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Regis Kreitchmann,
Brookie M Best,
Jiajia Wang,
Alice Stek,
Edmund Caparelli,
D Heather Watts,
Elizabeth Smith, David E Shapiro,
Steve Rossi,
Sandra K Burchett,
Elizabeth Hawkins,
Mark Byroads,
Tim R Cressey,
Mark Mirochnick
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ABSTRACT: BACKGROUND:: Reduced atazanavir exposure has been demonstrated during pregnancy with standard atazanavir/ritonavir dosing. We studied an increased dose during the third trimester of pregnancy. METHODS:: IMPAACT 1026s is a prospective, non-blinded pharmacokinetic study of HIV-infected pregnant women taking antiretrovirals for clinical indications, including two cohorts (with or without tenofovir) receiving atazanavir/ritonavir 300/100 mg once daily during the 2 trimester (2 trim), 400/100 mg during the 3 trimester (3 trim) and 300/100 mg postpartum (PP). Intensive steady-state 24-hour pharmacokinetic profiles were performed. Atazanavir concentrations were measured by HPLC. Pharmacokinetic targets were the 10 percentile atazanavir AUC (29.4 mcg*hr/mL) in non-pregnant adults on standard dose and 0.15 mcg/mL, minimum trough concentration. RESULTS:: Atazanavir pharmacokinetic data were available for 37 women without tenofovir, 35 with tenofovir; Median (range) pharmacokinetic parameters are presented for 2, 3 trim and PP and number who met target/total. * indicates p<0.05 compared to PP. Atazanavir without tenofovir: AUC 30.5 (9.19-93.8), 45.7 (11-88.3), and 48.8 (9.9-112.2) mcg-hr/mL, and 8/14, 29/37 and 27/34 met target. C24h was 0.49 (0.09-4.09), 0.71 (0.14-2.09), and 0.90 (0.05-2.73) mcg/mL; 13/14, 36/37 and 29/34 met target. Atazanavir with tenofovir: AUC 26.2 (6.8-60.9)*, 37.7 (0.72-88.2)*, and 58.6 (6-149) mcg-hr/mL, and 7/17, 23/32 and 27/29 met target. C24h was 0.44 (0.12-1.06)*, 0.57 (0.02-2.06)*, and 1.26 (0.09-5.43) mcg/mL; 7/17, 23/32 and 27/29 met target.Atazanavir/ritonavir was well tolerated with no unanticipated adverse events. CONCLUSIONS:: Atazanavir/ritonavir increased to 400/100mg provides adequate atazanavir exposure during the third trimester and should be considered during the second trimester.
JAIDS Journal of Acquired Immune Deficiency Syndromes 02/2013; · 4.43 Impact Factor
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Tim R Cressey,
Brookie M Best,
Jullapong Achalapong,
Alice Stek,
Jiajia Wang,
Nantasak Chotivanich,
Prapap Yuthavisuthi,
Pornnapa Suriyachai,
Sinart Prommas, David E Shapiro,
D Heather Watts,
Elizabeth Smith,
Edmund Capparelli,
Regis Kreitchmann,
Mark Mirochnick
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ABSTRACT: AIM: To describe the pharmacokinetics and safety of indinavir boosted with ritonavir (IDV/r) during the second and third trimesters of pregnancy and in the postpartum period. METHODS: IMPAACT P1026s is an on-going, prospective, non-blinded study of antiretroviral pharmacokinetics (PK) in HIV-infected pregnant women with a Thai cohort receiving IDV/r 400/100 mg twice daily during pregnancy through 6-12 weeks postpartum as part of clinical care. Steady-state PK profiles were performed during the second (optional) and third trimesters and at 6-12 weeks postpartum. PK targets were the estimated 10(th) percentile IDV AUC (12.9 μg.h/mL) in non-pregnant historical Thai adults and a trough concentration of 0.1 μg/mL, the suggested minimum target. RESULTS: Twenty-six pregnant women were enrolled; thirteen entered during the second trimester. Median (range) age was 29.8 (18.9-40.8) years and weight 60.5 (50.0-85.0) kg at the third trimester PK visit. The 90% confidence limits for the geometric mean ratio of the indinavir AUC(0-12) and Cmax during the second trimester and postpartum (ante/post ratios) were 0.58 (0.49-0.68) and 0.73 (0.59-0.91), respectively; third trimester/postpartum AUC(0-12) and Cmax ratios were 0.60 (0.53-0.68) and 0.63 (0.55-0.72), respectively. IDV/r was well tolerated and 21/26 women had a HIV-1 viral load <40 copies/mL at delivery. All twenty-six infants were confirmed HIV negative. CONCLUSION: IDV exposure during the second and third trimesters was significantly reduced compared to postpartum and ∼30% of women fail to achieve a target trough concentration. Increasing the dose of IDV/r during pregnancy to 600/100 mg twice daily may be preferable to ensure adequate drug concentrations.
