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Haematological safety of perinatal zidovudine in pregnant HIV-1-infected women in Thailand: secondary analysis of a randomized trial.

Briand N, Lallemant M, Jourdain G, Techapalokul S, Tunthanathip P, Suphanich S, Chanpoo T, Traisathit P, McIntosh K, Le Coeur S - PLoS Clin Trials (2007)

Bottom Line: Between 26 and 35 wk, haemoglobin, leucocytes, and absolute neutrophil counts decreased in zidovudine-exposed compared to unexposed women (mean difference [95% CI] -0.4 [-0.5 to -0.3], -423 [-703 to -142], -485 [-757 to -213], respectively).At delivery, the differences were not statistically significant, except for mean haemoglobin level, which remained slightly lower in the long zidovudine treatment group (difference: 0.2 g/dl).This result provides reassurance about the safety of early initiation of zidovudine prophylaxis during pregnancy to maximize prevention of perinatal HIV.

View Article: PubMed Central - PubMed

Affiliation: Institut National d'Etudes Démographiques, Paris, France. nelly.briand@ined.fr

ABSTRACT

Objectives: To respond to the primary safety objective of the Perinatal HIV Prevention Trial 1 (PHPT-1) by studying the evolution of haematological parameters according to zidovudine exposure duration in HIV-1-infected pregnant women.

Design: Multicenter, randomized, double-blind, controlled trial of different durations of zidovudine prophylaxis.

Setting: 27 hospitals in Thailand.

Participants: 1,436 HIV-infected pregnant women in PHPT-1.

Intervention: Zidovudine prophylaxis initiation at 28 or 35 wk gestation.

Outcome measures: Haemoglobin level, leucocytes, total lymphocyte counts, and absolute neutrophil counts were measured at 26, 32, and 35 wk and at delivery. The evolution of haematological parameters was estimated between 26 and 35 wk (zidovudine/placebo) and between 35 wk and delivery to compare a long versus short zidovudine exposure. For each parameter, linear mixed models were adjusted on baseline sociodemographic variables, HIV clinical stage, CD4 count, and viral load.

Results: Between 26 and 35 wk, haemoglobin, leucocytes, and absolute neutrophil counts decreased in zidovudine-exposed compared to unexposed women (mean difference [95% CI] -0.4 [-0.5 to -0.3], -423 [-703 to -142], -485 [-757 to -213], respectively). However, between 35 wk and delivery, the haematological parameters increased faster in women exposed to long rather than short durations of zidovudine (0.1 [0.0 to 0.1]; 105 [18 to 191]; 147 [59 to 234], respectively). At delivery, the differences were not statistically significant, except for mean haemoglobin level, which remained slightly lower in the long zidovudine treatment group (difference: 0.2 g/dl). Zidovudine had no negative impact on the absolute lymphocyte counts.

Conclusion: Zidovudine initiated at 28 wk gestation rather than 35 wk had a transient negative impact on the evolution of haematological parameters, which was largely reversed by delivery despite continuation of zidovudine. This result provides reassurance about the safety of early initiation of zidovudine prophylaxis during pregnancy to maximize prevention of perinatal HIV.

No MeSH data available.


Related in: MedlinePlus

Haematological Parameters between 26 Weeks' Gestation and Delivery in HIV-Infected Women According to Zidovudine ExposureMeasurements occurred at the same visit in the two groups. All values are expressed as means and 95% CIs. Comparison of long (zidovudine exposure from 28 wk of gestation) versus short (zidovudine exposure from 35 wk of gestation) regimens was done by Student's t-test. Broken line, short arm; solid line, long arm. *p < 0.05, **p < 0.01, ***p < 0.001.(A) Haemoglobin level.(B) Leucocyte counts.(C) Absolute neutrophil counts.(D) Absolute lymphocyte counts.
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pctr-0020011-g002: Haematological Parameters between 26 Weeks' Gestation and Delivery in HIV-Infected Women According to Zidovudine ExposureMeasurements occurred at the same visit in the two groups. All values are expressed as means and 95% CIs. Comparison of long (zidovudine exposure from 28 wk of gestation) versus short (zidovudine exposure from 35 wk of gestation) regimens was done by Student's t-test. Broken line, short arm; solid line, long arm. *p < 0.05, **p < 0.01, ***p < 0.001.(A) Haemoglobin level.(B) Leucocyte counts.(C) Absolute neutrophil counts.(D) Absolute lymphocyte counts.

Mentions: The observed evolutions of the mean haemoglobin, leucocyte, absolute neutrophil count, and absolute lymphocyte count, between 26 wk of gestation and delivery, are presented in Figure 2 by randomization arms. The mean haemoglobin level increased steadily between 26 wk and delivery in women randomized to the short regimen (Figure 2A). In women randomized to the long regimen, haemoglobin decreased slightly from 26 to 32 wk, and then increased until delivery. The mean haemoglobin levels, similar at pre-entry in both groups, were significantly lower in women randomized to the long regimen at 32 and 35 wk gestation and, to a lesser extent, at delivery. The mean leucocyte (Figure 2B) and neutrophil (Figure 2C) counts decreased slightly until 35 wk and then increased sharply until delivery, with a more rapid decrease and subsequent increase in women randomized to the long regimen. The mean counts were significantly lower at 32 and 35 wk gestation in women randomized to the long regimen, but did not differ between the two groups at delivery. The lymphocyte counts (Figure 2D) remained stable until 35 wk of gestation and then increased until delivery, with no difference between the two groups.


