medicine , David Geffen School of Medicine at the University of California, Los Angeles , Los Angeles , CA , USA.
² b Center for Biostatistics in AIDS Research , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
³ c University of North Carolina Project-Malawi , Lilongwe , Malawi.
⁴ d Perinatal HIV Research Unit , Chris Hani Baragwanath Hospital , Soweto , South Africa.
⁵ e Malawi College of Medicine , Johns Hopkins Project , Chichiri , Malawi.
⁶ f BJGMC Clinical Trials Unit , Pune , India.
⁷ g Division of Infectious Diseases , Johns Hopkins School of Medicine , Baltimore , MD , USA.
⁸ h Wits Reproductive Health and HIV Institute , Johannesburg , South Africa.
⁹ i Stellenbosch University , Cape Town , South Africa.
¹⁰ j Makerere University, Johns Hopkins University Research Collaboration , Mulago Kampala , Uganda.
¹¹ k Department of Obstetrics and Gynecology , University of Zimbabwe , Harare , Zimbabwe.
¹² l Department of Obstetrics and Gynecology , University of North Carolina School of Medicine , Chapel Hill , NC , USA.
¹³ m University of Zimbabwe , Harare , Zimbabwe.
¹⁴ n University of Zimbabwe College of Health Sciences Clinical Trials Research Centre , Harare , Zimbabwe.
¹⁵ o Centre for the AIDS Programme of Research in South Africa and School of Clinical Medicine , University of KwaZulu Natal , Durban , South Africa.
¹⁶ p Family Health International 360 , Durham , NC , USA.
¹⁷ q Anova Health Institute , Johannesburg , South Africa.
¹⁸ r School of Public Health & Family Medicine , University of Cape Town , Cape Town , South Africa.
¹⁹ s Division of AIDS , National Institute of Allergy and Infectious Diseases National Institutes of Health , Bethesda , MD , USA.
²⁰ t Eunice Kennedy Shriver National Institute of Child Health and Human Development , National Institutes of Health , Bethesda , MD , USA.
²¹ u Department of Pathology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.

PMID: 30890061
PMCID: PMC6428202
DOI: 10.1080/15284336.2018.1537327

Abstract

Background: IMPAACT PROMISE 1077BF/FF was a randomized study of antiretroviral therapy (ART) strategies for pregnant and postpartum women with high CD4+ T-cell counts. We describe postpartum outcomes for women in the study who were randomized to continue or discontinue ART after delivery.

Methods: Women with pre-ART CD4+ cell counts ≥350 cells/mm³ who started ART during pregnancy were randomized postpartum to continue or discontinue treatment. Women were enrolled from India, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. The primary outcome was a composite of progression to AIDS-defining illness or death. Log-rank tests and Cox regression models assessed treatment effects. Incidence rates were calculated per 100 person-years. A post hoc analysis evaluated WHO Stage 2/3 events. All analyses were intent-to-treat.

Findings: 1611 women were enrolled (June 2011-October 2014) and 95% were breastfeeding. Median age at entry was 27 years, CD4+ count 728 cells/mm³ and the majority of women were Black African (97%). After a median follow-up of 1.6 years, progression to AIDS-defining illness or death was rare and there was no significant difference between arms (HR: 0·55; 95%CI 0·14, 2·08, p = 0.37). WHO Stage 2/3 events were reduced with continued ART (HR: 0·60; 95%CI 0·39, 0·90, p = 0.01). The arms did not differ with respect to the rate of grade 2, 3, or 4 safety events (p = 0.61).

Interpretation: Serious clinical events were rare among predominately breastfeeding women with high CD4+ cell counts over 18 months after delivery. ART had significant benefit in reducing WHO 2/3 events in this population.

Trial registration: ClinicalTrials.gov NCT01061151.

Keywords: HIV and breastfeeding; HIV/AIDS; antiretroviral therapy (ART); postpartum maternal health.

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Conflict of interest statement

Disclosure statement

No potential conflict of interest was reported by the authors.

