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
Preconception Counseling and Care for HIV-Infected Women of Childbearing Age
Reproductive Options for HIV-Concordant and Serodiscordant Couples
(Last updated:9/14/2011)
Panel’s Recommendations:
• For serodiscordant couples who want to conceive, expert consultation is recommended so that approaches can be tailored to specific needs, which may vary from couple to couple (AIII).
• Partners should be screened and treated for genital tract infections before attempting to conceive (AII).
• For an HIV-infected female with an HIV-uninfected male partner, the safest conception option is artificial insemination, including the option of self-insemination with her partner’s sperm during the peri-ovulatory period (AIII).
• For HIV-infected men with an HIV-uninfected female partner, the use of sperm preparation techniques coupled with either intrauterine insemination, in vitro fertilization, or intracytoplasmic sperm injection should be considered if using donor sperm from an HIV-uninfected male for insemination is unacceptable (AII).
• In a serodiscordant couple who wishes to conceive, initiation of antiretroviral therapy (ART) for the HIV-infected partner is recommended if the infected partner has a CD4 count <550 cells/mm3 (AI). For HIV-infected individuals with CD4 counts >550 cells/mm3, initiation of ART could be considered (BIII). If therapy is initiated, maximal viral suppression is recommended before conception is attempted (AIII).
• Data are insufficient at the current time to recommend peri-conception administration of antiretroviral (ARV) pre-exposure prophylaxis for HIV-uninfected partners to reduce the risk of sexual transmission (AIII). |
For serodiscordant couples who want to conceive, expert consultation is recommended so that approaches can be tailored to specific needs, which may vary from couple to couple.
Before attempting to conceive, both partners should be screened for genital tract infections. If any such infections are identified, they should be treated because genital tract inflammation is associated with genital tract shedding of HIV [1-2]. Semen analysis is recommended for HIV-infected males before conception is attempted because HIV, and possibly ART, may be associated with a higher prevalence of semen abnormalities such as low sperm count, low motility, higher rate of abnormal forms, and low semen volume [3-6]. If such abnormalities are present, the uninfected female partner may be exposed unnecessarily and for prolonged periods to her partner’s infectious genital fluids when the likelihood of getting pregnant naturally is low or even nonexistent.
Observational studies have demonstrated a decreased rate of transmission of HIV among heterosexual serodiscordant couples on ART compared with those not on therapy [7-9]. HPTN 052 is a randomized clinical trial designed to evaluate whether immediate versus delayed initiation of ART by HIV-infected individuals with CD4 counts of 350–550 cells/mm3 could prevent sexual transmission of HIV among serodiscordant couples. Preliminary data from this study showed that earlier initiation of ART led to a significant reduction in transmission of HIV to the uninfected partner [10]. Of 28 cases of HIV infection documented to be genetically linked to the infected partner, 27 occurred among the 877 couples in which the HIV-infected partner delayed initiation of ART until the CD4 count fell below 250 cells/mm3, whereas only 1 case of HIV infection occurred among the 886 couples with an HIV-infected partner who began immediate ART; 17 of the 27 transmissions in the delayed therapy group occurred in individuals with CD4 counts >350 cells/mm3. These are the first data from a randomized trial to demonstrate that provision of treatment to infected persons can reduce the risk of transmission to their uninfected sexual partners [11]. Based on the results from HPTN 052, initiation of ART would be recommended for the infected partner in a serodiscordant couple who has a CD4 count of ≤550 cells/mm3 if the couple wishes to conceive. For HIV-infected individuals with CD4 counts >550 cells/mm3, initation of therapy could be considered, although the benefit of ART in reducing sexual transmission from individuals with higher CD4 counts has not been determined. Before conception is attempted, maximal viral suppression is recommended if an infected individual is on ART for his/her own health or does not require therapy but opts to start an ART to prevent sexual transmission.
It is important to recognize that no single method (including treatment of the infected partner) is fully protective against transmission of HIV. Effective ART that decreases plasma viral load to undetectable levels is also associated with decrease in the concentration of virus in genital secretions. However, discordance between plasma and genital viral loads has been reported, and individuals with an undetectable plasma viral load may have detectable genital tract virus [12-13]. Additionally, ARV drugs vary in their ability to penetrate the genital tract [14]. Thus, maximal viral suppression may not completely eliminate risk of heterosexual transmission.
Reducing the risk of perinatal transmission is another potential rationale for starting ART prior to conception in HIV-infected women who do not yet need treatment for their own health. Data suggest that early and sustained control of HIV viral replication may be associated with decreasing residual risk of perinatal transmission [15-16], but that does not completely eliminate the risk of perinatal transmission [16]. In addition, there are mixed reports on the possible effects of combination ARV drug regimens on prematurity and low birth weight, with some but not all data suggesting that such outcomes may be more frequent in women on ARV drugs at conception [17-18] (see Special Considerations Regarding the Use of Antiretroviral Drugs by HIV-Infected Pregnant Women and their Infants).
The implications of initiating therapy prior to conception solely for prevention of sexual and/or perinatal transmission should be discussed with the patient. These issues include willingness and ability to commit to potential lifelong therapy, the potential risks versus benefits of stopping or continuing the regimen after conception in the male or postpartum in the female, and the need for strict adherence to achieve maximal viral suppression. Consultation with an expert in HIV care is strongly recommended.
