Uses
Oral and IV zidovudine are used in conjunction with other antiretroviral agents for treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults, adolescents, and pediatric patients. Oral and IV zidovudine are used for treatment of HIV-1 infection in pregnant women and for prevention of perinatal HIV transmission in a regimen that includes intrapartum IV zidovudine prophylaxis in the mother and oral or IV zidovudine prophylaxis in the neonate. In addition, oral zidovudine is used in conjunction with other antiretroviral agents for postexposure prophylaxis of HIV infection in health-care personnel and other individuals exposed occupationally via percutaneous injury or mucous membrane or skin contact with blood, tissue, or other body fluids associated with a risk for transmission of the virus.
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Treatment of HIV Infection
Oral and IV zidovudine are used in conjunction with other antiretroviral agents for treatment of HIV-1 infection in adults, adolescents, and pediatric patients who are antiretroviral-naive (have not previously received antiretroviral therapy) or antiretroviral-experienced (previously treated).
Zidovudine is used in multiple-drug regimens that include another HIV nucleoside reverse transcriptase inhibitor (NRTI) (dual NRTIs) and an HIV integrase strand transfer inhibitor (INSTI), HIV nonnucleoside reverse transcriptase inhibitor (NNRTI), or HIV protease inhibitor (PI) in INSTI-, NNRTI-, or PI-based regimens.
(See Dual NRTI Options under Treatment of HIV Infection: Antiretroviral-naive Adults and Adolescents, in Uses.) If the dual NRTI option of lamivudine and zidovudine is used in conjunction with other antiretrovirals for treatment of HIV-1 infection, a fixed-combination preparation containing both drugs (lamivudine/zidovudine; Combivir) is commercially available and can be used in adults and adolescents weighing 30 kg or more to decrease pill burden and improve adherence.
Zidovudine has been used in triple NRTI regimens (i.e., single-class NRTI regimens) that include zidovudine and 2 other NRTIs. A fixed-combination preparation containing abacavir, lamivudine, and zidovudine (abacavir/lamivudine/zidovudine; Trizivir) is commercially available and can be used in adults and adolescents weighing 40 kg or more to provide a triple NRTI regimen and to decrease pill burden and improve adherence.
(See All-NRTI Regimens under Treatment of HIV Infection: Antiretroviral-naive Adults and Adolescents, in Uses.) The most appropriate antiretroviral regimen cannot be defined for each clinical scenario and selection of specific antiretroviral agents for use in such regimens should be individualized based on information regarding antiretroviral potency, potential rate of development of resistance, known toxicities, and potential for pharmacokinetic interactions as well as virologic, immunologic, and clinical characteristics of the patient. For information on the general principles and guidelines for use of antiretroviral therapy, including specific recommendations for initial therapy in antiretroviral-naive patients and recommendations for changing antiretroviral regimens,
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Antiretroviral-naive Adults and Adolescents
Although monotherapy and 2-drug regimens that include only NRTIs are no longer recommended for treatment of HIV infection, early studies evaluating safety and efficacy of zidovudine for initial antiretroviral therapy in antiretroviral-naive HIV-infected adults used zidovudine monotherapy or 2-drug regimens of zidovudine and didanosine, lamivudine, or zalcitabine (no longer commercially available in the US). While results of these early studies indicated that zidovudine monotherapy or 2-drug NRTI regimens in antiretroviral-naive patients may be associated with initial declines in plasma HIV-1 RNA levels, subsequent studies showed that such regimens were less effective in providing durable suppression of HIV replication than 3-drug regimens that also included an agent from another class (i.e., PI or NNRTI).
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Dual NRTI Options
For initial treatment regimens in antiretroviral-naive HIV-infected adults and adolescents, the US Department of Health and Human Services (HHS) Panel on Antiretroviral Guidelines for Adults and Adolescents states that the dual NRTI option of tenofovir disoproxil fumarate (tenofovir DF) and emtricitabine (or lamivudine) is the recommended dual NRTI option for use in most INSTI-, NNRTI-, and PI-based regimens recommended for initial treatment. These experts state that abacavir and lamivudine (or emtricitabine) also is a recommended dual NRTI option for use in initial treatment regimens in antiretroviral-naive adults and adolescents, but should be used only in those who are negative for human leukocyte antigen (HLA)-B*5701. These recommendations are based on safety and efficacy data from clinical trials, long-term clinical experience, and availability of fixed-combination preparations containing NRTIs.
