- Silver Spring, MD 20905
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To evaluate the efficacy of intravenous immunoglobulin (IVIG) for prevention of viral, opportunistic, and minor bacterial infections in children infected with human immunodeficiency virus (HIV). Randomized, double-blind,... more
To evaluate the efficacy of intravenous immunoglobulin (IVIG) for prevention of viral, opportunistic, and minor bacterial infections in children infected with human immunodeficiency virus (HIV). Randomized, double-blind, placebo-controlled, outpatient clinical trial comparing subjects treated with 400 mg of IVIG per kilogram of body weight every 28 days with those given albumin placebo. Twenty-eight clinical centers in mainland United States and Puerto Rico. Three hundred seventy-six children infected with human immunodeficiency virus with clinical or immunologic evidence of HIV disease, 313 of whom had entry CD4+ counts of at least 0.20 x 10(9)/L (greater than or equal to 200/mm3). The incidence of laboratory-proven and clinically diagnosed viral, opportunistic, and bacterial infections. Viral infections and minor bacterial infections contributed more frequently to morbidity in children with entry CD4+ counts of at least 0.20 x 10(9)/L (together over five times as frequent) than did serious bacterial infection, the primary outcome measure of the trial. Opportunistic infections occurred at a similar rate as laboratory-proven serious bacterial infections. In this group of children, IVIG was significantly associated with a decrease in the rate of viral infections and minor bacterial infections per 100 patient-years (36.0 vs 54.0 episodes of viral infection per 100 patient-years, IVIG vs placebo, P = .01; and 115.1 vs 159.7 episodes of minor bacterial infection per 100 patient-years, IVIG vs placebo, P = .02), as well as a decrease in the rate of serious bacterial infections per 100 patient-years (26.4 vs 48.2 episodes per 100 patient-years; P = .002). There was no apparent difference in the rate of opportunistic infections between treatment arms. Beneficial effect of IVIG was seen across multiple infectious outcome measures, with reductions in serious and minor viral and bacterial infections observed in children with entry CD4+ counts of at least 0.20 x 10(9)/L.
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The importance of youth engagement in designing, implementing and evaluating programs has garnered more attention as international initiatives seek to address the HIV crisis among this population. Adolescents, however, are not often... more
The importance of youth engagement in designing, implementing and evaluating programs has garnered more attention as international initiatives seek to address the HIV crisis among this population. Adolescents, however, are not often included in HIV implementation science research and have not had opportunities to contribute to the development of HIV-related research agendas. Project Supporting Operational AIDS Research (SOAR), a United States Agency for International Development-funded global operations research project, involved youth living with HIV in a meeting to develop a strategic implementation science research agenda to improve adolescent HIV care continuum outcomes, including HIV testing and counseling (HTC) and linkage to care. Project SOAR convened a 2-day meeting of 50 experts, including four youth living with HIV. Participants examined the literature, developed research questions, and voted to prioritize these questions for the implementation science research agenda. Th...
Research Interests: Philosophy of Agency, Implementation Science, Positive Youth Development, Adolescent, Medicine, and 11 moreYouth, Biological Sciences, HIV and AIDS, HIV Prevention, AIDS, Hiv aids adolescent, HIV testing, Sub Saharan Africa, Psychology and Cognitive Sciences, Medical and Health Sciences, and HIV testing and counseling
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In October 1987, 1,323 Massachusetts residents were randomly interviewed by telephone to explore their exposure to AIDS educational efforts, levels of knowledge about AIDS, and whether that knowledge modified their behavior. Gay/bisexual... more
In October 1987, 1,323 Massachusetts residents were randomly interviewed by telephone to explore their exposure to AIDS educational efforts, levels of knowledge about AIDS, and whether that knowledge modified their behavior. Gay/bisexual males, iv drug users and heterosexual respondents were compared as were blacks, Hispanics, and whites. While 81% of respondents had read or heard mass media stories about AIDS, in the previous week, only 5% had ever been counseled about AIDS by a physician. Over 97% of black (N = 152) and white respondents (N = 1,057), as well as gay/bisexual males (N = 21) and iv drug users (N = 33) were aware that HIV can be transmitted by homosexual or heterosexual intercourse and by sharing needles when injecting drugs. However, 9% of the 55 Hispanics interviewed were unaware of male homosexual transmission, and 7% did not know about heterosexual transmission or the risks of needle sharing. Twenty percent of Hispanics, compared with 9% of other respondents, did not know HIV can be transmitted sexually by someone who appears healthy. Fifty-two percent of gay/bisexual males, 27% of iv drug users, and 21% of those who had multiple heterosexual partners in recent years reported adopting abstinence, monogamous relations, or condom use to avoid HIV exposure. Those who continued risky behavior were just as knowledgeable about HIV transmission, but they were less likely to report that they worry a great deal about getting AIDS, 14% vs 32%. The results indicate that new strategies and resources are needed to educate Hispanics. Physicians need to counsel more persons about HIV transmission and further efforts are needed to translate knowledge about HIV transmission into behavior change to avoid the virus.
