HIV is an RNA virus that belongs to the retrovirus (Retroviridae) family and Lentivirus subfamily.
The most common cause of HIV disease in the United States is HIV-1.
HIV-2, a related strain, is endemic to Western Africa. It is less virulent than HIV-1 and less transmissible. It has a longer incubation period, is associated with lower viral loads, and progresses to AIDS less often than HIV-1. HIV-2 is primarily seen in the United States in immigrants from West Africa.
Currently, it is estimated that two thirds to three fourths of new cases of HIV in women in the United States result from heterosexual transmission.
Without any intervention, maternal-to-child transmission (MTCT) of HIV occurs in 14% to 42% of live births, depending on the setting.
HIV infection results in progressive depletion of helper T cells.
The subset of T lymphocytes affected is defined phenotypically by the presence of the CD4 receptor, which is the primary docking protein for HIV.
Fusion and entry of the virus into the cell are facilitated by coreceptors, including CXCR4 and CCR5.
Infection results in functional impairment and gradual depletion of CD4 cells, leading to immunodeficiency and subsequent opportunistic infection.
HIV-RNA level (viral load) reflects active viral replication, and this can be used to track disease progression and therapeutic response. Higher viral loads predict more rapid disease progression.
The American College of Obstetricians and Gynecologists (ACOG) and CDC recommend offering HIV testing to all pregnant women:
as a routine part of antenatal care, unless the woman declines (opt-out approach).
with repeat testing in the third trimester to those in areas with high HIV prevalence, to those known to be at risk, and to those who declined earlier testing.
as a rapid screen on presentation to labor and delivery for any pregnant woman of unknown HIV status or any pregnant woman who tested negative in early pregnancy but is at high risk of infection (sexually transmitted infection [STI] diagnosis, illicit drug use, trade of sex for money or drugs, multiple partners, HIV-positive partner, signs/symptoms of HIV, or living in an area with high HIV incidence/prevalence) and was not tested in the third trimester.
It is important to know individual state law concerning HIV testing in pregnancy, as rules vary widely.
Studies have shown that the rate of acceptance of HIV testing varies with the approach.
When extensive pretest counseling is required and patients must specifically consent to testing (the opt-in approach), testing occurs less frequently. The opt-out approach includes counseling for basic information about HIV, the rationale for testing, the availability of therapeutic and preventive interventions, and recognition of ability to refuse testing.
Most patients test positive within 1 month of primary infection, however, seroconversion may take up to 6 months.
The most commonly used HIV screening test is a laboratory serum enzyme-linked immunosorbent assay (ELISA). A positive or indeterminate test is followed by a Western blot for confirmation.
Rapid HIV antibody assays are available and require about 5 to 20 minutes, depending on the test, to obtain a result. Rapid tests use a variety of specimens including blood, plasma, serum or saliva. Many of the simple bedside or office rapid tests are clinical laboratory improvement amendments (CLIA) waived. The sensitivity and specificity of these tests are comparable to the ELISA HIV test. Because the positive predictive value declines with decreasing seroprevalence, a positive result with a rapid HIV test must be confirmed by the Western blot test.
Appropriate posttest counseling is required. Important issues include:
The role of safe sex practices in preventing HIV transmission and limiting other STIs, including superinfection with resistant strains of HIV-1
HIV screening of older children who may have been perinatally infected
Encouraging substance abuse rehabilitation, if appropriate
Encouraging disclosure to sexual partners and health care providers; offer assistance with disclosure and consider issues related to possible domestic violence
Pregnancy intentions and information on effective contraception should be discussed on a routine basis with women of childbearing age. Current data suggest that
over 50% of pregnancies in HIV-positive women are unintended. In HIV-positive adolescents, the rate of unintended pregnancy is as high as 83%.
In pregnancies complicated by HIV disease, the major goals are to optimize maternal health and to reduce the risk of perinatal transmission. Ideally, a treatment plan will be made during preconception counseling that excludes drugs with teratogenic potential. HIV status should be assessed by viral load and CD4 count. Women on antiretroviral therapy should be encouraged to achieve an undetectable HIV-1 RNA viral load prior to conception to decrease the risk of MTCT.
Women who meet criteria to initiate HAART for maternal viral status should do so prior to pregnancy. Women who do not yet meet HAART criteria are generally not started until after the first trimester. Efavirenz should not be initiated in women who may become pregnant or during the first trimester of pregnancy.
Appropriate vaccinations to be administered (ideally before conception) include influenza, pneumococcus, hepatitis A, hepatitis B, tetanus. Rubella and varicella vaccine is given prepregnancy if the CD4 count is >200.
Women should be counseled on the importance of eliminating tobacco, alcohol, and illicit drug use prior to conception.
