Thursday, September 16, 2021

HIV Exposure During Pregnancy Case File

Posted By: Medical Group - 9/16/2021 Post Author : Medical Group Post Date : Thursday, September 16, 2021 Post Time : 9/16/2021
HIV Exposure During Pregnancy Case File
Eugene C. Toy, MD, Edward Yeomans, MD, Linda Fonseca, MD, Joseph M. Ernest, MD

Case 11
During an emergency cesarean section for breech presentation in labor on a patient with no prenatal care, a 25-year-old female obstetricsgynecology resident receives a needle stick on her index finger during closure of the fascia. She was wearing a single pair of gloves, and felt the suture needle prick her skin. No obvious blood was noted on her skin after the procedure, however. The resident expresses her concern to you, the attending physician, about the risk of HIV infection since the patient had an unknown status. She confides in you that she has been immunized against hepatitis B and tetanus, and had a negative HIV test at her new OB visit within the last month. She is currently 10 weeks pregnant.

➤ How should you proceed to determine her risk of acquiring HIV through this needle stick?
➤ What should the resident be advised to do at this time, and what would be different if the patient was known to be HIV positive?
➤ What are the potential complications for this patient?


ANSWERS TO CASE 11:
HIV Exposure During Pregnancy

Summary: This 25-year-old resident at 10 weeks pregnant has sustained a needle stick and is at risk of acquiring HIV and hepatitis C.

Most likely diagnosis: Risk of acquiring HIV, hepatitis C.
Next step: The patient’s HIV and hepatitis C status should be immediately determined. If the HIV status is positive, the resident should be offered advice regarding postexposure prophylaxis (PEP) for HIV.
Potential complications: Seroconversion to HIV; side effects of PEP to the resident and to the fetus.


ANALYSIS
Objectives
  1. Be able to advise patients about HIV risk after various exposures.
  2. Understand the risks and benefits of PEP in pregnancy.
  3. Be able to counsel an HIV-positive pregnant patient regarding means to reduce vertical transmission.
  4. Understand recommendations for intrapartum HIV prophylaxis.

Considerations

1. Risk of HIV after various exposures
The average resident reports almost 8 needlesticks over the time of a residency and 99% have reported at least one needlestick. Risk factors for needlestick accidents include lack of sleep and long work hours. Overall the average HIV transmission risk after mucus membrane exposure is approximately 0.09% and between 0.23% and 0.33% after percutaneous exposure to HIV-infected blood. The risk of transmission differs by type of injury and likely reflects the amount of viral exposure (Table 11–1).

An exposure that may place a health care worker at risk for HIV infection is defined by the Centers for Disease Control and Prevention (CDC) as a percutaneous injury (needlestick or laceration involving a sharp object) or contact of mucus membranes or nonintact skin with blood, tissue, or body fluids (including semen and vaginal secretions) that may be infected. Fluids not considered infectious (unless in the presence of blood) include feces, saliva, sputum, nasal secretions, urine, sweat, tears, and vomitus.

A low-risk injury is one that involves a solid needle, is artificial in nature, and the source patient has a viral load less than 1500 copies/mL.

Table 11–1 RISK OF ACQUIRING HIV WITH DIFFERENT EXPOSURES
RISK FACTOR
ODDS RATIO
Needle placed in the source patient’s artery or vein
4.3
Exposure to source patient who died of AIDS within 2 mo
5.6
Device visibly contaminated with source patient’s blood
6.2
Deep injury
15.2


Mucocutaneous exposures are generally considered low risk unless it involves a large volume of blood or the source patient has a viral load greater than 1500 copies/mL. High-risk exposures include those involving visible blood on a hollow needle or exposure to a needle that was in the artery or vein of the source patient.

Chlorhexidine, chloroxylenol, iodophor, and alcohol-based agents are virucidal against HIV, hepatitis C virus, and hepatitis B virus. Percutaneous exposure should be washed thoroughly with one of these agents. Mucocutaneous exposures should be flushed generously with water and eyes need to be copiously irrigated with saline or water.

