Baby Clenched Fists 3 Months High Lactic Acid
Pediatrics. Author manuscript; available in PMC 2008 Jan 30.
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PMCID: PMC2121306
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Serum lactate levels in infants exposed peripartum to antiretroviral agents to prevent mother-to-child manual of HIV: Agence Nationale de Recherches Sur le SIDA et les Hépatites Virales 1209 study, Abidjan, Republic of cote d'ivoire
Didier Koumavi Ekouevi
1Epidémiologie, santé publique et développement INSERM : U593, IFR99, Université Victor Segalen - Bordeaux II, ISPED, 146, Rue Leo Saignat 33076 BORDEAUX CEDEX,FR
twoANRS 1201/1202, Ditrame Plus, Plan PAC-CI ANRS, CHU Treichville, Abidjan,CI
Ramata Touré
3CEDRES, Middle de Diagnostic et de Recherches sur le SIDA CHU de Treichville, Abidjan,CI
Renaud Becquet
1Epidémiologie, santé publique et développement INSERM : U593, IFR99, Université Victor Segalen - Bordeaux II, ISPED, 146, Rue Leo Saignat 33076 BORDEAUX CEDEX,FR
Ida Viho
2ANRS 1201/1202, Ditrame Plus, Plan PAC-CI ANRS, CHU Treichville, Abidjan,CI
Charlotte Sakarovitch
aneEpidémiologie, santé publique et développement INSERM : U593, IFR99, Université Victor Segalen - Bordeaux II, ISPED, 146, Rue Leo Saignat 33076 BORDEAUX CEDEX,FR
François Rouet
iiiCEDRES, Centre de Diagnostic et de Recherches sur le SIDA CHU de Treichville, Abidjan,CI
Besigin Towne-Gold
2ANRS 1201/1202, Ditrame Plus, Program PAC-CI ANRS, CHU Treichville, Abidjan,CI
Patricia Fassinou
4Service de pédiatrie CHU Yopougon, Abidjan,CI
Valériane Leroy
iEpidémiologie, santé publique et développement INSERM : U593, IFR99, Université Victor Segalen - Bordeaux 2, ISPED, 146, Rue Leo Saignat 33076 BORDEAUX CEDEX,FR
Stéphane Blanche
vService d'immunologie, hématologie et rhumatologie pédiatriques AP-HP, Hôpital Necker - Enfants Malades, Université Paris Descartes - Paris 5, FR
François Dabis
1Epidémiologie, santé publique et développement INSERM : U593, IFR99, Université Victor Segalen - Bordeaux II, ISPED, 146, Rue Leo Saignat 33076 BORDEAUX CEDEX,FR
Ditrame Plus Study Group Anrs 1201/1202
threeCEDRES, Middle de Diagnostic et de Recherches sur le SIDA CHU de Treichville, Abidjan,CI
Abstruse
Background
Mitochondrial toxicity was described in infants exposed to long-term antiretroviral regimens (ARVs) containing nucleoside analogues for the prevention of mother-to-child manual of HIV (PMTCT). We measured the serum lactate levels in children born to HIV-ane infected (HIV+) African women receiving short-term ARV PMTCT regimens.
Methods
A prospective study was conducted in women-child pairs from the third trimester of pregnancy to three months of life. The exposed group was formed by children exposed in utero to nucleoside counterpart ARVs, zidovudine (ZDV) or ZDV + lamivudine (3TC) from 32–36 weeks of amenorrhea until delivery. All these women received nevirapine unmarried-dose (NVPsd) at the beginning of labor. The children received ZDV during the kickoff 7 days of life and a NVPsd at day iii. The control group was formed by infants born to HIV+ women who had received NVPsd only and not exposed to nucleoside analogue ARVs. Serum lactate levels were measured at iv, 6 and 12 weeks of life by Cobas Integra 400™.