Serodiscordant couples that wish to conceive should be referred for expert consultation. Appropriate screening and counseling on safe conception options depending on the gender of the infected partner should be addressed.
In the United States, approximately 19% of HIV/AIDS cases are due to injection drug use. Noninjection drug use (e.g., crack cocaine) also contributes to HIV transmission, and illicit drug use has been associated with higher vertical transmission rates. Rehabilitation resources should be provided.
Screening for domestic violence is important. Approximately two thirds of HIVpositive women have a lifetime or recent history of violence.
Addressing mental health concerns is paramount. Up to 50% of HIV-positive women experience depression—more than twice as often as HIV-positive men or the general population. HIV-positive women should be screened for depression in pregnancy and managed appropriately. Mental health status can affect medication adherence.
Variables associated with increased vertical transmission include the following:
High plasma or genital tract HIV viral load
Primary HIV infection or advanced AIDS
Low CD4 count
Sexually transmitted/genital tract coinfection
Placental disruption/abruption, chorioamnionitis
Active substance abuse
Invasive fetal monitoring or assessment (e.g., fetal scalp sampling, chorionic villus sampling, amniocentesis)
Prolonged rupture of membranes
Preterm delivery
Episiotomy
Instrumental delivery
Breast-feeding
All pregnant women should be offered treatment regardless of CD4 T-cell count or viral load to reduce MTCT (Table 24-1); women should be counseled on the
benefits and possible risks of HAART. A combined antiretroviral drug regimen is recommended and adherence must be stressed.
TABLE 24-1 Antiretroviral Therapy and Rates of Perinatal HIV Transmission
Treatment Category
Vertical Transmission Rate (%)
Untreated
20-30
Zidovudine monotherapy
10
Dual therapy
4
HAART
1-2
HAART, highly active antiretroviral therapy.
Initial evaluation should include:
History of HIV-related conditions and trend of prior CD4 T-cell counts and HIV viral loads
Current CD4 T-cell count and HIV viral load
Baseline complete blood cell count and liver function testing
Screening for hepatitis C virus and tuberculosis infection
Antiretroviral drug resistance studies in all women with HIV-1 RNA viral load levels above the threshold of resistance testing before initiating or changing HAART regimen
Appropriate prophylaxis in women at risk for opportunistic infections, as outlined in Table 24-2
For women who are not on antiretroviral therapy at the beginning of pregnancy, it may be delayed until after the first trimester in women with high CD4 cell count and low HIV viral load. Some evidence has shown that earlier initiation of antiretroviral (ARV) medications may lead to more effective viral suppression and reduce the risk of vertical transmission of HIV.
Decisions regarding an appropriate regimen should consider:
Previous and current ARV treatment and viral resistance. Women who are receiving ARVs for their own health should not discontinue during pregnancy. The current HAART regimen should be continued as long as it is tolerated and effectively leading to viral suppression.
Safety and toxicity profiles for specific drugs during pregnancy (considering both mother and fetus)
Medical comorbidities that may contraindicate certain medications
Patient compliance/adherence to treatment
Specific drug regimens should be selected in consultation with an HIV specialist.
To optimally suppress viral replication, minimize the risk of vertical transmission, and minimize the risk of new resistance mutations; strict adherence to the treatment regimen is crucial.
The use of zidovudine (AZT) alone in the antenatal period is now generally discouraged except in select circumstances including high CD4 count with very low viral load (< 1,000), patient refusal of HAART, or patient nonadherence to HAART. Combination therapy should be considered for all pregnant women, regardless of CD4 or HIV viral load.
TABLE 24-2 Opportunistic Infection Primary Prophylaxis
Opportunistic Infection
Indication
Recommendation
Pneumocystis jiroveci (formerly called Pneumocystis carinii) pneumonia
CD4 <200 cells/µL
Bactrim DS daily (preferred); dapsone 50 mg bid or 100 mg daily is alternative
Aerosol pentamidine 300 mg dose every 4 wk (may be considered in first trimester; may not achieve adequate distribution in lung in later pregnancy)
Toxoplasma gondii encephalitis
CD4<100
Bactrim DS daily (preferred) OR pyrimethamine 50 mg weekly + dapsone 50 mg daily + leucovorin 25 mg weekly OR dapsone 200 mg + pyrimethamine 75 mg + leucovorin 25 mg all weekly
Disseminated Mycobacterium avium complex
CD4 <50
Azithromycin 1,200 mg weekly OR rifabutin 300 mg by mouth daily (be aware of drug interactions with antiretroviral therapy; rule out active TB)
Prophylaxis against opportunistic pathogens is indicated at specific CD4 counts, and this treatment should be initiated or maintained in pregnancy. Consult an HIV expert when treatment or secondary prophylaxis/chronic maintenance therapy is needed.
