AIDS INFORMATION NEWSLETTER Michael Howe, MSLS, Editor AIDS Information Center VA Medical Center, San Francisco January 27, 1995 Women and HIV Infection (Part XVIII) [Editor's Note: In Part XV of this series (16 December 1994) information was provided about survival for women and men with AIDS. On 27 December 1994 a press release about a NIAID study stated that HIV-infected women have an increased risk of death, rather than disease progression. That press release is reprinted below. For more information about the study, see: Melnick SL. Sherer R. Louis TA. et al. Survival and Disease Progression According to Gender of Patients with HIV Infection: The Terry Beirn Community Programs for Clinical Research on AIDS. JAMA. 1994;272(24):1915-1921. Also included in this part of the series is an article, "Nutritional Considerations for Women with HIV," by Leslie Hanna that was published in the 1994 December issue of Bulletin of Experimental Treatments for AIDS (BETA), a quarterly publication of the San Francisco AIDS Foundation (SFAF).] HIV-Infected Women Have Increased Risk of Death, Not Disease Progression HIV-infected women are one-third more likely to die without an AIDS-defining condition than are HIV-infected men, according to a study from the National Institute of Allergy and Infectious Diseases (NIAID), reported in the Dec. 28 Journal of the American Medical Association. The investigators could not identify why the women had a greater risk of relatively early death but suggest that important factors may involve poorer access to or use of health care resources among HIV-infected women as compared to men, domestic violence and lack of social supports for women. The findings stem from 15 months of observations of more than 4,500 people enrolled in a prospective study of HIV disease progression and survival. Among the surviving HIV-infected people in the study, no gender differences occurred in the risk of subsequently developing an AIDS-associated condition. For these women and men, the most commonly occurring AIDS-associated conditions included Pneumocystis carnii pneumonia, an invasive form of the fungal infection candidiasis and extreme weight loss. "To date, this study is the largest prospective analysis to compare survival and disease progression between HIV-infected women and men while controlling for predictors of disease," says Jack Killen, M.D., director of the NIAID Division of AIDS (DAIDS). "We anticipate that these study data will help in the pursuit of improved therapies for people with HIV disease and AIDS." AIDS among women in the United States now represents nearly 13 percent of all U.S. cases, a more than 20-fold increase since 1981. The disease is the leading cause of death for women in New York City aged 25 to 44, and among the top five leading causes of death for other U.S. women of the same age, reports the Centers for Disease Control and Prevention (CDC). Some 51,235 women and 344,776 men in the United States have developed AIDS as of June 30, 1994, according to the CDC. Nearly half of the women acquired the virus through injection drug use and more than 35 percent from heterosexual contact. The NIAID Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) conducted the study. Among those HIV-infected people who enrolled without a previous history of AIDS-associated conditions, 27.5 percent of the women experienced death as the first observable event, compared to 12.2 percent of the men. "We cannot discern definitively the reasons for the poorer survival of the women," explains lead author Sandra L. Melnick, Dr.P.H., an epidemiologist with the Basic Sciences Program of DAIDS. "Further study of the relative contributions of diverse social factors, including access to care, homelessness, substance abuse and pregnancy, would enhance our understanding of the complex patterns of HIV disease progression and survival in women and men." For the study, researchers examined the survival and opportunistic infections among 768 women and 3,779 men enrolled in one or more clinical trials between September 1990 and September 1993 at 17 centers of the CPCRA. Compared to the men, the women were younger (36 versus 38 years), more likely to be African American or Hispanic (78 percent versus 44 percent) and more likely to have reported a history of injectable drug use (49 percent versus 27 percent). The women had higher counts of CD4+ T cells, the immune system cells targeted by HIV, with a midpoint in the range of counts of 240 cells per cubic millimeter of blood versus 137 for the men at enrollment. The frequency of certain opportunistic diseases varied by gender, noted coauthor Lawrence R. Deyton, M.S.P.H., M.D., chief of the HIV Research Branch in DAIDS. The women had significantly greater risk--38 percent--of developing bacterial pneumonia. When the researchers restricted the analysis to participants with a history of injection drug use, the women had a 53 percent greater risk than the