Research Interests: Demography, Health Behavior, Family Medicine, Health Education, Preventive medicine, and 15 moreMedicine, Worry, Humans, Female, Male, Sexual Behavior, Massachusetts, African Americans, Adult, Public health systems and services research, Curriculum and Pedagogy, European Continental Ancestry Group, Preventive, Condom, and Acquired immunodeficiency syndrome
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In 1994, the hypothesis that transmission of human immunodeficiency virus (HIV) from mother to child could be interrupted became a reality when it was shown that a regimen of zidovudine given to HIV‐infected pregnant women and their... more
In 1994, the hypothesis that transmission of human immunodeficiency virus (HIV) from mother to child could be interrupted became a reality when it was shown that a regimen of zidovudine given to HIV‐infected pregnant women and their newborn infants could reduce the risk of perinatal transmission by two‐thirds. An understanding of the pathogenesis of transmission is crucial for interpreting these results, for design of future interventions and for understanding the natural history of perinatal HIV infection. This paper will review current information regarding the timing of and risk factors for perinatal HIV transmission, and the relationship between the timing of transmission and design of efforts to interrupt transmission and to slow disease progression in infected infants.
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Research Interests: Pediatrics, Cambodia, Mild Cognitive Impairment, Medicine, Antiretroviral Therapy, and 15 moreHumans, Child, Female, Male, Infant, Preschool, Randomized Controlled Trial, Intelligence tests, Intelligence quotient, Cohort Studies, Child Behavior Checklist, Child preschool, Cognitive dysfunction, Paediatrics and reproductive medicine, and HIV infections
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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... more
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.
Research Interests: Medicine, HIV, Biological Sciences, Prospective studies, Humans, and 15 moreFemale, Infant, AIDS, Mothers, Meta Analysis, Newborn Infant, Proportional hazards model, Odds ratio, Prognosis, Disease Progression, Confidence Interval, Psychology and Cognitive Sciences, Medical and Health Sciences, HIV infections, and hazard ratio
Nucleoside reverse transcriptase inhibitors (NRTIs) have been associated with mitochondrial toxicity in individuals receiving treatment. A report of two deaths in Europe attributed to mitochondrial dysfunction in HIV-uninfected infants... more
Nucleoside reverse transcriptase inhibitors (NRTIs) have been associated with mitochondrial toxicity in individuals receiving treatment. A report of two deaths in Europe attributed to mitochondrial dysfunction in HIV-uninfected infants with perinatal NRTI exposure prompted a review of five U.S. cohorts. Deaths in HIV-exposed children <60 months of age and HIV-uninfected or indeterminate were reviewed. Review included birth history; perinatal antiretroviral drug exposure; hospital, laboratory, and clinic records; death reports; autopsy results; and local physician queries. Deaths were classified as unrelated (Class 1), unlikely related (Class 2), possibly related (Class 3), or highly suggestive or proven relationship (Class 4), to mitochondrial dysfunction; sudden infant death syndrome (SIDS) was categorized separately. Among over 20,000 children of HIV-infected women, over half of whom had been exposed to NRTIs, 223 died. In HIV-uninfected children, 26 deaths were attributed to Class 1, and 4 were attributed to SIDS. In HIV-indeterminate children, 141, 10, 3, and 0 were Classes 1, 2, 3, and 4, respectively; 33 were due to SIDS and 6 could not be classified. There was no indication that antiretroviral exposure was associated with Class 2 or 3 deaths, or deaths from SIDS. A search for mitochondrial dysfunction among living children in these cohorts is ongoing.