Each institution is required by the Occupational Safety and Health Administration (OSHA) to have their own policy regarding management of exposures to various infectious agents and this should be reviewed. In general the clinical scenario and time of exposure should be documented. Relevant clinical information about the source patient should be documented including risk factors for HIV infection. Serologic test results should be obtained from the source patient for HIV, hepatitis B, and hepatitis C. Selecting the appropriate HIV-PEP regimen may be complex so it is strongly recommended that prior to starting a regimen, consultation occurs with an infectious diseases specialist who has expertise in antiretroviral therapy and HIV transmission. Resources for consultation include: PEPline at telephone 888-448-4911 or http://www.ucsf.edu/hivcntr/Hotlines/; HIV Antiretroviral Pregnancy Registry at http://www.apregistry.com/index.htm; and HIV/AIDS Treatment Information Service at http://aidsinfo.nih.gov.

Regardless of whether PEP has been administered, the healthcare worker should be offered postexposure counseling (including psychologic counseling), testing, and medical evaluation. Antibody testing using ELISA should be used for seroconversion monitoring at baseline, 6 weeks, 12 weeks, and 6 months after exposure. Testing at 12 months should be performed in those individuals that become infected with hepatitis C after exposure to a source patient that was coinfected with HIV and hepatitis C. Extended follow-up for 12 months is also warranted if the clinical judgment of the person’s health care provider deems it necessary. In addition, HIV testing should be performed on any exposed individual who has an illness compatible with an acute retroviral syndrome regardless of the interval since exposure.

2. Understanding the risks and benefits of postexposure prophylaxis (PEP) in pregnancy
Medications used in PEP to HIV include nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTIs, NNRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), protease inhibitors, and more recently an infusion inhibitor. The CDC recommendations depend on level of exposure risk (Tables 11–2 and 11–3). Persons that are placed on PEP should complete four full weeks of medications. Due to side effects, 17% to 47% of individuals on PEP do not complete the entire 4-week regimen. Approximately 41% will experience one or more symptoms, most commonly nausea (26.5%) and fatigue (22.8%).

The most commonly used two-drug regimens include two nucleosides. Zidovudine (ZDV) and lamivudine (3TC), also known in combination as Combivir, are taken twice daily. Tenofovir (TDF) and emtricitabine (FTC) are available in a once-daily combined formulation named Truvada. Common side effects of Combivir include GI upset, headaches, and malaise. Truvada is better tolerated, but there is less experience with this drug combination for PEP. Uncommon side effects of Truvada include rash, diarrhea, and weakness. Three-drug regimens usually involve adding a protease inhibitor such as Kaletra (lopinavir/ritonavir). Most protease inhibitors can cause GI upset and are cytochrome P450 inducers, so care should be taken if on other medications (Table 11–4).

While the effects of antiretroviral drugs in pregnancy and on the developing fetus are limited, there is growing data regarding the safety of many of these medications. There are, however, anti-HIV medications which should be avoided in pregnancy including the following:

Efavirenz is Class D and significant malformations (anencephaly, anophthalmia, and cleft palate) have been associated with its use in monkeys

Table 11–2 RECOMMENDED HIV PEP FOR PERCUTANEOUS INJURIES

EXPOSURE

TYPE
HIV-1
HIV-2
UNKNOWN
SOURCE
HIV
NEGATIVE
Low-risk
2-drug PEP.
Expanded
≥ 3-drug PEP.
Generally no PEP; however consider 2-drug PEP if source
with risk factors or exposure to infected person is likely.a
No PEP.
High-risk
Expanded
≥ 3-drug PEP.
Expanded
≥ 3-drug PEP
Generally no PEP; however consider 2-drug PEP if source
with risk factors or exposure to infected person is likely.a

No PEP.

a”Consider” indicates PEP is optional and decision to initiate PEP is based on discussion of risks and benefits with treating clinician.

receiving efavirenz during the first trimester at a dose comparable to human therapeutic exposure. There have also been three case reports of neural tube defects in humans after first-trimester exposure. Its use should be avoided in the first trimester and women of childbearing potential must be counseled on the risks and avoidance of pregnancy.

Table 11–3 RECOMMENDED HIV PEP FOR MUCOCUTANEOUS MEMBRANE EXPOSURE
EXPOSURE
TYPE
HIV-1
HIV-2
UNKNOWN
SOURCE
HIV
NEGATIVE
Small volume
(few drops)
2-drug PEP.
2-drug PEP.
No PEP.
No PEP.
Large volume
(major splash)
2-drug PEP.
Expanded
> 3-drug PEP.
Generally no PEP; however consider
2-drug PEP if source with risk factors or exposure to infected person is likely.a
No PEP.
a”Consider” indicates PEP is optional and decision to initiate PEP is based on discussion of risks and benefits with treating clinician.