British Journal of Clinical Pharmacology 01/2013; · 2.96 Impact Factor
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ABSTRACT: OBJECTIVE: To assess whether there was a difference in HIV seroprevalence between eligible women who declined and those who agreed to participate in a study of voluntary counseling and testing among women entering labor with unknown HIV status in South Africa. METHODS: Anonymous cord blood specimens were collected-as dried blood spots-from all women approached for participation in a cluster-randomized trial. No patient identifiers were included on the cord blood specimens. The dried blood spots were analyzed for HIV antibody via enzyme immunoassay and western blotting. RESULTS: Of 7238 women screened for study participation, 1041 (14.4%) had undocumented HIV status; of these women, 542 were eligible for inclusion and 343 enrolled. Based on 513 evaluable samples, the overall seroprevalence was 13.3% (95% confidence interval [CI], 10.4-16.5), which was similar to the 13.1% (95% CI, 9.7-17.2) seroprevalence among the 343 enrolled women. CONCLUSION: Seroprevalence among eligible women was similar to that among enrolled women, which indicates that study participation did not select for a group with an HIV seroprevalence substantially different from that among women who declined to enroll.
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 11/2012; · 1.41 Impact Factor
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Karin Nielsen-Saines,
Lauren Komarow,
Susan Cu-Uvin,
Gonzague Jourdain,
Karin L Klingman, David E Shapiro,
Lynne Mofenson,
Laura Moran,
Thomas B Campbell,
Jane Hitti,
Susan Fiscus,
Judith Currier
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ABSTRACT: The impact of maternal antiretrovirals (ARVs) during pregnancy, labor, and postpartum on infant outcomes is unclear.
Infants born to HIV-infected mothers in ARV studies were followed for 18 months.
Between June 2006 and December 2008, 236 infants enrolled from Africa (n = 36), India (n = 47), Thailand (n = 152), and Brazil (n = 1). Exposure to ARVs in pregnancy included ≥ 3 ARVs (10%), zidovudine/intrapartum ARV (81%), and intrapartum ARV (9%). There were 4 infant infections (1 in utero, 3 late postpartum) and 4 deaths with 1.8% mortality (95% confidence interval [CI], 0.1%-3.5%) and 96.4% HIV-1-free survival (95% CI, 94.0%-98.9%). Birth weight was ≥ 2.5 kg in 86%. In the first 6 months, Indian infants (nonbreastfed) had lowest median weights and lengths and smallest increases in growth. After 6 months, African infants had the lowest median weight and weight-for-age z scores. Infants exposed to highest maternal viral load had the lowest height and height-for-age z scores. Serious adverse events occurred in 38% of infants, did not differ by country, and correlated with less maternal ARV exposure. Clinical diagnoses were seen in 84% of Thai, 31% of African, and 9% of Indian infants. Congenital defects/inborn errors of metabolism were seen in 18 (7.6%) infants, of which 17 were Thai (11%: 95% CI, 6.7%-17.0%); none had first trimester ARV exposure.
Infant follow-up in large international cohorts is feasible and provides important safety and HIV transmission data following maternal ARV exposure. Increased surveillance increases identification of congenital/inborn errors.
PEDIATRICS 05/2012; 129(6):e1525-32. · 4.47 Impact Factor
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ABSTRACT: Although use of efficacious interventions, including antiretrovirals (ARVs), has dramatically reduced the rate of mother-to-child transmission of human immunodeficiency virus, the safety of in utero ARV exposure remains of concern.