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The optimal neonatal antiretroviral (ARV) regimen for prevention of HIV mother-to-child transmission (MTCT) is unknown for infants born to mothers who receive no ARVs during pregnancy. As part of a protocol comparing the efficacy of 3... more
The optimal neonatal antiretroviral (ARV) regimen for prevention of HIV mother-to-child transmission (MTCT) is unknown for infants born to mothers who receive no ARVs during pregnancy. As part of a protocol comparing the efficacy of 3 neonatal ARV regimens in preventing HIV-1 MTCT in neonates born to mothers who receive no prenatal treatment with ARVs, we devised a 3-dose nevirapine (NVP) regimen with the goal of maintaining the NVP plasma concentration >100 ng/mL (10 times the in vitro median inhibitory concentration of 10 ng/mL) during the first 2 weeks of life. NVP concentrations were measured in 14 newborns participating in a pharmacokinetics substudy during the second week of life and in single samples from 30 more newborns on day 10 to 14. The median NVP elimination half-life was 30.2 hours (range: 17.8 to 50.3 hours). The NVP concentration remained greater than the target of 100 ng/mL in all samples collected through day 10 of life. By day 14, more than half of the newborns in the pharmacokinetic substudy had NVP levels <100 ng/mL, although only 1 neonate had no detectable NVP. Although this regimen failed to meet our 100-ng/mL target, it did maintain detectable NVP concentrations in nearly all newborns through the end of the second week of life and is to be used in the parent efficacy protocol.
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Research Interests: Pediatrics, Virology, Medicine, Syphilis, Pregnancy, and 15 moreHumans, Female, Coinfection, Young Adult, Infant, Risk factors, Newborn Infant, Treponematosis, mother to child transmission of HIV /AIDS prevention, Adult, Risk Factors, Prenatal Care, Congenital syphilis, Paediatrics and reproductive medicine, and HIV infections
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Research Interests: Adolescent, Medicine, England, Multivariate Analysis, Antiretroviral Therapy, and 15 moreHumans, Low Birth Weight, Female, Male, Newborn Infant, Adult, New England, Combination drug therapy, Fetal death, Confidence Interval, Apgar Score, Adverse effect, Medical and Health Sciences, HIV infections, and Infant Premature
Research Interests: Infectious Diseases, Medicine, Birth Weight, Biological Sciences, Pregnancy, and 15 moreHumans, Female, Hiv Infection, Infectious, Newborn Infant, Human immunodeficiency virus, Adult, Oxford university, Cesarean Section, Gestational Age, Pregnancy Outcome, Immunoglobulin, Medical and Health Sciences, HIV infections, and Infant Premature
Research Interests: Medicine, England, HIV, Pregnancy, Humans, and 15 moreHIV / AIDS treatment, Female, Male, Newborn Infant, Combination drug therapy, Lamivudine, New England Journalof Medicine, Infant Formula, Nevirapine, postpartum period, Anti-retroviral agents, Medical and Health Sciences, Paediatrics and reproductive medicine, HIV infections, and Zidovudine
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The safety and pharmacokinetics of nelfinavir coadministered with zidovudine and lamivudine were studied in 26 infants during the first 6 weeks of life. Cohort 1 infants (n = 7) received 10 mg/kg 3 times a day, and cohort 2 infants (n =... more
The safety and pharmacokinetics of nelfinavir coadministered with zidovudine and lamivudine were studied in 26 infants during the first 6 weeks of life. Cohort 1 infants (n = 7) received 10 mg/kg 3 times a day, and cohort 2 infants (n = 19) received 40 mg/kg twice a day. Two cohort 1 infants at week 1 and none at week 6 exceeded the target 24-hour area under the curve (AUC) of 30 μg·h/mL, equal to the 10th percentile of the AUC for adults receiving standard nelfinavir dosing. In cohort 2, the median 24-hour AUC was 38 μg·h/mL at both time points, with considerable variability among the infants. Three of 11 cohort 2 infants at week 1 and 4 of 11 at week 6 did not meet the AUC target. Median nelfinavir oral clearance was 2.1 L/h/kg at weeks 1 and 6. The median ratio of the plasma concentrations of the nelfinavir metabolite M8 to unchanged nelfinavir increased from 0.16 (range: 0-0.38) during week 1 to 0.56 (range: 0.4-1.47) during week 6 (P < 0.01). There were no significant differ...