Results
A total of 836 blood samples from 338 infants were nerveless (262 exposed and 76 controls). Median lactacidemia was 1.8 mmol/l, Interquartile Range [1.ii–2.seven mmol/l]). Overall serum lactate levels ≥2.5 mmol/fifty, defining hyperlactatemia were observed in 39 of the 292 infants who had at to the lowest degree two serum lactate measurements, xiii.iv%, 95% conviction Interval [ix.6–17.8%]. The 3-month period prevalence of hyperlactatemia did non differ between the exposed group (13.1%) and the control group (14.3%) (p=0.84). All serum lactate levels returned to normal values in all subsequent samples No case of symptomatic hyperlactatemia was detected during the study menstruation.
Conclusion
Increased lactate levels were identified equally in infants whose mother received a short-term of nucleoside analogues or NVPsd for PMTCT. Although not rare, hyperlactatemia was not related to short-term exposure to nucleoside analogue ARVs
Keywords: hyperlactatemia, HIV infection, children, HIV infection, mitochondrial injury, vertical transmission, Africa
Keywords: Developed, Anti-Retroviral Agents, agin furnishings, pharmacokinetics, therapeutic use, Disease Transmission, Vertical, prevention & command, Female, HIV Infections, prevention & control, HIV-one, Humans, Infant, Babe, Newborn, Lactic Acid, blood, Maternal-Fetal Exchange, Mitochondria, drug furnishings, pathology, Pregnancy, Pregnancy Trimester, Tertiary, Prospective Studies
Introduction
A possible mitochondrial toxicity has been hypothesized in infants exposed to long-term regimens of antiretrovirals (ARVs) used for the prevention of mother-to-kid manual of HIV (PMTCT), post-obit a case study of symptomatic astringent lactic acidosis (1). Later on, children with neurological symptoms and biochemical and histological signs of mitochondrial dysfunction were described within the French Perinatal Report (2, 3). In a systematic screening of neurological symptoms presented by uninfected children of this big cohort, the eighteen-calendar month incidence of this miracle was estimated at 0.3% in children exposed perinatally to nucleoside analogues (iii). Later several cohorts reported that a significant number of exposed just asymptomatic children had increased lactate levels within the 6-week postnatal phase of the ARVs prophylaxis exposure (4–half dozen) and sometimes persisting several weeks or months after. This biological aberration was a probable upshot of an acute asymptomatic mitochondrial toxicity (iii). In ane of these studies, hyperlactatemia was defined by a lactate value ≥v/mmol/l and was observed in 26% of the infants (4). The serum lactate measurement was considered there as a surrogate marker of mitochondrial dysfunction and could thus be used to investigate mitochondrial toxicity in adults and infants (4, vii). Yet, the high potential of artefactual values of lactate level is well known for this laboratory measurement (8). Recently Noguera et al (6) confirmed these observational data with a control group and acceptable biological internal controls, thus strengthening the hypothesis that zidovudine (ZDV) exposed children had a pregnant gamble of transient asymptomatic hyperlactatemia. Long term consequences of this mitochondrial injury are non known.
In Africa, where brusk-term regimens of ARVs are oftentimes used for PMTCT since 2000 (9, 10), there has not yet been any written report to explore this possible mitochondrial toxicity. We hypothesized that the screening of elevated lactate levels could help to early place the infants presenting possible mitochondrial dysfunction. The objective of our study was to judge the frequency of high lactate levels in infants born to HIV-1 infected women and exposed during pregnancy to short-term of ZDV or brusk-term of ZDV + lamivudine (3TC) used for PMTCT in comparison to infants exposed to nevirapine single-dose (NVPsd) only. We investigated also the gamble factors associated to high lactate levels, including the maternal ARV regimen.
Methods
Pattern
The ANRS 1209 study was a prospective observational accomplice fix up in neonates born to HIV-1 infected women within the ANRS 1201/1202 Ditrame Plus project which evaluated the safe and field effectiveness in reducing female parent-to-kid transmission of HIV with brusk-term combinations of ZDV+NVPsd and of ZDV+3TC+NVPsd (11) followed by alternatives to prolonged breastfeeding in Abidjan, Côte d'Ivoire (12).
