Home >
Guidelines >
Perinatal Guidelines > HIV-Infected Pregnant Women Who Have Previously Received Antiretroviral Treatment or Prophylaxis but Are Not Currently Receiving Any Antiretroviral Medications
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
Antepartum Care
HIV-Infected Pregnant Women Who Have Previously Received Antiretroviral Treatment or Prophylaxis but Are Not Currently Receiving Any Antiretroviral Medications
(Last updated:9/14/2011)
Panel’s Recommendations:
• Obtain an accurate history of all prior antiretroviral (ARV) regimens used for treatment of HIV disease or prevention of transmission, including virologic efficacy, tolerance to the medications, results of prior resistance testing, and any adherence issues (AIII).
• If HIV RNA is above the threshold for resistance testing (e.g., >500–1,000 copies/mL), ARV drug-resistance studies should be performed before starting an ARV drug regimen (see Antiretroviral Drug Resistance and Resistance Testing in Pregnancy) (AIII). In women who present late in pregnancy, therapy or prophylaxis should be initiated pending results of resistance testing (BIII).
• Choose and initiate a combination ARV drug regimen based on results of resistance testing and prior history of antiretroviral therapy (ART) while avoiding drugs with teratogenic potential (efavirenz in the first trimester of pregnancy) or with known adverse potential for the mother (AII).
• Consult specialists in treatment of HIV infection about the choice of ART in women who previously received ARVs for their own health (AIII).
• Perform repeat ARV drug-resistance testing (AI), assess adherence, and consult with an HIV treatment specialist to guide changes in ARV drugs in women do not achieve virologic suppression on their ARV regimens (see Monitoring of the Woman and Fetus During Pregnancy). |
During a previous pregnancy, HIV-infected women may have received ARV drugs solely for prevention of perinatal transmission. At any time in the past, they also may have discontinued ARVs given to them for treatment of their own disease. A small number of clinical trials or observational studies have generated information about how effective ART is in individuals who previously received ARV prophylaxis. The data are limited to outcomes with therapy containing nevirapine initiated after the use of peripartum single-dose nevirapine [1-5].
Initial reports suggested a diminished virologic and clinical response to nevirapine-based ART if therapy was initiated within 6 months of intrapartum single-dose nevirapine exposure [1-3]. Subsequent reports have confirmed that a shorter interval between intrapartum single-dose nevirapine exposure and therapy initiation is associated with decreased efficacy of therapy and suggested that the diminished response may persist 12–24 months following exposure [4-5]. In addition, the subsequent failure of non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART after single-dose nevirapine has been associated with lower CD4 count and higher HIV-RNA plasma concentration at the time of single-dose nevirapine exposure, and genotypic resistance to nevirapine. Adding other ARVs to single-dose nevirapine (e.g., use of an ARV “tail”) decreases rates of nevirapine resistance [6-7] (see Antiretroviral Drug Resistance and Resistance Testing in Pregnancy), but the effect on clinical response to the subsequent initiation of NNRTI-based ART is unknown.
There is concern that time-limited use of ARV drugs during pregnancy for prophylaxis of perinatal transmission may lead to genotypic resistance and thus reduced efficacy of the ARV drugs when used for treatment. Rates of resistance appear to be low, based on standard genotyping, after prophylaxis for prevention of perinatal transmission with combination ARVs consisting of zidovudine, lamivudine, and nevirapine [8-9]. However, particularly in women whose virus was inadequately suppressed during the period of prophylaxis, minority populations of virus with resistance to nevirapine or lamivudine have been detected using sensitive allele-specific polymerase chain reaction (PCR) techniques [9-11]. Only limited data are available on the impact of these resistance-conferring minority variants on prediction of virologic or clinical failure of subsequent ART, and the PCR-based assays are not widely available. Both standard and sensitive genotyping techniques appear to show a low rate of resistance to protease inhibitors (PIs) after pregnancy-limited use of PI-based combination ARV regimens for prophylaxis, but these results reflect assessments in only small numbers of women [11-12]. However, to date, treatment failure has not been demonstrated with reinitiation of combination ARV regimens (particularly those containing the dual nucleoside reverse transcriptase inhibitor [NRTI] backbone of zidovudine and lamivudine) following prophylactic use in pregnancy for prevention of transmission, although controlled observations are lacking.
Given the lack of substantive data, it is reasonable to use results of initial resistance testing, if available, to make preliminary decisions about ARV regimens in women whose only previous exposure to ARVs was during pregnancy for prophylaxis of perinatal transmission. However, interpretation of resistance testing following discontinuation of ARV drugs can be complex because drug-resistance testing is most accurate if performed while an individual is taking the ARV regimen or within 4 weeks of treatment discontinuation. In the absence of selective drug pressure, resistant virus may revert to wild-type virus, and although detection of drug-resistance mutations is informative for choosing a regimen, a negative finding does not rule out the presence of archived drug-resistant virus that could re-emerge once drugs are reinitiated. Therefore, when selecting a new regimen for use during the current pregnancy, all information from the previous pregnancy—including regimens received, viral response, laboratory testing (including HLA-B*5701 results), and any tolerance or adherence issues—as well as the results of resistance testing should be taken into consideration. If the woman presents late in pregnancy, therapy or prophylaxis should be initiated pending results of resistance testing. Careful monitoring of virologic response to the chosen ARV regimen is important.
