CDC NATIONAL AIDS HOTLINE TRAINING BULLETIN #37 - March 25, 1993
Centers for Disease Control and Prevention

Vaginal Yeast Infection Questions

1. "The label revisions state that frequently recurrent vaginal yeast infections, (frequent is defined as within a two month period), especially infections that don't clear up easily with treatment, can be an early sign of HIV infection or AIDS. The label directs the reader with questions on the relationship between recurrent vaginal yeast infections and AIDS to call CDC NAH. What, specifically, can we provide callers regarding the relationship?"

The Food and Drug Administration (FDA) revised the wording on labels of nonprescription vaginal yeast preparations as a medical precaution. The label includes information on possible underlying causes of recurrent vaginal yeast infections; one of these could be infection with HIV. This revision does not imply that women with vaginal yeast infections have HIV infection or AIDS. The intent of this labeling revision is to encourage women who have recurrent vaginal symptoms to seek the advice of a physician to see if there is an underlying medical condition.

2. "Almost the same day as the FDA notified CDC NAH of their labeling revisions, NIAID forwarded us a press release titled New Clinical Trial for Prevention of Yeast Infections in HIV- Infected Women Begins. The press release states '...research suggests that yeast infections are the earliest and most common opportunistic infections afflicting women with HIV...' Does CDC concur with this statement?"

This statement was made based on the findings of one study, thus the qualifier "from one study" should be added after "research." More research is needed to confirm this statement. Vaginal yeast infection is not an opportunistic infection and is not an AIDS indicator disease under the 1993 surveillance case definition for AIDS.

3. "The press release continues '...in advanced HIV disease, yeast infections in the mouth and throat can make eating difficult, leading to weight loss. If the infection spreads to the bloodstream and other parts of the body, serious illness and even death can result...' Is this also true of vaginal yeast infection?"

Vaginal candidiasis is a localized infection--even in women who are infected with HIV. Occasionally, such as when the patient has uncontrolled diabetes mellitus, vaginal candidiasis may spread locally to the vulva and adjoining skin areas. Widely disseminated candidiasis is an opportunistic infection.

Questions Regarding Women

4. "Questions regarding an article from the American Journal of Public Health, November 1990, 'Epidemiology of Reported Cases of AIDS in Lesbians, United States 1989-89,' by CDC authors including Dr. Ruth Berkelman: Can information in this article be considered CDC-approved for use on-line? Also, is it still true that there have been two reported, but no documented, cases of female-to-female sexual transmission of HIV?"

Yes. If a summary of this article is prepared, we would appreciate the opportunity to review the information before it is provided to callers. An update of the article offering further information has been published (Reference 2, copy attached). It would be more accurate to say that there have been several reported cases where female-to-female sexual transmission of HIV may have occurred. Seroconversion has not been documented in any of the case reports. 5. "Last fall, a New England Journal of Medicine article reported that women are much more easily infected by men than vice versa. [July, 1992 JAMA, pages 28 and 29, concur.] It was widely reported in the press for over a week in November that CDC stated it is 20 times more likely for a woman to get infected from a man than vice versa. How does CDC respond to these statements?"

It may be true that sexual transmission of HIV is more likely from men to women than women to men. However, the exact risk is not quantifiable for reasons explained in earlier Q/As (Reference 1).

6. "Although gynecological disorders are not currently listed among the opportunistic infections which can lead to an AIDS diagnosis, a recent issue of Clinical Courier, summarizing proceedings of the December 1990 Women and HIV Infection Conference, stated that 'gynecological infections and subsequent changes in their pattern and frequency may be the first clue to HIV infection in women.' Does CDC concur with this statement?"

Physicians should be alert to the possibilities of HIV infection in their female patients. The CDC AIDS case surveillance definition was expanded on January 1, 1993, to include invasive cervical cancer in persons with HIV infection. An underlying medical cause (including the possibility of infection with HIV) should be considered by physicians when women present with recurring or complicated cases of some gynecologic conditions (e.g., genital herpes or vaginal candidiasis).

7. "NAH training materials currently include the following statement on disease progression:

'Studies have now shown that in the United States and Europe approximately 50 percent of men with HIV infection develop AIDS within 10 years of infection. CDC currently states that over time most HIV-infected persons will eventually develop AIDS.