Ethical permissions
The ANRS 1201/1202 Ditrame Plus project was granted ethical permission in Côte d'Ivoire from the ethical commission of the National AIDS Control Programme, and in France from the institutional review lath of the French Agence Nationale de Recherches sur le Sida (ANRS). As part of the Ditrame Plus projection, the study presented here was included in the institutional review board approval.
Patients
Between May 2002 and February 2005, we enrolled consecutively in this sub-study three groups of infants built-in to HIV-i infected pregnant women (Table 1). Cohort 1 was exposed to maternal short-term ZDV initiated at 36 weeks of amenorrhea. Accomplice 2 was exposed to maternal curt-term ZDV+3TC initiated at 32 weeks of amenorrhea. In these two cohorts, mothers received too NVPsd at the offset of the labour and the newborns ZDV syrup (2mg/kg/6 hours) during their first week of life and NVPsd (2mg/kg) at Twenty-four hours two. The tertiary cohort was used every bit a control group formed between Feb 2004 and February 2005 of infants exposed to a NVPsd PMTCT regimen of known efficacy (xiii) and recommended by the international (fourteen) and national guidelines implemented after the end of the Ditrame Plus cohort.
Tabular array 1
Antiretroviral interventions among HIV-infected mothers and infants for the prevention of mother-to-child transmission of HIV in the ANRS Ditrame Plus cohort in Abidjan, Côte d'Ivoire (2002–2005).
| Regimens | Mother | Infants | ||
|---|---|---|---|---|
| Prepartum (gestational age at the beginning) | Intrapartum | Postpartum | Postnatal | |
| Ditrame Plus 1.0 (Cohort 1, exposed) | ZDV 300 mg (36 weeks) | ZDV 600 mg + NVP 200 mg | - | ZDV syrup 2mg/kg × 4/day for ane week and NVP syrup 2mg/kg on day ii–3 |
| Ditrame Plus 1.1 (Cohort 2, exposed) | ZDV 300 mg + 3TC 150 mg (32 weeks) | ZDV 600 mg + NVP 200 mg | ZDV 300 mg + 3TC 150 mg (3 days) | ZDV syrup 2mg/kg × 4/day for one calendar week and NVP syrup 2mg/kg on day two–iii |
| National Programme (Accomplice iii, control) | - | NVP 200 mg | - | NVP syrup 2mg/kg on day 2–3 |
Biological Analyses
The lactate levels were determined according to ACTG mitochondrial dysfunction Focus Group Guidelines (fifteen). These guidelines specify in item how the venous lactate specimens must be nerveless for this purpose.
The serum lactate levels were systematically measured in children at 4, half-dozen and 12 weeks of life by Roche Cobas Integra 400™ in Treichville Infirmary University, CeDReS laboratory in Abidjan. All measures were performed on the supernatant after deproteineization with internal quality control as suggested past the manufacturer (Roche Diagnostics, Mannheim, Deutschland). CeDReS also participated in an external quality control program of lactate measurements organized past a Necker Academy Hospital Laboratory (Paris, French republic). The quality control was performed in ASQUALAB "Assurance de qualité des laboratories d'analyses médicales" in Corentin Celton Hospital (Moulineaux, France).
Capillary blood was collected in EDTA microtainer tubes (Becton Dickinson) in newborns at weeks 4 and 6 for the diagnosis of pediatric HIV infection. All samples nerveless at week 4 were systematically processed for a plasma HIV-ane RNA viral load measurement using the bDNA assay or a real time polymerase chain reaction (PCR) with the quantitative Taqman technology (xvi). The same technique was applied to the 6-week sample if the first one tested was positive. Maternal CD4 count was measured using flow cytometry (FASCAN).
Outcomes
We defined hyperlactatemia as at least two consecutives measures of lactate levels higher than ii.5 mmol/L at either four weeks (S4) and 6 weeks (S6) or S6 and calendar month three (M3). Repeated measurements were also realized at iv–vi months in case of diagnosis of hyperlactatemia at an earlier age, for studying farther the kinetics of the lactate levels in this subgroup.
