Title

Association of maternal viral load and CD4 count with perinatal HIV-1 transmission risk during breastfeeding in the PROMISE postpartum component

Presenter

Patricia Flynn

Authors

P. Flynn¹, T. Taha², M. Cababasay^3,4, K. Butler^3,4, M.G. Fowler⁵, L. Mofenson⁶, M. Owor⁷, S. Fiscus⁸, L. Stranix-Chibanda⁹, A. Coutsoudis¹⁰, D. Gnanashanmugam¹¹, N. Chakhtoura¹², K. McCarthy¹³, C. Mukuzunga¹⁴, B. Makanani¹⁵, D. Moodley¹⁶, T. Nematadzira^17,18, B. Kusakara^17,18, S. Patil¹⁹, T. Vhembo^17,18, R. Bobat¹⁰, B. Mmbaga²⁰, M. Masenya²¹, M. Nyati²², G. Theron²³, H. Mulenga²⁴, D. Shapiro^3,4, PROMISE Study Team

Institutions

¹St. Jude Children's Research Hospital, Infectious Diseases, Memphis TN, United States, ²Johns Hopkins Bloomberg School of Public Health, Epidemiology, Baltimore, United States, ³Center for Biostatistics in AIDS Research, Boston, United States, ⁴Harvard T. H. Chan School of Public Health, Boston, United States, ⁵Johns Hopkins University School of Medicine, Pathology, Baltimore, United States, ⁶Elisabeth Glaser Pediatric AIDS Foundation, Washington, DC, United States, ⁷Makerere University - Johns Hopkins University Research Collaboration, Kampala, Uganda, ⁸University of North Carolina School of Medicine, Microbiology and Immunology, Chapel Hill, United States, ⁹University of Zimbabwe, Paediatrics and Child Health, Harare, Zimbabwe, ¹⁰University of KwaZulu-Natal, Paediatrics and Child Health, Durban, South Africa, ¹¹National Institutes of Health, Division of AIDS, National Institute of Allergy and Immunology, Washington, DC, United States, ¹²National Institutes of Health, Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver Institute of Child Health and Human Development, Washington, DC, United States, ¹³FHI 360, Durham, United States, ¹⁴University of North Carolina - Lilongwe, Lilongwe, Malawi, ¹⁵University of Malawi, Department of Obstetrics and Gynecology, Blantyre, Malawi, ¹⁶University of KwaZulu-Natal, Centre for the AIDS Programme of Research in South Africa and School of Clinical Medicine, Durban, South Africa, ¹⁷University of Zimbabwe, Harare, Zimbabwe, ¹⁸University of California, San Francisco, United States, ¹⁹Byramjee Jeejeebhhoy Government Medical College and Johns Hopkins Clinical Trials Unit, Obstetrics and Gynecology, Pune, India, ²⁰Kilimanjaro Christian Medical Centre, Pediatrics, Moshi, Tanzania, United Republic of, ²¹Wits Reproductive Health and HIV Institute, Johannesburg, South Africa, ²²Perinatal HIV Research Unit, Chris Baragwanath Hospital, Johannesburg, South Africa, ²³Stellenbosch University, Obstetrics and Gynecology, Cape Town, South Africa, ²⁴Centre for Infectious Diseases Research in Zambia, George Clinic, Lusaka, Zambia

Background: In the PROMISE 1077BF trial, breastfeeding women with CD4 >350 cells/mm³ (or >country-specific ART threshold if higher) and their uninfected neonates were randomized to maternal ART (mART) or infant nevirapine prophylaxis (iNVP) until breastfeeding cessation or 18 months post-delivery, (whichever occurred first) and had low infant HIV-1 infection rates (0.7% overall). We assessed whether maternal viral load (MVL) or CD4 were associated with perinatal HIV transmission risk.
Methods: MVL was measured retrospectively on batched specimens collected at entry (7-14 days postpartum) and weeks 6, 14, 26, and 50 postpartum. CD4 was measured real-time at entry and weeks 14, 26, 38, and 50 postpartum. Infant HIV-1 NAT was obtained at weeks 1, 6, every 4 weeks until week 26, then every 12 weeks. Infant infection was defined as a positive HIV-1 NAT at any two post-entry timepoints. The associations of baseline and time-varying MVL and CD4 with transmission risk were assessed using proportional hazards regression models by randomized treatment arm, with MVL categorized as < 1000 or ≥1,000 copies/ml and CD4 categorized as < 500 or ≥ 500 cells/mm³, and adjustment for mART receipt during pregnancy.
Results: 2431 mother-infant pairs were randomized. Baseline MVL and CD4 are shown in Table 1. Baseline MVL (p= 0.11) and CD4 (p=0.51) were not significantly associated with infant HIV-1 infection. Time-varying MVL was significantly associated with infant HIV-1 infection in the mART arm (hazard ratio (95% CI): 12.04 (2.54, 57.06) but not in the iNVP arm (hazard ratio (95% CI): 1.04 (0.20 - 5.52)). Time-varying CD4 was not significantly associated with infant HIV-1 infection in either arm (hazard ratio (95% CI): 0.29 (0.05-1.59) in mART arm and 0.33 (0.07-1.57) in iNVP arm). Of 7 postnatal infections in mART arm, 2 had proximal MVL< 40 copies/ml.
Conclusions: With iNVP, MVL was not significantly associated with HIV-1 transmission during breastfeeding. However, among women receiving mART, increased MVL during breastfeeding was associated with increased risk of infant HIV-1 infection. These data emphasize the important role of adherence to mART in controlling MVL and preventing infant infection and suggest that iNVP should be considered in situations with documented poor maternal ART adherence.

	mART n=1,220	iNVP n=1,211
Baseline CD4 count
< 500 cells/mm3	162 (13%)	170 (14%)
≥ 500 cells/mm3	1,058 (87%)	1,041 (86%)

Baseline Maternal Viral Load
<400 copies/mL	672 (55%)	604 (50%)
400 - 1,000 copies/mL	239 (20%)	210 (17%)
≥ 1,000 copies/mL	309 (25%)	397 (33%)

[Table 1]

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