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Avy Violari, Jane C Lindsey,
Michael D Hughes,
Hilda A Mujuru,
Linda Barlow-Mosha,
Portia Kamthunzi,
Benjamin H Chi,
Mark F Cotton,
Harry Moultrie,
Sandhya Khadse,
Werner Schimana,
Raziya Bobat,
Lynette Purdue,
Susan H Eshleman,
Elaine J Abrams,
Linda Millar,
Elizabeth Petzold,
Lynne M Mofenson,
Patrick Jean-Philippe,
Paul Palumbo
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ABSTRACT: Nevirapine-based antiretroviral therapy is the predominant (and often the only) regimen available for children in resource-limited settings. Nevirapine resistance after exposure to the drug for prevention of maternal-to-child human immunodeficiency virus (HIV) transmission is common, a problem that has led to the recommendation of ritonavir-boosted lopinavir in such settings. Regardless of whether there has been prior exposure to nevirapine, the performance of nevirapine versus ritonavir-boosted lopinavir in young children has not been rigorously established.
In a randomized trial conducted in six African countries and India, we compared the initiation of HIV treatment with zidovudine, lamivudine, and either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 2 to 36 months of age who had no prior exposure to nevirapine. The primary end point was virologic failure or discontinuation of treatment by study week 24.
A total of 288 children were enrolled; the median percentage of CD4+ T cells was 15%, and the median plasma HIV type 1 (HIV-1) RNA level was 5.7 log(10) copies per milliliter. The percentage of children who reached the primary end point was significantly higher in the nevirapine group than in the ritonavir-boosted lopinavir group (40.8% vs. 19.3%; P<0.001). Among the nevirapine-treated children with virologic failure for whom data on resistance were available, more than half (19 of 32) had resistance at the time of virologic failure. In addition, the time to a protocol-defined toxicity end point was shorter in the nevirapine group (P=0.04), as was the time to death (P=0.06).
Outcomes were superior with ritonavir-boosted lopinavir among young children with no prior exposure to nevirapine. Factors that may have contributed to the suboptimal results with nevirapine include elevated viral load at baseline, selection for nevirapine resistance, background regimen of nucleoside reverse-transcriptase inhibitors, and the standard ramp-up dosing strategy. The results of this trial present policymakers with difficult choices. (Funded by the National Institute of Allergy and Infectious Diseases and others; P1060 ClinicalTrials.gov number, NCT00307151.).
New England Journal of Medicine 06/2012; 366(25):2380-9. · 53.30 Impact Factor
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ABSTRACT: Cluster heat maps were used to investigate relationships between body composition, lipid levels, and glucose metabolism in HIV-infected and HIV-uninfected children and young adults using data from a cross-sectional study. Three distinct clusters of participants were identified. One group had lower body fat and higher lipid measures and was mostly HIV infected. The other 2 groups were a mix of HIV-infected and HIV-uninfected participants. Of these, 1 cluster had more participants with higher body fat and insulin resistance, which are risk factors for future cardiovascular disease, and the other had relatively normal measurements on all outcomes.
JAIDS Journal of Acquired Immune Deficiency Syndromes 11/2011; 59(3):325-8. · 4.43 Impact Factor
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ABSTRACT: To compare post-operative motor function in dogs that received epidural morphine and low dose bupivacaine versus epidural morphine alone following splenectomy.
Prospective, randomized study.
16 client owned dogs undergoing routine splenectomy.
Following splenectomy dogs were randomly allocated into one of two groups. The morphine group (MOR) was administered epidural morphine (0.1 mg kg(-1)); the morphine-bupivacaine group (MORB) received epidural morphine (0.1 mg kg(-1)) and low dose bupivacaine [0.25 mg kg(-1), (0.167%)]. The adjusted final volume was 0.15 mL kg(-1) in both groups. Motor function and pain assessment were performed at pre-determined times using a simple numerical motor score and the University of Melbourne Pain Scale (UMPS) respectively. An arterial blood gas was performed 2 hours following epidural administration to check for respiratory compromise. If patients scored >7 on the UMPS or were deemed painful by the observer they were administered hydromorphone intravenously and dose and time of rescue analgesia were recorded.