The bachelor infant data included in the analysis of the determinants of hyperlactatemia were gender, HIV infection status, anthropometric data at nascence (weight, length) and compliance to ZDV syrup intake for the post-exposure prophylaxis. Maternal information included the ARV regimen (blazon and term) during pregnancy, intrapartum dose intake, age, clinical phase and CD4 count.
Statistical analysis
The prevalence of hyperlactatemia was estimated with its 95 percent confidence interval (CI). The group comparisons used Student's t-test or the not parametric Mann-Whitney U exam or one-way assay of the variance (ANOVA) for quantitative variables and the Chi-two exam or Fisher'southward verbal test for qualitative variables.
All factors potentially associated with hyperlactatemia were studied in univariate and so multivariate logistic regression. All tests were two-sided and a p-value <0.05 was considered pregnant. All the analyses were performed with STATA™ 8.0 (Stata Corporation, Higher Station, TX, USA).
Results
Clarification of the study sample
Between May 2002 and February 2005, 836 blood samples were collected from 338 infants (140 in cohort ane, 122 in accomplice two and 76 in the command group). Birthday, 23 infants were diagnosed as HIV-infected at iv weeks: six (4.iv%) in the ZDV group, 6 (4.9%) in the ZDV+3TC group and 11 (fourteen.ix%) in the sdNVP group. Among these infants, 159 (47%) initiated breastfeeding and 179 (53%) received formula feeding. Overall, three lactate measurements were performed in median per infant (range: one–5) and the mean lactate level was two.two mmol/L, (standard difference [SD] 1.4 mmol/Fifty). No statistical difference of mean lactate level was observed between the 3 groups (p=0.242) and between the exposed and the controls groups (p=0.530) when adjusting on the timing of the blood samples collected (Table ii).
Tabular array two
Lactate values (mmol/Fifty) co-ordinate to the exposure to antiretroviral prophylaxis and the timing of the blood collection. ANRS 1209 study, Abidjan, Côte d'Ivoire (2002–2005).
| Overall | Command group | Exposedgroup | | |||||
|---|---|---|---|---|---|---|---|---|
| Cohort iii sdNVP | All | Cohort 1 ZDV+ sdNVP | Cohort 2 ZDV+3TC+ sdNVP | p* | p** | p*** | ||
| Lactate values (total) | ||||||||
| Number of samples | 836 | 194 | 642 | 323 | 319 | |||
| Min-Max | 0.2–eleven.seven | 0.6–6.iii | 0.three–11.7 | 0.3–10.5 | 0.2–eleven.7 | |||
| Hateful (SD) mmol/L | 2.2 (1.4) | 2.3 (one.ane) | ii.2 (1.v) | 2.0 (1.ane) | 2.3 (1.6) | 0.009 | 0.530 | 0.242 |
| Lactate values (week-four) | ||||||||
| Age of infants (days) | 29 [28–31] | 31 [29–34] | 28 [28–30] | 29 [28–30] | 28 [28–30] | 0.570 | ||
| Number of samples | 299 | 73 | 226 | 117 | 109 | |||
| Min-Max | 0.2–eleven.7 | 0.9–v.7 | 0.two–11.7 | 0.6–7.5 | 0.2–11.seven | |||
| Mean (SD) mmol/L | ii.2 (i.4) | 2.2 (0.9) | ii.2 (1.5) | two.1 (1.one) | 2.3 (ane.8) | 0.283 | 0.976 | 0.499 |
| Lactate values (week-6) | ||||||||
| Age of infants (days) | 44 [42–46] | 46 [44–50] | 44 [42–46] | 44 [42–46] | 44 [42–46] | |||
| Number of samples | 264 | 65 | 199 | 101 | 98 | |||
| Min-Max | 0.3–10.five | 0.9–v.seven | 0.3–9.9 | 0.6–ten.5 | 0.iii–9.9 | |||
| Hateful (SD) mmol/L | 2.4 (1.5) | ii.3 (1.two) | 2.2 (1.v) | 2.2 (1.v) | two.half dozen (1.9) | 0.149 | 0.638 | 0.273 |
| Lactate values (month-3) | ||||||||
| Age of infants (days) | 92 [ninety–93] | 93 [92–100] | 91 [90–92] | 93 [92–94] | 91 [ninety–92] | |||
| Number of samples | 264 | 65 | 170 | 79 | 91 | |||
| Min-Max | 0.3–8.1 | 0.nine–6.3 | 0.3–viii.1 | 0.3–6.three | 0.4–8.1 | |||
| Hateful (SD) mmol/L | 2.i (1.1) | 2.3 (i.1) | two.0 (1.two) | 1.7 (i.1) | ii.two (one.1) | 0.006 | 0.104 | 0.006 |