Haematological safety of perinatal zidovudine in pregnant HIV-1-infected women in Thailand: secondary analysis of a randomized trial.

Briand N, Lallemant M, Jourdain G, Techapalokul S, Tunthanathip P, Suphanich S, Chanpoo T, Traisathit P, McIntosh K, Le Coeur S - PLoS Clin Trials (2007)

Haematological Parameters between 26 Weeks' Gestation and Delivery in HIV-Infected Women According to Zidovudine ExposureMeasurements occurred at the same visit in the two groups. All values are expressed as means and 95% CIs. Comparison of long (zidovudine exposure from 28 wk of gestation) versus short (zidovudine exposure from 35 wk of gestation) regimens was done by Student's t-test. Broken line, short arm; solid line, long arm. *p < 0.05, **p < 0.01, ***p < 0.001.(A) Haemoglobin level.(B) Leucocyte counts.(C) Absolute neutrophil counts.(D) Absolute lymphocyte counts.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC1863515&req=5

pctr-0020011-g002: Haematological Parameters between 26 Weeks' Gestation and Delivery in HIV-Infected Women According to Zidovudine ExposureMeasurements occurred at the same visit in the two groups. All values are expressed as means and 95% CIs. Comparison of long (zidovudine exposure from 28 wk of gestation) versus short (zidovudine exposure from 35 wk of gestation) regimens was done by Student's t-test. Broken line, short arm; solid line, long arm. *p < 0.05, **p < 0.01, ***p < 0.001.(A) Haemoglobin level.(B) Leucocyte counts.(C) Absolute neutrophil counts.(D) Absolute lymphocyte counts.
Mentions: The observed evolutions of the mean haemoglobin, leucocyte, absolute neutrophil count, and absolute lymphocyte count, between 26 wk of gestation and delivery, are presented in Figure 2 by randomization arms. The mean haemoglobin level increased steadily between 26 wk and delivery in women randomized to the short regimen (Figure 2A). In women randomized to the long regimen, haemoglobin decreased slightly from 26 to 32 wk, and then increased until delivery. The mean haemoglobin levels, similar at pre-entry in both groups, were significantly lower in women randomized to the long regimen at 32 and 35 wk gestation and, to a lesser extent, at delivery. The mean leucocyte (Figure 2B) and neutrophil (Figure 2C) counts decreased slightly until 35 wk and then increased sharply until delivery, with a more rapid decrease and subsequent increase in women randomized to the long regimen. The mean counts were significantly lower at 32 and 35 wk gestation in women randomized to the long regimen, but did not differ between the two groups at delivery. The lymphocyte counts (Figure 2D) remained stable until 35 wk of gestation and then increased until delivery, with no difference between the two groups.

Bottom Line: Between 26 and 35 wk, haemoglobin, leucocytes, and absolute neutrophil counts decreased in zidovudine-exposed compared to unexposed women (mean difference [95% CI] -0.4 [-0.5 to -0.3], -423 [-703 to -142], -485 [-757 to -213], respectively).At delivery, the differences were not statistically significant, except for mean haemoglobin level, which remained slightly lower in the long zidovudine treatment group (difference: 0.2 g/dl).This result provides reassurance about the safety of early initiation of zidovudine prophylaxis during pregnancy to maximize prevention of perinatal HIV.

View Article: PubMed Central - PubMed

Affiliation: Institut National d'Etudes Démographiques, Paris, France. nelly.briand@ined.fr

ABSTRACT

Objectives: To respond to the primary safety objective of the Perinatal HIV Prevention Trial 1 (PHPT-1) by studying the evolution of haematological parameters according to zidovudine exposure duration in HIV-1-infected pregnant women.

Design: Multicenter, randomized, double-blind, controlled trial of different durations of zidovudine prophylaxis.

Setting: 27 hospitals in Thailand.

Participants: 1,436 HIV-infected pregnant women in PHPT-1.

Intervention: Zidovudine prophylaxis initiation at 28 or 35 wk gestation.

Outcome measures: Haemoglobin level, leucocytes, total lymphocyte counts, and absolute neutrophil counts were measured at 26, 32, and 35 wk and at delivery. The evolution of haematological parameters was estimated between 26 and 35 wk (zidovudine/placebo) and between 35 wk and delivery to compare a long versus short zidovudine exposure. For each parameter, linear mixed models were adjusted on baseline sociodemographic variables, HIV clinical stage, CD4 count, and viral load.

Results: Between 26 and 35 wk, haemoglobin, leucocytes, and absolute neutrophil counts decreased in zidovudine-exposed compared to unexposed women (mean difference [95% CI] -0.4 [-0.5 to -0.3], -423 [-703 to -142], -485 [-757 to -213], respectively). However, between 35 wk and delivery, the haematological parameters increased faster in women exposed to long rather than short durations of zidovudine (0.1 [0.0 to 0.1]; 105 [18 to 191]; 147 [59 to 234], respectively). At delivery, the differences were not statistically significant, except for mean haemoglobin level, which remained slightly lower in the long zidovudine treatment group (difference: 0.2 g/dl). Zidovudine had no negative impact on the absolute lymphocyte counts.

Conclusion: Zidovudine initiated at 28 wk gestation rather than 35 wk had a transient negative impact on the evolution of haematological parameters, which was largely reversed by delivery despite continuation of zidovudine. This result provides reassurance about the safety of early initiation of zidovudine prophylaxis during pregnancy to maximize prevention of perinatal HIV.

No MeSH data available.


Related in: MedlinePlus