There were no statistically significant differences in motor scores, pain scores, amount of rescue analgesia administered or PaCO2 between treatment groups. No dogs demonstrated respiratory depression or profound motor dysfunction at any time point during the study. 9/16 (56%) dogs did not require rescue analgesia during the first 18 hours following splenectomy.
The combination of low dose bupivacaine (0.25 mg kg(-1)) and morphine (0.1 mg kg(-1)) when administered epidurally has little effect on post-operative motor function. This combination can be used without concern of motor paralysis in healthy animals.
Veterinary Anaesthesia and Analgesia 05/2011; 38(3):213-23. · 0.94 Impact Factor
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Paul Palumbo, Jane C Lindsey,
Michael D Hughes,
Mark F Cotton,
Raziya Bobat,
Tammy Meyers,
Mutsawashe Bwakura-Dangarembizi,
Benjamin H Chi,
Philippa Musoke,
Portia Kamthunzi,
Werner Schimana,
Lynette Purdue,
Susan H Eshleman,
Elaine J Abrams,
Linda Millar,
Elizabeth Petzold,
Lynne M Mofenson,
Patrick Jean-Philippe,
Avy Violari
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ABSTRACT: Single-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown.
We conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age, in six African countries, who qualified for treatment according to World Health Organization (WHO) criteria. Results are reported for the cohort that included children exposed to single-dose nevirapine prophylaxis. The primary end point was virologic failure or discontinuation of treatment by study week 24. Enrollment in this cohort was terminated early on the recommendation of the data and safety monitoring board.
A total of 164 children were enrolled. The median percentage of CD4+ lymphocytes was 19%; a total of 56% of the children had WHO stage 3 or 4 disease. More children in the nevirapine group than in the ritonavir-boosted lopinavir group reached a primary end point (39.6% vs. 21.7%; weighted difference, 18.6 percentage-points; 95% confidence interval, 3.7 to 33.6; nominal P=0.02). Baseline resistance to nevirapine was detected in 18 of 148 children (12%) and was predictive of treatment failure. No significant between-group differences were seen in the rate of adverse events.
Among children with prior exposure to single-dose nevirapine for perinatal prevention of HIV transmission, antiretroviral treatment consisting of zidovudine and lamivudine plus ritonavir-boosted lopinavir resulted in better outcomes than did treatment with zidovudine and lamivudine plus nevirapine. Since nevirapine is used for both treatment and perinatal prevention of HIV infection in resource-limited settings, alternative strategies for the prevention of HIV transmission from mother to child, as well as for the treatment of HIV infection, are urgently required. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00307151.).
New England Journal of Medicine 10/2010; 363(16):1510-20. · 53.30 Impact Factor
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ABSTRACT: To characterize total body bone mineral content (BMC) and total body and spinal bone mineral density (BMD) in perinatally HIV-infected and uninfected children/youth across puberty.
HIV-infected (7-24 years) were randomly selected from six strata based on Tanner stage/protease inhibitor use. HIV-uninfected were frequency-matched by Tanner group and sociodemographic background to the HIV-infected.
Dual-energy X-ray absorptiometry (DXA) measured BMC and BMD. Linear regression models tested differences in bone outcomes by HIV and the interaction of HIV by Tanner group (1-2, 3-4, 5). Models were performed separately by sex and adjusted for DXA scanner, race/ethnicity, height, age and lean body mass.
HIV-infected (N = 236) and uninfected (N = 143) were comparable on sex and race/ethnicity. HIV-infected were slightly older (median 12.6 versus 11.9 years). In adjusted models, HIV-infected males had significantly lower total body BMC and total body and spinal BMD at Tanner 5, lower BMC at Tanner 3-4 and similar BMC and BMD at Tanner 1-2, compared to HIV-uninfected males. HIV-infected and uninfected girls did not differ significantly on any bone outcome, but there was a marginally significant interaction of HIV and Tanner group for spinal BMD. Kaletra/ritonavir was associated with lower BMC and total body BMD and nevirapine was associated with higher spinal BMD in a model with all HIV-infected.
Perinatally HIV-infected males showed more evidence of lower bone density especially in the final stage of pubertal development than HIV-infected girls and they may be at increased risk for bone disease during adulthood.