Data regarding 1112 infants enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group protocol P1025 born between 2002 and 2007 were analyzed for this study. Congenital anomalies were classified based on the Metropolitan Atlanta Congenital Defects Program guidelines. Associations between congenital anomalies and timing of first in utero exposure to ARVs were evaluated by logistic regression analysis.
Congenital anomalies were identified and confirmed in 61 of the 1112 infants, resulting in a prevalence of 5.49/100 live births (95% confidence interval, 4.22-6.99). Among the 80 anomalies identified, the organ systems involved included cardiovascular (n = 33), musculoskeletal (n = 15), renal (n = 9), genitourinary (n = 6), craniofacial (n = 4), and central nervous system (n = 2). First trimester exposure to efavirenz was associated with a significantly increased risk of congenital anomalies (odds ratio, 2.84; 95% confidence interval, 1.13-7.16). No significant associations were observed between exposure to other individual ARVs or classes of ARVs started at any time during pregnancy and infant congenital anomalies.
The observed rate of congenital anomalies in this cohort is higher than previously reported for the general population, but it is consistent with rates observed in other recent studies of children born to human immunodeficiency virus-infected women. Cardiovascular anomalies occurred most frequently. With the exception of a known teratogen (efavirenz), no statistically significant associations between in utero exposure to ARVs and congenital anomalies were identified.
The Pediatric Infectious Disease Journal 02/2012; 31(2):164-70. · 3.58 Impact Factor
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Russell B Van Dyke,
Nicole Ngo-Giang-Huong, David E Shapiro,
Lisa Frenkel,
Paula Britto,
Anuvat Roongpisuthipong,
Ingrid A Beck,
Praparb Yuthavisuthi,
Sinart Prommas,
Thanyawee Puthanakit,
Jullapong Achalapong,
Nantasak Chotivanich,
Wirawan Rasri,
Tim R Cressey,
Robert Maupin,
Mark Mirochnick,
Gonzague Jourdain
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ABSTRACT: Intrapartum single-dose (SD) nevirapine (NVP) reduces perinatal transmission of human immunodeficiency virus (HIV) infection but selects for NVP-resistant virus, which compromises subsequent NVP-based therapy. A 1-week "tail" of lamivudine and zidovudine after SD-NVP decreases the risk of resistance. We hypothesized that increasing the duration or potency of the tail would further reduce this risk to <10%, using a sensitive assay to measure resistance.
HIV-infected pregnant Thai women with a CD4 cell count >250 cells/μL, most receiving zidovudine, were randomized at 28-38 weeks gestation to receive 1 of 3 intrapartum and postpartum regimens: (A) zidovudine plus enteric-coated didanosine plus lopinavir and ritonavir for 7 days, (B) zidovudine plus enteric-coated didanosine for 30 days, or (C) regimen 1 for 30 days. The incidence of NVP resistance mutations at day 10 or week 6 post partum in each arm was compared with that of a historical comparison group who received prenatal zidovudine and SD-NVP. NVP resistance was identified by consensus sequencing and a sensitive oligonucleotide ligation assay (OLA).
At entry, the 169 participants had a median CD4 cell count of 456 cells/μL and an HIV load of 3.49 log(10) copies/mL. The incidence of mutations in each of the 3 P1032 arms was 0% by sequencing and 1.8%, 7.1%, and 5.3% by OLA in arms A, B, and C, respectively, compared with 13.4% by sequencing and 29.4% by OLA in the comparison group (P < .001 for each study arm vs comparison group). Grade 4 anemia developed in 1 woman.
A 7-day tail of highly active combination therapy or 1 month of dual therapy after SD-NVP prevents most NVP resistance to minimal toxicity.
The IMPAACT P1032 Clinical Trial is NCT00109590, and the PHPT-2 Clinical Trial is NCT00398684.
