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.
Highlights
In 1994, the PACTG 076-ANRS 024 trial showed the dramatic efficacy of zidovudine for the prevention of mother-to-child transmission of HIV: the rate of HIV transmission was reduced from 22.6% to 7.6% [1]
In the entire study population, at pre-entry visit planned at 26 wk of gestation, the median haemoglobin level was 10.7 (10.0 to 11.4) g/dl, the leucocyte count was 8,670 (7,200 to 10,300) cells/mm3, the absolute neutrophil count was 6,002 (4,896 to 7,300) cells/mm3, and the absolute lymphocyte count was 1,919 (1,476 to 2,425) cells/mm3
Between the pre-entry and 35-wk visits, we found that, after adjustment on variables at baseline, zidovudine intake still had a negative impact on the evolution of haemoglobin level, leucocyte counts, and absolute neutrophil counts, as shown by the mean (95% confidence interval [CI]) decrease associated with exposure to zidovudine, À0.4 (À0.5 to À0.3) g/dl/wk, p, 0.001; À423 (À703 to À142) cells/mm3/wk, p 1⁄4 0.003; À485 (À757 to À213) cells/mm3/wk, p, 0.001, respectively (Table 3)
Summary
In 1994, the PACTG 076-ANRS 024 trial showed the dramatic efficacy of zidovudine for the prevention of mother-to-child transmission of HIV: the rate of HIV transmission was reduced from 22.6% to 7.6% [1]. The impact of zidovudine exposure during pregnancy on haematological parameters of HIV-infected women has been assessed in several placebocontrolled studies. While one study showed a lower mean haematocrit at delivery in women exposed to zidovudine [4], other studies failed to demonstrate any effect of zidovudine exposure on haematological parameters [1,5]. A number of trials have looked at whether standard-course and short-course zidovudine are equivalent at reducing the risk of passing on HIV from mother to baby. The Perinatal HIV Prevention Trial-1 (PHPT-1) found that the short treatment course was substantially less effective at preventing HIV from being passed on from mother to baby. The researchers who had carried out the PHPT-1 trial wanted to do a subsequent analysis of data from that trial to find out whether there were any differences in these safety outcomes between standard and short course zidovudine
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