AIDS (London, England) 02/2010; 24(5):687-96. · 4.91 Impact Factor
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ABSTRACT: This study investigated the distribution of demographic characteristics, the prevalence of discrimination based on sexuality, gender, and race, and relationships with psychological distress among 178 working-class sexual minorities (i.e., who identified as lesbian, gay, or bisexual (LGB) or had ever engaged in same-sex sexual behaviors) recruited to the United for Health Study (2003-2004). The results indicated considerable heterogeneity in responses to items assessing sexual orientation and sexual behavior, with a majority of sexual minority participants not identifying as LGB (74.2%). The authors found significant demographic differences in LGB identification by gender, race/ethnicity, nativity, and socioeconomic factors. In addition, LGB participants had higher levels of psychological distress than non-LGB-identified sexual minorities. Linear regression analyses revealed that reports of racial/ethnic discrimination and sexuality discrimination were associated with higher levels of psychological distress among sexual minority participants. The results underscore the need to collect multiple measures of sexuality in conducting research on racially diverse working-class communities; to consider demographic factors in collecting sexuality data; and to disaggregate information on sexuality by LGB identification. Findings also highlight the importance of addressing discrimination in ameliorating problematic mental health outcomes among working-class sexual minorities.
International Journal of Health Services 01/2010; 40(4):589-608. · 1.21 Impact Factor
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AIDS patient care and STDs 10/2009; 23(10):799-801. · 2.68 Impact Factor
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ABSTRACT: To compare the distribution of lipid and glucose abnormalities and altered fat distribution among vertically HIV-infected patients and controls.
Cross-sectional multicenter study on HIV-infected (HIV-positive) patients, 7-24 years of age, stratified by Tanner stage and protease inhibitor use (protease inhibitor, n = 161 and non- protease inhibitor, n = 79) and seronegative controls (HIV-negative, n = 146).
Measurements included fasting lipids, glucose, insulin, 2-h oral glucose tolerance test, dual-energy X-ray absorptiometry, anthropometry, and antiretroviral therapy and medical histories. Multiple linear regression models were used to compare distributions between HIV-positive and HIV-negative groups.
Both HIV-positive groups had long exposures to antiretroviral therapy. Protease inhibitor and nonprotease inhibitor groups had similar current CD4 cell count and HIV-1 RNA, but the protease inhibitor group had lower nadir CD4 cell count, higher peak HIV-1 RNA, and more advanced Centers for Disease Control disease stage. In adjusted analyses, both HIV-positive groups had significantly lower mean Z scores for height, weight, BMI, and total and limb fat than the HIV-negative group. Mean triglycerides were significantly higher and high-density lipoprotein cholesterol lower in both HIV-positive groups relative to the HIV-negative group. The protease inhibitor group also had significantly higher mean total, low-density lipoprotein, and non-high density lipoprotein cholesterol. Mean fasting insulin was higher in both HIV-positive groups, and 2-h glucose and insulin were higher in the protease inhibitor group. Ritonavir was associated with increasing dyslipidemia and altered glucose metabolism.
In a large group of vertically HIV-infected children and youth with extensive antiretroviral therapy exposure, height, weight, and total and limb fat were lower than in controls. There was a high prevalence of lipid abnormalities among those on protease inhibitors and evidence of developing insulin resistance, factors that may accelerate lifetime risk for cardiovascular disease.
