HIV/AIDS Among Women
Isabel T. Lagomasino
Gustavo Rodriguez
The first case of acquired immunodeficiency syndrome (AIDS) among women was reported at the start of the epidemic in 1981.1 By 2002, human immunodeficiency virus (HIV) disease was the fifth leading cause of death for women 25 to 34 years old in the United States and the sixth leading cause for women 35 to 44 years old, accounting for approximately 5% of deaths among women 25 to 44 years old.2 Women now make up approximately 27% of HIV infection and AIDS cases in the United States, and the majority are exposed through heterosexual contact.2 Several biologic and social risk factors place women at greater risk for HIV infection, and their disease burden is compounded by the risk for vertical transmission. Multifaceted treatment and prevention programs must be developed and implemented to address the specific needs of women at risk and infected with HIV.
Epidemiology
Over the past two decades, women have accounted for an increasing proportion of new HIV infections and AIDS diagnoses. Within the United States, ethnic minority women are disproportionately affected. Compared to White women, for example, African Americans have 25 times the rate of AIDS diagnoses and Latinos 6 times the rate.2 In 2002, HIV disease was the leading cause of death for African-American women 25 to 34 years old, accounting for 14.7% of deaths.2 Younger women are also at greater risk; teenagers account for 50% of new infections, of whom 61% are females and more than half are African American.3 Heterosexual women acquire HIV at an earlier age than heterosexual men, likely due to infection by older sex partners.4
By 1995, heterosexual contact surpassed intravenous drug use as the major mode of HIV transmission for women.5 The 2003 HIV/AIDS Surveillance Report estimates that 79% of HIV infection and AIDS cases among women were due to heterosexual contact; 19% to intravenous drug use; and 2% to other causes, including hemophilia, blood transfusions, perinatal exposure, and unknown or unidentified risks.2 Five states—New York, Florida, New Jersey, Texas, and North Carolina—accounted for 52% of newly reported cases of HIV infection.2 Although HIV infection and AIDS cases among women were originally concentrated among intravenous drug users in the Northeast, increasingly, women infected thorough heterosexual contact reside
in the South and rural areas.2 Those infected through intravenous drug use often use cocaine and amphetamines rather than heroin, both of which have been associated with increased needle sharing.6 Use of crack cocaine, although not a direct mode of transmission, has been reported to increase the risk of heterosexual spread through increases in high-risk behaviors, including higher numbers of sex partners and the exchange of sex for drugs.7
in the South and rural areas.2 Those infected through intravenous drug use often use cocaine and amphetamines rather than heroin, both of which have been associated with increased needle sharing.6 Use of crack cocaine, although not a direct mode of transmission, has been reported to increase the risk of heterosexual spread through increases in high-risk behaviors, including higher numbers of sex partners and the exchange of sex for drugs.7
Risk Factors
Both biologic and social risk factors may increase the risk of HIV infection among women. The odds of male-to-female heterosexual transmission has been estimated to be as much as 20 times higher than that of female-to-male transmission.8 Susceptibility increases when biologic factors are present that provide direct viral access to the bloodstream, that cause inflammation or immune activation that results in greater numbers and susceptibility of target cells, or that facilitate the survival of HIV in mucosa.9 In addition to viral HIV load, risk factors thus include receptive anal intercourse, cervical ectopy, genital ulcer disease or other sexually transmitted disease, use of hormonal contraceptives, and pregnancy.9,10 Cervical ectopy refers to the extension of columnar epithelium from the endocervix to the proximal portion of the cervix, immediately adjacent to squamous epithelium. Characteristic of cervical immaturity, the area of ectopy is fragile and promotes easy access to blood and lymphatic systems.11 Although not clearly understood, contraceptive hormones may increase cervical ectopy or produce thinning of vaginal epithelia. Pregnancy is similarly a time of increased progesterone levels and ectopy.12