For HIV-discordant couples in which the female is the HIV-infected partner, the safest form of conception is artificial insemination, including the option to self-inseminate with the partner’s sperm during the peri-ovulatory period. Condom use should be advised at all times.
For HIV-discordant couples in which the male is the HIV-infected partner, the use of sperm preparation techniques coupled with either intrauterine insemination, in vitro fertilization, or intracytoplasmic sperm injection has been reported to be effective in avoiding seroconversion in uninfected women and offspring in several studies [19-20]. The National Perinatal HIV Hotline (1-888-448-8765) is a resource for a list of institutions offering reproductive services for HIV-serodiscordant couples. More data are needed to demonstrate the complete efficacy of these techniques, and couples should be cautioned about the potential risk of transmission of HIV to the uninfected partner and to their offspring [20]. Discordant couples who do not have access to assisted reproduction services and who still wish to try to conceive after comprehensive counseling should be advised that timed, peri-ovulatory unprotected intercourse after the infected partner has achieved maximal viral suppression (with use of condoms at all other times) may reduce but not completely eliminate the risk of sexual transmission [20]. Should the uninfected woman become pregnant, she should be regularly counseled regarding consistent condom use to decrease her risk of sexual transmission of HIV and the possible risk of perinatal transmission (see Monitoring of HIV Uninfected Pregnant Women with a Partner Known to be HIV Infected).
Periconception pre-exposure prophylaxis may offer an additional option in the future to minimize risk of transmission of HIV within discordant couples. Pre-exposure prophylaxis is use of ARV medications by an HIV-uninfected individual to maintain blood and genital drug levels sufficient to prevent acquisition of HIV. An experimental 1% tenofovir gel used intravaginally both before and after sex reduced the incidence of HIV infection among women by up to 54% in a randomized, placebo-controlled trial conducted in South Africa [21]. This product is not available commercially, and additional trials are needed to confirm these findings. Five efficacy trials of pre-exposure prophylaxis with oral ARV agents (primarily tenofovir alone) are currently under way [22]. In 1 study of daily tenofovir/emtricitabine in HIV-seronegative men who have sex with men, there was a 44% reduction in the risk of acquisition of HIV compared with placebo [23-24]. However, the FEM-PrEP clinical trial, designed to study whether HIV-uninfected women at high risk of being exposed to HIV can safely use a daily dose of tenofovir/emtricitabine to prevent infection, was stopped early by its Data and Safety Monitoring Board (DSMB) because it was highly unlikely the study would be able to demonstrate the effectiveness of tenofovir/emtricitabine in preventing HIV infection in the study population. The approximate rate of new HIV infections among trial participants was 5 percent per year. A total of 56 new HIV infections had occurred, with an equal number of infections in participants assigned to tenofovir/emtricitabine and those assigned to a placebo pill [25].
Several studies evaluating the efficacy of pre-exposure prophylaxis among heterosexual discordant couples are ongoing but data are not yet available. Currently data are insufficient to recommend periconception administration of pre-exposure prophylaxis to uninfected partners to reduce the risk of sexual transmission. In addition, the use of pre-exposure prophylaxis during pregnancy and lactation for HIV-uninfected women with HIV-infected partners has not been studied and cannot be recommended at this time. If pre-exposure prophylaxis is proven safe and efficacious in ongoing trials, this approach may offer an option for safer attempts at conception. However, it will be important to have outcome studies that examine adverse events, including risk of congenital abnormalities.
MONITORING OF HIV-UNINFECTED PREGNANT WOMEN WITH PARTNERS KNOWN TO BE HIV INFECTED
Clinicians increasingly may be faced with the situation in which an HIV-uninfected woman presents during pregnancy and relates that she has an HIV-infected partner. As is recommended for all pregnant women, the woman should be notified that HIV screening is recommended and that she will receive an HIV test as part of the routine panel of prenatal tests unless she declines. In addition, she should receive a second HIV test during the third trimester, preferably before 36 weeks of gestation, as is recommended for high-risk women. Furthermore, if the pregnant woman presents in labor without results of third-trimester testing, she should be screened with a rapid HIV test on the labor and delivery unit. If at any time during pregnancy the clinician suspects that a pregnant woman may be in the “window” period of seroconversion (i.e., has signs or symptoms consistent with acute HIV infection), then a plasma HIV RNA test should be used in conjunction with an HIV antibody test. If the plasma HIV RNA is negative, it should be repeated in 2 weeks. All HIV-uninfected pregnant women with HIV-infected partners should always use condoms during sexual intercourse to prevent acquisition of HIV. Women should be counseled regarding the symptoms of acute retroviral syndrome (i.e., fever, pharyngitis, rash, myalgia, arthralgia, diarrhea, headache) and the importance of seeking medical care and testing if they experience such symptoms.
If results from either conventional or rapid HIV testing are positive, then the woman should receive appropriate evaluation and interventions to reduce perinatal transmission of HIV, including immediate initiation of appropriate ARV prophylaxis and consideration of elective cesarean delivery according to established guidelines (see Transmission and Mode of Delivery). In cases where confirmatory test results are not readily available (e.g., rapid testing during labor), it is still appropriate to initiate interventions to reduce perinatal transmission (see Infant Antiretroviral Prophylaxis).
If HIV test results are negative, HIV-uninfected women with HIV-infected partners should continue to be regularly counseled regarding consistent condom use to decrease their risk of sexual transmission of HIV. Women with primary HIV infection during pregnancy or lactation are at high risk of transmitting HIV to their infants [26-27].
References
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