AIDS (London, England) 04/2009; 23(6):661-72. · 4.91 Impact Factor
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ABSTRACT: Treatment failure and drug resistance create obstacles to long-term management of HIV-1 infection. Nearly 60% of infected persons fail their first highly active antiretroviral therapy (HAART) regimen, partially because of nonadherence, requiring a switch to a second regimen to prevent drug resistance. Among HIV-infected youth, a group with rising infection rates, treatment switch is often delayed; virologic and immunologic consequences of this delay are unknown. We conducted a retrospective, longitudinal study of drug resistance outcomes of initial HAART in U.S. youth enrolled between 1999-2001 in a multicenter, observational study and experiencing delayed switch in their first nonsuppressive treatment regimen for up to 3 years. HIV-1 genotyping was performed on plasma samples collected longitudinally, and changes in drug resistance mutations, CD4+ T cell numbers and viral replication capacity were assessed. Forty-four percent (n = 18) of youth in the parent study experiencing virologic nonsuppression were maintained on their initial HAART regimen for a median of 144 weeks. Drug resistance was detected in 61% (11/18) of subjects during the study. Subjects on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens developed more (8/10) drug resistance mutations than those on protease-inhibitor (PI) regimens (2/7) (p = 0.058). Subjects developing NNRTI-resistance (NNRTI-R), showed a trend toward lower CD4+ T cell gains (median: -6 cells/mm(3) per year) than those without detectable NNRTI-R (median: +149 cells/mm(3) per year) (p = 0.16). HIV-1-infected youth maintained on initial nonsuppressive NNRTI-based HAART regimens are more likely to develop drug-resistant viremia than with PI-based HAART. This finding may have implications for initial treatment regimens and transmission risk in HIV-infected youth, a group with rising infection rates.
AIDS patient care and STDs 06/2008; 22(7):545-52. · 2.68 Impact Factor
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Patricia M Flynn,
John Rodman, Jane C Lindsey,
Brian Robbins,
Edmund Capparelli,
Katherine M Knapp,
Jose F Rodriguez,
James McNamara,
Leslie Serchuck,
Barbara Heckman,
Jaime Martinez
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ABSTRACT: Zidovudine (ZDV) and lamivudine (3TC) metabolism to triphosphates (TP) is necessary for antiviral activity. The aims of this study were to compare ZDV-TP and 3TC-TP concentrations in adolescents receiving twice daily (BID) and once daily (QD) regimens and to determine the metabolite concentrations of ZDV and 3TC during chronic therapy on a QD regimen. Human immunodeficiency virus-infected patients (12 to 24 years) taking ZDV (600 mg/day) and 3TC (300 mg/day) as part of a highly active antiretroviral therapy regimen received QD and BID regimens of ZDV and 3TC for 7 to 14 days in a crossover design. Serial blood samples were obtained over 24 h on the QD regimen. Intracellular mono-, di-, and triphosphates for ZDV and 3TC were measured. The median ratio of BID/QD for ZDV-TP predose concentrations was 1.28 (95% confidence interval [CI] = 1.00 to 2.45) and for 3TC-TP was 1.12 (95% CI = 0.81 to 1.96). The typical population estimated half-lives (+/- the standard error of the mean) were 9.1 +/- 0.859 h for ZDV-TP and 17.7 +/- 2.8 h for 3TC-TP. Most patients had detectable levels of the TP of ZDV (24 of 27) and 3TC (24 of 25) 24 h after dosing, and half-lives on a QD regimen were similar to previously reported values when the drugs were given BID. Lower, but not significantly different, concentrations of ZDV-TP were demonstrated in the QD regimen compared to the BID regimen (P = 0.056). Although findings were similar between the BID and QD groups, the lower concentrations of ZDV and the number of patients below the level of detection after 24 h suggests that ZDV should continue to be administered BID.
Antimicrobial Agents and Chemotherapy 11/2007; 51(10):3516-22. · 4.84 Impact Factor
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Patricia M Flynn,
Bret J Rudy, Jane C Lindsey,
Steven D Douglas,
Janet Lathey,
Stephen A Spector,
Jaime Martinez,
Margarita Silio,
Marvin Belzer,
Lawrence Friedman,
Lawrence D'Angelo,
Elizabeth Smith,
Janice Hodge,
Michael D Hughes
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ABSTRACT: The PACTG 381 cohort included 120 adolescents infected via high-risk behaviors and treated with at least two NRTIs plus either a protease inhibitor or an efavirenz-containing HAART regimen. After 24 weeks of therapy, only 69 of 118 (59%) evaluable subjects had undetectable viral loads. We now present findings of the study after 3 years of follow-up. Virologic, immunologic, and treatment information were collected from subjects every 12 weeks beyond the first 24 weeks of therapy through 156 weeks. Of the 120 subjects starting HAART, 44 (37%) stayed on study treatment for the 3 years of observation. Twenty-nine (24%) subjects reached and maintained undetectable viral loads. Poorer adherence (p = 0.016), higher baseline viral load (p = 0.010), and CD8 naive counts (p = 0.034) predicted virologic failure. Immunologic measurements improved from entry to the end of follow-up in the subjects with undetectable viral loads. CD4 counts at the end of study were not significantly different from HIV-uninfected youth, but CD4%, CD8 counts and percent, and CD8 activation markers remained significantly different. Adolescents infected with HIV via high-risk behaviors have less than optimal responses to HAART therapy with only 24% achieving and maintaining undetectable viral loads over 3 years. Immunologic improvement was demonstrated and CD4 counts in subjects with virologic control reached levels in HIV-uninfected adolescents. Interventions, especially those focused on adherence, are necessary to improve HAART outcomes in adolescents.
