7 results on '"Hudgens, Michael G"'
Search Results
2. Maternal and Breastmilk Viral Load: Impacts of Adherence on Peripartum HIV Infections Averted—The Breastfeeding, Antiretrovirals, and Nutrition Study.
- Author
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Davis, Nicole L., Miller, William C., Hudgens, Michael G., Chasela, Charles S., Sichali, Dorothy, Kayira, Dumbani, Nelson, Julie A. E., Fiscus, Susan A., Tegha, Gerald, Kamwendo, Deborah D., Rigdon, Joseph, Stringer, Jeffrey S. A., Juliano, Jonathan J., Ellington, Sascha R., Kourtis, Athena P., Jamieson, Denise J., and van der Horst, Charles
- Abstract
Background: Antiretroviral (ARV) interventions are used to reduce HIV viral replication and prevent mother-to-child transmission. Viral suppression relies on adherence to ARVs. Methods: A 2-phase study was conducted using data from the Breastfeeding, Antiretrovirals, and Nutrition study. We included mothers randomized to 28 weeks of postpartum ARVs 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 ARV adherence significantly reduced the odds of having detectable (≥40 copies/mL) breastmilk RNA, compared with poor adherence (Odds Ratio (OR) 0.23, 95% CI: 0.08 to 0.67; OR 0.36, 95% CI: 0.16 to 0.81, respectively). Detectable breastmilk RNA was associated with increased breastmilk transmission compared with undetectable breastmilk RNA (hazard ratio 3.8, 95% CI: 1.2 to 12.1). All transmitting mothers had ≥1 plasma viral load specimen >100 copies per milliliter. An estimated similar number of transmissions would occur with 90% adherence compared with 100%. Conclusions: Helping patients adhere to ARVs throughout breastfeeding is important for realizing the full potential of recommended ARV interventions to prevent mother-to-child HIV transmission. Maintaining plasma viral load <100 copies per milliliter may prevent breastmilk transmission. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
3. Antiretroviral Drug Concentrations in Breastmilk, Maternal HIV Viral Load, and HIV Transmission to the Infant: Results From the BAN Study.
- Author
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Davis, Nicole L., Corbett, Amanda, Kaullen, Josh, Nelson, Julie A. E., Chasela, Charles S., Sichali, Dorothy, Hudgens, Michael G., Miller, William C., Jamieson, Denise J., and Kourtis, Athena P.
- Abstract
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 2-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 study. Among these, we included all mothers who transmitted HIV to their infants between 2 and 28 weeks and 15% of mothers who did not (n = 27 and 227, respectively). Spearman correlation coefficients (r2) were used to assess the correlation between maternal plasma and breastmilk ARV concentration. Associations between the median effective drug concentration (EC50) and detectable maternal viral load (plasma: >40 copies per milliliter, breastmilk: >56 copies per milliliter) 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 to 28 weeks. Results: All ARV compounds exhibited substantial correlations between maternal plasma and breastmilk concentrations (r2: 0.85–0.98, P -value <0.0001). Having plasma drug concentration above the EC50 was associated with lower odds of having detectable HIV RNA [maternal plasma odds ratio (OR) 0.64, 95% confidence interval (CI): 0.45 to 0.91; breastmilk OR 0.22, 95% CI: 0.14 to 0.35] and a reduced rate of breastmilk HIV transmission (hazard ratio 0.40, 95% CI: 0.18 to 0.93). Having breastmilk drug concentration above the EC50 was also associated with lower odds of having detectable maternal HIV RNA (plasma OR 0.62, 95% CI: 0.45 to 0.85; breastmilk OR 0.42, 95% CI: 0.29 to 0.59). Conclusions: Ensuring adequate drug concentration is important for viral suppression and preventing breastmilk HIV transmission. [ABSTRACT FROM AUTHOR]
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- 2019
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4. Quantification of the Latent HIV-1 Reservoir Using Ultra Deep Sequencing and Primer ID in a Viral Outgrowth Assay.
- Author
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Sook-Kyung Lee, Shuntai Zhou, Baldoni, Pedro L., Spielvogel, Ean, Archin, Nancie M., Hudgens, Michael G., Margolis, David M., and Swanstrom, Ronald
- Abstract
Background: In this study, we measured the latent HIV-1 reservoir harboring replication-competent HIV-1 in resting CD4+ T cells in participants on highly active antiretroviral therapy, quantitating the frequency of latent infection through the use of a Primer ID-based Ultra Deep Sequencing Assay (UDSA), in comparison to the readout of the quantitative viral outgrowth assay (QVOA). Methods: Viral RNA derived from culture wells of QVOA that scored as HIV-1 p24 capsid antigen positive were tagged with a specific barcode during cDNA synthesis, and the sequences within the V1–V3 region of the HIV-1 env gene were analyzed for diversity using the Primer ID-based paired-end MiSeq platform. We analyzed samples from a total of 19 participants, 2 initially treated with highly active antiretroviral therapy in acute infection and 17 treated during chronic infection. Phylogenetic trees were generated with all viral lineages detected from culture wells derived from each participant to determine the number of distinct viral lineages growing out in each well, thus capturing another level of information beyond the well being positive for viral antigen. The infectious units per million (IUPM) cell values estimated using a maximum likelihood approach, based on the number of distinct viral lineages detected (VOA-UDSA), were compared with those obtained from QVOA measured using limiting dilution. Results: IUPM estimates determined by VOA-UDSA ranged from 0.14 to 3.66 and strongly correlated with the IUPM estimates determined by QVOA (r = 0.94; P < 0.0001). Conclusions: VOA-UDSA may be an alternative readout for that currently used for QVOA. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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5. Cervicovaginal and Rectal Fluid as a Surrogate Marker of Antiretroviral Tissue Concentration: Implications for Clinical Trial Design.