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HIV exposed uninfected (HEU) infants are a growing population with potentially poor health outcomes. We evaluated morbidity and mortality in HEU formula-fed infants enrolled in the NICHD HPTN 040/PACTG 1043 trial. Infectious morbidity,... more
HIV exposed uninfected (HEU) infants are a growing population with potentially poor health outcomes. We evaluated morbidity and mortality in HEU formula-fed infants enrolled in the NICHD HPTN 040/PACTG 1043 trial. Infectious morbidity, mortality, and undernutrition were evaluated within a cohort of 1,000 HEU infants enrolled between 4/2004 and 4/2010 in Brazil (N=766) and South Africa (N=234) as part of the NICHD/HPTN 040 trial of three different antiretroviral regimens to decrease intrapartum HIV vertical transmission. Twenty three percent of infants had at least 1 infectious serious adverse effect (ISAE). Infants born to mothers with <12 years of education (AOR 2.6, 95% CI 1.2-5.9), with maternal viral load of >1,000,000 copies/mL at delivery (AOR 9.9, 95% CI 1.6-63.1) were more likely to have ISAEs. At 6 months, the infant mortality rate per 1,000 live births overall was 22 ± 2.6, 9.1 ± 1.8 in Brazil, and 64.1 ± 3 in South Africa. Undernutrition and stunting peaked at 1 mon...
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Congenital cytomegalovirus (CMV) infection (cCMV) is an important cause of hearing loss and cognitive impairment. Prior studies suggest that HIV-exposed children are at higher risk of acquiring cCMV. We assessed the presence, magnitude,... more
Congenital cytomegalovirus (CMV) infection (cCMV) is an important cause of hearing loss and cognitive impairment. Prior studies suggest that HIV-exposed children are at higher risk of acquiring cCMV. We assessed the presence, magnitude, and risk factors associated with cCMV among infants born to HIV-infected women, who were not receiving antiretrovirals during pregnancy. cCMV and urinary CMV load were determined in a cohort of infants born to HIV-infected women not receiving antiretrovirals during pregnancy. Neonatal urines obtained at birth were tested for CMV DNA by qualitative and reflex quantitative real-time PCR. Urine specimens were available for 992 (58.9%) of 1684 infants; 64 (6.5%) were CMV-positive. Mean CMV load (VL) was 470,276 copies/ml (range: <200-2,000,000 copies/ml). Among 89 HIV-infected infants, 16 (18%) had cCMV versus 42 (4.9%) of 858 HIV-exposed, uninfected infants (p <0.0001). cCMV was present in 23.2% of infants with in utero and 9.1% infants with intra...
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Sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and cytomegalovirus (CMV) may lead to adverse pregnancy and infant outcomes. The role of combined maternal... more
Sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and cytomegalovirus (CMV) may lead to adverse pregnancy and infant outcomes. The role of combined maternal STIs in HIV mother-to-child transmission (MTCT) was evaluated in mother-infant pairs from NICHD HPTN 040. Urine samples from HIV-infected pregnant women during labor were tested by polymerase chain reaction (PCR) for CT, NG, and CMV. Infant HIV infection was determined by serial HIV DNA PCR testing. Maternal syphilis was tested by VDRL and confirmatory treponemal antibodies. A total of 899 mother-infant pairs were evaluated. Over 30% had at least one of the following infections (TP, CT, NG, and/or CMV) detected at the time of delivery. High rates of TP (8.7%), CT (17.8%), NG (4%), and CMV (6.3%) were observed. HIV MTCT was 9.1% (n = 82 infants). HIV MTCT was 12.5%, 10.3%, 11.1%, and 26.3% among infants born to women with CT, TP, NG or CMV respectivel...