AIDS Research and Human Retroviruses 11/2007; 23(10):1208-14. · 2.25 Impact Factor
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ABSTRACT: The purpose of this work was to examine the effects of HIV infection and the impact of highly active antiretroviral treatment with protease inhibitors on neurodevelopmental functioning during the first 3 years of life.
Pediatric AIDS Clinical Trials Group 219/219C is a longitudinal cohort study that has enrolled HIV-infected (HIV+) and HIV-exposed but uninfected (HIV-) infants and children since 1993. Longitudinal profiles of neurodevelopmental functioning as measured by the Bayley Scales of Infant Development were compared by HIV-infection status before and after the availability of highly active antiretroviral therapy with a protease inhibitor and within infants with Bayley tests available before and after initiating protease inhibitor therapy.
In the pre-protease inhibitor era, mean mental and motor scores in HIV+ (n = 54) infants <1 year of age were significantly lower than those among HIV- infants (n = 221) and remained lower up to 2 years of age. After protease inhibitors became available, mean mental and motor functioning of HIV+ infants (n = 91) <1 year of age were still significantly lower than those of HIV- infants (n = 838). However, against a background of declining scores among the HIV- infants, there was evidence of limited improvement in the HIV+ infants relative to their uninfected peers. Among infants who had Bayley II evaluations before and after starting a protease inhibitor, there was a trend to improved mental and motor scores after initiation of protease inhibitor therapy.
The suppression of systemic viral replication and subsequent substantial improvements in survival and immunologic status brought about by highly active antiretroviral therapy have been followed by limited improvements in neurodevelopmental functioning in young children. Additional longitudinal research is needed to better understand the role of antiretroviral therapy as well as the impact of genetic and environmental factors on neurodevelopmental functioning in children affected by HIV.
PEDIATRICS 04/2007; 119(3):e681-93. · 4.47 Impact Factor
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ABSTRACT: The responses to HAART in HIV-infected adolescents infected through risk behaviors are not well defined. PACTG 381 collected intensive immunologic and virologic data on youth naive to or with minimal exposure to antiretroviral therapy who began HAART. Subjects were evaluated according to their weeks 16-24 virologic response. Comparisons with a cohort of HIV-uninfected adolescents from the REACH cohort were performed. Cox proportional hazards models were used to identify baseline and week 24 predictors of virologic failure. Only 69 of 120 subjects (58%) achieved virologic suppression by weeks 16-24, whereas 55 of 69 (80%) demonstrated control to week 60. Higher CD4+ naive T cells (CD4+/62L+/RA+: hazard ratio [HR], 2.13; p = 0.018), higher CD8+ activated T cells (CD8+/CD38+/DR+: HR, 1.40, p = 0.028 per 100 cells/mm3) and higher CD8+ naive T cells (CD8+/62L+/RA+: HR, 1.72; p = 0.005) at weeks 16-24 in subjects with early viral success were predictive of subsequent failure. By week 60, total CD4+ T cells remained significantly lower than in uninfected controls. Adolescents beginning HAART achieve moderate rates of viral suppression by weeks 16-24. In those who do achieve early virologic control, suppression to week 60 is high although total CD4+ T cells remain significantly lower than in uninfected controls. Several T cell markers were predictive of subsequent virologic failure in subjects achieving short-term success. Further study is warranted to determine whether these predictors provide any benefit to clinical management.