Clinical Infectious Diseases 12/2011; 54(2):285-93. · 9.15 Impact Factor
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Patricia M Flynn,
Mark Mirochnick, David E Shapiro,
Arlene Bardeguez,
John Rodman,
Brian Robbins,
Sharon Huang,
Susan A Fiscus,
Koen K A Van Rompay,
James F Rooney,
Brian Kearney,
Lynne M Mofenson,
D Heather Watts,
Patrick Jean-Philippe,
Barbara Heckman,
Edwin Thorpe,
Amanda Cotter,
Murli Purswani
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ABSTRACT: Tenofovir (TFV) is effective in preventing simian immunodeficiency virus (SIV) transmission in a macaque model, is available as the oral agent tenofovir disoproxil fumarate (TDF), and may be useful in the prevention of mother-to-child transmission of human immunodeficiency virus (HIV). We conducted a trial of TDF and TDF-emtricitabine (FTC) in HIV-infected pregnant women and their infants. Women received a single dose of either 600 mg TDF, 900 mg TDF, or 900 mg TDF-600 mg FTC at labor onset or prior to a cesarean section. Infants received no drug or a single dose of TDF at 4 mg/kg of body weight or of TDF at 4 mg/kg plus FTC at 3 mg/kg as soon as possible after birth. All regimens were safe and well tolerated. Maternal areas under the serum concentration-time curve (AUC) and concentrations at the end of sampling after 24 h (C(24)) were similar between the two doses of TDF; the maximum concentrations of the drugs in serum (C(max)) and cord blood concentrations were higher in women delivering via cesarean section than in those who delivered vaginally (P = 0.04 and 0.046, respectively). The median ratio of the TFV concentration in cord blood to that in the maternal plasma at delivery was 0.73 (range, 0.26 to 1.95). Without TDF administration, infants had a median TFV concentration of 12 ng/ml 12 h after birth. Following administration of a single dose of TDF at 4 mg/kg, infant TFV concentrations fell below the targeted level, 50 ng/ml, by 24 h postdose. In HIV-infected pregnant women and their infants, 600 mg of TDF is acceptable as a single dose during labor. Low concentrations at birth support infant dosing as soon after birth as possible. Rapidly decreasing TFV levels in infants suggest that multiple or higher doses of TDF will be necessary to maintain concentrations that are effective for viral suppression.
Antimicrobial Agents and Chemotherapy 09/2011; 55(12):5914-22. · 4.84 Impact Factor
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ABSTRACT: To compare the prepartum and postpartum feasibility and acceptance of voluntary counseling and rapid testing (VCT) among women with unknown HIV status in South Africa.
Eligible women were randomized according to the calendar week of presentation to receive VCT either while in labor or after delivery.
Of 7238 women approached, 542 (7.5%) were eligible, 343 (63%) were enrolled, and 45 (13%) were found to be HIV infected. The proportions of eligible women who accepted VCT were 66.8% (161 of 241) in the intrapartum arm and 60.5% (182 of 301) in the postpartum arm, and the difference of 6.3% (95% CI, -1.8% to 14.5%) was not significant. The median times (44 and 45 minutes) required to conduct VCT were also similar in the 2 arms. In the intrapartum arm, all women in true labor received their test results before delivery and all those found to be HIV positive accepted prophylaxis with nevirapine before delivery.
Rapid testing in labor wards for women with an unknown HIV status is feasible and well accepted, and allows for a more timely antiretroviral prophylaxis than postpartum testing.
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 01/2011; 113(1):44-9. · 1.41 Impact Factor
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ABSTRACT: Conflicting results have been reported among studies of protease inhibitor (PI) use during pregnancy and preterm birth. Uncontrolled confounding by indication may explain some of the differences among studies.
In total, 777 human immunodeficiency virus (HIV)-infected pregnant women in a prospective cohort who were not receiving antiretroviral (ARV) treatment at conception were studied. Births <37 weeks gestation were reviewed, and deliveries due to spontaneous labor and/or rupture of membranes were identified. Risk of preterm birth and low birth weight (<2500 g) were evaluated by using multivariable logistic regression.
Of the study population, 558 (72%) received combination ARV with PI during pregnancy, and a total of 130 preterm births were observed. In adjusted analyses, combination ARV with PI was not significantly associated with spontaneous preterm birth, compared to ARV without PI (odds ratio [OR], 1.22; 95% confidence interval [CI], 0.70-2.12). Sensitivity analyses that included women who received ARV prior to pregnancy also did not identify a significant association (OR, 1.34; 95% CI, 0.84-2.16). Low birth weight results were similar.