The dual NRTI option of zidovudine and lamivudine is no longer recommended for initial treatment regimens in nonpregnant antiretroviral-naive adults and adolescents because it has greater toxicity than the dual NRTI options of tenofovir DF and emtricitabine or abacavir and lamivudine and requires twice-daily dosing. However, the dual NRTI option of zidovudine and lamivudine is one of several preferred dual NRTI options for initial treatment regimens in antiretroviral-naive pregnant women
(see Pregnancy under Cautions: Pregnancy, Fertility, and Lactation) and for initial treatment regimens in pediatric patients(see Pediatric Patients under Uses: Treatment of HIV-1 Infection) . When the dual NRTI option of lamivudine and zidovudine is used in conjunction with other antiretrovirals, the fixed-combination preparation containing both drugs (lamivudine/zidovudine; Combivir) can be used in adults and adolescents weighing 30 kg or more.A dual NRTI option of zidovudine and stavudine should not be used at any time because of antagonistic antiretroviral effects.
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All-NRTI Regimens
Zidovudine has been included in NRTI regimens that include 3 or 4 NRTIs (without any drugs from another class). However, triple and quadruple NRTI regimens are not usually recommended for treatment of HIV infection in antiretroviral-naive adults or adolescents because such regimens have inferior virologic efficacy or have not been adequately studied. In addition, regimens that only include NRTIs are not usually recommended in antiretroviral-experienced patients.
(See Antiretroviral-experienced Adults and Adolescents under Uses: Treatment of HIV Infection.) Zidovudine has been used in a triple NRTI regimen that includes abacavir, lamivudine, and zidovudine. The fixed-combination preparation containing these 3 NRTIs (abacavir/lamivudine/zidovudine; Trizivir) can be used in adults and adolescents weighing 40 kg or more. Abacavir/lamivudine/zidovudine is intended only for regimens that require all 3 drugs, and clinicians should consider that data are limited regarding use in patients with baseline viral loads exceeding 100,000 copies/mL. Although a triple NRTI regimen of abacavir, lamivudine, and zidovudine offers the advantages of fewer drug interactions, low pill burden and ease of administration (because of the commercially available fixed-combination preparation), and spares patients from potential adverse effects associated with PIs and NNRTIs, there is evidence that triple NRTI regimens have inferior virologic efficacy. Therefore, experts state that a triple NRTI regimen that includes abacavir, lamivudine, and zidovudine is not recommended for initial therapy in antiretroviral-naive adults and adolescents and should be used only when other regimens cannot be used.
A triple NRTI regimen of lamivudine, tenofovir DF, and zidovudine has been used and has been shown to have antiretroviral activity; however, this regimen should be used only when other regimens cannot be used.
A quadruple NRTI regimen of abacavir, lamivudine, tenofovir DF, and zidovudine is not recommended for initial therapy in antiretroviral-naive adults and adolescents because of inferior virologic activity. In an open-label pilot study, a quadruple NRTI regimen was compared with an NNRTI-based regimen of efavirenz with lamivudine and zidovudine and both regimens had similar efficacy and tolerability. However, a larger, open-label study comparing a similar quadruple NRTI regimen (abacavir, emtricitabine, tenofovir DF, zidovudine) with a standard NNRTI- or PI-based regimen found that substantially fewer patients receiving the quadruple NRTI regimen achieved HIV-1 RNA levels below 200 copies/mL.
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Antiretroviral-experienced Adults and Adolescents
Although monotherapy or 2-drug regimens that include only NRTIs are no longer recommended for treatment of HIV infection, early studies evaluating the safety and efficacy of zidovudine in antiretroviral-experienced (previously treated) patients used such regimens. Subsequent studies indicated that regimens that include zidovudine, another NRTI (e.g., lamivudine, didanosine), and a PI (e.g., indinavir, ritonavir, saquinavir) or NNRTI (e.g., nevirapine) were more effective in increasing CD4 T-cell counts and decreasing plasma HIV-1 RNA levels in previously treated patients than zidovudine monotherapy or 2-drug NRTI regimens.
Zidovudine has been used in triple NRTI regimens in antiretroviral-experienced HIV-infected adults and adolescents, but triple NRTI regimens are not usually recommended because of inferior virologic efficacy or lack of data.
A triple NRTI regimen that includes abacavir (300 mg twice daily) and the fixed-combination preparation containing lamivudine and zidovudine (Combivir; 150 mg of lamivudine and 300 mg of zidovudine twice daily) has been evaluated in a 48-week, open-label study in HIV-infected patients who previously received antiretroviral regimens that included 1 or 2 NRTIs without any other antiretroviral agents. At the start of the study, 34% of patients had baseline plasma HIV-1 RNA levels less than 400 copies/mL and 11% had levels less than 50 copies/mL; the median CD4 T-cell count was 506/mm. At 48 weeks, 82% of patients had plasma HIV-1 RNA levels less than 400 copies/mL and 56% had levels less than 50 copies/mL (intent-to-treat analysis). Patients with baseline HIV-1 RNA levels less than 5000 copies/mL were more likely to achieve levels less than 400 copies/mL at week 48 than those with baseline levels exceeding 5000 copies/mL. At 48 weeks, the median change from baseline CD4 T-cell count was 66 cells/mm. While triple NRTI regimens are not generally recommended, some experts state that a regimen of the fixed combination of abacavir, lamivudine, and zidovudine (abacavir/lamivudine/zidovudine) may be considered when other regimens cannot or should not be used (e.g., because of concerns regarding drug interactions, toxicity, adherence).
