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Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States
Failure of Viral Suppression
(Last updated: March 28, 2014; last reviewed: March 28, 2014)
If an ultrasensitive HIV RNA assay indicates failure of viral suppression (that is, persistent HIV viral load >20 to 75 copies/mL, depending on the assay used) after an adequate period of treatment:
Assess resistance and adherence (AII).
Consult an HIV treatment expert (AIII).
Scheduled cesarean delivery is recommended for HIV-infected pregnant women who have HIV RNA levels >1,000 copies/mL near the time of delivery (AII).
Rating of Recommendations: A = Strong; B = Moderate; C = Optional Rating of Evidence: I = One or more randomized trials with clinical outcomes and/or validated laboratory endpoints; II = One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = Expert opinion
A three-pronged approach is indicated for management of women on antiretroviral (ARV) regimens who have suboptimal suppression of HIV RNA (that is, detectable virus at any time during pregnancy using ultrasensitive assays). They should be:
Evaluated for resistant virus (if plasma HIV RNA is >500 to 1,000 copies/mL);
Assessed for adherence, tolerability, incorrect dosing, or potential problems with absorption (e.g., nausea/vomiting, lack of attention to food requirements); and
Considered for ARV regimen modification.
Experts in the care of ARV-experienced adults should be consulted, particularly if a change in drug regimen is necessary. Hospitalization can be considered for directly observed drug administration, adherence education, and treatment of comorbidities such as nausea and vomiting.
Among 662 pregnancies followed in Italy between 2001 and 2008, treatment modification during pregnancy was independently associated with an HIV-1 RNA level >400 copies/mL in late pregnancy (adjusted odds ratio, 1.66; 95% confidence interval, 1.07–2.57; P = 0.024), highlighting the importance of using potent and well-tolerated regimens during pregnancy to maximize effectiveness and minimize need to modify treatment.1
HIV RNA levels should be assessed 2 to 4 weeks after an ARV drug regimen is initiated or changed to provide an initial assessment of effectiveness.2 Baseline HIV RNA levels have been shown to affect the time to response in both pregnant and non-pregnant individuals, with no difference in response between pregnant and non-pregnant women.3,4 Most patients with an adequate viral response at 24 weeks have had at least a 1 log copies/mL HIV RNA decrease within 1 to 4 weeks after starting therapy.2 In a retrospective multicenter cohort of 378 pregnant women, 77.2% achieved HIV RNA <50 copies/mL by delivery, with success of viral suppression varying by baseline HIV RNA level. With baseline <10,000 copies/mL, gestational age at initiation did not affect success up to 26.3 weeks. With baseline >10,000 copies/mL, however, delaying initiation past 20.4 weeks significantly reduced ability for achieving maximal suppression at delivery.3 In data on 1,070 HIV-infected treatment-naive pregnant women participating in IMPAACT P1025, a prospective cohort study, later initiation of combination antiretroviral therapy (cART) at >32 weeks’ gestation also was associated with a significantly higher risk of having viral load >400 copies/mL at delivery.5 The role of therapeutic drug monitoring in reducing the risk of virologic failure is still undefined.6,7
A recent systematic review and meta-analysis of adherence to cART during and after pregnancy in low-, middle-, and high-income countries (27% of studies were from the United States) found that a pooled estimate of 73.5% of pregnant women had adequate (>80%) adherence to cART.8 Evaluation of and support for adherence during pregnancy is critical to achievement and maintenance of maximal viral suppression.
