Risk Factors for Detectable HIV-1 RNA at Delivery

In the United States, more than 6000 women with HIV become pregnant each year. Numerous interventions have been put into place which can decrease the risk of newborn HIV infection to less than one percent for many patients. The Women and Infants Transmission Study (WITS) previously published data showing that the odds of newborn HIV transmission (aka vertical transmission) increases approximately 2.4 fold for every log₁₀ increase in number of HIV copies in maternal viral load at the time of delivery. The authors’ goal for this paper was to use data from WITS--a multicenter, prospective, natural history cohort study-- for women who gave birth between 1998 and 2005, received highly active antiretroviral therapy (HAART) during pregnancy, and had a documented HIV-1 RNA level checked to answer the study question of whether administration of a “boosting” (ability to enhance the actions of other antiretrovirals) protease inhibitor medication like ritonavir was associated with lower HIV-1 RNA levels at the time of delivery. The authors also wanted to describe characteristics of the women that were associated with detectable HIV-1 RNA levels at delivery.

For the study, 630 women were divided into either HAART-experienced or HAART-naïve categories in an effort to separate the women based on their likely duration of treatment. Only 17 percent received a “boosting” ritonavir regimen; most regimens (89 and 95 percent, respectively) contained AZT and lamivudine nucleoside reverse-transcriptase inhibitor therapies. Though women in the HAART-experienced group differed from women in the HAART-naïve group in several ways and were more likely to have received a “boosted” regimen, slightly more than half of the women in each category had detectable amounts of HIV-1 RNA at their first study measurement in pregnancy. Though there were several predictors for detectable HIV-1 RNA at delivery—including pre-pregnancy HAART exposure, young maternal age, black race, illicit substance use, detectable HIV-1 RNA at enrollment, and earlier year of enrollment—the type of HAART regimen that patients were administered was not associated with a decreased likelihood of having detectable HIV-1 RNA at delivery. In fact, in both groups the use of a “boosting” protease inhibitor was associated with a higher chance of having a detectable HIV-1 RNA level both at enrollment and at delivery. The overall rate of detectable HIV-1 RNA at delivery was 32 percent, being 37 percent in the HAART-experienced group and 24 percent in the HAART-naïve group. Of the 335 women with detectable HIV-1 RNA at enrollment, 162 (48%) of women were still detectable at delivery. Conversely, of the 295 women who entered the study with an undetectable HIV-1 RNA level, 13 percent had detectable HIV-1 RNA at the time of delivery.

Despite rates of vertical transmission below 1 percent for the last five years of WITS, the authors found that 32 percent of the women receiving HAART between 1998 and 2005 had detectable HIV-1 RNA at delivery. This was a surprising finding, along with the observation that “boosting” protease inhibitors failed to decrease rates of detectable HIV-1 RNA at delivery. Given the limitations inherent in the retrospective study design, it is unclear whether women receiving the “boosted” protease inhibitor regimen had more advanced disease, thus making their HIV harder to manage. In addition, the study design was unable to standardize prescribing practices, meaning that not all patients on the “boosting” protease inhibitor regimens received the increase in dosing typically recommended during the third trimester of pregnancy. Two encouraging trends observed were that in the later years of the study, there were fewer women that were HAART-naïve and lower rates of women with detectable HIV-1 RNA at delivery.

This article represents a worthwhile contribution to the existing literature for perinatal HIV because the authors attempted to validate a HAART approach that is routinely used when managing HIV positive pregnant patients. Though there was limited information collected on medication dosage, adherence, resistance patterns, and the exact timing of HAART administration, the study definitely confirmed known risk factors for detectable HIV-1 RNA at delivery. Furthermore, the investigators’ findings that the type of HAART regimen did not appear to impact the likelihood of a patient achieving an undetectable viral load highlights the need for quality, prospective research in this area. When attempting to identify the ideal HAART regimen to decrease the HIV-1 viral load in pregnant patients, it is important for providers not to be dogmatic when the situation does not allow for the standard medication regimens to be utilized. Finally, even when detectable HIV-1 RNA levels are present at delivery, careful adherence to other intrapartum and postpartum prevention methods can allow for healthy, HIV-seronegative infants to be born to HIV positive mothers.

--Summarized by Barrett Robinson, MD, MPH

Citation:
Katz, Ingrid T, et al. “Risk factors for detectable HIV-1 RNA at delivery among women receiving highly active antiretroviral therapy in the Women and Infants Transmission Study.” Journal of Acquired Immune Deficiency Syndrome 2010;54: 27-34.

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Abstract