Unfortunately, such information is primarily limited to studies on men ... However, other natural history studies have incorporated both women and men. For example, findings from a study of persons infected with HIV by transfusion did not indicate any overall difference in disease progression between men and women.'

In published proceedings from the December 1990 U.S. Public Health Service conference on Women and HIV Infection, however, it was reported that women 'are too often diagnosed in the later stages of their infection.' Present data indicate that women are too frequently diagnosed with AIDS at or near the time of death. According to Dr. Ruth Berkelman, M.D., [then] Chief of the Surveillance Branch, Division of HIV/AIDS, Centers for Disease Control, 'In 1990, 11% of women were diagnosed with AIDS the same month they died. This compares to approximately 8.5% of men who reported homosexual contact who were diagnosed with AIDS the same month they died.' Additionally, the issue of shorter survival time for women is a subject of ongoing discussion in the medical literature, whether this disparity is attributed to biological difference or to medical or socioeconomic factors including misdiagnosis, later diagnosis, poverty and subsequent lack of access to medical services, inaccessibility of experimental treatments, etc.

Will you please comment on these issues, and on CDC's current position regarding relative survival time of women and men with HIV disease?"

CDC is continuing to examine the full range of conditions found in HIV-infected women. CDC has supported a natural history study of HIV-infected injecting drug users, approximately 1/3 of whom are women. In addition, four sites have been funded to conduct natural history studies in HIV- infected women. These studies are being conducted with the PHS collaborating group for study of HIV infection in women. These natural history studies continue to examine gynecologic problems in HIV-infected women, including the possible increased likelihood of certain gynecologic cancers; the frequency and severity of infections (including pelvic inflammatory disease, pneumonias, and candidal infections of the vagina, oral cavity, and esophagus); and survival after infection with HIV and after AIDS diagnosis.

Additional studies are being carried out to determine biologic factors in the heterosexual transmission of HIV, as well as to help determine: 1) behavioral risk factors for acquisition of HIV; 2) biologic risk factors for HIV infection, such as genital ulcer disease and hormonal and other factors; 3) early course of HIV after infection; and 4) the impact of counseling on behaviors in women.

The effect of social factors such as access to health care, cultural values and attitudes, family structure, and social- support systems, on the natural history of HIV disease in women is also being examined.

As mentioned in the first paragraph of this response, some of the studies on the natural history of HIV infection/AIDS in women involve survival analyses. Both women and heterosexual men with AIDS survive, on average, for a shorter period of time than men with AIDS who report sexual contact with other men, possibly reflecting the impact of other factors, such as injecting drug use or low socioeconomic status. Survival following diagnosis of AIDS has improved in recent years partly due to better and available treatments. The medical community needs to be more aware of medical concerns associated with HIV infection and AIDS in women so that critical early intervention can be instituted.

8. "We receive calls from women who state they are unable to insist their male partners use condoms, perhaps due to monetary or cultural concerns. Male partners may be at risk by being IDUs or bisexual. This type of call is very common for the SIDA service. Many HIV/AIDS CBOs tell women in this situation to use spermicidal foam to protect themselves. When callers ask us directly if there is anything they can do to protect themselves, can we say that spermicidal foam inserted into the vagina no earlier than 30 minutes before vaginal intercourse may be better than no protection at all?"

No. There is no evidence that spermicides used alone will protect a woman from HIV infection, and frequent use may actually enhance the passage of the virus across the vaginal mucosa since spermicide may irritate mucous membranes.

Pediatric Questions

9. "We have received an update from NIAID, and two articles from TIA's Current Awareness packet (CAP) regarding the early diagnostic value of a test to detect IgA antibodies to HIV in infants. We have several related questions:

a. What process does FDA use to approve new tests?"

Test kits are regulated by the FDA as medical devices through the 510(k) process or through the submission of a Premarket Approval Application.

b. "How close to approval is the HIV-IgA assay?"

No public information is available on this topic.

c. "Is the HIV-IgA antibody test available to infants outside these studies?"

Until a test is finally approved by the FDA for diagnostic use, the test is only available through clinical trials for research use only.

d. "We understand that IgA antibodies do not travel across the placenta, but do researchers know why?"

