Time to viral load suppression in antiretroviral‐naive and ‐experienced HIV‐infected pregnant women on highly active antiretroviral therapy: implications for pregnant women presenting late in gestation

Abstract

Objective To compare time to achieve viral load <400 copies/ml and <1000 copies/ml in HIV-infected antiretroviral (ARV) -naive versus ARVexperienced pregnant women on highly active antiretroviral therapy (HAART).Design Retrospective cohort study.Setting Three university medical centers, USA.Population HIV-infected pregnant women initiated or restarted on HAART during pregnancy. MethodsWe calculated time to viral load <400 copies/ml and <1000 copies/ ml in HIV-infected pregnant women on HAART who reported at least 50% adherence, stratifying based on previous ARV exposure history.Main outcome measures Time to HIV viral load <400 copies/ml and <1000 copies/ml. ResultsWe evaluated 138 HIV-infected pregnant women, comprising 76 ARVnaive and 62 ARV-experienced. Ninety-three percent of ARV-naive women achieved a viral load < 400 copies/ml during pregnancy compared with 92% of ARV-experienced women (P = 0.82). The median number of days to achieve a viral load < 400 copies/ml in the ARV-naive cohort was 25.0 (range 3.5-133; interquartile range 16-34) days compared with 27.0 (range 8-162.5; interquartile range 18.5-54.3) days in the ARV-experienced cohort (P = 0.02). In a multiple predictor analysis, women with higher adherence (adjusted relative hazard [aRH] per 10% increase in adherence 1.29, 95% confidence interval [CI] 1.08-1.54, P = 0.01) and receiving a non-nucleotide reverse transcriptase inhibitor (NNRTI) -based regimen (aRH 2.48, 95% CI 1.33-4.63, P = 0.01) were more likely to achieve viral load <400 copies/ml earlier. Increased baseline HIV log 10 viral load was associated with a later time of achieving viral load <400 copies/ml (aRH 0.60, 95% CI 0.39-0.92, P = 0.02). In a corresponding model of time to achieve viral load <1000 copies/ml, adherence (aRH per 10% increase in adherence 1.79, 95% CI 1.34-2.39, P < 0.001), receipt of NNRTI (aRH 2.95, 95% CI 1.23-7.06, P = 0.02), and CD4 cell count (aRH per 50 count increase in CD4 1.12, 95% CI 1.03-1.22, P = 0.01) were associated with an earlier time to achieve viral load below this threshold. Increasing baseline HIV log 10 viral load was associated with a longer time of achieving viral load <1000 copies/ml (aRH 0.54, 95% CI 0.34-0.86, P = 0.01). In multiple predictor models, previous ARV exposure was not significantly associated with time to achieve viral load below thresholds of <400 copies/ml and <1000 copies/ml.Conclusions Pregnant women with 50% adherence, whether ARV-naive or ARV-experienced, on average achieve a viral load <400 copies/ml within a median of 26 days and a viral load of <1000 copies/ml within a median of 14 days of HAART initiation. Increased adherence, receipt of NNRTI-based regimen and lower baseline HIV log 10 viral load were all statistically significant predictors of earlier time to achieve viral load <400 copies/ml and <1000 copies/ ml. Increased CD4 count was statistically significant as a predictor of earlier time to achieve viral load <1000 copies/ml.

Integrase inhibitors in late pregnancy and rapid HIV viral load reduction

“…This is consistent with prior literature describing the effect of INSTI-based ART in pregnancy, however, a strength of our study is that we compared INSTI- and non-INSTI-containing ART directly. 8,9,11–14 Additionally, we describe the clinical practice of using regimens that did not fall under 1 st line recommended maternal treatment at the time of the study. 1 According to these data, pregnant HIV-infected women are prescribed newer potent ART options or regimens that are convenient once-a-day options, likely in order to promote adherence.…”

Detectable Viral Load in Late Pregnancy among Women in the Rwanda Option B+ PMTCT Program: Enrollment Results from the Kabeho Study

“…Shorter duration of ART has been associated with higher risk of detectable VL in a number of studies [8, 11–12, 19]. The median time to reach viral suppression, defined as <50 copies/ml, in a study of South African women initiating EFV-based ART was 13.7 weeks, although this varied by pre-ART VL [8].…”

“…The median time to reach viral suppression, defined as <50 copies/ml, in a study of South African women initiating EFV-based ART was 13.7 weeks, although this varied by pre-ART VL [8]. In a study from the US, using a VL of <400 copies/ml as the threshold for detectability, the median number of days to achieve viral suppression were similar between ARV-naïve and ARV-experienced cohorts of pregnant women, at 25 and 27 days, respectively [12]. PI-based ART has been associated with slower viral suppression in some studies from developed countries [11–12]; however, we could not assess this as EFV-based ART was used in the Rwanda, as recommended by the WHO guidelines [1].…”

“…In a study from South Africa, in pregnant women with median pre-ART VL of 10,000 copies/ml, the median time from ART initiation to VL <1000 copies/ml was 24 days and to <50 copies/ml was 94 days [8]. Factors associated with detectable VL at delivery included higher VL levels at ART initiation, <50% adherence to treatment, shorter duration of ART, and receipt of protease inhibitor (PI)-based regimens [8–12]. …”

Full Viral Suppression, Low-Level Viremia, and Quantifiable Plasma HIV-RNA at the End of Pregnancy in HIV-Infected Women on Antiretroviral Treatment

“…The significant link between HIV-RNA levels at the start of pregnancy and HIV-RNA at the end of pregnancy or time to viral suppression, already shown in other studies, 16,[18][19][20] reinforces the importance of adequate treatment of women with high viral load in early pregnancy.…”