Introduction
In resource-rich settings, we have had remarkable success in preventing mother-to-child transmission of HIV. The overwhelming majority of those infected with HIV live in resource-poor countries. Worldwide, as of December 2007, UNAIDS estimated there were over 33 million people living with HIV/AIDS: 31 million adults and 2.5 million children. Most HIV infections among children are due to mother-to-child transmission. Half of the 31 million HIV-infected adults are women [1].
Prevalence and risk factors in the USA
In the USA, most HIV-infected people do not have AIDS. The Centers for Disease Control and Prevention (CDC) estimated that as of June 2007, the cumulative number of HIV infections in the USA was over 1.6 million [2]. An increase of 40,000 new infections per year is anticipated in the USA. The number of AIDS cases already reported to the CDC is 956,109, and more than 530,000 of these people have died. While worldwide approximately half of adults with HIV are women, this is not the case in the USA. However, HIV among women is increasing; women now constitute 19% of the cumulative reported AIDS cases in the USA, with a total of over 180,000 diagnosed by June 2007, and over 26% of all AIDS cases reported in 2007.
Expanded treatment regimens have improved the prognosis for HIV-positive patients, with a decrease in progression to AIDS and a decrease in deaths due to AIDS. However, AIDS remains an important cause of death in women, especially minority women in the 25–44 years age group. Currently more women with HIV acquired this infection heterosexually (80%) than via their own injection drug use (19%). However, many infections in women can be traced to injection drug use in their sexual partners.
Minority women are disproportionately affected. Black and Hispanic women comprise 24% of the US adult and adolescent female population, but 82% of female AIDS cases.
Seroprevalence varies widely per region. In some cities more than 1% of all pregnant women are HIV positive; in Los Angeles County approximately 0.1%.
Risk factors for acquiring HIV infection include: injection drug use or other needle sharing, cocaine/crack use, commercial sex work, multiple sexual partners, a bisexual male partner, residing in areas of high HIV prevalence such as sub-Saharan Africa, the presence of other STIs, especially syphilis, and blood transfusion in the USA between 1978 and 1985. Any woman with a sexual partner with these risk factors is also at risk; many women are not aware of their partners’ risk. All women with active tuberculosis or cervical cancer should be considered high risk.
Diagnosis of HIV infection and AIDS
Voluntary, confidential screening should be offered to all pregnant women. This is the official recommendation by the US Public Health Service, the CDC [3], and also by the American College of Obstetricians and Gynecologists (ACOG) [4].
Several studies have demonstrated that by screening only those pregnant patients acknowledging risk factors such as those listed above, approximately half of HIV infections will be missed; in some populations, up to 70% of HIV-infected pregnant women had no apparent risk factors. Enzyme-linked immunoassay (ELISA or EIA) and confirmatory Western blot to HIV antibodies are used for adult diagnosis. A period of several months between infection and seroconversion is possible, although 2 months or less is typical. Patients undergoing screening must be informed of this “window period” and should have testing repeated in approximately 2 months if they had recent high-risk exposure.
Testing should be repeated in the third trimester in women at increased risk and should be considered in all pregnant women if local seroprevalence among women is > 0.5%. [3, 4]
Maternal anti-HIV IgG crosses the placenta and remains in the neonatal circulation for up to 12–18 months and is not useful to diagnose infection in the neonate. Testing the neonate will identify HIV-seropositive mothers and identify infants at risk for HIV. HIV DNA or RNA polymerase chain reaction (PCR) is used to demonstrate HIV infection in the neonate. With these techniques, infants can be diagnosed by 2 months of age.
An HIV-positive patient has AIDS when she develops an AIDS-indicator opportunistic infection such as Pneumocystis carinii pneumonia (PCP) or active tuberculosis, wasting, invasive cervical cancer or CD4 count below 200, indicating severe immunocompromise.
Despite intensive research efforts, many questions remain unanswered.