There are nine chemically different classes of human immunoglobulins (Ig)--four kinds of IgG and two kinds of IgA, plus IgM, IgE, and IgD. IgG is the major immunoglobulin in the blood and can travel across the placenta. This transfer of IgG across the placenta is what is referred to as passively acquired antibodies. The molecules of other Igs are much larger than the IgG and are therefore too large to cross the placenta. Even though IgA is found in serum, IgA concentrates in body fluids such as tears, saliva, respiratory and gastrointestinal secretions, and breast milk. Thus, breastfed infants passively receive IgA which protects their digestive tracts.

e. "Maternal IgG antibodies will remain in an infant up to 15 months before the infant develops her/his own antibodies. What happens to the maternal antibodies?"

Once the infant's immune system begins to mature, the infant begins to develop its own antibodies in the different classes described above. The infant's passively acquired maternal antibodies gradually disappear as the infant grows and responds to infections.

f. "In both the CAP articles, the HIV-IgA assay's sensitivity was directly related to the HIV+ infants age, that is, the younger the infant the less likely the test could detect infection. We know that no single assay has proved to be completely reliable as an indicator of early infection. Could this indicate HIV transmission at birth, with a 3 month antibody development period?"

The answer to this question has not yet been determined.

g. "Are IgA antibodies only produced by infants, or does everyone infected with HIV produce them?"

IgA antibodies can be produced by anyone with a functioning immune system exposed to any type of antigen. IgA is only one type of antibody produced by people (including infants) infected with HIV.

h. "Are there, or might there be, other antibodies that could be tested to determine HIV infection?"

No. Standardized HIV enzyme immunoassays (EIAs) look for all antibodies that react with HIV. However, IgM antibodies are poor responders on the EIAs; IgD and IgE usually develop in response to allergens and have little to do with HIV infection.

Other Questions

10. "Is it true that FDA does not have specific regulations regarding condoms? Do manufacturers set their own standards (thickness, strength, size, etc.), and if they change standards, they only have to register again with FDA?"

Since 1976, condoms have been regulated under the Medical Device Amendments to the Food, Drug, and Cosmetic Act. Within the FDA, the Center for Devices and Radiological Health is responsible for assuring the safety and effectiveness of condoms as medical devices.

While FDA performance standards have not been established for condoms, FDA does recognize the American Society for Testing and Materials (ASTM) Standard Specifications for Rubber Contraceptives (condoms) D3492-83 as a basis for the condom definition. However, if manufacturers choose to deviate from any of the ASTM specifications, they are required to submit a premarket notification to the FDA at least 90 days before proposing to initiate commercial distribution in the United States.

The FDA has also adapted its inspection sampling criteria to conform with the ASTM Standard D3492-83 for latex condoms. Beginning in the spring of 1987, FDA undertook an expanded program to inspect latex condom manufacturers, repackagers, and importers to evaluate their quality control and testing procedures. In testing condoms, FDA uses a waterleak test in which a condom is filled with 300 ml of water and checked for leaks. FDA criteria and the industry-acceptable quality level for condoms specify that in any given batch, the failure rate must not exceed four leaking condoms per 1000 condoms.

11. "Bernita Starks of EPA asked one of our staff a question at a conference. California, especially, uses reclaimed water, usually for washing cars, dishes, etc. She currently tells people that she does not think HIV can be transmitted in reclaimed water, but wanted CDC's expert opinion."

HIV is not transmitted by water. Transmission of bloodborne pathogens has not been reported through the use of any type of water source. Any bloodborne virus introduced into a water source would be greatly diluted, making it noninfectious. Many lay persons have expressed fear that HIV might be transmitted via contact with sewage. Studies of hepatitis B virus, a bloodborne virus that is found in much higher concentrations in blood than is HIV, show that the risk of transmission of HBV via sewage is virtually non-existent; the risk of HIV transmission from sewage would be even less.

12. "We know of reported HIV transmission through acupuncture needles. We encourage callers who have questions about tattoo needles or acupuncture to contact their local health department to find out what local sterilization procedures are in place for these types of establishments. Prevention information and questions are asked quite often regarding tattoo, ear and body piercing, electrolysis, and hair scissors used at barber or beauty shops for haircut and for manicure. Do HIV prevention guidelines exist from organizations representing any of these types of establishments?