men. Additionally, compared to the men, the women had higher percentages of mycobacterial infections other than Mycobacterium avium complex (0.5 versus 0.4 percent), but less frequent episodes of the AIDS-related cancer Kaposi's sarcoma (0.2 versus 4.8 percent) and oral hairy leukoplakia (2 versus 5.5 percent). Four women reported cervical malignancies, but screening for such cancers was not performed in the study. NIAID started the CPCRA in 1989, naming the network in 1991 for Terry Beirn, the late former manager at the American Foundation for AIDS Research and a health policy consultant for Sen. Edward Kennedy. CPCRA involves physicians and nurses in primary care settings in community-based clinical research. The CPCRA is designed to include leading scientists, institutions and a demographically diverse population in a program of HIV/AIDS research. The network ensures that potentially effective therapies can be translated into standard patient care for all infected people, notes Dr. Killen. Recompeted in September 1994, CPCRA has 16 units in 15 U.S. cities. Of the more than 15,000 patients enrolled in CPCRA studies as of December 1994, 43 percent are African American, 21 percent are Hispanic, 31 percent are white, 22 percent are women and 27 percent describe themselves as injection drug users. For more information about CPCRA trials, call the AIDS Clinical Trials Information Service at 1-800-TRIALS-A. NIAID, a component of the National Institutes of Health (NIH), supports investigators and scientific studies at universities, medical schools, hospitals and research institutions in the United States and abroad aimed at preventing, diagnosing and treating such illnesses as AIDS, tuberculosis and asthma as well as allergies. NIH is an agency of the U.S. Public Health Service, part of the U.S. Department of Health and Human Services. (PRESS RELEASE. National Institite of Allergy and Infectious Diseases, National Intitutes of Health, December 27, 1994.) Nutritional Considerations for Women with HIV by Leslie Hanna, Associate Editor of BETA. Nutritional interventions continue to gain prominence in the healthcare of persons with HIV, and knowledge about the interplay between nutritional status and HIV infection is slowly increasing. Little is currently known about the gender-specific needs of HIV-infected persons. While all women, HIV positive and negative, are likely to have certain nutritional needs that differ from those of men, most of the nutritional studies relating to HIV conducted thus far have been among men. Given an overall lack of research into nutrition and HIV, it is not surprising that there is little gender-specific nutritional data for women with HIV and their providers to rely upon or even to refer to. Despite the uncertainties, there are some general guidelines that HIV positive women can follow. HIV Infection Metabolism and nutrient needs change with the onset of HIV infection. Certain nutrients, including some known to play immune-supportive roles, are routinely deficient in HIV-infected persons (see "Vitamins, Minerals & Supplemention" below). As people with HIV live longer, due in part to advances in successful prophylaxis of opportunistic infections, appropriate nutritional interventions become even more important. Nutritional care may help avoid or counteract HIV-related depletion of nutrient stores, malnutrition, weight loss and wasting, which can be life- threatening. Optimizing nutritional status and lean body mass provide a foundation for maintaining health and weight, as well as for optimal absorption of any medications a person may be taking. Although different sorts of interventions may be needed at different stages of HIV disease, early, aggressive intervention is a key strategy. Nutritional Concerns of Women with HIV Many women with HIV are at least borderline malnourished, whether due to HIV or to secondary causes like suboptimal dietary patterns or eating disorders or drug use, according to Lisa Ploss, RD, MPH. Malnutrition itself depresses immunity, increasing susceptiblity to opportunistic infections that may lead to hospitalization, prolonged recovery and secondary complications. Malnutrition also adversely affects one's ability to absorb medications as well as his/her quality of life. Wasting may begin early in HIV disease, while CD4 cell counts are relatively high. Since women, whose early symptoms of HIV disease often go undetected, tend to present for healthcare later than men with HIV disease, one possibly gender-related challenge is to begin nutritional intervention with women as soon as possible, to protect against wasting and other conditions that may occur at any disease stage. A woman's nutritional status and needs are affected by her age, hormonal state (premenstrual, menstrual, pregnant, menopausal) and overall health (HIV and other conditions). Psychosocial and environmental factors are also influential, e.g., body image, caretaking and access to food. Women with