Table 11–4 PRIMARY SIDE EFFECTS AND TOXICITIES ASSOCIATED WITH ANTIRETROVIRAL AGENTS
CLASS AND AGENT
SIDE EFFECT AND TOXICITY
NRTIs (nucleoside reverse transcriptase inhibitors)
Zidovudine
(Retrovir, ZDV, AZT)
Anemia, neutropenia, nausea, headache, insomnia, muscle pain/weakness
Lamivudine (Epivir, 3TC)
Abdominal pain, nausea, diarrhea, rash, and pancreatitis
Stavudine (Zerit, d4T)
Peripheral neuropathy, headache,diarrhea, nausea, pancreatitis, insomnia, elevated liver function tests (LFTs), anemia, neutropenia
Didanosine (Videx, ddI)
Pancreatitis, lactic acidosis, neuropathy, diarrhea, abdominal pain, nausea
Emtricitabine
(Emtriva, FTC)
Headache, nausea, vomiting, diarrhea, rash, skin discoloration
NtRTIs (nucleoside analogue reverse transcriptase inhibitors)
Tenofovir (Viread, TDF)
Nausea, diarrhea, vomiting, flatulence, and headache
NNRTIs (non-nucleoside reverse transcriptase inhibitors)
Efavirenz (Sustiva, EFV)
Rash (including Steven-Johnson), insomnia, somnolence, dizziness, nightmares, and teratogenicity
Protease inhibitors
Indinavir (Crixivan, IDV)
Abdominal pain, nephrolithiasis, and indirect hyperbilirubinemia
Nelfinavir (Viracept,NFV)
Diarrhea, nausea, abdominal pain,weakness, and rash
Ritonavir (Norvir, RTV)
Weakness, diarrhea, nausea, elevated cholesterol/triglycerides, oral paresthesia, taste alteration
Saquinavir
(Invirase, SQV)
Diarrhea, abdominal pain, nausea,hyperglycemia, elevated LFTs
Atazanavir
(Reyataz, ATV)
Nausea,headache, rash,abdominal pain, diarrhea, vomiting, indirect hyperbilirubinemia
Lopinavir/Ritonavir
(Kaletra) LPV/RTV
Diarrhea, fatigue, headache, nausea, increased cholesterol/triglycerides
Fusion inhibitor
Enfuvirtide
(Fuzeon, T-20)
Local site reaction, bacterial pneumonia, insomnia, depression, peripheral neuropathy, cough


Delavirdine and zalcitabine (which is no longer available in the United States) are not recommended secondary to rodent studies showing potential for teratogenicity and developmental toxicity.

Nevirapine is a Class B drug and while there is no evidence of human teratogenicity, there is increased risk of rash-associated, and potential fatal liver toxicity among those with CD4 counts more than 250/mm3 when first initiating therapy.

The use of didanosine (Class B) and stavudine (Class B) individually have a good safety record in pregnancy. However, fatal cases of lactic acidosis have been reported when used together.

Tenofovir is a Class B drug but there is insufficient data to recommend its use. Studies in monkeys have shown decreased fetal growth and reduction in fetal bone density. Clinical studies in humans have shown bone demineralization with chronic use, especially in children. There is also significant placental passage in humans so the clinical significance is unknown.

Reyataz (atazanavir) is a Class B drug with theoretical concerns regarding increased indirect bilirubin levels which may exacerbate physiologic hyperbilirubinemia in the neonate even though transplacental passage is very low. Insufficient data currently exists to recommend its use.

Other drugs that are not recommended as of yet due to insufficient data include: darunavir, fosamprenavir, tipranavir, enfuvirtide, maraviroc, and raltegravir.