No evidence of an association between use of combination ARV with PI during pregnancy and preterm birth was found. Our study supports current guidelines that promote consideration of combination ARV for all HIV-infected pregnant women.
The Journal of Infectious Diseases 04/2010; 201(7):1035-44. · 6.41 Impact Factor
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Susan B Brogly,
Marc Foca,
Jaime G Deville,
Mark Mirochnick,
Gwendolyn B Scott,
Lynne M Mofenson,
Jennifer S Read,
Rolando M Viani,
Sandra K Burchett,
Ellen R Cooper,
Renee Browning, David E Shapiro
JAIDS Journal of Acquired Immune Deficiency Syndromes 01/2010; 53(1):154-7. · 4.43 Impact Factor
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Tim R Cressey,
Russell Van Dyke,
Gonzague Jourdain,
Thanyawee Puthanakit,
Anuvat Roongpisuthipong,
Jullapong Achalapong,
Prapap Yuthavisuthi,
Sinart Prommas,
Nantasak Chotivanich,
Robert Maupin,
Elizabeth Smith, David E Shapiro,
Mark Mirochnick
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ABSTRACT: Lopinavir (LPV) exposure is reduced during the third trimester of pregnancy. We report the pharmacokinetics of standard LPV-ritonavir dosing (400/100 mg twice daily) in the immediate and early postpartum period when initiated during labor. In 16 human immunodeficiency virus-infected Thai women, the median (range) LPV area under the concentration-time curve and maximum and minimum concentrations in plasma were 99.7 (66.1 to 180.5) microg x h/ml, 11.2 (8.0 to 17.5) microg/ml, and 4.6 (1.7 to 12.5) microg/ml, respectively, at 41 (12 to 74) h after delivery. All of the women attained adequate LPV levels through 30 days postpartum. No serious adverse events were reported.
Antimicrobial Agents and Chemotherapy 03/2009; 53(5):2189-91. · 4.84 Impact Factor
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David E. Shapiro
06/2008; , ISBN: 9780471462422
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Nancy A Wade,
Jashvant D Unadkat,
Sharon Huang, David E Shapiro,
Anita Mathias,
Salih Yasin,
Gregory Ciupak,
D Heather Watts,
Isaac Delke,
Mobeen Rathore,
Jane Hitti,
Lisa Frenkel,
Renee Samelson,
Mary Elizabeth Smith,
Lynne Mofenson,
Sandra K Burchett
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ABSTRACT: This study evaluates the safety, tolerance, and pharmacokinetics of stavudine (d4T) in human immunodeficiency virus (HIV)-infected zidovudine (ZDV)-intolerant/refusing pregnant women and of single-dose d4T in their infants. Women received d4T and lamivudine (3TC) from enrollment until labor. During labor, women received oral 3TC and either intravenous or oral d4T. Infants received ZDV and 3TC for 6 weeks and a single dose of oral d4T at weeks 1 and 6. Mean maternal antenatal d4T pharmacokinetics (terminal plasma half-life [T1/2], 83.5+/-16.8 min; area under the plasma-concentration time curve [AUC0-infinity), 81.6+/-22.0 microg.min/mL; n=6) were not significantly different from those during labor (T(1/2), 87.3+/-24.7 min; AUC0-infinity, 88.1+/-16.6 microg.min/mL; n=6). Umbilical-cord and maternal plasma concentrations were not significantly different from one another. The oral clearance of d4T in infants was significantly greater at week 6 versus week 1 (6.8+/-1.0 vs. 5.6+/-1.2 mL/min/kg). There were no toxicities, in women or infants, that required discontinuation or modification of the study drug. No infants had positive HIV viral diagnostic tests. d4T with or without 3TC is a potential alternative to ZDV for HIV-infected pregnant women.
The Journal of Infectious Diseases 01/2005; 190(12):2167-74. · 6.41 Impact Factor
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ABSTRACT: To assess skills and preferred learning formats in teaching health promotion (HP).
A self-administered needs assessment of Maternal and Child Health (MCH) educators from multiple disciplines was conducted on a convenience sample taken nationally via e-mail using Dillman's method. Respondents rated ability to use, and desire to improve skills in, different teaching strategies (brainstorming, case method, collaborative learning, mini-presentation, reflective exercise, role play) and health concepts (partnership, communication, HP/illness prevention, time management, education, advocacy). Preferred learning formats were assessed with 5-point Likert scale and were analyzed using ANOVA.
