Virologic Determinants of Breast Milk Transmission of HIV-1

Fiscus, Susan A.; Aldrovandi, Grace M.

doi:10.1007/978-1-4614-2251-8_5

Cited by 13 publications

(11 citation statements)

References 126 publications

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“…Limited data exist on the degree of breast milk viral load decline secondary to antiretroviral therapy [21]. For mothers taking ART the average HIV RNA in MP was 3.30log vs 0.77log in BM (2.53 log difference), which is consistent with previously reported data [32]. The exact mechanism of HIV transmission through breast milk is somewhat unclear but is believed to involve both cell free and cell associated virus [32].…”

Section: Discussionsupporting

confidence: 83%

“…Additionally, drug transporters have been identified in breast tissue, including MRP1, OCT1, and OCT3; however, expression of MRP4 has not been identified [30,31]. Lopinavir and ritonavir are substrates for MRP1 while ZDV and 3TC are substrates for MDR4 [32]. Additionally, 3TC is a substrate of OCT1 and 3.…”

Section: Discussionmentioning

confidence: 99%

“…The number of mothers with undetectable HIV RNA in plasma compared to breast milk was also quite different (65% vs 97% undetectable, respectively). In general, BM HIV RNA is 2-3 logs lower than matched plasma and highly correlated [32]. Limited data exist on the degree of breast milk viral load decline secondary to antiretroviral therapy [21].…”

Section: Discussionmentioning

confidence: 99%

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Antiretroviral Pharmacokinetics in Mothers and Breastfeeding Infants from 6 to 24 Weeks Post-Partum: Results of the Ban Study

Corbett

Kayira²,

White³

et al. 2013

Antiviral Therapy

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Background An intensive, prospective, open-label pharmacokinetic (PK) study in a subset of HIV-infected mothers and their uninfected infants enrolled in the Breastfeeding, Antiretroviral, and Nutrition study was performed to describe drug exposure and antiviral response. Methods Women using Combivir®[zidovudine (ZDV)+ lamivudine (3TC)]+Aluvia®[lopinavir/ritonavir(LPV/RTV)] were enrolled. Breast milk (BM) and mother and infant plasma (MP, IP) samples were obtained over 6hrs after observed dosing at 6, 12, or 24wks post-partum for drug concentrations and HIV RNA. Results 30 mother/infant pairs (10 each at 6, 12,and 24wks post-partum) were enrolled. Relative to MP, BM concentrations of ZDV and 3TC were 35% and 21% higher, while LPV and RTV were 80% lower. Only 3TC was detected in IP with concentrations 96% and 98% lower than MP and BM, respectively. Concentrations in all matrices were similar at 6-24wks. The majority (98.3%) of BM concentrations were >HIVwt IC50, with one having detectable virus. There was no association between PK parameters and MP or BM HIV RNA. Conclusions ZDV and 3TC concentrated in BM while LPV and RTV did not, possibly due to protein binding and drug transporter affinity. Undetectable to low ARV concentrations in IP suggests prevention of transmission while breast feeding may be due to ARV effects on systemic or BM HIV RNA in the mother. Low IP 3TC exposure may predispose an infected infant to HIV resistance, necessitating testing and treating infants early.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Antiretroviral Pharmacokinetics in Mothers and Breastfeeding Infants from 6 to 24 Weeks Post-Partum: Results of the Ban Study

Corbett

Kayira²,

White³

et al. 2013

Antiviral Therapy

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“…4 Second, virus may be transiently produced locally. 4, 5 Both cell-associated and cell-free virus in breastmilk appear to increase HIV transmission. To date, no breastmilk viral threshold has been identified below which breastmilk HIV transmission has not occurred.…”

Section: Introductionmentioning

confidence: 99%

Maternal and Breastmilk Viral Load: Impacts of Adherence on Peripartum HIV Infections Averted—The Breastfeeding, Antiretrovirals, and Nutrition Study