HIV, especially those who care for children and/or other family members, may require special encouragement to take the initiative to care for their bodies. Nutrition is one of the relatively few areas in which the individual can exert a great deal of influence and control, says Kristen Weaver, RN, MSN, CNSN; doing so has immediate and long-term benefits both physically and psychologically. A dietitian familiar with and knowledgable about HIV disease can help HIV positive women of all ages and health statuses design and implement appropriate, individualized programs. Minimally, it is important for women with HIV and their providers to follow calorie intake, weight and, if possible, lean body mass. Age The nutritional needs of a woman with HIV will vary somewhat depending on her age, although, relative to HIV negative women, calorie requirements even for post-menopausal women remain high. The chronic inflammatory state that HIV causes means that calorie requirements remain high for women with HIV of all ages, according to Mary Romeyn, MD. Consistent with levels of growth and activity, the nutrient needs of HIV positive teenagers are high. During these years, a woman achieves 50% of her adult body weight and 15-20% of her height. Dietitians suggest that teenagers eat nutrient-dense snacks that are easy to make and similar to what their peers may be eating, such as blenderized drinks made with ice cream or yogurt, quesadillas and macaroni and cheese. Dairy products may be difficult to digest for HIV positive people of any age. Because lactose intolerance is common in persons with HIV, non-dairy substitutes may be preferable. For example, tofu, which is made from soybeans and may be used in e.g., place of cheese, is high in protein, easily digested and tastes good (because it easily absorbs the flavors of other cooking ingredients). Regardless of serostatus, pregnant women experience some degree of immunosuppression. HIV positive pregnant women may be at increased risk for developing various infections. Nutritional interventions are aimed at optimizing immune system strength. Ms. Ploss recommends adding 300 calories and 10 grams of protein daily to estimated pre-pregnancy needs, and taking prenatal vitamins. A recent study suggested that vitamin A repletion in pregnant HIV positive women with vitamin A deficiencies decreased the likelihood of perinatal HIV transmission (see "Women and HIV/AIDS" in the September 1994 issue of BETA, p.74). Some increased nutrient needs can be met by adding extra servings of foods from the basic food pyramid (see graphic where). Pregnant women should discuss the use of nutrient supplements with their physicians. Consultation with a dietitian who can assess individual needs and variables may be particularly valuable for an HIV positive woman during pregnancy. Premature menopause may occur more frequently in HIV positive women, according to Ms. Weaver. In all menopausal women, decreased production of estrogen causes the release of calcium from bones. Since HIV infection elevates calcium needs, it is even more important for HIV positive menopausal women to receive adequate amounts of calcium. Calcium supplements may be taken in the form of calcium citrate (easier to digest than other forms) or, most simply, calcium-enriched antacids such as Tums. Weight-bearing exercise has been recommended to maintain bone strength as well as lean body mass. Women with HIV may experience more severe hot flashes, sometimes mistaken for night sweats, which may depress appetite and food intake as well as disrupt sleep. Current research efforts are evaluating the use of vitamin C and E supplements to alleviate hot flashes. Metabolism usually slows with age, loss of lean body mass and muscle tone, and increases in fat storage. However, because HIV infection elevates metabolic rates, and to guard against the removal of protein from muscles, older women with HIV need to continue to receive adequate amounts of protein as well as vitamins and minerals. Studies of eating patterns in older adults suggest that their diets often are relatively low in important nutrients (and high in sugars, fats and alcohol). It is important for older women with HIV to eat nutrient-dense foods to prevent weight loss and age-related nutrient deficiencies and immune system deterioration. Dr. Romeyn suggests that, while high levels of dietary fats are generally to be avoided by HIV-infected persons (fats are difficult to metabolize and often cause the individual to feel ill), sugar in fact may be helpful. Sugar is easily absorbed, spares protein from being broken down to provide energy and gives pleasure, which is important for quality of life. Eating enough carbohydrates, i.e., sugar, reduces the need for the body to break down protein stores, i.e., muscle, as a source of fuel. Impaired taste bud function and taste alteration, which may be caused by drugs taken for the treatment of HIV or other infections, may result in further