Fifty-seven percent of respondents (n = 180) taught in an urban setting, 26% suburban, and 17% rural. Most taught at academic health centers (35%), public health clinics (25%), or hospitals (17%). Seventy-five percent were female; average age was 42 years (SD--9.1 years). Specific disciplines showed no major difference in mean responses compared with others. The greatest barriers to integrating HP into teaching were time (82%) and budget (58%). Although a majority of all respondents felt comfortable in their abilities to use the teaching strategies and concepts, an equal percentage still wanted to improve these skills. One-third of respondents had experience using web-based study: 64% of them indicated web-based study as their preferred method of continuing education.
While a majority of MCH educators felt confident using various teaching strategies to teach the integration of HP into practice, most still wished to improve their personal skills. Use of an inexpensive, time-efficient modality to access and learn to teach HP was appealing to respondents across disciplines.
Maternal and Child Health Journal 07/2004; 8(2):87-93. · 2.24 Impact Factor
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ABSTRACT: In this randomized, double-blinded, placebo-controlled, crossover trial of 42 human subjects, we examined the speed of onset of cutaneous anesthesia by eutectic mixture of local anesthetics (EMLA) cream after brief (approximately 10-s) pretreatment of the underlying skin with low-frequency (55 kHz) ultrasound. Four treatments were compared: ultrasound pretreatment followed by application of 1 g EMLA or placebo cream for 5 min, 10 min, 15 min, and 60 min without ultrasound pretreatment as positive control. Pain was tested by pricks with a 20 g needle. Pain scores and patient preference for EMLA or placebo cream were measured at each time point. Based on both pain scores and patient preference, cutaneous anesthesia was achieved in the EMLA groups as compared with placebo at all time points. After ultrasound pretreatment and then 5, 10, or 15 min after EMLA cream application, pain scores and overall preference were statistically indistinguishable from EMLA cream application for 60 min (without ultrasound pretreatment). There were no significant adverse effects. Low-frequency ultrasound pretreatment appears to be safe and effective in producing rapid onset of EMLA cream in this model, with results as early as 5 min. IMPLICATIONS: A prospective, randomized, double-blinded, placebo-controlled clinical trial demonstrated rapid onset of cutaneous anesthesia by pretreatment of the skin with ultrasound before application of EMLA cream.
Anesthesia & Analgesia 03/2004; 98(2):371-6, table of contents. · 3.29 Impact Factor
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John PA Ioannidis,
Athina Tatsioni,
Elaine J Abrams,
Marc Bulterys,
Robert W Coombs,
James J Goedert,
Bette T Korber,
Marie Jeanne Mayaux,
Lynne M Mofenson,
Jack Moye Jr,
Marie-Louise Newell, David E Shapiro,
Jean Paul Teglas,
Bruce Thompson,
Jeffrey Wiener
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ABSTRACT: Objective: To evaluate whether maternal human immunodeficiency virus type 1 (HIV-1) RNA levels in the serum/plasma of mothers at or close to the time of delivery affects the rate of disease progression among vertically HIV-1-infected children and whether it correlates with other parameters affecting infant disease progression.
Methods: International meta-analysis of eight studies with 574 HIV-1 infected infants with available maternal HIV-1 RNA measurements at or close to delivery and clinical follow-up. The primary outcome was disease progression (stage C disease or death, n = 178). Cohort-stratified Cox models were used.
Results: Higher maternal HIV-1 RNA level at or close to delivery significantly increased disease progression risk [hazard ratio (HR), 1.25; 95% confidence interval (CI), 1.04-1.52 per 1 log10 increase; P = 0.02) with a borderline effect on mortality (HR, 1.26; 95% CI, 0.96-1.65; P = 0.10]. The association with disease progression risk was strong in the first 6 months of life (HR, 1.77; 95% CI, 1.28-2.45; P = 0.001), but not subsequently (HR, 1.03; 95% CI, 0.81-1.30). Maternal HIV-1 RNA, early infant HIV-1 RNA (at 30-200 days after birth) and infant CD4 were independent predictors of disease progression in the first 6 months. Maternal HIV-1 RNA at or close to delivery correlated with early infant HIV-1 RNA (r = 0.26, P < 0.001). Effects were independent of maternal and infant treatment.