Davis

Miller

Hudgens

et al. 2016

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Antiretroviral interventions are used to reduce HIV viral replication and prevent mother-to-child transmission. Viral suppression relies on adherence to antiretrovirals. Methods A two-phase study was conducted using data from the Breastfeeding, Antiretrovirals and Nutrition study. We included mothers randomized to 28 weeks of postpartum antiretrovirals with ≥1 plasma or breastmilk specimen. All mothers who transmitted HIV to their infants from 2-28 weeks (n=31) and 15% of mothers who did not (n=232) were included. Adherence was measured by pill count [categorized as poor (0-80%), partial (81-98%) and near perfect (>98%)]. Associations between adherence and breastmilk RNA were assessed using mixed effects models. Cox models were used to estimate associations between breastmilk RNA and HIV transmission. Using Monte Carlo simulation, we estimated the number of transmissions that would occur had everyone randomized to maternal ARVs been 90% and 100% adherent. Results Partial or near perfect antiretroviral adherence significantly reduced the odds of having detectable (≥40 copies/ml) breastmilk RNA, compared to poor adherence (OR 0.23, 95% CI 0.08-0.67; OR 0.36, 95% CI 0.16-0.81, respectively). Detectable breastmilk RNA was associated with increased breastmilk transmission, compared to undetectable breastmilk RNA (HR 3.8, 95% CI 1.2-12.1). All transmitting mothers had ≥1 plasma viral load specimen >100 copies/ml. An estimated similar number of transmissions would occur with 90% adherence compared with 100%. Conclusions Helping patients adhere to antiretrovirals throughout breastfeeding is important for realizing the full potential of recommended antiretroviral interventions to prevent mother-to-child HIV transmission. Maintaining plasma viral load <100 copies/ml may prevent breastmilk transmission.

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“…[3] The second is by local production of virus in the breastmilk. [3,4] To further add to the complexity, there are differential levels of antiretroviral exposure in breastmilk and infant plasma both within and between classes of drugs. [2] Only ZDV and 3TC have been shown to concentrate to any real extent in breastmilk, among the ARVs that have been evaluated to date.…”

Section: Introductionmentioning

confidence: 99%

Antiretroviral Drug Concentrations in Breastmilk, Maternal HIV Viral Load, and HIV Transmission to the Infant: Results From the BAN Study

Davis

Corbett

Kaullen

et al. 2019

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background: Concentration of antiretroviral (ARV) drug found in plasma, and amounts of drug excreted into breastmilk, may affect HIV viral load and potentially perinatal HIV transmission. Methods: In this cohort study with two-phase sampling, we included mothers randomized to postpartum maternal ARVs or daily infant nevirapine during 28 weeks of breastfeeding in the Breastfeeding, Antiretrovirals and Nutrition (BAN) study. Among these, we included all mothers who transmitted HIV to their infants between 2-28 weeks and 15% of mothers who did not (n=27 and 227, respectively). Spearman correlation coefficients (r2) were used to assess correlation between maternal plasma and breastmilk ARV concentration. Associations between the median effective drug concentration (EC50) and detectable maternal viral load (plasma: >40 copies/ml, breastmilk: >56 copies/ml) were assessed using mixed effects models. Cox models were used to estimate the association between maternal or infant plasma drug concentration and breastmilk HIV transmission from 2-28 weeks.

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Virologic Determinants of Breast Milk Transmission of HIV-1

Cited by 13 publications

References 126 publications

Antiretroviral Pharmacokinetics in Mothers and Breastfeeding Infants from 6 to 24 Weeks Post-Partum: Results of the Ban Study

Antiretroviral Pharmacokinetics in Mothers and Breastfeeding Infants from 6 to 24 Weeks Post-Partum: Results of the Ban Study

Maternal and Breastmilk Viral Load: Impacts of Adherence on Peripartum HIV Infections Averted—The Breastfeeding, Antiretrovirals, and Nutrition Study

Antiretroviral Drug Concentrations in Breastmilk, Maternal HIV Viral Load, and HIV Transmission to the Infant: Results From the BAN Study

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