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Pediatric Patients
Zidovudine is used in conjunction with other antiretrovirals for treatment of HIV-1 infection in children 4 weeks of age or older. In addition, the drug is used in neonates for prevention of perinatal HIV transmission as part of a regimen that includes intrapartum IV zidovudine prophylaxis in the mother and oral or IV zidovudine prophylaxis in the neonate.
(See Uses: Prevention of Perinatal HIV Transmission.) For initial treatment of HIV-infected pediatric patients, the HHS Panel on Antiretroviral Therapy and Medical Management of HIV-infected Children recommends a PI or NNRTI and 2 NRTIs (dual NRTIs). These experts state that the preferred dual NRTI options for initial treatment regimens in pediatric patients are zidovudine and either lamivudine or emtricitabine (can be used in pediatric patients of any age) or abacavir and either lamivudine or emtricitabine (can be used in those 3 months of age or older who are negative for HLA-B*5701).
When the dual NRTI option of lamivudine and zidovudine is used, the fixed-combination preparation containing both drugs (lamivudine/zidovudine; Combivir) can be used in pediatric patients weighing 30 kg or more.
Zidovudine and didanosine is an alternative (not a preferred) dual NRTI option that can be used in initial treatment regimens in children 2 weeks of age or older.
Zidovudine and abacavir is an alternative (not a preferred) dual NRTI option that can be used in initial treatment regimens in children 3 months of age or older who are negative for HLA-B*5701.
A dual NRTI option of zidovudine and stavudine should not be used at any time because of antagonistic antiretroviral effects.
Antiretroviral regimens that contain only NRTIs are not recommended for initial treatment in antiretroviral-naive children because of inferior virologic efficacy.
For further information on treatment of HIV infection in pediatric patients,
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Prevention of Perinatal HIV Transmission
Zidovudine is used for treatment of HIV-1 infection in pregnant women and also is used for prophylaxis in pregnant HIV-infected women and their neonates to prevent perinatal transmission of HIV.
In the US, multiple-drug antiretroviral regimens are considered the standard of care for treatment of HIV-1 infection in pregnant women and for prevention of perinatal HIV transmission. The HHS Panel on Treatment of HIV-infected Pregnant Women and Prevention of Perinatal Transmission states that all pregnant HIV-infected women in the US should receive multiple-drug antiretroviral therapy, regardless of the woman's plasma HIV-1 RNA level or CD4 T-cell count. In addition, to decrease the risk of perinatal HIV transmission, the HHS panel states that pregnant HIV-infected women with plasma HIV-1 RNA levels exceeding 1000 copies/mL (or unknown HIV-1 RNA levels) near the time of delivery should receive an intrapartum IV zidovudine prophylaxis regimen and all neonates born to HIV-infected women (HIV-exposed neonates) should receive an oral or IV zidovudine prophylaxis regimen. In certain situations (e.g., infant born to a woman who did not receive antepartum or intrapartum antiretrovirals or received only intrapartum antiretrovirals), a 3-dose nevirapine prophylaxis regimen is recommended in the neonate in addition to the usual neonatal zidovudine prophylaxis regimen. Combined antepartum, intrapartum, and neonatal antiretroviral prophylaxis is recommended since this strategy reduces perinatal HIV transmission by several mechanisms, including lowering maternal antepartum viral load and providing pre- and postexposure prophylaxis in the infant. Maternal and neonatal regimens recommended for prevention of perinatal HIV transmission in the US may differ from those used in other countries (e.g., resource-limited countries).
Multiple-drug regimens in pregnant women are more effective than single-drug regimens in reducing perinatal transmission of HIV. The HHS panel recommends that all HIV-infected pregnant women in the US receive a potent multiple-drug antiretroviral regimen that includes at least 3 drugs. The choice of antiretrovirals to include in antenatal regimens should be individualized based on the woman's antiretroviral history, resistance testing, and the known risks of adverse effects and teratogenicity associated with the drugs. For initial treatment in antiretroviral-naive pregnant women, a regimen that includes 2 NRTIs (dual NRTIs) and a ritonavir-boosted PI or an NNRTI is recommended. The preferred dual NRTI options for use in pregnant women are abacavir and lamivudine, tenofovir DF and emtricitabine (or lamivudine), or lamivudine and zidovudine. Use of zidovudine alone during pregnancy for prevention of perinatal HIV transmission is not optimal, but may be an option in some HIV-infected pregnant women not currently receiving antiretroviral therapy who have plasma HIV-1 RNA levels less than 1000 copies/mL and wish to minimize fetal exposure to antiretrovirals.
