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
Lessons From Clinical Trials of Antiretroviral Interventions to Reduce Perinatal Transmission of HIV
Perinatal Transmission of HIV and Maternal HIV RNA Copy Number
(Last updated:9/14/2011)
Panel’s Recommendation:
• All HIV-infected pregnant women should be counseled about and administered antiretroviral (ARV) drugs during pregnancy for prevention of perinatal transmission, regardless of their HIV RNA levels (AI). |
Mother-to-child transmission has been observed across the entire range of plasma HIV RNA levels, including in women with undetectable viral loads [1-3]. In PACTG 076, an HIV RNA threshold below which there was no risk of transmission was not identified; zidovudine was effective in reducing transmission regardless of maternal HIV RNA copy number [4-5].
HIV RNA levels correlate with risk of transmission even in women treated with ARV agents [6-9]. Although the risk of perinatal transmission in women with undetectable HIV RNA levels appears to be extremely low, transmission has been reported even among women with very low or undetectable levels of maternal HIV RNA [10]. Additionally, although HIV RNA may be an important risk factor for transmission, other factors also appear to play a role [6, 9, 11].
Although there is a general correlation between viral loads in plasma and in the genital tract, discordance also has been reported, particularly between HIV proviral load in blood and genital secretions, especially in the presence of other genital tract infections [12-15]. Penetration of ARV drugs into the female genital tract has been shown to vary between drugs [16-17]. If exposure to HIV in the maternal genital tract during delivery is a risk factor for perinatal transmission, plasma HIV RNA levels may not always be an accurate indicator of risk. Long-term changes in one body compartment with ARV drugs may or may not be associated with comparable changes in other compartments. Additional studies are needed to determine the effect of ARV drugs on genital tract viral load and the association between such effects and the risk of perinatal transmission of HIV. In the short-course zidovudine trial in Thailand, plasma and cervicovaginal HIV RNA levels were reduced by zidovudine prophylaxis, and each independently correlated with perinatal transmission [18].
Because transmission can occur even when HIV RNA copy numbers are low or undetectable, all HIV-infected women should be counseled about and administered ARV drugs during pregnancy, regardless of their HIV RNA levels.
References
1. Cao Y, Krogstad P, Korber BT, et al. Maternal HIV-1 viral load and vertical transmission of infection: the Ariel Project for the prevention of HIV transmission from mother to infant. Nat Med. 1997 May;3(5):549-552.
2. Mayaux MJ, Teglas JP, Mandelbrot L, et al. Acceptability and impact of zidovudine for prevention of mother-to-child human immunodeficiency virus-1 transmission in France. J Pediatr. 1997;131(6):857-862.
3. Thea DM, Steketee RW, Pliner V, et al. The effect of maternal viral load on the risk of perinatal transmission of HIV-1. New York City Perinatal HIV Transmission Collaborative Study Group. AIDS. 1997 Mar 15;11(4):437-444.
4. Sperling RS, Shapiro DE, Coombs RW, et al. Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1996 Nov 28;335(22):1621-1629.
5. Shapiro DE, Sperling RS, Coombs RW. Effect of zidovudine on perinatal HIV-1 transmission and maternal viral load. Pediatric AIDS Clinical Trials Group 076 Study Group. Lancet. 1999 Jul 10;354(9173):156; author reply 157-158.
6. Shaffer N, Roongpisuthipong A, Siriwasin W, et al. Maternal virus load and perinatal human immunodeficiency virus subtype E transmission, Thailand. J Infect Dis. 1999;179(3):590-599.
7. Mofenson LM, Lambert JS, Stiehm ER, et al. Risk factors for perinatal transmission of human immunodeficiency virus type 1 in women treated with zidovudine. Pediatric AIDS Clinical Trials Group Study 185 Team. N Engl J Med. 1999 Aug 5;341(6):385-393.
8. Garcia PM, Kalish LA, Pitt J, et al. Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal transmission. Women and Infants Transmission Study Group. N Engl J Med. 1999 Aug 5;341(6):394-402.
9. Maternal viral load and vertical transmission of HIV-1: an important factor but not the only one. The European Collaborative Study. AIDS. 1999 Jul 30;13(11):1377-1385.
10. Tubiana R, Le Chenadec J, Rouzioux C, et al. Factors associated with mother-to-child transmission of HIV-1 despite a maternal viral load <500 copies/ml at delivery: a case-control study nested in the French perinatal cohort (EPF-ANRS CO1). Clin Infect Dis. 2010 Feb 15;50(4):585-596.
11. Mock PA, Shaffer N, Bhadrakom C, et al. Maternal viral load and timing of mother-to-child HIV transmission, Bangkok, Thailand. Bangkok Collaborative Perinatal HIV Transmission Study Group. AIDS. 1999 Feb 25;13(3):407-414.
12. Hart CE, Lennox JL, Pratt-Palmore M, et al. Correlation of human immunodeficiency virus type 1 RNA levels in blood and the female genital tract. J Infect Dis. 1999 Apr;179(4):871-882.
13. Iversen AK, Larsen AR, Jensen T, et al. Distinct determinants of human immunodeficiency virus type 1 RNA and DNA loads in vaginal and cervical secretions. J Infect Dis. 1998 May;177(5):1214-1220.
14. Shaheen F, Sison AV, McIntosh L, Mukhtar M, Pomerantz RJ. Analysis of HIV-1 in the cervicovaginal secretions and blood of pregnant and nonpregnant women. J Hum Virol. 1999 May-Jun;2(3):154-166.
15. Rasheed S, Li Z, Xu D, Kovacs A. Presence of cell-free human immunodeficiency virus in cervicovaginal secretions is independent of viral load in the blood of human immunodeficiency virus-infected women. Am J Obstet Gynecol. 1996 Jul;175(1):122-129.
16. Yeh RF, Rezk NL, Kashuba AD, et al. Genital tract, cord blood, and amniotic fluid exposures of seven antiretroviral drugs during and after pregnancy in human immunodeficiency virus type 1-infected women. Antimicrob Agents Chemother. 2009 Jun;53(6):2367-2374.
17. Dumond JB, Yeh RF, Patterson KB, et al. Antiretroviral drug exposure in the female genital tract: implications for oral pre- and post-exposure prophylaxis. AIDS. 2007 Sep 12;21(14):1899-1907.
18. Chuachoowong R, Shaffer N, Siriwasin W, et al. Short-course antenatal zidovudine reduces both cervicovaginal human immunodeficiency virus type 1 RNA levels and risk of perinatal transmission. J Infect Dis. 2000;181(1):99-106.