Conclusions: Higher maternal HIV-1 RNA at or close to delivery strongly predicts disease progression for HIV-1-infected infants, especially in their first 6 months of life and correlates with the early peak of viremia in the infected child.
AIDS 01/2004; 18(1):99-108. · 6.24 Impact Factor
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John P A Ioannidis,
Athina Tatsioni,
Elaine J Abrams,
Marc Bulterys,
Robert W Coombs,
James J Goedert,
Bette T Korber,
Marie Jeanne Mayaux,
Lynne M Mofenson,
Jack Moye,
Marie-Louise Newell, David E Shapiro,
Jean Paul Teglas,
Bruce Thompson,
Jeffrey Wiener
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ABSTRACT: To evaluate whether maternal human immunodeficiency virus type 1 (HIV-1) RNA levels in the serum/plasma of mothers at or close to the time of delivery affects the rate of disease progression among vertically HIV-1-infected children and whether it correlates with other parameters affecting infant disease progression.
International meta-analysis of eight studies with 574 HIV-1 infected infants with available maternal HIV-1 RNA measurements at or close to delivery and clinical follow-up. The primary outcome was disease progression (stage C disease or death, n = 178). Cohort-stratified Cox models were used.
Higher maternal HIV-1 RNA level at or close to delivery significantly increased disease progression risk [hazard ratio (HR), 1.25; 95% confidence interval (CI), 1.04-1.52 per 1 log10 increase; P = 0.02) with a borderline effect on mortality (HR, 1.26; 95% CI, 0.96-1.65; P = 0.10]. The association with disease progression risk was strong in the first 6 months of life (HR, 1.77; 95% CI, 1.28-2.45; P = 0.001), but not subsequently (HR, 1.03; 95% CI, 0.81-1.30). Maternal HIV-1 RNA, early infant HIV-1 RNA (at 30-200 days after birth) and infant CD4 were independent predictors of disease progression in the first 6 months. Maternal HIV-1 RNA at or close to delivery correlated with early infant HIV-1 RNA (r = 0.26, P < 0.001). Effects were independent of maternal and infant treatment.
Higher maternal HIV-1 RNA at or close to delivery strongly predicts disease progression for HIV-1-infected infants, especially in their first 6 months of life and correlates with the early peak of viremia in the infected child.
AIDS 01/2004; 18(1):99-108. · 6.24 Impact Factor
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Arlene D Bardeguez, David E Shapiro,
Lynne M Mofenson,
Robert Coombs,
Lisa M Frenkel,
Mary Glenn Fowler,
Sharon Huang,
Rhoda S Sperling,
Bethann Cunningham,
Jorge Gandia,
Robert Maupin,
Carmen D Zorrilla,
Theodore Jones,
Mary Jo O'Sullivan
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ABSTRACT: Zidovudine prophylaxis is recommended to reduce perinatal HIV-1 transmission, but there are limited data on long-term effects on women's health. Pediatrics AIDS Clinical Trials Group (PACTG) 288 was a prospective observational study among US women randomized to zidovudine or placebo in PACTG 076 that was designed to evaluate and compare postpartum clinical, immune, and viral parameters between randomized treatment arms. Forty-eight percent (226/474) of eligible women enrolled in the study (mean follow-up of 4.1 years). Progression and time to AIDS or death were similar in both groups, observed in 21 (19%) zidovudine group women and 29 (25%) placebo group women (RR = 0.73, 90% CI: 0.46-1.17). No significant differences in CD4 lymphocyte count or HIV RNA levels were detected. Genotypic zidovudine resistance was detected in 10% of 156 women (9% of zidovudine group women and 11% of placebo group women). Based on our data, ZDV monotherapy could be considered as chemoprophylaxis to reduce perinatal HIV transmission for minimally symptomatic HIV-infected pregnant women with a low viral load and normal CD4 cell count who do not want to receive highly active antiretroviral therapy because of concern about potential side effects or who wish to reduce fetal exposure to multiple drugs during pregnancy.