All pregnant women in the US who have plasma HIV-1 RNA levels exceeding 1000 copies/mL (or unknown HIV-1 RNA levels) near the time of delivery should receive the intrapartum IV zidovudine prophylaxis regimen initiated at the onset of labor and continued until delivery. Scheduled cesarean delivery also is recommended for such women to help decrease the risk of perinatal HIV transmission. The intrapartum IV zidovudine prophylaxis regimen is not required in women who have been receiving a multiple-drug antiretroviral regimen and have plasma HIV-1 RNA levels that have consistently been 1000 copies/mL or lower during late pregnancy and/or near delivery, provided there are no concerns about adherence to or tolerance of the antiretroviral regimen.
In those who are currently receiving a multiple-drug antiretroviral regimen that is well tolerated and providing adequate virologic suppression, the regimen should be continued on schedule as much as possible during labor and delivery. If the intrapartum IV zidovudine prophylaxis is indicated and the current antiretroviral regimen includes oral zidovudine, IV zidovudine should be substituted for oral zidovudine until after delivery; other antiretrovirals included in the woman's regimen can be continued orally during labor.
All HIV-exposed neonates should receive the neonatal zidovudine prophylaxis regimen initiated as soon as possible after delivery (preferably within 6-12 hours). A 6-week neonatal zidovudine prophylaxis regimen is recommended to reduce the risk of perinatal HIV transmission; however a 4-week zidovudine prophylaxis regimen can be considered for infants born to mothers who were receiving a recommended multiple-drug antiretroviral regimen and have had consistent viral suppression during the pregnancy, provided there are no concerns about the mother's adherence to the treatment regimen. In situations when an HIV-infected woman received no antiretroviral therapy prior to and/or during labor, the HHS panel recommends that the neonate receive a 3-dose nevirapine regimen in addition to the 6-week zidovudine prophylaxis regimen. The HHS panel states that, for US patients, decisions to include any additional antiretrovirals for prophylaxis with the recommended intrapartum and neonatal zidovudine prophylaxis regimens should be made in consultation with a pediatric HIV specialist (preferably before delivery) and should be accompanied by maternal counseling regarding the potential risks and benefits. These experts also state that, because safety and dosage data are not available, use of antiretrovirals other than zidovudine and nevirapine cannot be recommended for prophylaxis in premature HIV-exposed neonates.
For information on the risk of perinatal transmission of HIV and some additional information regarding recommendations for use of antiretroviral agents for prevention of perinatal HIV transmission, In addition, clinicians can consult the National Perinatal HIV Hotline at 888-448-8765 for information regarding antiretroviral treatment of pregnant HIV-infected women and their infants and prevention of perinatal HIV transmission.
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Postexposure Prophylaxis following Occupational Exposure to HIV
Oral zidovudine is used in conjunction with other antiretrovirals for postexposure prophylaxis of HIV infection following occupational exposure (PEP) in health-care personnel and other individuals exposed occupationally via percutaneous injury (e.g., needlestick, cut with sharp object) or mucous membrane or nonintact skin (e.g., chapped, abraded, dermatitis) contact with blood, tissue, or other body fluids that might contain HIV.
The US Public Health Service (USPHS) states that the preferred regimen for PEP following an occupational exposure to HIV is a 3-drug regimen of raltegravir used in conjunction with emtricitabine and tenofovir DF (may be administered as the fixed combination emtricitabine/tenofovir DF; Truvada). These experts recommend several alternative regimens that include an INSTI, NNRTI, or PI and 2 NRTIs (dual NRTIs). The preferred dual NRTI option for use in PEP regimens is emtricitabine and tenofovir DF (may be administered as emtricitabine/tenofovir DF; Truvada); alternative dual NRTIs are tenofovir DF and lamivudine, lamivudine and zidovudine (may be administered as the fixed combination lamivudine/zidovudine; Combivir), or zidovudine and emtricitabine.
Because management of occupational exposures to HIV is complex and evolving, consultation with an infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or the National Clinicians' Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) is recommended whenever possible. However, initiation of PEP should not be delayed while waiting for expert consultation.
For information on types of occupational exposure to HIV and associated risk of infection, management of occupational exposure to HIV, efficacy and safety of postexposure chemoprophylaxis, and recommendations regarding postexposure prophylaxis,
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Postexposure Prophylaxis following Nonoccupational Exposure to HIV
Zidovudine is used in conjunction with other antiretrovirals for postexposure prophylaxis of HIV infection following nonoccupational exposure (nPEP) in individuals who have had exposure to blood, genital secretions, or other potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.
For additional information on nonoccupational exposure to HIV and recommendations regarding postexposure prophylaxis,