Numerous social factors place women at risk for HIV infection. Cultural norms and attitudes may discourage sexual education or the use of safe-sex methods, while promoting acceptance of promiscuity among men.13 Poverty may increase risk for women through multiple mechanisms. In the midst of multiple issues related to survival, the need to negotiate safe sex practices may be perceived as less important and women may feel less empowered to engage in such discussions. They may be forced to rely on men who engage in high-risk sexual behaviors and are more likely to exchange sex for gifts or money.13 Violence may result directly in unwanted sexual acts. Women exposed to early childhood traumas may also be more likely to engage in high-risk behaviors, and those fearing violence may be less able to negotiate barrier methods of protection. Commercial sex workers are at especially high risk, as are incarcerated women, who may have high-risk partners, engage in unprotected sex and sex exchange, and use intravenous drugs.13
In an interesting exploration of racial disparities in rates of sexually transmitted infections, differences between the sexual networks of Blacks and Whites are theorized to also contribute to elevated risks for African Americans.14 Compared to Whites, Blacks are more likely to report having overlapping sexual partners and to have more closed sexual networks. The low male-to-female ratio that results from high mortality and incarceration rates among Black men results in low marriage rates, greater tolerance by women of high-risk behaviors by men, and increased high-risk behaviors among women. The marginal economic status of many African-American men contributes to fewer long-term partnerships, and high rates of incarceration promote further risk for infection for individuals and their sexual networks.14
HIV Illness
Although disease progression of HIV infection appears to be similar for women and men, several studies have reported lower survival rates among women. Differences have mostly been attributed not to biologic factors but to disease stage, socioeconomic factors, and access to care.5 A large cohort study from the late 1980s found that 3-fold differences in mortality rates from HIV infection were mostly accounted for by disease stage (56% of excess risk), age
(12%), ethnicity (11%), mode of transmission (8%), gender (8%), and interactions among these variables (5%).15 A subsequent large-scale, multisite, multicity study examined mortality rates for women and men infected with HIV in each of six CD4 strata, adjusting results for age, ethnicity, mode of transmission, history of intravenous drug use, and Karnofsky score. Disease progression was found to be similar for both genders, but the mortality rate was higher among women, especially for African-American women and those using intravenous drugs, although deaths were mostly from non–HIV-related causes.16 The excess mortality was postulated to be secondary to socioeconomic factors, including poverty, homelessness, domestic violence, substance abuse, lack of social support, and limited access to care.16
(12%), ethnicity (11%), mode of transmission (8%), gender (8%), and interactions among these variables (5%).15 A subsequent large-scale, multisite, multicity study examined mortality rates for women and men infected with HIV in each of six CD4 strata, adjusting results for age, ethnicity, mode of transmission, history of intravenous drug use, and Karnofsky score. Disease progression was found to be similar for both genders, but the mortality rate was higher among women, especially for African-American women and those using intravenous drugs, although deaths were mostly from non–HIV-related causes.16 The excess mortality was postulated to be secondary to socioeconomic factors, including poverty, homelessness, domestic violence, substance abuse, lack of social support, and limited access to care.16
Gender differences in biologic markers of HIV infection, including CD4 counts and plasma HIV ribonucleic acid (RNA) levels, have been reported but are of unclear significance. Uninfected women have higher CD4 counts than uninfected men, and infected women maintain higher counts than infected men throughout much of their disease course.17 Women have also been found to have lower HIV RNA levels than men at the same CD4 counts, although this difference seems to equalize when CD4 counts fall below 200 106/L.18 Disease progression and survival at given CD4 counts or HIV RNA levels have not consistently been found to be different for women and men, however; thus recommendations for initiating antiretroviral therapy are no different for genders. Some studies report, however, that women may progress to AIDS at higher CD4 counts and lower viral levels, suggesting that perhaps they should be treated earlier in the course of HIV infection.18 Additional research is required in this area.