AIDS Research and Human Retroviruses 04/2006; 22(3):213-21. · 2.25 Impact Factor
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ABSTRACT: To investigate the prescription of analgesic drugs to hospitalized critically ill dogs and cats and determine compliance of nursing staff in administering the prescribed analgesics.
Cross-sectional study.
272 dogs and 79 cats hospitalized in an intensive care unit during a 2-month period.
Patient treatment orders were examined daily for details regarding prescribed and administered analgesic drugs.
A mean of 39% of cats and dogs in the intensive care unit were prescribed analgesic drugs each day, the most common of which were opioids. Local anesthetic drugs, nonsteroidal anti-inflammatory drugs, and ketamine were prescribed less frequently. Cats were less likely than dogs to receive analgesics after traumatic injury, but the difference was not significant. There was no difference between species in frequency of prescription of analgesic drugs after surgery. Most patients were prescribed a single class of analgesic drug; only 13% had orders for multiple analgesics. Of the patients for which analgesics were prescribed, 64% received them exactly as prescribed, 23% had at least 1 reduction in dosing, and 13% had at least 1 increase in dosing. When a decrease in dosing occurred, the drugs were opioids in each instance, whereas when drug dosing was increased, the drugs were of various types.
Discrepancies sometimes existed between the dose of analgesic prescribed and that administered. This appeared to occur primarily because of concerns about adverse effects of opioid drugs. Strategies to reduce these effects may improve pain management in critically ill dogs and cats.
Journal of the American Veterinary Medical Association 09/2005; 227(3):425-9. · 1.79 Impact Factor
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Susan Schuval, Jane C Lindsey,
Jack T Stapleton,
Russell B Van Dyke,
Paul Palumbo,
Lynne M Mofenson,
James M Oleske,
Joseph Cervia,
Andrea Kovacs,
Wayne N Dankner, [......],
Gregory Ciupak,
Nancy Webb,
Michelle Eagle,
Dorothy Smith,
Roslyn Hennessey,
Melissa Goodman-Kerkau,
Donna Klinzman,
Georg Hess,
Dietmar Zdunek,
Myron J Levin
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ABSTRACT: GB virus C (GBV-C) infection occurs in 20-40% of human immunodeficiency virus (HIV)-infected adults, and coinfection is associated with improved HIV disease outcome.
To determine the prevalence of GBV-C infection in children who were perinatally infected with HIV, we conducted a cross-sectional prevalence survey in a cohort of perinatally infected HIV-positive children selected from a large, multicenter observational protocol. A blood specimen was obtained and tested for GBV-C viremia with the use of a qualitative GBV-C RNA assay and screened for past GBV-C infection with enzyme-linked immunosorbent assay to detect antibodies to the GBV-C envelope protein E2 (E2 Ab).
The 354 children who participated in the substudy were relatively healthy, with a median CD4 of 784 cells/mm and median HIV-1 viral load of 1055 copies/mL. The prevalence of GBV-C viremia was 20 of 353 or 5.7% (95% confidence interval, 3.5-8.6%), and the prevalence of E2 Ab was 12 of 354 or 3.4% (95% confidence interval, 1.8-5.8%). GBV-C viremic patients were older than patients without past GBV-C infection (median age, 12.8 years versus 10.7 years). Median CD4 lymphocyte counts were highest in subjects without GBV-C infection and lowest in those with E2 Ab.
GBV-C prevalence rates are lower in children with perinatal HIV infection than those reported for HIV-infected adults. With the exception of evidence that GBV-C viremic children had lower rates of Centers for Disease Control and Prevention HIV disease category C disease before GBV-C testing, we did not find evidence of improved HIV disease outcome in coinfected patients, but the number of HIV/GBV-C-coinfected children was small.
The Pediatric Infectious Disease Journal 06/2005; 24(5):417-22. · 3.58 Impact Factor
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ABSTRACT: Weight and height growth of HIV-infected children tends to lag behind that of uninfected children of similar age. Previous reports of the effect of highly active antiretroviral therapy (HAART) on the growth of HIV-infected children have been contradictory.
