HIV Disease in WomenPamela Juba, M.D., HIV specialist and Assistant Professor at University of Florida Health Science Center / Jacksonville. Associate Director of Adult Programs of the Rainbow Center for Women, Adolescents, Children and Families.
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IntroductionThe World Health Organization estimates that women comprise 45 - 50% of the total number of persons living with HIV/AIDS in the world. In the United States the number of reported AIDS cases from July 1998-1999 showed 23% of these cases in women with 80% of those in African American or Hispanic women. As this percentage of the total cases continues to increase, clinics that specialize in HIV care will need to meet the specific needs of HIV infected women. Globally, as well as in the Jacksonville area, the main mode of transmission is heterosexual contact. The other modes of transmission include intravenous drug abuse, perinatal transmission and receipt of infected blood or blood products. Women, especially African American women are at the greatest risk often due to lower socioeconomic status, poverty, and poor access to medical care and limited support systems. Though there are some differences regarding presenting symptoms and specific problems for HIV infected women, the morbidity, mortality rate, treatment, and treatment response is similar in men and women who are infected. Treatment guidelines have been published for HIV infected adults called Department of Health and Human Services Panel on Clinical Practices for Treatment of HIV Infection. This is accessible on the web at http://www.hivatis.org. TransmissionIn the north Florida area less than one percent of HIV infected adults reported blood or blood product transfusion as their risk factor and 21% reported IVDU. Sexual contact, both heterosexual and homosexual, represented 54% of the HIV cases. In women receptive vaginal intercourse carries a risk of infection of 0.1-0.2% per episode whereas the risk from rectal intercourse is even greater at 0.1-3% per episode. Risk of transmission from receipt of infected blood or blood products are as high as 95% from a single unit. Occupational exposure continues to be a concern for health care workers. The risk of transmission depends on the size of the needle, location of the inoculum, viral load of the patient but is approximately 0.67% per exposure. There are currently guidelines for postexposure prophylactics and can be found on the above-mentioned website. In the United States the number of cases of AIDS in women through June 1999 showed 42% had listed IVDU as their risk and 3% receipt of blood or blood products. All these exposure rates vary by geographical location with the transmission rate related to the prevalence within the community. Transmission is related not only to the infectiousness of the host but also the susceptibility of the recipient. If the host has recently become infected or is at the advances stages of HIV disease, they may have a very heavy viral burden. Any sexual contact during this time increases the risk of transmission to their partner. Though the use of highly active antiretroviral therapy (HAART) decreases the viral burden and risk of transmission, the risk is not completely eliminated. Studies have shown that virus may still be detectable in semen or in vaginal secretions despite a nondetectable viral load in the plasma. Other factors that may increase infectivity from a male partner may include ulcerative disease, lack of circumcision and trauma during sexual activity. For heterosexual transmission factors that present in women, which may contribute to infectivity, include presence of menstruation, ulcerative and nonulcerative genital tract disease, cervical ectopy, local trauma, and inflammation of the genital or rectal mucosa. Several studies have looked at nonbarrier contraceptive methods, which have been inconclusive. The genetic and immunological factors of the host also play a critical role in the risk of acquisition of HIV disease. For example cohort studies on Nairobi sex workers who were repeatedly exposed to HIV but remained uninfected have helped to identify factors that may lead to complete protection. In individuals who genetically lack the receptor, CCR5, necessary for the virus to enter the CD4 cell for replication, were found to be resistant to sexual transmission of the virus. There are probably other immunologic factors as 5-10% of the population that are HIV infected are termed nonprogressors as they show no evidence of immunologic deterioration despite infection. Barrier methods reduce the risk of sexual transmission yet in the African American population the use of condoms is often limited due to fear of distrust, poor education regarding transmission and risks of domestic violence. This is one of the reasons that heterosexual transmission rates continue to increase in this group of women especially in the southeastern United States. Disease in ProgressionGender based difference in the course of HIV infection continues to be a concern and the object of several past and ongoing studies. Many studies have shown that women present later in the course of their disease tend to receive less care and often are not offered similar treatments or access to clinical trials when compared to similar HIV infected men. Predictors of disease progression based on CD4 counts or viral load (HIV RNA PCR) are the same for women in men. But in one study women had HIV RNA levels 30 - 50% lower than men who had comparable CD4 counts. This implies that lower viral loads in women do not provide the same benefit seen in men. Another study suggested that women had a more rapid CD4 cell loss and faster progression to AIDS than men at similar HIV RNA levels. To date there is no difference in the DHHS guidelines regarding the time to initiate HAART for women versus men. As more studies are done to regarding disease progression further recommendations may propose different criteria for initiation of treatment. Several opportunistic infections occur with greater frequency in women. For example hospitalizations for women due to recurrent bacterial pneumonia is found with greater frequency. Also women more often have esophageal candidiasis, cytomegalovirus, recurrent herpes simplex virus, and aspergillus. But women are less likely than men to have Kaposi's sarcoma, lymphoma or pneumocystis carinii pneumonia. Presenting complaints found in women when they access medical care are often due to dermatological disease, weight loss due to wasting syndrome or dysphagia from esophageal cadidiasis, recurrent vaginitis or severe genital herpes simplex virus. Any sign or symptom that is now a visible sign of their infection often leads to their first visit for medical care. TreatmentHAART is now considered the standard treatment of care for HIV infected individuals. We now know that the goal of treatment is viral suppression and immunologic reconstitution. Our present approved antiretrovirals includes three categories of antiretrovirals: nucleoside reverse transcriptase inhibitors, protease inhibitors and nonnucleoside reverse transcriptase inhibitors. There are several drugs within each of these categories, each with its own potential side effects. These do not differ in women or men or their direct effect on viral replication. When choosing a regiment several issues need to be considered such as