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Health benefits of postpartum antiretroviral therapy (ART) for human immunodeficiency virus (HIV) positive women with high CD4+ T-counts have not been assessed in randomized trials. Asymptomatic, HIV-positive, non-breastfeeding women with... more
Health benefits of postpartum antiretroviral therapy (ART) for human immunodeficiency virus (HIV) positive women with high CD4+ T-counts have not been assessed in randomized trials. Asymptomatic, HIV-positive, non-breastfeeding women with pre-ART CD4+ T-cell counts ≥ 400 cells/mm3 started on ART during pregnancy were randomized up to 42 days after delivery to continue or discontinue ART. Lopinavir/ritonavir plus tenofovir/emtricitabine was the preferred ART regimen. The sample size was selected to provide 88% power to detect a 50% reduction from an annualized primary event rate of 2.07%. A post-hoc analysis evaluated HIV/AIDS-related and World Health Organization (WHO) Stage 2 and 3 events. All analyses were intent to treat. 1652 women from 52 sites in Argentina, Botswana, Brazil, China, Haiti, Peru, Thailand and the US were enrolled (1/2010-11/2014). Median age was 28 years and major racial categories were Black African (28%), Asian (25%) White (15%). Median entry CD4 count was 696...
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Cytomegalovirus (CMV) urinary shedding in HIV-infected pregnant women was evaluated to determine whether it poses an increased risk for congenital CMV infection (cCMV). A subset of mother-infant pairs enrolled in the perinatal NICHD HPTN... more
Cytomegalovirus (CMV) urinary shedding in HIV-infected pregnant women was evaluated to determine whether it poses an increased risk for congenital CMV infection (cCMV). A subset of mother-infant pairs enrolled in the perinatal NICHD HPTN 040 study (distinguished by no antiretroviral use before labor) was evaluated. Maternal and infant urines were tested by qualitative real-time polymerase chain reaction (RT-PCR) for CMV DNA with quantitative RT-PCR performed on positive specimens. Urine specimens were available for 260 women, 85.4% from the Americas and 14.6% from South Africa. Twenty-four women (9.2%) had detectable CMV viruria by qualitative PCR. Maternal CMV viruria was not associated with mean CD4 cell counts or HIV viral load but was associated with younger maternal age (p=0.02). Overall, ten of 260 infants (3.8%) had cCMV. Women with detectable peripartum CMV viruria were more likely to have infants with cCMV than those without: 20.8% (5/24) versus 2.1% (5/236), (p=0.0001). Wo...
Research Interests: Adolescent, Medicine, Biological Sciences, Pregnancy, Humans, and 15 moreFemale, Cytomegalovirus, Prevalence, Adult, Odds ratio, Oxford university, Cytomegalovirus Infections, Predictive value of tests, Clinical Infectious Diseases, Confidence Interval, CMV and HIV, real time polymerase chain reaction, Human Cytomegalovirus, Medical and Health Sciences, and HIV infections
HIV and malaria geographically overlap. HIV protease inhibitors kill malaria parasites in vitro and in vivo, but further evaluation in clinical studies is needed. Thirty-one children from Malawi aged 4-62 months were followed every 3... more
HIV and malaria geographically overlap. HIV protease inhibitors kill malaria parasites in vitro and in vivo, but further evaluation in clinical studies is needed. Thirty-one children from Malawi aged 4-62 months were followed every 3 months and at intercurrent illness visits for ≤47 months (September 2009-December 2011). We compared malaria parasite carriage by blood smear microscopy (BS) and confirmed clinical malaria incidence (CCM, or positive BS with malaria symptoms) in children initiated on HIV antiretroviral therapy (ART) with zidovudine, lamivudine, and either nevirapine (NVP), a non-nucleoside reverse transcriptase inhibitor, or lopinavir-ritonavir (LPV-rtv), a protease inhibitor. We found an association between increased time to recurrent positive BS, but not CCM, when anti-malarial treatment and LPV-rtv based ART were used concurrently and when accounting for a LPV-rtv and antimalarial treatment interaction (adjusted HR 0.39; 95% CI (0.17,0.89); p = 0.03). LPV-rtv in comb...