Age- and gender-adjusted height and weight z scores were studied for 192 HIV-infected children, 4 months to 17 years of age, who had been treated with antiretroviral therapy for at least 16 weeks. These children, in clinically and immunologically stable condition, were enrolled into one of 4 HAART regimens and evaluated for 96 weeks.
At baseline, these HIV-infected children were significantly shorter than uninfected children (mean z score, -0.57; 95% confidence interval, -0.73 to -0.41; P < 0.001). Children with greater viral loads at baseline were significantly shorter and lighter than children with smaller viral loads (both P < 0.001). Administration of HAART led to an increase in mean weight z scores to normal values (mean z score increase, from -0.16 to >0) by week 48 and an increase in mean height z scores of 72% toward normal values (mean z score increase, from -0.57 to -0.16) by week 96. Younger children gained height more rapidly (P < 0.001), and children with greater baseline viral loads gained weight more rapidly (P < 0.001). There was no evidence of differential height or weight changes in 48 weeks between children with different degrees of virologic control.
HAART improved the average weight gain of HIV-infected children from subnormal to normal after 1 year and improved average height growth to nearly normal after 2 years.
The Pediatric Infectious Disease Journal 04/2005; 24(4):352-7. · 3.58 Impact Factor
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Susan Schuval,
Russell B Van Dyke, Jane C Lindsey,
Paul Palumbo,
Lynne M Mofenson,
James M Oleske,
Joseph Cervia,
Andrea Kovacs,
Wayne N Dankner,
Elizabeth Smith,
Barbara Nowak,
Gregory Ciupak,
Nancy Webb,
Michelle Eagle,
Dorothy Smith,
Roslyn Hennessey,
Melissa Goodman-Kerkau,
Myron J Levin
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ABSTRACT: To evaluate the prevalence of hepatitis C virus (HCV) infection in children with perinatal human immunodeficiency virus (HIV) infection.
Cross-sectional substudy.
Multicenter study from 41 sites in the United States.
Children with perinatal HIV infection were randomly selected from a large, long-term, follow-up protocol.
Hepatitis C infection was defined as having positive test results on both HCV antibody and HCV RNA assays.
Five hundred thirty children enrolled in the substudy; definitive HCV test results were available for 525 children. Eighty-three percent were of a minority race or ethnicity. They were equally distributed by sex, had a median age of 10.7 years, and were relatively healthy, with 75% having CD4+ lymphocyte counts greater than 500 cells/mm3. Eight of 525 children (1.5%; 95% confidence interval [CI], 0.7%-3.0%) infected with HIV were coinfected with HCV. In contrast, the rate of HCV infection in a serosurvey of more than 2700 children aged 6 to 11 years from the National Health and Nutrition Examination Survey was 0.2% (95% CI, 0.04%-0.6%). In our study, there were no differences between children coinfected with HIV and HCV and those without HCV infection in terms of demographic characteristics, CD4+ or CD8+ T-lymphocyte counts, HIV 1 RNA levels, preterm or mode of delivery, or liver disease; however, the number of children coinfected with HIV and HCV was small.
While HCV prevalence infection rates are low in children with perinatal HIV infection, they are 8 to 10 times higher than reported in HCV serosurveys of children in the United States.
Archives of Pediatrics and Adolescent Medicine 11/2004; 158(10):1007-13. · 4.14 Impact Factor
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Patricia M Flynn,
Bret J Rudy,
Steven D Douglas,
Janet Lathey,
Stephen A Spector,
Jaime Martinez,
Margarita Silio,
Marvin Belzer,
Lawrence Friedman,
Lawrence D'Angelo,
James McNamara,
Janice Hodge,
Michael D Hughes, Jane C Lindsey
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ABSTRACT: Adolescents represent the fastest growing demographic group of new human immunodeficiency virus (HIV) infections in the United States. At present, there is little information available about their response to therapy.
We studied 120 adolescents infected via high-risk behaviors who began receiving highly active antiretroviral therapy (HAART), to determine their virologic and immunologic response to therapy.