decreased food intake. Because compromised taste buds still detect sugar, the pleasure derived from eating it may encourage further eating. Hormones Women of childbearing age experience extreme fluctuations in hormones and hormonal levels, which affect metabolic rate, appetite, eating habits, food intake, glucose tolerance, mood and behavior. Thus, Ms. Weaver recommends incorporating hormonal factors into nutritional interventions and strategies for HIV positive women. Many women with HIV experience menstrual abnormalities including heavier or lighter menstrual flows. Heavy periods may lead to anemia, which in a woman with HIV may be further exacerbated by the use of AZT and/or other drugs. HIV positive women, particularly those experiencing heavy periods, are advised to choose iron-rich foods. Some women report experiencing more intense episodes of premenstrual syndrome (PMS): breast swelling and pain, bloating, fatigue, head and body aches, irritability, mood shifts and cramping. These symptoms can occur before and during menstruation. The physiological effects of HIV and PMS may be additive, according to Ms. Weaver. Some basic guidelines for relief of PMS are to eat the right amounts of foods from all food groups, exercise and take supplements that include the B vitamins, magnesium and vitamin E. Fatty acids are integrally involved in the rise and fall of hormone levels throughout the menstrual cycle; taking supplements may help maintain hormonal balance. Ms. Weaver suggests taking supplements of evening primrose oil, an essential fatty acid that can be found in capsule form in health-food stores. Some people feel that avoiding salt and drinks with caffeine, such as coffee, tea and colas, helps to reduce or eliminate the symptoms of PMS. Related Concerns of Women with HIV Lisa Ploss discussed with BETA various lifestyle, psychosocial and physiological influences that bear on an HIV positive woman's dietary patterns and nutritional strategies. Is she responsible for caring for and feeding others, such as children, parents or other family members? The added financial burdens of childcare may force an HIV-infected woman to neglect her own healthcare. Does she live with others, or alone, or in a recovery house or a single room occupancy hotel? Does she have access to equipment for preparing and storing food, and to food itself? For women who become too fatigued or ill to care for others, alterations in roles can be very difficult. Body image, which changes greatly with weight loss and illness in general, may be a particular concern for women. Eating disorders such as anorexia nervosa and bulemia, common among women, can be extremely damaging in women with HIV, and present great challenges to creating an effective intervention for optimizing nutritional status. Fatigue, depression and lack of appetite are common complaints among women with HIV and may be related to hormonal shifts, psychosocial influences (e.g., caretaking), opportunistic infections and the use of medications. Food Eating well provides a foundation for any nutritional strategy. While use of a daily high-potency multivitamin is recommended, food contains calories, fiber and other important (and incompletely understood) substances that vitamins and supplements do not contain. General Nutritional Guidelines for HIV Positive Women The following was compiled from an interview with Lisa Ploss, RD, MPH, the HIV Services Nutritionist at Lyon-Martin Women's Health Services in San Francisco, CA, and excerpts from an article she previously wrote. Consult with a physician or registered dietitian before making any drastic dietary changes and to help bring weight within a healthy range. Choose a variety of foods from each food group every day. (See the "Food Pyramid.") Emphasize grains, grain products, fruits and vegetables, which contain high amounts of vitamins and minerals. Eat small, frequent meals or snacks at least 3 times a day--4 or 5 times if possible. Drink 6-8 glasses of fluids every day. Avoid fluids that increase urination such as alcohol, coffee or tea. Take a balanced high-potency multivitamin supplement at least once a day. Prenatal vitamins have more of the necessary micronutrients. Remember that a vitamin or mineral supplement cannot substitute for a well-balanced diet or for a food group. Maintain weight at your usual weight range or 5-10% higher, unless overweight. If weight is below ideal body weight range, increase intake of carbohydrates and protein-rich foods. If you feel that your weight needs to change, seek the assistance of a physician or dietitian. Establish a regular exercise program to build and maintain muscle tissue. Overly strenuous exercise is neither necessary nor recommended. Exercise that involves muscle resistance is important for stimulating muscle tissue. Increasing or at least maintaining muscle tissue, or lean body mass, appears both to help someone stay healthy longer and to recover faster and better, if s/he becomes ill. Dietary Items to Include in Daily Diet: 2-3 servings of dairy and calcium alternatives (Milk, yogurt, cheese and ice cream. Other high-calcium foods include bok choy, spinach and other dark green, leafy vegetables, broccoli, sardines with bones, calcium-fortified tofu or soy milk and calcium- fortified orange juice. Yogurt contains different types of bacteria such as Lactobacillus acidophilus that may prevent or ameliorate Candida albicans infections and diarrhea by restoring normal bacteria. Again, lactose intolerance may make digesting dairy products problematic. A dietitian may recommend suitable substitutes or lactase supplements to offset the symptoms of lactose intolerance.) 