Half or more of perinatal transmission occurs around the time of delivery. Transmission rarely occurs during the first and second trimesters, but frequently occurs with breastfeeding. In the absence of antiretroviral treatment, reported rates of transmission range from 14% to 40%.
Many factors have been associated with increased transmission, with some studies reporting conflicting results. These include: higher viral load, advanced maternal disease, lower maternal CD4 count, use of scalp electrodes, amniocentesis, prolonged rupture of membranes, chorioamnionitis, concurrent syphilis infection, prematurity, a previous HIV-infected infant, and maternal substance abuse. Nearly all the studies addressing these factors found maternal viral load and/or CD4 count to correlate with perinatal transmission.
Two studies have demonstrated an approximately 50% decreased risk of perinatal HIV transmission with elective cesarean section prior to the onset of labor or rupture of membranes [5, 6]. These patients, however, received either no antiretroviral therapy or zidovudine monotherapy. These studies had no data regarding maternal viral load and did not evaluate maternal risk of elective cesarean section. Currently, most HIV-positive pregnant women receiving care at referral centers are using highly active combination antiretroviral therapy (HAART). Studies to date have not demonstrated a benefit of cesarean delivery in women on combination antiretroviral therapy with adequately controlled viral loads.
The May 2000 ACOG Committee Opinion on the use of cesarean delivery in HIV-infected women recommends that women with plasma viral load greater than 1000 copies/mL be offered a scheduled cesarean delivery [7]. If cesarean delivery is chosen, it should be done before rupture of membranes or onset of labor, and scheduled at 38 weeks’ gestation. Patients should be counseled that maternal morbidity associated with cesarean delivery may be greater in HIV-infected women. The Committee Opinion also recommends that pregnant women receive appropriate antiretroviral therapy. Increased maternal viral load, usually measured by plasma HIV RNA PCR, has consistently been associated with higher perinatal transmission rates. However, perinatal transmission can occur at any viral load, even with undetectable maternal plasma viremia, although this is infrequent. The risk of transmission is less than 1% if viral load at delivery is < 1000 copies/mL and the woman is on antiretroviral therapy.
The virus is present in breast milk and can infect the nursing infant, increasing the risk of perinatal transmission by an additional 10–20% in women not on antiretroviral treatment.
Role of zidovudine and other antiretroviral medications
The publication of the results of the AIDS Clinical Trials Group (ACTG) Protocol 076 in 1994 had a major impact on the management of HIV infection during pregnancy [8]. This study reported a highly significant reduction in perinatal transmission of HIV by use of zidovudine (ZDV, Retrovir®, AZT) in a selected group of relatively healthy HIV-positive women. They received oral ZDV during the second and third trimesters, IV ZDV intrapartum, and 6 weeks neonatal oral ZDV. ZDV was tolerated well, with no significant side effects. Perinatal HIV transmission was reduced from 23% in the placebo group to 8% in the ZDV group. Since dissemination of these recommendations and increased implementation of prenatal testing and the ZDV regimen, perinatal HIV transmission rates have decreased dramatically throughout the USA.
Several international studies have demonstrated the efficacy of shorter courses of ZDV, although this was not as effective as the “076 regimen” [9]. If the woman received no antiretroviral treatment, intrapartum or neonatal ZDV prophylaxis alone may be of some benefit. An epidemiologic study from the state of New York found that administration of ZDV only to the neonate significantly reduced transmission if initiated within 48 hours of birth [10].
Essentially all studies evaluating ZDV use in pregnancy have demonstrated decreased perinatal transmission with ZDV use; therefore it is recommended that ZDV be offered to all HIV-infected pregnant women regardless of HIV plasma viral load or CD4 count, plus additional antiretrovirals in most cases (see below) [11].
With the increased screening for maternal HIV infection and the widespread perinatal use of ZDV, there has been a dramatic decrease in perinatally acquired HIV in the USA. An estimated < 250 HIV-infected infants are born annually in the USA, while worldwide over 1000 infected infants are born daily.