Figures

**Figure 1:**
Description of the PROMISE 1077 BF/FF women included in the analysis. This analysis includes all women on three-drug ART during pregnancy who were randomized postpartum to continue or discontinue, as well as all women randomized to continue ART at cessation of breastfeeding (black boxes).

**Figure 2:**
CONSORT flow diagram for women included in the analysis^*

**Figure 3:**
CD4 T-cell counts over time (median, 10^th and 90^th percentile, and proportion <350 cells/mm³). The median CD4 T-cell counts in the continue (blue) and discontinue (red) arms are shown at each follow-up visit. The proportion with CD4 T-cells below 350 cells/mm³ are shown across the top of the figure at each time point.

**Figure 4:**
Survival curves for key study findings (A) Primary Composite Endpoint; (B) WHO 2 and 3 events; (C) Safety Endpoint

See this image and copyright information in PMC

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References

1. Calvert C, Ronsmans C. The contribution of HIV to pregnancy-related mortality: a systematic review and meta-analysis. AIDS 2013;27(10):1631–1639. - PMC - PubMed
1. Wandabwa JN, Doyle P, Longo-Mbenza B, et al. Human immunodeficiency virus and AIDS and other important predictors of maternal mortality in Mulago Hospital Complex Kampala Uganda. BMC Public Health 2011;11:565. - PMC - PubMed
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1. Zash RM, Souda S, Leidner J, et al. High Proportion of Deaths Attributable to HIV Among Postpartum Women in Botswana Despite Widespread Uptake of Antiretroviral Therapy. AIDS Patient Care STDS 2017;31(1):14–19. - PMC - PubMed
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[1] Calvert C, Ronsmans C. The contribution of HIV to pregnancy-related mortality: a systematic review and meta-analysis. AIDS 2013;27(10):1631–1639. - PMC - PubMed

[2] Calvert C, Ronsmans C. The contribution of HIV to pregnancy-related mortality: a systematic review and meta-analysis. AIDS 2013;27(10):1631–1639. - PMC - PubMed

[3] Wandabwa JN, Doyle P, Longo-Mbenza B, et al. Human immunodeficiency virus and AIDS and other important predictors of maternal mortality in Mulago Hospital Complex Kampala Uganda. BMC Public Health 2011;11:565. - PMC - PubMed

[4] Wandabwa JN, Doyle P, Longo-Mbenza B, et al. Human immunodeficiency virus and AIDS and other important predictors of maternal mortality in Mulago Hospital Complex Kampala Uganda. BMC Public Health 2011;11:565. - PMC - PubMed

[5] Moran NF, Moodley J. The effect of HIV infection on maternal health and mortality. Int J Gynaecol Obstet 2012;119 Suppl 1:S26–29. - PubMed

[6] Moran NF, Moodley J. The effect of HIV infection on maternal health and mortality. Int J Gynaecol Obstet 2012;119 Suppl 1:S26–29. - PubMed

[7] Zash RM, Souda S, Leidner J, et al. High Proportion of Deaths Attributable to HIV Among Postpartum Women in Botswana Despite Widespread Uptake of Antiretroviral Therapy. AIDS Patient Care STDS 2017;31(1):14–19. - PMC - PubMed

[8] Zash RM, Souda S, Leidner J, et al. High Proportion of Deaths Attributable to HIV Among Postpartum Women in Botswana Despite Widespread Uptake of Antiretroviral Therapy. AIDS Patient Care STDS 2017;31(1):14–19. - PMC - PubMed

[9] Lathrop E, Jamieson DJ, Danel I. HIV and maternal mortality. Int J Gynaecol Obstet 2014;127(2):213–215. - PMC - PubMed

[10] Lathrop E, Jamieson DJ, Danel I. HIV and maternal mortality. Int J Gynaecol Obstet 2014;127(2):213–215. - PMC - PubMed

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Maternal health outcomes among HIV-infected breastfeeding women with high CD4 counts: results of a treatment strategy trial

Affiliations

Maternal health outcomes among HIV-infected breastfeeding women with high CD4 counts: results of a treatment strategy trial

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Conflict of interest statement

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