DS, double strength; bid, twice daily; TB, tuberculosis.
Adapted from Kaplan JE, Benson C, Holmes KK, et al; Centers for Disease Control and Prevention; National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America.
Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. MMWR Recomm Rep 2009;58(RR-4);1-207.
Nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)
Nonnucleoside reverse transcriptase inhibitor (NNRTI)
Protease inhibitor (PI)
Entry inhibitor
Integrase inhibitor
HAART is the combination of three or four drugs from at least two different classes. It has been shown to dramatically reduce the risk of vertical transmission. Regimens typically include two NRTIs plus a booster PI or an NNRTI for pregnant women who have never received ARV medications (ARV-naïve).
Most extensively studied HIV medication in pregnancy. The preferred NRTI combination among ARV-naïve women is zidovudine and lamivudine based on extensive safe clinical experience in pregnancy and efficacy studies in preventing perinatal transmission.
TABLE 24-3 Preclinical and Clinical Data on Antiretrovirals in Pregnancy
Antiretroviral Drug
FDA Pregnancy Category
Placenta Passage
Long-Term Animal Carcinogenicity Studies
Animal Teratogenicity Studies
Nucleoside and nucleotide analogue reverse transcriptase inhibitors
Abacavir (Ziagen, ABC)
C
Yes (rats)
Positive (malignant and nonmalignant tumors of the liver, thyroid, preputial, and clitoral glands)
Positive (fetal anasarca and skeletal malformations)
Didanosine (Videx, ddI)
B
Yes (human)
Negative
Negative
Emtricitabine, (Emtriva, FTC)
B
Yes (mice and rabbits)
Negative
Negative
Lamivudine (Epivir, 3TC)
C
Yes (human)
Negative
Negative
Stavudine (Zerit, d4T)
C
Yes (rhesus monkey)
Positive (liver and bladder tumors)
Negative
Tenofovir (Viread)
B
Yes (human)
Positive (hepatic adenomas)
Negative
Zalcitabine (HIVID, ddC)
C
Yes (rhesus monkey)
Positive (thymic lymphoma)
Positive (hydrocephalus)
Zidovudine (AZT)
C
Yes (human)
Positive (noninvasive vaginal epithelial tumors)
Positive (and fetal resorption)
Nonnucleoside reverse transcriptase inhibitors
Delavirdine (Rescriptor)
C
Unknown
Positive (hepatocellular adenomas, carcinomas)
Positive (VSD)
Efavirenz (Sustiva)
D
Yes (monkey, rat, rabbit)
Positive (hepatocellular adenomas, carcinomas, pulmonary alveolar/bronchiolar adenomas in females)
Positive (anencephaly, anophthalmia, microphthalmia)
Nevirapine (Viramune)
B
Yes (human)
Positive (hepatocellular adenomas and carcinomas)
Negative
Protease inhibitors
Amprenavir (Agenerase)
C
Minimal/variable (human)
Positive (hepatocellular adenomas and carcinomas)
Negative (but deficient ossification and thymic elongation)
Atazanavir
B
Minimal/variable (human)
Positive (hepatocellular adenomas)
Negative
Darunavir (Prezista)
B
Unknown
Not completed
Negative
Fosamprenavir (Lexiva)
C
Unknown
Positive (benign and malignant liver tumors)
Negative (deficient ossification with amprenavir)
Indinavir (Crixivan)
C
Minimal (human)
Positive (thyroid adenomas and carcinomas)
Negative (but extra ribs)
Lopinavir/ritonavir (Kaletra)
C
Yes (human)
Minimal/variable (human)
Positive (hepatocellular adenomas and carcinomas)
Nelfinavir (Viracept)
B
Minimal/variable (human)
Positive (thyroid follicular adenomas and carcinomas)
Negative
Ritonavir (Norvir)
B
Minimal (human)
Positive (liver adenomas and carcinomas)
Negative (but cryptorchidism)
Saquinavir (Fortovase)
B
Minimal (human)
Negative
Negative
Tipranavir (Aptivus)
C
Unknown
In progress
Negative (decreased ossification and weights)
Entry inhibitor
Enfuvirtide (Fuzeon)
B
Unknown
Not done
Negative
Maraviroc (Selzentry)
B
Unknown
In progress
Negative
Integrase inhibitors
Raltegravir (Isentress)
C
Yes (rats)
In progress
Negative (extranumerary ribs)
FDA, U. S. Food and Drug Administration; VSD, ventricular septal defect.
Adapted from Benson CA, Kaplan JE, Masur H, et al; Centers for Disease Control and Prevention; National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America. Treating opportunistic infections among HIV-infected adults and adolescents. MMWR Recomm Rep 2004;53(RR-15);1-112.
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