Because maternal antenatal viral load correlates with risk of perinatal transmission of HIV, suppression of HIV RNA to undetectable levels should be achieved as rapidly as possible. The addition of raltegravir in late pregnancy has been suggested for women who have high viral loads and/or in whom multiple drug-resistant mutations have resulted in incomplete suppression of viremia because of the ability of raltegravir to rapidly suppress viral load (approximately 2 log copies/mL decrease by Week 2 of therapy).9-12 However, the efficacy and safety of this approach have not been evaluated and only anecdotal reports are available. In the setting of a failing regimen related to non-adherence and/or resistance, there are concerns that the addition of a single agent may further increase risk of resistance and potential loss of future effectiveness with raltegravir. A recent report found a 10- to 23-fold increase in transaminase levels following introduction of a raltegravir-containing regimen in late pregnancy, with return to normal levels after raltegravir discontinuation.13 Therefore, at the current time, this approach cannot be routinely recommended. Scheduled cesarean delivery is recommended for HIV-infected pregnant women who have HIV RNA levels >1,000 copies/mL.
Floridia M, Ravizza M, Pinnetti C, et al. Treatment change in pregnancy is a significant risk factor for detectable HIV-1 RNA in plasma at end of pregnancy. HIV Clin Trials. 2010;11(6):303-311. Available at http://www.ncbi.nlm.nih.gov/pubmed/21239358.
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Available at http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf.
Read PJ, Mandalia S, Khan P, et al. When should HAART be initiated in pregnancy to achieve an undetectable HIV viral load by delivery? AIDS. 2012;26(9):1095-1103. Available at http://www.ncbi.nlm.nih.gov/pubmed/22441248.
Rachas A, Warszawski J, Le Chenadec J, et al. Does pregnancy affect the early response to cART? AIDS. 2013;27(3):357-367. Available at http://www.ncbi.nlm.nih.gov/pubmed/23079802.
Katz I, Leister E, et al. Factors associated with lack of viral suppression at delivery: IMPAACT P1025. Paper #1022. Paper presented at: Conference on Retroviruses and Opportunistic Infections; 2012.
Liu X, Ma Q, Zhang F. Therapeutic drug monitoring in highly active antiretroviral therapy. Expert Opin Drug Saf. 2010;9(5):743-758. Available at http://www.ncbi.nlm.nih.gov/pubmed/20350281.
Matsui DM. Therapeutic drug monitoring in pregnancy. Ther Drug Monit. 2012;34(5):507-511. Available at http://www.ncbi.nlm.nih.gov/pubmed/22846897.
Nachega JB, Uthman OA, Anderson J, et al. Adherence to antiretroviral therapy during and after pregnancy in low-income, middle-income, and high-income countries: a systematic review and meta-analysis. AIDS. 2012;26(16):2039-2052. Available at http://www.ncbi.nlm.nih.gov/pubmed/22951634.
Grinsztejn B, Nguyen BY, Katlama C, et al. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial. Lancet. 2007;369(9569):1261-1269. Available at http://www.ncbi.nlm.nih.gov/pubmed/17434401.
Papendorp SG, van den Berk GE. Preoperative use of raltegravir-containing regimen as induction therapy: very rapid decline of HIV-1 viral load. AIDS. 2009;23(6):739. Available at http://www.ncbi.nlm.nih.gov/pubmed/19279447.
Pinnetti C, Baroncelli S, Villani P, et al. Rapid HIV-RNA decline following addition of raltegravir and tenofovir to ongoing highly active antiretroviral therapy in a woman presenting with high-level HIV viraemia at week 38 of pregnancy. J Antimicrob Chemother. 2010;65(9):2050-2052. Available at http://www.ncbi.nlm.nih.gov/pubmed/20630894.
McKeown DA, Rosenvinge M, Donaghy S, et al. High neonatal concentrations of raltegravir following transplacental transfer in HIV-1 positive pregnant women. AIDS. 2010;24(15):2416-2418. Available at http://www.ncbi.nlm.nih.gov/pubmed/20827058.
Renet S, Closon A, Brochet MS, Bussieres JF, Boucher M. Increase in transaminase levels following theuse of raltegravir in a woman with a high HIV viral load at 35 Weeks of pregnancy. J Obstet Gynaecol Can. 2013;35(1):68-72. Available at http://www.ncbi.nlm.nih.gov/pubmed/23343800.