- Author
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Cottrell, Mackenzie L., Prince, Heather M. A., Allmon, Andrew, Mollan, Katie R., Hudgens, Michael G., Sykes, Craig, White, Nicole, Malone, Stephanie, Dellon, Evan S., Madanick, Ryan D., Shaheen, Nicholas J., Patterson, Kristine B., and Kashuba, Angela D. M.
- Abstract
Background: Quantifying tissue drug concentrations can yield important information during drug development, but complicates pharmacokinetic study design. Mucosal fluids collected by direct aspiration (cervicovaginal fluid; CVF) or swab (rectal fluid; RF) might be used as tissue concentration surrogates, but these relationships are not well characterized. Methods: Forty-nine healthy women, given a single oral dose of tenofovir, maraviroc, emtricitabine, or raltegravir at 50%-200% of the treatment dose, provided 13 plasma, 12 CVF, 12 RF and one cervical, vaginal and rectal tissue biopsy over 48 hours. Relationships between these paired samples were characterized by linear and multiple linear regression. Adjusted r2 values were used to select the final predictive models. Results: CVF exposure increased linearly with dose for all antiretrovirals (r2 ≥ 0.23, P ≤ 0.02) except raltegravir (r2 = 0.08, P = 0.19). In RF, only emtricitabine increased linearly with dose (r2 = 0.27, P = 0.01). For all antiretrovirals, CVF and RF concentrations significantly correlated with mucosal tissue concentrations (female genital tract r2 ≥ 0.37, rectal tissue r2 ≥ 0.50, P ≤ 0.001). In the final multivariate models, plasma and fluid concentrations were both associated with FGT concentrations for all antiretrovirals (r2 ≥ 0.81, P < 0.001). The same was noted for rectal tissue (r2 ≥ 0.58, P < 0.001) except for tenofovir, for which RF alone was predictive of tissue concentration (r2 = 0.91, P < 0.001). Conclusions: Mucosal fluids were positively correlated with tissue concentrations and including plasma concentrations improved the regression models in most cases. Dose linearity in CVF, but not RF, suggests a saturation process in lower gastrointestinal tract tissue. These findings suggest that mucosal fluid and plasma concentrations may be used for qualitative inference of tissue concentrations for these antiretrovirals. [ABSTRACT FROM AUTHOR]
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- 2016
- Full Text
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6. Comparing HIV Case Detection in Prison During Opt-In vs. Opt-Out Testing Policies.
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Rosen, David L., Wohl, David A., Golin, Carol E., Rigdon, Joseph, May, Jeanine, White, Becky L., Leone, Peter A., Hudgens, Michael G., and Bowling, James Michael
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- 2016
- Full Text
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7. Protein Binding of Lopinavir and Ritonavir During 4 Phases of Pregnancy.
- Author
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Patterson, Kristine B., Dumond, Julie B., Prince, Heather A., Jenkins, Amanda J., Scarsi, Kimberly K., Wang, Ruili, Malone, Stephanie, Hudgens, Michael G., and Kashuba, Angela D. M.
- Abstract
To investigate the intraindividual pharmacokinetics (PKs) of total (protein bound plus unbound) and unbound lopinavir/ritonavir (LPV/RTV) and to assess whether the pediatric formulation (100 mg/25 mg) can overcome any pregnancy-associated changes.Prospective longitudinal PK study.HIV-infected pregnant antiretroviral therapy-naive and experienced women receiving LPV/RTV 400 mg/100 mg tablets twice daily. Intensive PK evaluations were performed at 20-24 weeks (PK1), 30 weeks (PK2) followed by empiric dose increase using the pediatric formulation (100 mg/25 mg twice daily), 32 weeks (PK3), and 8 weeks postpartum (PK4).Twelve women completed prespecified PK evaluations. Median (range) age was 28 (18-35) years and baseline BMI was 32 (19-41) kg/m2. During pregnancy, total area under the time concentration (AUC0-12h) for LPV was significantly lower than postpartum (PK1, PK2, or PK3 vs. PK4, P = 0.005). Protein-unbound LPV AUC0-12h remained unchanged during pregnancy [PK1: 1.6 (1.3-1.9) vs. PK2: 1.6 (1.3-1.9) μg·h/mL, P = 0.4] despite a 25% dose increase [PK2 vs. PK3: 1.8 (1.3-2.1) μg·h/mL, P = 0.5]. Protein-unbound LPV predose concentrations (C12h) did not significantly change despite dose increase [PK2: 0.10 (0.08-0.15) vs. PK3: 0.12 (0.10-0.15) μg/mL, P = 0.09]. Albumin and LPV AUC0-12h fraction unbound were correlated (rs = 0.3, P = 0.03).Total LPV exposure was significantly decreased throughout pregnancy despite the increased dose. However, the exposure of unbound LPV did not change significantly regardless of trimester or dose. Predose concentrations of unbound LPV were not affected by the additional dose and were 70-fold greater than the minimum efficacy concentration. These findings suggest dose adjustments may not be necessary in all HIV-infected pregnant women. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
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