3. Counseling an HIV-positive pregnant patient regarding means to reduce vertical transmission
Standard criteria for initiation of antiretroviral therapy in the treatmentnaïve patient according to the Department of Health and Human Services (DHHS) in 2008 are as follows: presence of an AIDS-defining illness or a CD4 count of less than 350 cells/mm, patients with HIV-associated nephropathy, or patients coinfected with hepatitis B. Clinical scenarios delineated and published by the Public Health Service Task Force (2008) help to describe optimal management strategies for women that are of childbearing age and are HIV positive. All scenarios reaffirm the importance of providing antiretroviral drugs during pregnancy, labor and to the infant to decrease vertical transmission. In all scenarios neonatal administration of zidovudine should be administered for 6 weeks started within 6 to 12 hours after birth.

Women receiving antiretroviral drugs that reduce HIV viral loads to less than 1000 copies/mL have a very low risk of transmission. However, viral load is not the determining factor when deciding the use of antiretroviral drugs in pregnancy because transmission can occur even at low or undetectable levels. Combination antiretroviral regimens are more effective than single-drug regimens in reducing transmission during pregnancy, so prophylactic antiretroviral drugs should be offered to all HIV-infected pregnant women, regardless of CD4 count or viral load.

Unadjusted for mode of delivery, women receiving antiretroviral therapy have an approximate 1.2% risk of vertical transmission. Among women with a viral load of less than 1000 copies/mL the transmission rate was 0.5% to 0.8% regardless of mode of delivery. ACOG has recommended that a scheduled cesarean delivery (prior to labor or ROM) at 38 weeks should be considered for all HIV-infected women with viral loads of more than 1000 copies/mL around the time of delivery. For women with a viral load less than 1000 copies/mL, data regarding the benefit of scheduled cesarean delivery has not been sufficient to prove this as the recommended mode of delivery. Prior to cesarean section zidovudine should be administered intravenously for at least 3 hours.

Factors that increase risk of transmission include elevated viral load, decreased CD4 count, and prolonged rupture of membranes. The risk of transmission increases 2% over the baseline risk for each hourly increment following membrane rupture. Therefore, assuming a baseline risk for transmission of 1%, the risk at 1 hour would be theoretically 1.02% and would increase to 1.16% at 8 hours post rupture of membranes.


4. Recommendations for intrapartum prophylaxis
Intrapartum management of the HIV-infected mother includes avoiding instrumentation and assisted second-stage delivery, and avoidance of placement of fetal scalp electrode and rupturing of membranes when possible. In addition an episiotomy should not be used if possible. Zidovudine is the antiretroviral drug of choice in maternal intrapartum and neonatal postpartum regimens (Tables 11–5 and 11–6).

HIV-infected women of childbearing age, but who are not currently pregnant and have indications for antiretroviral therapy should initiate therapy as per adult treatment guidelines. Drugs that have teratogenic potential or insufficient data to use in pregnancy should be avoided.

The HIV-infected woman who is antiretroviral naïve and does not require treatment for her own health should still be offered antiretroviral therapy during pregnancy and in the intrapartum period to decrease the risk of vertical transmission. Drug resistance testing is recommended prior to initiating drug therapy. One can consider delaying therapy initiation until after completion of the first trimester to decrease the risk of teratogenicity. The previously listed contraindicated drugs should be avoided, and the antiretroviral regimen used prenatally should be continued during the intrapartum period with ZDV given as a continuous infusion while

Table 11–5 MATERNAL INTRAPARTUM/POSTPARTUM
DRUG
DOSING
DURATION
Zidovudine (ZDV, AZT)
2 mg/kg IV over 1 h, followed
by continuous infusion of
1 mg/kg per hour.
Onset of labor until
delivery of infant.

Table 11–6 NEONATAL
DRUG
DOSING
DURATION
> 35 wk infant zidovudine
(ZDV, AZT)
2 mg/kg orally (or 1.5 mg/kg intravenously) started as close to birth as possible, then every 6 h.
Birth to 6 wk.
30-35 wk infant zidovudine
(ZDV, AZT)
2 mg/kg orally (or 1.5 mg/kg intravenously) started as close to birth as possible, then every 12 h, advanced to every 8 h at 2 wk of age.
Birth to 6 wk.
< 30 wk zidovudine
(ZDV, AZT)
2 mg/kg orally (or 1.5 mg/kg intravenously) started as close to birth as possible every 12 h,
advanced to every 8 h at 4 wk of age.
Birth to 6 wk.

other agents are continued orally. Drug therapy should be discontinued postpartum unless there is an indication for continued therapy.