concerns of adherence, potential side effects or development of resistance. Adherence is essential for these medications to be effective and prevent development of resistance. Several studies have looked at the adherence and viral load and found that in patients who admitted to missing less than 5% of their dosages, 81% had a nondetectable viral load. In patients who missed approximately 20% of their doses only 50% of the patients had nondetectable viral load. As this virus replicates rapidly and has frequent mutations, this can lead to rapid drug resistance. Several systems have been tried to increase adherence such as patient education, support systems, pillboxes, close contact with the clinic for reminders or questions, patient beeper systems and even directly observed therapy. All of these do improve adherence but are often very laborious for clinic staff as well as expensive. Sex, race, income, age or gender does not seem to affect adherence. Also physicians and other medical personnel are poor predictors of adherence. When dealing with female patients in choosing there regiment the provider must consider whether she is working outside the home, caring for children, concerned about confidentiality, has difficulty with pill swallowing or on other medications that interact with their HIV medications. The efficacy of oral contraceptives is affected by several of the protease inhibitors as well as the nonnucleoside reverse transciptase inhibitors. Also protease inhibitors are metabolized by the cytochrome P450 enzyme system and their use with other medications with potential interactions need to be considered. Complications from the present medications appear to occur at similar rates in men and women. Hyperlipidemia, hypertriglyceridemia and glucose intolerance occurs in many patients especially those on protease inhibitors. Standard treatments for these conditions are used but often with lower effect. Also lactic acidosis is a rare but life-threatening complication from the nucleoside reverse transcriptase inhibitors and some studies have shown this to occur more frequently in women. As patients are living longer on these treatments we are noticing other complications such as lipodystrophy often called fat redistribution syndrome. This is characterized by truncal obesity, buffalo hump (with normal cortisol levels), enlarged breasts and with or without loss of subcutaneous fat in the extremities, face and buttocks. The etiology of this condition is not understood and is seen more commonly associated with certain medications such as protease inhibitors. The process does not seem to be reversible by changing treatment regiments or discontinuing HAART all together. This can be very discerning to our HIV infected women as it quite noticeable by family and friends. At the present time no treatments have shown a significant affect on these conditions. Gynecological DisordersGynecological problems continue to comprise a large portion of the medical problems that HIV infected women encounter. These may be directly related to the HIV infection or related to the high-risk populations and their sexual behaviors. As discussed above, condom use is still often lower than expected leading to continued acquisition of STDS, recurrent vaginitis and even unexpected pregnancies. Severe herpes simplex virus requiring hospitalization for IV treatment and pain control may even be the presenting symptom for some of these HIV infected women. Menstrual irregularity and even amenorrhea occurs with increased frequency in HIV infected women. Often this is due to weightloss, substance abuse, the presence of opportunistic infections as well as the use of progestational agents either for birth control (DepoProvera) or appetite stimulation (Megace). With advanced HIV disease and marked wasting patients are often amenorrheic. Vaginitis and ulcerative disease can often be chronic and debilitating. As the immune system deteriorates the frequency of HSV increases but usually respond to suppressive doses of acyclovir, famvir, or valtrex. Recurrence or difficult to treat candida vaginitis may respond to oral or topical antifungals but ongoing suppressive treatment is not recommended. Avoiding douching and improving the immunological status of the patient should lead to improvement in all these conditions. Cervical dysplasia continues to be a serious problem for a majority of our patients. We know the role that the human papillomavirus plays in the development and progression of cervical neoplasia. There are 70 subtypes of HPV and they are categorized as low, intermediate or high risk based on their ability to be oncogenic. It has been estimated that 50% of sexually active adults have been infected with HPV but HIV infected women have shown a high degree of persistent HPV with oncogenic subtypes. This often translates into a high percentage of abnormal Paps smears. Since these lesions are often multifocal, a colposcopy is recommended for all women with ASCUS (atypical squamous cells of undermined significance) or SIL (squamous intraepithelial lesion). Patients found to have cervical intraepithelial neoplasia on colposcopy should be considered for standard therapies such as LEEP (loop electrosurgical excision procedure), cryotherapy or conization. Response to treatment is lower than seen in noninfected women with recurrence rates reported as high as 40-60%. Many women are considered for hysterectomies after multiple treatments due to the risk of progression to invasive cervical carcinoma. In 1998 the Centers for Disease Control and Prevention expanded the surveillance case definition of AIDS. Invasive cervical carcinoma was included as an AIDS defining condition acknowledging the significance of this in HIV infected women. Though the percentage of women with this AIDS defining condition is very small; the mortality rate is high. In a large study on women, the rate of ICC in HIV infected women was 144 per 1,000 person-years as compared to 0 per 1,000 person-years in HIV negative women. Prevention through screening Paps smears and intervention for mild dysphasia is essential to prevent progression to ICC. We know that this rate of progression to invasive cervical carcinoma (ICC) is more rapid in HIV infected women and correlates with degree of immunosuppression. Treatment includes radiation and chemotherapy but response is poor especially in very immunosuppressed patients. If the patient is responding to their antiretroviral regiment with improved immune status their chances for response increases. ConclusionMany women are diagnosed with HIV disease during pregnancy. This is a critical time for these women to accept their chronic illness and start treatment to prevent perinatal transmission. Depression, substance abuse, discrimination and the social stigmatization are important factors to be addressed at this time to ensure the best outcome for these patients. A multi-disciplinary program that provides medical care along with social services, psychological services, education, nutrition and access to other specialties is required to meet the needs of these women. The Rainbow Center, located at Shands Hospital provides care such as this and has continued to grow providing comprehensive, multi-disciplinary care for women and their family members. References
Jacksonville Medicine / June/July, 2001What's New
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