2-3 servings of protein (Including all types of meat, fish, poultry, eggs, beans, cheese, nuts and tofu) 5 or more servings of fruits and vegetables (Including dark green and orange fruits and vegetables) 6 or more servings of breads, cereals, tortillas, rice and pastas (Preferably whole grain-enriched) Adequate amounts of iron, vitamin B12 and folate in an HIV positive woman's diet can help prevent or reduce the seriousness of anemia, which more women experience than men. Good dietary sources of iron include liver, poultry, meat, fish, iron-fortified cereals, dried apricots, soybeans, spinach and other dark green, leafy vegetables. Cooking in cast iron pots and skillets may also increase the iron in your diet. Dietary sources of vitamin B12 include meat, fish, poultry, shellfish, milk, yogurt, cheese and eggs. Nutrient-Dense Snacks Bagels and tuna Macaroni and cheese Whole-grain toaster waffles and fruit Burritos Whole grain cereal with milk Blender drinks made with fruit, ice cream or yogurt Bean soup topped with toast cubes and shredded cheese Powerbars Vitamins, Minerals & Supplementation According to Dr. Romeyn, the altered metabolic state of a person with HIV virtually necessitates the use of nutrient supplements in order to ensure that all necessary nutrients are being received. Since many people with HIV have reduced food intake as well as impaired abilities to absorb nutrients, supplements are especially important. Several nutrients are believed to be involved in immune system health: vitamins A, B6, C and E; beta carotene; and minerals including copper, iodine, iron, magnesium, manganese, selenium and zinc. Several nutrients are routinely deficient in persons with HIV disease, especially B6, B12, copper and zinc. Other nutrients that may be deficient in HIV-infected persons are folate and vitamins B1 and B2. Deficiencies of B12 and magnesium in people with HIV have been associated with peripheral neuropathy. One study examined HIV positive persons with decreased levels of B6 and B12 who reported slight cognitive abnormalities. Restoring levels of B6 and B12 alleviated the cognitive symptoms. Low levels of these B vitamins may indicate problems with gastrointestinal absorptive abilities; a person with low levels should be evaluated to determine the cause(s) and the corrective action that should be implemented (e.g., intramuscular administration of B vitamins). Ms. Weaver and Ms. Ploss recommend that malnutrition or deficiencies of certain micronutrients and megadosing should be explored routinely as part of the work-up of a person with HIV who presents with nonspecific symptoms. Supplemental use of some nutrients is considered safe, regardless of dose. For example, excess amounts of vitamins B1 and B2 are excreted; B12 is considered nontoxic (albeit poorly absorbed). According to Dr. Romeyn, magnesium, required for the metabolism of other minerals, is an important mineral that is almost impossible to get too much of (except for someone with kidney failure)--it is hard to get enough from foods, to absorb and to retain. However, iron, zinc and copper supplementation must be approached cautiously, says Dr. Romeyn. Even for women, whose iron needs tend to be higher than those of men, high levels of iron supplementation are not recommended--adverse effects of overly high daily doses of iron range from constipation to iron storage and metabolism abnormalities that damage tissues and organs. There are blood tests that can determine iron needs and appropriate doses for the individual. Taking high daily levels of zinc has been associated with decreased survival in people with HIV disease. Megadosing, or taking high amounts of vitamin and mineral supplements (in doses larger than 10 times the Recommended Daily Allowance, or RDA), is common yet controversial in HIV disease. Megadosing may enhance immune status and protect against micronutrient deficiencies common in HIV disease. A placebo effect can increase energy levels, appetite and overall sense of well being, Ms. Weaver adds. However, concerns exist about megadosing-related toxicities and nutrient/drug interactions, about which there are little data. Megadosing-related toxicity may present as diarrhea (e.g., associated with vitamin C). Ms. Weaver recommends