JAIDS Journal of Acquired Immune Deficiency Syndromes 03/2003; 32(2):170-81. · 4.43 Impact Factor
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Ruth E Tuomala, David E Shapiro,
Lynne M Mofenson,
Yvonne Bryson,
Mary Culnane,
Michael D Hughes,
M J O'Sullivan,
Gwendolyn Scott,
Alice M Stek,
Diane Wara,
Marc Bulterys
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ABSTRACT: Some studies suggest that combination antiretroviral therapy in pregnant women with human immunodeficiency virus type 1 (HIV-1) infection increases the risk of premature birth and other adverse outcomes of pregnancy.
We studied pregnant women with HIV-1 infection who were enrolled in seven clinical studies and delivered their infants from 1990 through 1998. The cohort comprised 2123 women who received antiretroviral therapy during pregnancy (monotherapy in 1590, combination therapy without protease inhibitors in 396, and combination therapy with protease inhibitors in 137) and 1143 women who did not receive antiretroviral therapy.
After standardization for the CD4+ cell count and use or nonuse of tobacco, alcohol, and illicit drugs, the rate of premature delivery (<37 weeks of gestation) was similar among the women who received antiretroviral therapy and those who did not (16 percent and 17 percent, respectively); the rate of low birth weight (<2500 g) was 16 percent among the infants born to both groups; and the rate of very low birth weight (<1500 g) was 2 percent for the group that received antiretroviral therapy and 1 percent for the group that did not. The rates of low Apgar scores (<7) and stillbirth were also similar or the same in the two groups. After adjustment for multiple risk factors, combination antiretroviral therapy was not associated with an increased risk of premature delivery as compared with monotherapy (odds ratio, 1.08; 95 percent confidence interval, 0.71 to 1.62) or delivery of an infant with low birth weight (odds ratio, 1.03; 95 percent confidence interval, 0.64 to 1.63). Seven of the women who received combination therapy with protease inhibitors (5 percent) had infants with very low birth weight, as compared with nine women who received combination therapy without protease inhibitors (2 percent) (adjusted odds ratio, 3.56; 95 percent confidence interval, 1.04 to 12.19).
As compared with no antiretroviral therapy or monotherapy, combination therapy for HIV-1 infection in pregnant women is not associated with increased rates of premature delivery or with low birth weight, low Apgar scores, or stillbirth in their infants. The association between combination therapy with protease inhibitors and an increased risk of very low birth weight requires confirmation.
New England Journal of Medicine 06/2002; 346(24):1863-70. · 53.30 Impact Factor
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ABSTRACT: Objective: To identify modifiable obstetric factors associated with the failure of zidovudine chemoprophylaxis to prevent perinatal human immunodeficiency virus type 1 (HIV-1) transmission.
Methods: We analyzed data from Pediatric AIDS Clinical Trials Group protocol 076, a randomized, double-masked, placebo-controlled trial that demonstrated that a zidovudine regimen could prevent perinatal HIV-1 transmission. We estimated the zidovudine treatment effect using the relative reduction in transmission risk among women randomized to treatment with zidovudine compared with women randomized to receive placebo. Univariate and multivariate statistical analyses were used to assess whether the treatment effect differed in magnitude according to potential antepartum or intrapartum risk factors.
Results: In the univariate analysis, the zidovudine treatment effect was found to differ significantly in magnitude according to quartile of maternal weight at the time of study entry (interaction test, P = .03); among women in the heaviest-weight quartile (weight more than 82 kg), there was a 26% relative reduction in transmission risk, compared with a 79% relative reduction among the other three quartiles (interaction test, P = .05). In the zidovudine treatment group, women who transmitted HIV-1 were significantly more likely than nontransmitters to have had antepartum procedures or conditions associated with increased risk of fetal exposure to maternal blood or cervicovaginal secretions (43% compared with 19%, P = .04). In the multivariate analysis, adjustment for the plasma HIV-1 RNA level and CD4+ cell percentage did not eliminate the differential treatment effect according to these factors.
Conclusion: High maternal weight and conditions associated with fetal exposure to maternal blood or cervicovaginal secretions may diminish the efficacy of zidovudine chemoprophylaxis.
Obstetrics and Gynecology 11/1999; 94(6):897-908. · 4.73 Impact Factor