The occurrence of HIV-related illnesses appears to be similar for women and men. Common manifestations that appear equally in both genders include Pneumocystis jiroveci (formerly carinii) pneumonia, esophageal candidiasis, mycobacterial infections, bacterial pneumonias, and non-Hodgkin’s lymphomas. Gynecologic infections, especially bacterial vaginosis, may be common among HIV-infected women, although rates may be similarly high among women not infected but at high risk secondary to demographic and behavioral risk factors.5 HIV-infected women have been found to have increased risk for cervical cancer, leading to the inclusion of cervical cancer as an AIDS-defining condition in 1993. They have extremely high rates of human papillomavirus (HPV), the sexually transmitted DNA virus responsible for most cases of cervical cancer, and increased rates of squamous cervical lesions.19 HPV infections have been associated with low CD4 counts and elevated HIV RNA levels.19 Among women with HIV, HPV infections are more persistent than among those without, and infection may be more likely to extend outside the cervix to the vagina and vulva. Infections with HPV-16 and HPV-18, the strains most associated with cervical cancer, may also be more common.20
Sexuality and Pregnancy
Pregnancy and Contraception
Pregnancy does not appear to influence disease progression among HIV-infected women.21 Overall, obstetric outcomes for women with HIV appear to be similar to those of noninfected women, although lower CD4 percentages have been associated with low-birth-weight infants and a trend toward preterm births.22 However, in the absence of HIV-specific interventions, the risk of vertical transmission from infected mother to infant in industrialized countries such as the United States is roughly 25%.23 HIV may be transmitted in utero, at birth, or through breast feeding.
Among HIV-infected women who do not breast feed, approximately one third of vertical transmissions occur in utero (95% of them in the 2 months before delivery) and two thirds occur around the time of delivery.23 Transmission is more likely in the presence of elevated
maternal HIV RNA levels or decreased CD4 counts. Obstetric complications that increase risk include prolonged rupture of membranes, chorioamnionitis, and in some studies, amniocentesis, maternal sexually transmitted infections, intrapartum maternal hemorrhage, and use of intrapartum fetal scalp electrodes or sampling.24 Preterm infants and those with a birth weight less than 2500 g may be more likely to become infected. Rates of HIV transmission though breast feeding are estimated to be 15% to 16%.25 Risk factors for transmission through breast feeding similarly include low CD4 counts and elevated viral loads, as well as the mother being recently infected with HIV or having breast pathology (i.e., cracked nipples, mastitis) or the infant having oral thrush.26
maternal HIV RNA levels or decreased CD4 counts. Obstetric complications that increase risk include prolonged rupture of membranes, chorioamnionitis, and in some studies, amniocentesis, maternal sexually transmitted infections, intrapartum maternal hemorrhage, and use of intrapartum fetal scalp electrodes or sampling.24 Preterm infants and those with a birth weight less than 2500 g may be more likely to become infected. Rates of HIV transmission though breast feeding are estimated to be 15% to 16%.25 Risk factors for transmission through breast feeding similarly include low CD4 counts and elevated viral loads, as well as the mother being recently infected with HIV or having breast pathology (i.e., cracked nipples, mastitis) or the infant having oral thrush.26
Fortunately, antiretroviral agents dramatically reduce the risk of vertical transmission. Two large cohort studies found that rates of transmission were reduced from 20% among women not receiving antiretroviral therapy to 5% to 10% for those on zidovudine and to 1% to 2% for women taking multiagent regimens.27 The benefits of these antiviral combinations must be weighed against their potential risks, however, which include the development of resistant mutations in the mother or infant, maternal complications (possible hepatic failure, gestational diabetes, and preeclampsia), and effects on the fetus (possible preterm delivery, very low birth weight, and mitochondrial dysfunction). Elective cesarean delivery at 38 weeks’ gestation also appears to reduce the risk of infection. A meta-analysis of 15 prospective cohort studies found that HIV-infected women undergoing cesarean section had roughly half the odds of vertical transmission.28 The association held even for women receiving antiretroviral therapy before or during delivery and for whose neonates received antitretrovirals. More recent work has not shown a protective effect for cesarean section among women with low HIV RNA levels and has called attention to the morbidity associated with cesarean section among HIV-infected women.29 Similarly, although women in industrialized countries who have access to sanitary breastmilk substitutes have been encouraged not to breastfeed, the risks and benefits must be more carefully weighed in developing countries.26
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