Who can callers contact for information?"

Establishments involved in providing personal services (e.g., tattooing, acupuncture, piercing) to clients are regulated at the state or local level. Callers should be referred to their respective state health departments or state governments to see what regulations cover beauticians, barbers, cosmetologists, and other personal service workers in their jurisdiction. Interested callers may question their own personal service workers about the measures they use to maintain and disinfect their equipment.

13. "We receive questions about morticians and funeral directors. One caller reported that the National Association of Morticians said that HIV was no longer viable 48 hours after death. Please comment on this. Callers also complain that funeral directors still refuse to take HIV+ people after death. A caller was distressed because his dead brother's last request had been not to be cremated, and the only place that would accept the body would cremate only. Please comment on how we could discuss this point if the mortician is calling, and where loved ones of a deceased PWA can complain if morticians will not accept the body or accept only with limitations."

No one knows exactly how long HIV will remain viable in the blood and tissues after an HIV-infected person dies. To find this answer, the exact time of death would have to be noted and then timed sampling of the deceased's blood would have to be performed. In addition, amounts of virus circulating in the blood vary. All blood, even that in corpses, should be considered potentially infectious; and all workers involved with preparation of the body (e.g., morticians, embalmers) should use universal precautions.

The National Funeral Directors Association, a service organization to 15,000 of the 23,000 funeral homes in the United States, has stated that nonprovision of services to persons because of their HIV status is a violation of the Americans with Disabilities Act. Funeral homes are not federally regulated. However, many states or local areas have instituted anti-discriminatory legislation. Callers may check with their respective state or local health department or the department that licenses funeral homes about local ordinances regarding this issue. In addition, callers may contact the Funeral Services Consumer Assistance Program at 1-800-662-7666 (Fax: 708-827-6342).

14. "A doctor reportedly told an HIV+ client he had "reactive airway disease." Symptoms were shortness of breath and bronchial spasms. Are you aware of such a disease?"

Reactive airway disease is essentially synonymous with asthma or the component of other lung diseases which are similar to asthma, and is not related to HIV infection. This condition is characterized by difficulty breathing and often by wheezing. The air passages react to noxious stimuli such as allergens, infectious agents, or irritants (such as smoke) by constricting and forming mucus which sometimes plugs the airways. The caller should be referred to his or her physician. They may be able to obtain more information about their diagnosis from their state or local chapter of the American Lung Association.

15. "A caller said his state hotline said that CDC informed them an HIV antibody test can be performed by a finger prick, collecting a small amount of blood, and using an ELISA format to screen the blood sample for antibodies. is this a reliable and approved procedure?"

The heel-stick blood collection method for use in dried-blood spot specimens has been used effectively for metabolic screening of newborns for almost 30 years. The FDA has licensed some EIAs for use with dried-blood samples. Studies have shown that testing dried-blood samples, which have been properly collected on filter paper, gives the same sensitivity and specificity as ELISA tests alone on serum or plasma. This method has also proved useful in performing large-scale screening programs, especially in developing countries, and seroepidemiologic studies, but it is not recommended for routine testing purposes. The western blot test is not licensed for use with these dried specimens, so any ELISA- reactive specimens would have to be repeated by whole blood or serum testing.

16. "We understand that researchers discovered HIV in seminal fluid, but not in sperm cells. Is it known why HIV is not in sperm?" HIV is not present in every cell in the human body; it mainly infects CD4+ cells. CD4+ cells are found in semen, but whether HIV infect spermatozoa is controversial. Reports have differed as to whether CD4 receptors are present on human spermatozoa and whether spermatozoa in HIV-infected men contain retrovirus-like structures by electron microscopy. No studies have found spermatozoa alone infective via special culturing procedures, and the question of their ability to acquire virus or cause infection in patients remains unanswered.

References

1. CDC National AIDS Hotline Training Bulletin #27.

2. Chu SY, Hammett TA, Buehler JW. "Update: epidemiology of reported cases of AIDS in women who report sex only with other women, United States, 1980-1991." AIDS 1992;6:518-9.