Frequency of hyperlactatemia
A total of 292 infants (86%) who had at to the lowest degree two consecutive lactate measurements were available for this estimation, and 39 of them had hyperlactatemia. Thus, the prevalence of hyperlactatemia in this population was 13.iv%, (CI: 9.6–17.eight%). It was 11.half-dozen% (CI: 6.3–19.0%) among 112 infants from cohort 1, 14.v%, (CI: eight.5–22.five%) in 110 infants of cohort 2 and 14.3%, (CI: 7.1%–24.7%) in 70 infants of control group (p=0.79) (Figure 1). The prevalence of hyperlactatemia was xiii.ane% in the overall exposed group and 14.3% in the command grouping (p=0.84). Serious lactate levels (≥ 5 mmol/50) were identified in 34/836 (iv.0%) blood samples collected and 5 children presented confirmed (≥ two samples) astringent hyperlactatemia amongst 292 infants who had ii consecutive measurements. No divergence was observed betwixt the three groups (p=0.574).
Frequency of hyperlactatemia* in infants born to HIV-infected mothers and exposed to antiretovirals during pregnancy. ANRS 1269 report, Abidjan, Côte d'Ivoire (2002–2005)
sdNVP: unmarried-dose of nevirapine
ZDV+sdNVP: zidovudine (ZDV) from 36 weeks of gestation and single-dose of nevirapine
ZDV+3TC+sdNVP: zidovudine (ZDV) + lamivudine (3TC) from 32 weeks of gestation and single-dose of nevirapine
*>=2.five mmol/L on ii consecutives measurements in a series of iii
Factors associated with hyperlactatemia in infants exposed to nucleoside antiretrovirals
In univariate and so multivariate analyses, none of the following variables was found to be significantly associated with hyperlactatemia: child characteristics (gender, HIV status at week 4, twin birth, baby ZDV prophylaxis, birth weight) and maternal characteristics (duration of prepartum prophylaxis with ZDV, CD4, WHO clinical stage and age). No difference of frequency of hyperlactatemia was institute co-ordinate to the infant HIV status at calendar week-four (4.8% in HIV-infected infant versus 14.0% amidst the not HIV-infected, p=0.229).
Evolution of neonatal hyperlactatemia
The kinetics of hyperlactatemia is documented in 28 of 31 infants exposed to ZDV (n=12) or ZDV+3TC (northward=xix) and shows a return to normal values for 25 children (Figure 2). Three infants had persistent hyperlactatemia at month vi and their lactate levels were respectively 3.3 mmol/L (ZDV grouping), iii.6 mmol/50 (ZDV group) and 5.7 mmol/L (ZDV+3TC group) at that time.
Kinetics of development of lactate measurements & in 28 infants born from HIV-infected mothers presenting hyperlactatemia in first three months of life. ANRS 1269 study in the Ditrame Plus cohort in Abidjan, Côte d'Ivoire (2002–2005)
W4 = 4 weeks of life
W8 = half dozen weeks of life
W12=12 weeks of life
W16–W24=between xvi and 24 weeks of life
& Median range and interquartile values of lactate measurements
Clinical manifestations
None of the children who presented a biologically confirmed hyperlactatemia in the commencement iii months of life developed any of the following symptomatic clinical manifestations: intestinal pain, muscular or neurological symptoms, either earlier or after the biological diagnosis was made. There was non record of special clinical manifestation in the iii children with persistent hyperlactatemia. All these infants with abnormal biological values were afterward clinically followed at least until their second birthday and ane male person infant death was reported at calendar week 38, whose presumptive cause was astringent anemia. His serum lactate values were 2.half dozen mmol/L at week-four, 3.3 mmol/L at calendar week-6, i.8 mmol/50 at calendar month 3 and ii.7 mmol at month 6.
