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Discontinuation of ART Postpartum: No Evidence for Altered Viral Set Point [Letters to the Editor]
  JAIDS Journal of Acquired Immune Deficiency Syndromes: Volume 44(1) 1 January 2007 pp 116-117
Tungsiripat, Marisa MD*; Drechsler, Henning MD; Aberg, Judith A MD
*Department of Infectious Diseases Cleveland Clinic Foundation Cleveland, OH Division of Infectious Diseases University Hospital Basel Basel, Switzerland Division of Infectious Diseases New York University New York, NY
To the Editor:
The safety of discontinuation of potent antiretroviral therapy (ART) in the setting of structured treatment interruptions has recently been questioned.1-3 During pregnancy, HIV-infected women commonly initiate ART but also subsequently frequently discontinue it in the postpartum period. Although prior studies report that pregnancy itself does not lead to accelerated HIV progression or death,4-6 HIV-1 RNA levels have been described to increase in the postpartum period from delivery to 12 weeks postpartum in HIV-infected women who discontinued ART at delivery, as expected, but also in those who received nucleoside monotherapy, combination nucleoside therapy, and no ART.7 These findings of increasing viral load postpartum were consistent with prior results from smaller studies conducted during the era of zidovudine (ZDV) monotherapy.8-10 Also, one of these studies found that in women who stopped ZDV at delivery, HIV-1 RNA values increased to levels higher than before ZDV was started during pregnancy.9
Considering these prior reports of increases in HIV viral load postpartum independent of ART, women who choose to discontinue ART at delivery may be at risk for additional increases in HIV-1 RNA postpartum. Thus, in light of recent data questioning the safety of treatment interruptions,1-3 we aimed to evaluate changes in HIV-1 RNA levels before and after pregnancy in women who discontinued ART in the postpartum period.
This retrospective study was performed at the Washington University (WU) outpatient HIV clinic. The Institutional Review Board for WU approved the protocol, and all aspects of the study were conducted in compliance with the Human Studies Committee. To identify pregnancies in HIV-infected women under care during the 4-year period from September 1999 to September 2003, medical records were reviewed for positive urine chorionic gonadotropin (UCG) and -human chorionic gonadotropin (HCG) values. All available inpatient and outpatient records were reviewed from the time of HIV diagnosis until up to 96 weeks postpartum.
Data collected included (1) patient demographics, (2) surrogate markers of HIV disease (HIV-1 RNA levels and CD4+ cell counts before, during, and after pregnancy), (3) specifics regarding ART (type, duration, timing, and toxicities), and (4) pregnancy characteristics (delivery method and outcomes). The first available values for HIV RNA levels and CD4+ cell counts during the defined time intervals before, during, and after pregnancy were used for statistical comparison.
For statistical comparisons, we used the Wilcoxon signed rank test and applied the Bonferroni correction for multiple comparisons. The data set was analyzed using Microsoft Excel (Seattle, WA) and the SPSS software package (version 11.5 for Windows; SPSS/Systat, Chicago, IL). P values of <0.05 were considered significant.

A total of 155 pregnancies were identified in 114 women. The outcomes of the 155 pregnancies were as follows: 16 miscarriages, 14 abortions, 10 lost to follow-up, and 115 completed pregnancies. Of the 115 completed pregnancies, ART was discontinued at delivery in 60 pregnancies. We focused on values from these 60 pregnancies to evaluate the effect of ART discontinuation at delivery.
The median age of the women was 24 years. Seventy-seven percent (88 of 114 women) were African American, and 23% were white. Median (interquartile range [IQR]) baseline values before pregnancy) were 3.66 (IQR: 2.6-4.34) log10 copies/mL for HIV-1 RNA level and 550 (IQR: 326-749) cells/μL for CD4+ lymphocyte count.
Antiretroviral Therapy
Of the 115 women with completed pregnancies, 114 (99%) received ART. Of these, 103 (90%) women were treated with nonnucleoside reverse transcriptase inhibitor (NNRTI)- or protease inhibitor (PI)-based regimens, 9 (8%) were treated with nucleoside reverse transcriptase inhibitor (NRTI) combination regimens, and 2 (2%) were treated with ZDV monotherapy. ART was started before pregnancy in 12 (10%) of the women. In the remaining 102 (90%) women, ART was started at a median time point of 22 gestational weeks and was taken for a median of 16 weeks during pregnancy. Five women (4%) changed ART because of toxicity during pregnancy, most from nevirapine to a PI or fixed-dose combination of ZDV, lamivudine, and abacavir.
Table 1 outlines HIV-1 RNA levels and CD4+ cell counts before pregnancy, during pregnancy, at delivery, and postpartum in the women who discontinued ART at delivery. In women with prepregnancy and pre-ART data available, median HIV-1 RNA levels postpartum were 3.65 (IQR: 2.91-4.18) log10 copies/mL at 12 to 96 weeks compared with 3.63 (IQR: 2.81-4.01) log10 copies/mL prepartum. This was not significantly different. The median postpartum CD4+ count (643 cells/μL, IQR: 428-844 cells/μL) did not differ significantly from the baseline value before pregnancy (550 cells/μL, IQR: 326-749 cells/μL).
Fifty-one percent of women had an undetectable viral load (<400 copies/mL) at the time of delivery, and the viral load was <1000 copies/mL at delivery in 77% of women. Vertical transmission occurred in 4 of 116 children.
For postpartum women on ART, decreased adherence11 and changes in ART pharmacokinetics may account for some of the previously observed increased HIV viral loads in the women continuing ART after delivery.7 Because increases in HIV viral load have also been observed in women on no ART in prior studies,7 suggesting the contribution of pregnancy-related factors, we aimed to compare postpartum viral loads with prepregnancy values in the era of highly active antiretroviral therapy (HAART) in women who chose to discontinue ART after delivery.
When the HIV-1 RNA values in these women 12 to 36 weeks postpartum were compared with prepregnancy values, no significant differences were seen. The viral load returned to the prepregnancy set point by this time and showed no apparent tendency to increase thereafter. The number of patients was too small to draw conclusions in extended postpartum periods of >36 weeks, however. Limitations of our study include its sample size, its retrospective nature, and the relatively short follow-up time.
During the 4-year period of our study, 41 of the 114 women had more than 1 pregnancy. The risks of treating HIV-infected women without an indication for ART other than to reduce the risk of vertical transmission episodically for multiple pregnancies are unknown. Of the 41 women who had more than 1 pregnancy during the period of our study, 2 developed new K103N mutations between pregnancies documented by genotype when the women presented for medical care with the second pregnancy. Both had been treated with nevirapine-based regimens and had achieved undetectable viral loads at delivery of the first pregnancy. Both women had continued the nevirapine-based ART after delivery.
Clinical implications of an increased viral load set point in the postpartum period would include the potential for accelerated HIV progression, increased risk of development of viral resistance, and potential for increased transmissibility. Our results did not suggest that such a change occurred. The decision on how to manage ART postpartum in women who did not meet treatment criteria before pregnancy remains difficult.
Marisa Tungsiripat, MD*
Henning Drechsler, MD
Judith A. Aberg, MD
*Department of Infectious Diseases Cleveland Clinic Foundation Cleveland, OH Division of Infectious Diseases University Hospital Basel Basel, Switzerland Division of Infectious Diseases New York University New York, NY
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