Update: epidemiology of reported cased of AIDS in women who report sex only with other women, United States, 1980-1991

In a previous report using national surveillance data from 1 June 1980 through 30 September 1989 [1] we examined various demographic characteristics and behavioral risk factors among 79 women with AIDS who reported sexual contact only with other women. Since that report, an additional 85 cases of women with AIDS who had sexual relations only with female partners were reported to the Centers for Disease Control (CDC) through 30 June 1991. We now report an update of that analysis.

We used national surveillance data for 18199 cases of AIDS in adult women reported between 1 June 1980 and 30 June 1991. Methods have been described in detail previously [1]. Briefly, women were determined to have had sexual contact only with other women based on responses to the following two questions on AIDS case reports:

(1) after 1977 and preceding the diagnosis of AIDS, did this patient have sexual relations with a male partner?

(2) after 1977 and preceding the diagnosis of AIDS, did this patient have sexual relations with a female partner?

AIDS case reports from state and local health departments include basic demographic information and exposures to HIV. Recorded data (for example, gender, sexual contact with male or female partner, mode of exposure) were confirmed directly with reporting health departments and corrected for all reports with discrepant responses.

Two women who reported sexual contact only with women were initially reported to have no identified mode of HIV exposure. These cases were further investigated by the local health departments following a standard protocol [2]. After follow-up, both women were determined to have had sexual contact with female and male partners: one was reported to have had sexual contact with a bisexual man and one was reported to have had sexual contact with a male intravenous drug user (IVDU).

As of 30 June 1991, there were 164 women with AIDS who reported sexual contact only with other women, representing 0.9% of all reported adult women with AIDS in the United States. Of these, 152 (93%) were IVDU; the remaining 12 (7%) had received blood transfusions before March 1985.

As in the previous report, women with AIDS who report sexual contact only with other women represent a very small proportion of the total number of women with AIDS in the United States, and all had a history of intravenous drug use of receipt of blood transfusions. Although these data cannot exclude the possibility of female-to-female transmission of HIV, it appears to be extremely rare. This is consistent with the lower efficiency of female-to-male transmission compared with male-to-female transmission [3] and the presence of antibodies in the vaginal mucosa, which may inhibit HIV transmission [4-6]. However, exposure to vaginal secretions and menstrual blood represent a route of HIV transmission. Women who have sexual contact with other women, like all women, need to be aware of their potential for exposure to HIV, including risk behaviors of their sexual partners.

It is important to emphasize that by far the major means of HIV transmission in women who have sexual contact with other women is intravenous drug use. Hence, prevention of HIV infection among women who have sexual contact only with other women should focus on efforts to prevent and reduce intravenous drug use.

Finally, our data are based on reported sexual behaviors, not self-identified sexual orientation. Women who identify as lesbians may have sex with men [7]. Programs to prevent HIV transmission among women who identify as lesbian should be aware that, as with bisexual and heterosexual women, lesbian women can also acquire HIV from heterosexual transmission.

S.Y. Chu, T.A. Hammett and J.W. Buehler, Surveillance Branch, Division of HIV/AIDS, National Center for Infectious Diseases, Centers for Disease Control, Atlanta, GA 30333, USA.

Date of receipt: 24 February 1992.

References

1. Chu SY, Buchler JW, Berkelman RL: Epidemiology of reported cases of AIDS in lesbians, United States, 1980-1989. Am J Public Health 1990, 80:1380-1381.

2. Castro KG, Lifson AR, White CR, ET AL: Investigations of AIDS patients with no previously identified risk factors. Jama 1988. 259:1338-1342.

3. Padian NS, Shiboski SG, Jewell NP: Female-to-male transmission of human immunodeficiency virus. JAMA 1991. 266:1664-1667.

4. Belec L, Georges AJ, Steenman G, Martin PMV: Antibodies to human immunodeficiency virus in vaginal secretions of heterosexual women. J Infect Dis 1989, 160:385-391.

5. Lu NS, Belec L, Martin PMV, Pillot J: Enhanced local immunity in vaginal secretions of HIV-infected women (letter). Lancet 1991, 338:323-324.

6. Forrest BD: Women, HIV, and mucosal immunity. Lancet 1991, 337:835-836.

7. Sanders SA, Reinisch JM, Ziemba-Davis M: Self-labeled sexual orientation and sexual behavior among women. V International Conference on AIDS. Montreal. June 1989 [abstract].