Discussion
In adults and children, the ascent of lactate levels may be observed in physiological circumstances such every bit during and immediately after exercise, in hypermetabolic states and in the context of affliction conditions (8). Thus, the diagnosis of nucleoside reverse transcriptase inhibitors related hyperlactatemia requires exclusion of others causes, such as dehydratation, vigorous do, alcohol intoxication, renal failure, hyperthyroidism and exposure to others drugs (17). However, hyperlactatemia is commonly artefactual due to sampling methods: in vivo by the utilise of tourniquets or as a result of fist clenching or hand pumping when venous specimens are drawn and in vitro if adequate plasma collection tubes are not used (xviii, 19).
In order to sympathize the significance of elevated lactate levels in infants exposed to ARVs, our study included also a control group formed by infants born to HIV-infected mothers and exposed to sdNVP, a non nucleoside reverse transcriptase inhibitor.
We have also undertaken internal and external quality controls with an independent laboratory to validate the lactate measurements. Moreover, we defined high lactate levels as 2 consecutives levels >ii.5 mmol/L, thus taking into business relationship just high and sustained lactatemia. Nosotros believe therefore our estimates are minimally biased regarding an artefactual mensurate. In our report, the overall frequency of high lactate levels was estimated at 13% and did not differ according to the type of ARV exposure. No difference was as well found betwixt groups when comparing the mean value of serum lactates of the exposed and command groups.
These results are in relative contradiction with those from a controlled study in Spain, where one-half of exposed children presented hyperlactatemia (6). This discrepancy could be explained by a longer exposure to NRTIs in the Spanish written report, both for prenatal and postnatal periods. In industrialized countries, prophylactic treatment are mostly initiated at the start of the second trimester of pregnancy and continued in the newborn for half-dozen weeks (xx, 21). In addition a high dose of ZDV is given intravenously during labor, while children in our study were exposed in utero to oral ZDV alone in median for four weeks or to ZDV+3TC in median for viii weeks, and the labor dose was only given orally. Every bit expected, we observed that the infants from cohort 2 had higher hateful lactates than infants from cohort 1 or 3. This could be related to either the longer catamenia of exposure or an exposure to 2 analogues nucleosides such as ZDV and 3TC.
It is likewise important to underline that our control group took into account the pregnancy effect as well as the maternal HIV infection status, that was not performed in the Spanish written report (6). We can conclude therefore that, in our study the high lactate levels although not rare, were not related to short-term exposure to the nucleoside analogues.
In that location are potential limitations to our investigation. An enrolment bias could be discussed because we have enrolled the control group in a more limited time menstruation than the other groups. However the bear on of this selection procedure on the lactate measurements should be express every bit all the laboratory assessments were performed by the same laboratory. We were not able to measure out arterial pH to identify lactic acidosis, also as the lactate-pyruvate ratio to explore mitochondrial part, for logistical reasons. However, the strengths of this observational written report remain the large sample size and the utilise of a control group which has taken into account both the HIV infection condition of the mother and the exposure to ARV drugs. Indeed, with 53 infants in each grouping we had a lxxx% statistical power to detect a mean departure between the infants exposed to NRTIs with hateful lactate levels estimated at 2.88 mmol/L and those not exposed to NRTIs with mean lactate levels estimated at one.61/mmol/50 according to the results by Nogurera et al (6).