The patient that is HIV-infected and antiretroviral naïve who has indications for antiretroviral therapy for maternal health reasons should also have drug resistance testing prior to initiation of therapy. Therapy should be started in this group of patients immediately even if medications must begin during the first trimester.

The infected mother who is receiving antiretroviral therapy and becomes pregnant should continue her regimen if it is suppressing the virus unless she is taking efavirenz or other potentially teratogenic drugs in the first trimester. Also to be avoided is the combination of didanosine and stavudine which have the potential for adverse effects to the mother. If viremia is not being successfully suppressed, drug resistance testing should be done. As a general rule drug therapy should not be halted in the first trimester. As with other HIV-positive patients, zidovudine should be given as a continuous infusion during labor while other antiretroviral agents are continued orally and in the postpartum period.

The pregnant woman who is HIV-infected and has had prior exposure to antiretroviral therapy but is not receiving therapy at the time of conception should have a complete history. Assessment should be made as to whether antiretroviral therapy is necessary for the health of the mother. Antiretroviral therapy should be started after resistance testing and continued as described in the preceding discussion during the intrapartum and postpartum period if indicated.

The HIV-infected woman who has received no antiretroviral therapy prior to presenting in labor should have one of the following regimens instituted: (1) zidovudine given to the mother intravenously and the infant for 6 weeks started within 6 to 12 hours after birth; or (2) zidovudine given as a continuous infusion during labor plus single-dose nevirapine at labor onset with single dose nevirapine plus zidovudine for the infant for 6 weeks. This regimen increases the risk of nevirapine resistance. Evaluation of the mother in the postpartum period should be undertaken to assess need for continued antiretroviral therapy.

An HIV-infected mother who presents after 36 weeks, is not on antiretroviral therapy, and in whom the viral load and CD4 count is unknown and will likely not be available prior to delivery should be started on antiretroviral therapy. She should be counseled that a scheduled cesarean section will likely reduce vertical transmission risk. The cesarean section should be scheduled at 38 weeks’ gestation on the best available dating information. Prior to surgery zidovudine should be started 3 hours prior to surgery and the infant should be treated as discussed in the preceding discussion. Prophylactic antibiotics at the time of cesarean section are recommended and continued antiretroviral therapy in the postpartum period is dictated by the CD4 count and viral load when they become available.

The HIV-infected woman who has elected a scheduled cesarean delivery but who presents in early labor or soon after rupture of membranes should have intravenous zidovudine started immediately. The decision to allow vaginal delivery or proceed to cesarean section should be made in the context of available clinical information such as how rapidly labor is progressing and how long membrane rupture has occurred.

Rapid testing for women in labor who presents with unknown HIV status is available and accurate. This allows the pregnant women to learn her HIV status and receive antiretroviral prophylaxis during labor and be referred for further workup postpartum. Antiretroviral therapy should be started immediately after a positive rapid HIV test result.

HIV transmission via breast milk has been well-documented and there is no safe way to treat breast milk to eliminate the virus and allow safe breastfeeding. The Public Health Service does not recommend breastfeeding for HIV-infected women in the United States, where safe and affordable alternatives are available.


Comprehension Questions

11.1 A 30-year-old surgical resident who is 10 weeks’ pregnant is stuck by a needle from a patient who is known to be HIV positive. Which of the following serological testing for the source patient is appropriate?
A. Hepatitis A
B. Hepatitis C
C. Cytomegalovirus
D. Herpes simplex virus

11.2 Which of the following antiretroviral drugs or drug combinations has the best safety profile in pregnancy?
A. Efavirenz
B. Delavirdine
C. Didanosine with stavudine
D. Nelfinavir

11.3 Which of the following should be a part of intrapartum management of an HIV-infected mother?
A. Intravenous administration of zidovudine as part of medication in labor
B. Early rupture of membranes
C. Placement of a scalp electrode
D. Instrumentation to assist second-stage of labor


ANSWERS

11.1 B. Regardless of whether PEP has been administered, the health care worker should be offered postexposure counseling (including psychological counseling), testing, and medical evaluation. Antibody testing using ELISA should be used for seroconversion monitoring at baseline, 6 weeks, 12 weeks, and 6 months after exposure. It is not required that the source patient be offered counseling. Hepatitis B and C and HIV viral load should be performed on the source patient.