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Antiretroviral therapy (ART) guidelines for HIV-1-infected children specify both absolute CD4 cell count and CD4 percentage thresholds at which consideration should be given to initiating ART. This leads to clinical dilemma when one... more
Antiretroviral therapy (ART) guidelines for HIV-1-infected children specify both absolute CD4 cell count and CD4 percentage thresholds at which consideration should be given to initiating ART. This leads to clinical dilemma when one marker is below the threshold, whereas the other is above. Data were obtained on a large group of children followed longitudinally in trials and cohort studies in Europe and the USA. Follow-up was censored 6 months after the start of any antiretroviral drug other than zidovudine monotherapy. Discordance between CD4 cell count and percentage was defined in relation to ART initiation thresholds in World Health Organization (WHO) and European paediatric treatment guidelines. The relative prognostic value of CD4 cell count and percentage for progression to AIDS/death was investigated using time-updated Cox proportional hazards models, stratified by age. Among 3345 children, with a total of 21,815 pairs of CD4 measurements analysed, 980 developed AIDS and/or ...
Research Interests: Medicine, HIV, Biological Sciences, Antiretroviral Therapy, Humans, and 15 moreChild, Europe, United States, Female, Male, Infant, AIDS, Longitudinal Studies, Highly Active Antiretroviral Therapy, Prognosis, Disease Progression, Child preschool, Psychology and Cognitive Sciences, Medical and Health Sciences, and HIV infections
The optimal neonatal antiretroviral (ARV) regimen for prevention of HIV mother-to-child transmission (MTCT) is unknown for infants born to mothers who receive no ARVs during pregnancy. As part of a protocol comparing the efficacy of 3... more
The optimal neonatal antiretroviral (ARV) regimen for prevention of HIV mother-to-child transmission (MTCT) is unknown for infants born to mothers who receive no ARVs during pregnancy. As part of a protocol comparing the efficacy of 3 neonatal ARV regimens in preventing HIV-1 MTCT in neonates born to mothers who receive no prenatal treatment with ARVs, we devised a 3-dose nevirapine (NVP) regimen with the goal of maintaining the NVP plasma concentration &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;100 ng/mL (10 times the in vitro median inhibitory concentration of 10 ng/mL) during the first 2 weeks of life. NVP concentrations were measured in 14 newborns participating in a pharmacokinetics substudy during the second week of life and in single samples from 30 more newborns on day 10 to 14. The median NVP elimination half-life was 30.2 hours (range: 17.8 to 50.3 hours). The NVP concentration remained greater than the target of 100 ng/mL in all samples collected through day 10 of life. By day 14, more than half of the newborns in the pharmacokinetic substudy had NVP levels &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;100 ng/mL, although only 1 neonate had no detectable NVP. Although this regimen failed to meet our 100-ng/mL target, it did maintain detectable NVP concentrations in nearly all newborns through the end of the second week of life and is to be used in the parent efficacy protocol.
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Lifelong antiretroviral therapy (ART) provision to all pregnant HIV-positive women ("Option B+") has been recommended by the World Health Organization since 2013, but there remain limited data on the effects of Option B+ on long-term... more
Lifelong antiretroviral therapy (ART) provision to all pregnant HIV-positive women ("Option B+") has been recommended by the World Health Organization since 2013, but there remain limited data on the effects of Option B+ on long-term HIV-free survival in breastfeeding HIV-exposed infants. The Kigali Antiretroviral and Breastfeeding Assessment for the Elimination of HIV (Kabeho) study enrolled HIV-positive women from the third trimester of pregnancy to 2 weeks postpartum in 14 heath facilities implementing Option B+ in Kigali, Rwanda. Mother-child pairs in the longitudinal observational cohort were followed until 24 months postpartum, with HIV diagnostic testing at 6 weeks, and 9, 18 and 24 months. The Kaplan-Meier method was used to estimate HIV transmission, survival, and HIV-free survival through 24 months. We enrolled 608 HIV-positive women in 2013-2014; birth outcome data were available for 600 women and 597 live-born infants. By 6 weeks, 11 infants had died and 3 infants had confirmed HIV infection (0.5% transmission; 95% confidence interval [CI] 0.2-1.6). At 9 months, there were 9 additional deaths and 2 new infections (cumulative transmission 0.9%, 95% CI 0.4-2.2). At 18 months, there were 6 additional deaths and no new infant infections. At 24 months, there were no additional child deaths and 1 new infection (cumulative 2.2%, 95% CI 0.7-7.0), for an overall 24-month HIV-free survival of 93.2% (95% CI 89.5-95.6). Low transmission rates and high HIV-free survival at 24 months were achieved in breastfeeding infants of HIV-positive mothers receiving universal ART in urban health facilities in Rwanda, though vigilance on maintaining viral suppression for ART-experienced women is needed. Abbreviations: ART = antiretroviral therapy, DBS = dried blood spot, eMTCT = Elimination of Mother-to-Child Transmission, Kabeho = The Kigali Antiretroviral and Breastfeeding Assessment for the Elimination of HIV Study, MTCT = mother-to-child transmission, PCR = polymerase chain reaction, PMTCT = prevention of mother-to-child transmission, VL = viral load, WHO = World Health Organization.
