Effects of Treatment Interruption After Pregnancy

Guidelines for treatment of HIV in pregnancy recommend initiation of ARV therapy after the first trimester in all pregnant patients in order to reduce maternal-to-child transmission (MTCT). This therapy is often discontinued after pregnancy if patients do not otherwise meet criteria for therapy. Studies (including SMART and TRIVACAN) have evaluated whether this treatment interruption may lead to harm, however have shown mixed results.
This study sought to evaluate women either on ZDV monotherapy or combination ARV therapy during pregnancy who elect to either continue or stop therapy postpartum by measuring clinical and laboratory outcomes. They looked at women enrolled in the Women and Infants Transmission Study (WITS), which was a multicenter longitudinal cohort study beginning in 1989. Women were recruited from Chicago, Massachusetts, New York City, San Juan, Brooklyn and Houston. They were enrolled either during pregnancy or within 7 days of delivery, and were followed for one year after delivery at two, six and twelve month increments. The 207 women enrolled were either on ZDV monotherapy or combination ARV therapy, and had CD4 counts greater than 350cell/uL. Of these women, 103 were on ZDV monotherapy (41 of whom stopped therapy after delivery, 62 continued) and 100 were on one or more antiretroviral drugs (18 stopped therapy at delivery, 82 continued).
They followed the risk of HIV disease progression by monitoring the slopes of CD4 lymphocyte counts and percentages of HIV RNA levels. Clinical progression was assessed by development of class B or C conditions. Immune activation was measured by measuring CD4 and CD8 counts and lymphocyte activation markers. They also sought to measure laboratory factors associated with cardiovascular events, including HS-CRP, lipid levels, leptin, Lp-PLA2, and IL-6.
They found the change in CD4 and HIV RNA levels did not differ between those stopping or continuing monotherapy or combination regimens. No women developed class C events, however the hazard ratio for developing a class B event was 2.09 for women stopping therapy (1.24 for monotherapy, 2.93 for those stopping combination) compared to those who continued. These class B events included cervical dysplasia/CIS, recurrent pneumonia, vaginal yeast infection >28 days, oropharnygeal candidiasis, other infections. They found CD8+CD38+ T cell and CD8+DR+ cell percentages were higher in women stopping therapy. For the markers of cardiovascular events, all values were similar except Lp-PLA2 levels were higher in the women continuing therapy.
They concluded that the overall data suggested no significant change in CD4 counts or RNA levels. They also concluded that the number of class B events were so low in both groups (16 events) that it was hard to conclude stopping therapy lead to an increased risk. They did find increased CD8+ activation in women stopping therapy, which may indicate faster disease progression, however longer follow-up would be needed to assess this hypothesis. The surrogate markers of cardiovascular risk were similar between groups, except Lp-PLA2 which has been an independent predictor of cardiovascular events in health populations (however further study is needed). They concluded that overall results are reassuring for stopping ART used solely for reduction of PMTCT, and that cessation does not lead to short term disease progression. However, this study was small, not randomized and with limited follow up (1 year). Further evaluation with randomized trials over longer periods of time would be helpful in the future.
--Summarized by Carey Eppes, MD

Watts, D.H., Lu, M., Thompson, B., Tuomala, R.E., et al. Treatment Interruption after Pregnancy: Effects on Disease Progression and Laboratory Findings. Infectious Diseases in Obstetrics and Gynecology. 2009.

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