11.2 D. While not the preferred protease inhibitor to be used in pregnancy, nelfinavir is the only above mentioned drug that has demonstrated a good safety profile for the mother and infant and has not demonstrated human teratogenicity. Efavirenz has been associated with anencephaly, neural tube defects, anophthalmia, and cleft palate. Rodent studies have shown potential for carcinogenicity and teratogenicity with the use of delavirdine. There have been cases of fatal lactic acidosis with the use of didanosine and stavudine in combination.

11.3 A. Intravenous administration of zidovudine is the cornerstone of therapy to decrease HIV vertical transmission. The Pediatric AIDS Clinical Trials Group protocol (PACTG) 076 demonstrated that the use of zidovudine in the antepartum and intrapartum periods and then administration to the newborn decreased transmission by approximately 70%. Intrapartum management of the HIV-infected mother includes avoiding instrumentation and assisted second-stage delivery as well as avoidance of placement of a fetal scalp electrode and artificial rupture of membranes if possible. In addition an episiotomy should not be used if possible.


Clinical Pearls

See US Preventive Services Task Force Study Quality levels of evidence in Case 1
➤ Any pt who experiences a needle stick should be offered post exposure counseling (Level III).
➤ Nelfinavir is the protease inhibitor that has been shown to have a good safety profile for the mother and infant (Level II-2).
➤ Route of delivery for HIV infected pregnant women depends on the viral load and prenatal medication use (Level II-3).

REFERENCES

1. Scheduled cesarean delivery and the prevention of vertical transmission of HIV infection. ACOG Committee Opinion Number 234, May 2000. Obstet Gynecol. 2001;73:279-281. 

2. Baggaley RF, Boily MC, White RG, Alary M. Risk of HIV-1 transmission for parenteral exposure and blood transfusion: a systematic review and meta-analysis. AIDS. 2006;20:805-812. 

3. Boyce JM, Pittet D. Guideline for hand hygiene in health-care settings. Recommendations of the healthcare infection control practices advisory committee and HICPAC/SHEA/APIC/IDSA hand hygiene task force. MMWR Recomm Rep. 2005;51(RR-16):1-45. 

4. Bulterys M, Jamieson DJ, O’Sullivan MJ, et al. Rapid HIV-1 testing during labor: a multicenter study. JAMA. 2004;292:219-223. 

5. Cardo DM, Culver DH, Ciesielski CA, et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. NEJM. 1997;337:1485-1490. 

6. CDC. Updated US Public Health service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR. 2005;54: 1-17. 

7. CDC. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States. MMWR. 2005;54:1-19. 

8. Conner EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. NEJM. 1994;331:1173-1180. 

9. Cooper ER, Chaurat M, Mofenson LM, et al. Combination antiretroviral strategies for the treatment of pregnant HIV-1 infected women and prevention of perinatal HIV-1 transmission. J Acquir Immune Defic Syndr Hum Retrovirol. 2002:55:592-597. 

10. DHHS Panel on Retroviral Guidelines for Adults and Adolescents-A working group of the Office of AIDS Research Advisory Council. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. AIDSinfo.nih.gov January, 2008. 1-127. 

11. European Collaborative Study. Mother-to-child transmission of HIV infection in the era of highly active antiretroviral therapy. Clin Infect Dis. 2005;40:458-465. 

12. Makary MA, Al-Attar A, Holzmueller CG, et al. Needlestick injuries among surgeons in training. NEJM. 2007;356:2693-2699. 

13. Parkin JM, Murphy M, Anderson J, El-Gadi S, Forster G, Pinching AJ. Tolerability and side-effects of post-exposure prophylaxis for HIV infection. Lancet. 2000;355:722-723. 

14. Public Health Service Task Force. Recommendations for use of antiretroviral drugs in pregnant HIV-infected women for maternal health and interventions to reduce perinatal HIV transmissions in the United States. AIDSinfo.nih.gov July, 2008. 1-98. 

15. Shapiro D, Tuomala R, Pollack H, et al. Mother-to child HIV transmission risk according to antiretroviral therapy, mode of delivery, and viral load in 2895 US women (PACTG 367). 11th Conference on retroviruses and Opportunistic Infections; February 8-11, 2004; San Fancisco, CA. Abstract 99.

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