that women who present with diarrhea and/or anemia, which may result from large doses of zinc, should be questioned about megadosing or use of multivitamins, because these may be side effects that could cloud diagnosis. Excessive doses of all the fat-soluble vitamins (A, D, E and K) can cause toxicities. Megadoses of vitamin A may be hepatotoxic. Excessive amounts of vitamin C (>10g/day) may cause diarrhea and also, if abruptly discontinued, may cause scurvy. Extended use of high levels of zinc (> 100mg/day) interferes with the body's ability to utilize another important mineral, copper, and may actually increase disease progression. Some people experiment with megadosing because they mistrust conventional therapies, which they may inappropriately discontinue. Megadosing also may be expensive. Optimal megadoses have yet to be established for persons with HIV disease. Although the RDA were not created for, and are inadequate for, persons with HIV, suggested guidelines regarding the use of high doses of supplements by persons with HIV are both preliminary and non-gender-specific. A physician's and/or dietitian's help should be enlisted to assess an individual's particular nutritional profile, i.e., micronutrient status, etc. This information may be used to create a specific, individualized supplementation program that goes beyond taking the recommended daily multivitamin. Perhaps the most fundamental principle in nutritional care is individualization. Universal recommendations are probably an appropriate place to begin, but may be of limited utility. Again, if nutritional problems are attacked early and aggressively, weight loss may be prevented, physiological and mechanical gut function improved (by utilizing the gut to its full extent), susceptibility to opportunistic infections reduced, response to medical therapies enhanced and, most importantly, overall quality of life and sense of well-being improved. Much research remains to be conducted, particularly with regard to the distinct needs of women with HIV. Alternative therapies such as megadosing need more investigation in order to establish when they are appropriate and what dosing regimens to use for appropriate effect, for men and women. Guidelines for Selecting a Dietitian In an interview with BETA, Lisa Ploss, RD, MPH, offered the following guidelines for finding a dietitian with whom to work. Either a dietitian or a nutritionist may help design an individualized nutritional strategy. A registered dietitian must complete an undergraduate program, supervised internship and training, and pass a national examination. Continuing education units also are required for continued registration. Nutritionists, however, at least in California, are not required to undergo any formal training. When meeting a dietitian or nutritionist for the first time, be sure that s/he discusses certain things: lifestyle (good recommendations are those that are practical); laboratory work and values; 24-hour or 3-day food records for use in baseline nutrient analysis; individualized recommendations. She suggests being cautious of someone who looks at certain isolated samples, e.g., hair, or who makes blanket recommendations without testing or taking into account individual variables. Hospital clinics can perform tests of lean body mass, as well. Statewide, the California Dietetic Association at 1-800-234-7348 provides dietitian referrals. Ask for a dietitian with experience working with people with HIV. Nationwide, individuals may call the National Center for Nutrition and Dietetics at 1-800-366-1655 to speak directly with a dietitian as well as to obtain referrals for a particular state. Sources Beach RS and others. Plasma vitamin B12 level as a potential cofactor in studies of human immunodeficiency virus infection.: association with neurological dysfunction. Archives of Neurology 49(5): 501-506. May 1992. Gilden D. Nutritional intervention in HIV disease. BETA: 3-11. March 1994. Ploss L, RD, MPH. Nutrition guidance for positive women. Positive Nutrition 4: 6-8. Winter 1994. Ploss L, RD, MPH. Personal Communication. November 2, 1994. Romeyn M, MD. Internal Medicine. Personal Communication. November 29, 1994. Weaver K, RN, MSN, CNSN. Nutritional concerns for the HIV-infected woman. Third Annual Women and HIV Update. San Francisco, October 14, 1994. Weaver K. Personal Communication. November 11, 1994. _________________________________________________________________ DISTRIBUTED FOR GENA by AEGIS/San Juan Capistrano - 714.248.2836: Copyright (c) 1994 December - Bulletin of Experimental Treatments for AIDS (BETA), a quarterly publication of the San Francisco AIDS Fouundation (SFAF). Reproduced with permission. Reproduction of this article (other than one copy for personal reference) requires written consent from the SFAF. For subscription information contact the BETA Subscription Office at 1.800.959.1059 or 1.510.549.4300, or via the internet at beta@sfsuvax1.sfsu.edu.