Subjects were enrolled at 28 sites of the Pediatric Acquired Immunodeficiency Syndrome Clinical Trials Group. After 16-24 weeks of HAART, 59% of subjects had reproducible undetectable virus loads, according to repeat measurements (virologic success). As enumerated by flow-cytometric analysis, increases in levels of CD4 helper cells (both naive and memory) and decreases in levels of CD8 suppressor cells were observed. Partial restoration of some immunologic parameters for patients who did not achieve virologic success was also observed, but to a more limited extent than for adolescents with virologic success. Adherence to HAART was the only predictor of achieving undetectable virus loads.
Adolescents have the capacity to improve their immunologic status with HAART. Lower than expected success in virologic control is related to lack of adherence, and efforts to improve treatment outcome must stress measures to assure adherence to medication.
The Journal of Infectious Diseases 08/2004; 190(2):271-9. · 6.41 Impact Factor
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ABSTRACT: To examine whether greater severity of HIV infection is associated with delayed initiation of pubertal development among perinatally HIV-infected children, and to compare sexual maturation of perinatally HIV-infected children with children in the general US population using the National Health and Nutrition Examination Survey III.
In a prospective cohort study, the authors studied 983 HIV-infected children aged 6 to 18 years, who had Tanner stage assessed on at least two occasions between 1995 and 2000. Analyses were conducted separately for girls and boys to identify factors associated with onset of puberty or adrenarche (progression beyond Tanner stage 1).
Among children who were in Tanner stage 1 at their first assessment, 185 of 413 (45%) girls and 144 of 434 (33%) boys entered puberty during the observation period. In multivariate longitudinal regression analyses adjusted for age, race/ethnicity, time interval between study visits, and other clinical factors, girls with severe immunosuppression (CD4% <15) were significantly less likely to enter adrenarche (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.29-0.83) and puberty (OR, 0.57; 95% CI, 0.33-0.96) compared with girls who were not immunosuppressed (CD4% > or =25). For boys, those with severe immunosuppression were significantly less likely to enter adrenarche (OR, 0.52; 95% CI, 0.28-0.96) and tended to be less likely to begin puberty (OR, 0.69; 95% CI, 0.39-1.22) compared with boys who were not immunosuppressed. Qualitative comparisons suggested that HIV-infected children may experience delayed puberty and adrenarche compared with similarly aged children in the general US population.
Immunosuppression was associated with delayed pubertal onset in perinatally HIV-infected children. Further studies of perinatally HIV-infected and uninfected children are needed to better quantify the delay in pubertal onset and to compare the pace of pubertal maturation.
JAIDS Journal of Acquired Immune Deficiency Syndromes 06/2003; 33(1):56-65. · 4.43 Impact Factor
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ABSTRACT: Human immunodeficiency virus (HIV)-infected children often suffer from impaired growth. Highly active antiretroviral therapy (HAART) successfully reduces HIV 1 (HIV-1) RNA to 400 copies/mL or less in many children.
To determine if age- and sex-adjusted growth z scores correlate with HIV-1 RNA level and if control of viral load for 48 and 96 weeks results in improved growth in children receiving highly active antiretroviral therapy.
Secondary analysis of the cohort of children receiving ritonavir nested in a randomized, open-label, clinical trial.
The Pediatric AIDS Clinical Trials Group Protocol 338 enrolled clinically stable, antiretroviral therapy-experienced, HIV-infected subjects aged 2 through 17 years. Using data from subjects randomized to ritonavir-containing regimens (n = 197), the association of growth z scores and HIV-1 RNA levels were examined.
Age- and sex-adjusted weight and height z scores.
Enrollment weights were comparable with age- and sex-adjusted norms, but subjects receiving ritonavir-containing antiretroviral therapy were significantly shorter (mean z score, -0.57 [29th percentile]; 95% confidence interval, -0.73 to -0.40). Higher HIV-1 RNA levels correlated with lower growth z scores (P<.01). Subjects achieving and maintaining HIV-1 RNA of 400 copies/mL or less through 48 and 96 weeks experienced worse growth than subjects with a less controlled viral load.
In this pediatric cohort, a significant decline in height and weight z scores was found despite control of viral replication. Further studies of growth are necessary to assess if nutritional and hormonal adjuvants to highly active antiretroviral therapy should be considered to improve growth in HIV-infected children.
Archives of Pediatrics and Adolescent Medicine 05/2002; 156(5):497-503. · 4.14 Impact Factor