Globally, 150,000 new paediatric human immunodeficiency virus type 1 (HIV-1) infections occurred in 2015. There remain complex challenges to the global elimination of paediatric HIV-1 infection. Thus, for the global community to achieve... more
Globally, 150,000 new paediatric human immunodeficiency virus type 1 (HIV-1) infections occurred in 2015. There remain complex challenges to the global elimination of paediatric HIV-1 infection. Thus, for the global community to achieve elimination of new paediatric HIV-1 infections, innovative approaches need to be explored. Immune-based approaches to prevention of mother-to-child transmission (MTCT) may help fill some of the remaining gaps and provide new opportunities to achieve an AIDS-free generation. Immune-based interventions to prevent MTCT of HIV-1 may include paediatric HIV vaccines and passive immunization approaches. Recent discoveries providing evidence of robust immune responses to HIV in infants open new and exciting prospects for paediatric HIV vaccines. Moreover, successful vaccination of infants has a different set of requirements than vaccination of adults and may be easier to achieve. Proof-of-concept has been established over the last two decades that passively administered HIV-1 Env-specific monoclonal antibody (mAbs) can prevent chimeric simian human immunodeficiency virus (SHIV) transmission to newborn nonhuman primates. There has been tremendous progress in isolating and characterizing broadly neutralizing antibodies to HIV, and clinical testing of these antibodies for treatment and prevention in both infants and adults is a major effort in the field. Immune-based interventions need to be actively explored as they can provide critically important tools to address persistent challenges in MTCT prevention. It is a pivotal time for the field with active discussions on the best strategy to further reduce HIV infection of infants and accomplish the World Health Organization Fast-Track 2030 goals to eliminate new paediatric HIV infections.
Background. The presence of antiretroviral drug-associated resistance mutations (DRMs) may be particularly problematic in human immunodeficiency virus (HIV)-infected pregnant women as it can lead to mother-to-child transmission (MTCT) of... more
Background. The presence of antiretroviral drug-associated resistance mutations (DRMs) may be particularly problematic in human immunodeficiency virus (HIV)-infected pregnant women as it can lead to mother-to-child transmission (MTCT) of resistant HIV strains. This study evaluated the prevalence and the effect of antiretroviral DRMs in previously untreated mother-infant pairs. Methods. A case-control design of 1:4 (1 transmitter to 4 nontransmitters) was utilized to evaluate DRMs as a predictor of HIV MTCT in specimens obtained from mother-infant pairs. ViroSeq HIV-1 genotyping was performed on mother-infant specimens to assess for clinically relevant DRMs. Results. One hundred forty infants acquired HIV infection; of these, 123 mother-infant pairs (88%) had specimens successfully amplified using ViroSeq and assessed for drug resistance genotyping. Additionally, 483 of 560 (86%) women who did not transmit HIV to infants also had samples evaluated for DRMs. Sixty-three of 606 (10%) women had clinically relevant DRMs; 12 (2%) had DRMs against >1 drug class. Among 123 HIV-infected infants, 13 (11%) had clinically relevant DRMs, with 3 (2%) harboring DRMs against >1 drug class. In univariate and multivariate analyses, DRMs in mothers were not associated with increased HIV MTCT (adjusted odds ratio, 0.8 [95% confidence interval, .4-1.5]). Presence of DRMs in transmitting mothers was strongly associated with DRM presence in their infants (P < .001). Conclusions. Preexisting DRMs were common in untreated HIV-infected pregnant women, but did not increase the risk of HIV MTCT. However, if women with DRMs are not virologically suppressed, they may transmit resistant mutations, thus complicating infant management.