Our report allows drawing some public health conclusions. It appears clearly that lactate measurement is neither a specific nor a sensitive marker of mitochondrial injury in this context, although 1 cannot dominion out the occurrence of mitochondrial injury in these cohorts (two–3). Based on our findings likewise as the literature from industrialized countries (3), at that place is no statement to justify any routine screening of hyperlactatemia in infants exposed perinatally to ARVs. Long-term follow-upwards including clinical investigations as well every bit more than advanced biological investigations of HIV-infected infants exposed perinatally to ARVs for PMTCT could help to notice all abnormalities which could be drug-related. The creation of an international registry to collect short and long-term ARV toxicity in such infants could assist in the future to certificate the overall affect of all ARV drugs used for PMTCT.
Acknowledgments
The authors wish to admit the back up of the Developing State Unit of measurement of the ANRS, peculiarly Drs Brigitte Bazin, Séverine Blesson and Pr Michel Kazatchkine, Manager of the ANRS. Zidovudine and lamivudine were provided past Glaxo Smith Kline International. Special cheers to Anne Vassaux for the laboratory update and her assistance to conduct external control and to Laurence Becquet for the authoritative management of the study. Finally, nosotros would like to thank the women and children who accepted to participate to the DITRAME PLUS project.
Abbreviations
- ANRS
- Agence Nationale de Recherches sur le Sida et les hépatites virales
- ARV
- antiretroviral therapy
- CI
- Confidence Interval
- HIV
- Human Immunodeficiency Virus
- NRTI
- nucleoside analogue reverse transcriptase inhibitor
- NNRTI
- non-nucleoside analogue reverse transcriptase inhibitor
- SD
- Standard Departure
- sdNVP
- single-dose of nevirapine
- 3TC
- lamivudine
- ZDV (AZT)
- zidovudine
APPENDIX
The ANRS 1209 Ditrame Plus study was coordinated by Didier K. Ekouevi and François Dabis. Ramata Toure and François Rouet were responsible for all laboratory aspects of this report. This study was part of the ANRS 1201/1202 Ditrame Plus project, of which members are listed beneath.
Composition of the ANRS 1201/1202 and 1209 DITRAME PLUS Study Group
Principal Investigators: François Dabis, Valériane Leroy, Marguerite Timite-Konan, Christiane Welffens-Ekra.
Coordination in Abidjan: Laurence Bequet, Didier K. Ekouévi, Besigin Tonwe-Gold, Ida Viho. Methodology, biostatistics and information management: Gérard Allou, Renaud Becquet, Katia Castetbon, Laurence Dequae-Merchadou, Charlotte Sakarovitch, Dominique Touchard.
Clinical team: Clarisse Amani-Bosse, Ignace Ayekoe, Gédéon Bédikou, Nacoumba Coulibaly, Christine Danel, Patricia Fassinou, Apollinaire Horo, Ruffin Likikouët, Hassan Toure.
Laboratory team: André Inwoley, Hervé Menan, François Rouet, Ramata Touré.
Psycho-social team: Hortense Aka-Dago, Alphonse Sihé.
Social sciences squad: Hélène Agbo, Hermann Brou, Annabel Desgrées-du-Loû, Annick Tijou-Traoré, Benjamin Zanou.
Scientific Committee: Stéphane Blanche, Jean-François Delfraissy, Philippe Lepage, Laurent Mandelbrot, Christine Rouzioux, Roger Salamon.
Footnotes
*Run into appendix
This written report was presented, in part, at the second International AIDS Social club Conference on HIV Pathogenesis and Handling, (Paris, French republic), July 2003, abstract N° 664 and at the XV International AIDS conference (Bangkok, Thailand), July 2004 (ThPeC7292).
Sponsorship
The main sponsor was the French Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS), France. Didier 1000. Ekouevi was a fellow of the French Charity Sidaction and is now a boyfriend of the European Clinical Trial Partnership (EDCTP). François Rouet was supported by the French Ministry building of Foreign Affairs. Renaud Becquet was a beau of the French Ministry of Education, Enquiry and Technology and is now a fellow of the French Charity Sidaction. Zidovudine was provided by Glaxo-Smith Kline International.
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2121306/
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