If the chosen regimen produces an insufficient viral response, decisions about switching regimens should be guided by repeat resistance testing and assessment of medication adherence. These measures should be undertaken in consultation with an HIV treatment specialist.
Some women who receive ART for their own health choose to discontinue the drugs for a variety of reasons, and the length of time between treatment termination and pregnancy may vary. In these cases, careful clinical and laboratory assessments are necessary before therapy is reinitiated during pregnancy. The evaluations should include a review of a woman’s prior history of virologic response and medication toxicity as well as her adherence to therapy. The appropriate choice of ARV regimen to be initiated during pregnancy will vary according to a woman’s history of ART; the indication for stopping therapy; the effect of prior therapy on clinical, virologic, and immunologic status; and the results of past and current testing for resistance and for HLA-B*5701. It may be possible, for example, to restart the same regimen in women with a history of prior ART associated with successful suppression of viral load who then stopped all drugs simultaneously (or staggered discontinuation if NNRTI based) and who have no evidence of resistance. On the other hand, the selection of an appropriate ARV regimen may be challenging even for health care providers experienced in HIV care in women with advanced HIV disease, a history of extensive prior ART, or previous significant toxicity or nonadherence to ARV drugs. In such cases, restarting the prior regimen for a week or two before performing a resistance assay may yield more accurate results. In addition to obtaining genotypic resistance testing, it is strongly recommended that specialists in the treatment of HIV infection be consulted early during the pregnancy about the choice of suitable ART.
References
1. Lockman S, Shapiro RL, Smeaton LM, et al. Response to antiretroviral therapy after a single, peripartum dose of nevirapine. N Engl J Med. 2007 Jan 11;356(2):135-147.
2. Coovadia A, Hunt G, Abrams EJ, Sherman G, Meyers T, Barry G, Malan E, Marais B, Stehlau R, Ledwaba J, Hammer SM, Morris L, Kuhn L. Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. Clin Infect Dis. 2009 Feb 15;48(4):462-72.
3. Chi BH, Sinkala M, Stringer EM, et al. Early clinical and immune response to NNRTI-based antiretroviral therapy among women with prior exposure to single-dose nevirapine. AIDS. 2007 May 11;21(8):957-964.
4. Lockman S, Hughes MD, McIntyre J, et al. Antiretroviral therapies in women after single-dose nevirapine exposure. N Engl J Med. 2010 Oct 14;363(16):1499-1509.
5. Stringer JS, McConnell MS, Kiarie J, et al. Effectiveness of non-nucleoside reverse-transcriptase inhibitor-based antiretroviral therapy in women previously exposed to a single intrapartum dose of nevirapine: a multi-country, prospective cohort study. PLoS Med. 2010;7(2):e1000233.
6. Chi BH, Sinkala M, Mbewe F, et al. Single-dose tenofovir and emtricitabine for reduction of viral resistance to non-nucleoside reverse transcriptase inhibitor drugs in women given intrapartum nevirapine for perinatal HIV prevention: an open-label randomised trial. Lancet. 2007 Nov 17;370(9600):1698-1705.
7. McIntyre JA, Hopley M, Moodley D, Eklund M, Gray GE, Hall DB, Robinson P, Mayers D, Martinson NA. Efficacy of short-course AZT plus 3TC to reduce nevirapine resistance in the prevention of mother-to-child HIV transmission: a randomized clinical trial. PLoS Med. 2009 Oct;6(10):e1000172. Epub 2009 Oct 27.
8. Perez H, Vignoles M, Laufer N, et al. Low rate of emergence of nevirapine and lamivudine resistance after post-partum interruption of a triple-drug regimen. Antivir Ther. 2008;13(1):135-139.
9. Lehman DA, Chung MH, Mabuka JM, et al. Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. J Acquir Immune Defic Syndr. 2009 Aug 15;51(5):522-529.
10. Rowley CF, Boutwell CL, Lee EJ, et al. Ultrasensitive detection of minor drug-resistant variants for HIV after nevirapine exposure using allele-specific PCR: clinical significance. AIDS Res Hum Retroviruses. 2010 Mar;26(3):293-300.
11. Paredes R, Cheng I, Kuritzkes DR, Tuomala RE. Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. AIDS. 2010 Jan 2;24(1):45-53.
12. Gingelmaier A, Eberle J, Kost BP, et al. Protease inhibitor-based antiretroviral prophylaxis during pregnancy and the development of drug resistance. Clin Infect Dis. 2010 Mar 15;50(6):890-894.