III. PREVENTION OF HIV
Chia Wang, MD, MS, and Connie Celum, MD, MPH

I. INTRODUCTION

Two decades into the human immunodeficiency virus (HIV) epidemic, scientists and clinicians on both the biomedical and behavioral fronts continue to be faced with daunting challenges. While scientists have made progress in vaccine development and in understanding the complexities of the viral-host immune response, highly effective, widely available biomedical preventative measures are still in developmental stages. Thus, there remains a critical need to identify and implement effective behavioral strategies and to more effectively address the complex forces that fuel the heterosexual HIV epidemic, including poverty, migration of populations, social and cultural disruption, gender discrimination, and stigma about sexually transmitted diseases (STDs) and HIV.

     Many of the measures that women can take to prevent acquisition of STDs and HIV have been known for the past decade: abstaining from intercourse, selecting low-risk partners, negotiating partner monogamy, and male condom use. However, the high rates of incident HIV infections among women in many parts of the world and the rising incidence among women in the United States is a testament to prevention barriers facing women in heterosexual relationships. Women are often unaware of their partners’ infection status or level of risk and, in many cases, are unable to insist on abstinence or to negotiate sexual safety with their partners. Importantly, in many parts of the world, prevalence figures suggest that girls are exposed to HIV earlier than boys (UNAIDS, 1999). Young girls are often emotionally immature, economically disadvantaged, and socially inexperienced, making them vulnerable to sexual relationships that may expose them to HIV and to other sexually transmitted infections that can potentiate HIV transmission. Women in economically disadvantaged nations and in socially marginalized groups in the industrialized world may have less access to medical care for treatment of STDs and contraception, and may also not feel empowered to negotiate for condom use, abstinence, or monogamy within their sexual relationships. Thus, culturally sensitive interventions that target both behavioral and biologic risk factors for HIV are necessary to reduce transmission to women and girls.

     This Guide is about the care of women who are already HIV-infected, and therefore the focus of this chapter is not on primary prevention strategies such as abstinence aimed at women who are not infected. The vast majority of women with HIV have become HIV positive through sexual activity, and require assistance in behavioral strategies to negotiate safer sex within existing relationships or, a much more challenging objective in this case, to negotiate abstinence.

     This chapter discusses issues regarding HIV testing, including risk assessment and pre- and posttest counseling, and then reviews models of behavioral intervention strategies for HIV prevention, published behavioral intervention trials, and some practical aspects of counseling women on how to reduce sexual risk behavior. Biologic cofactors that may increase risk and thus may be targets for intervention are briefly examined. Finally, new approaches to HIV and STD prevention, including microbicides, vaccines, and postexposure antiviral medication are reviewed. The important issues of substance abuse and strategies for changing drug use behavior are not addressed in this chapter, but are reviewed extensively in Chapter X.

II. RISK ASSESSMENT FOR STD/HIV INFECTIONS

• Unprotected sex increases a woman’s risk of HIV infection, based in large part on her partner(s)’ risk behaviors.
  Just as most people would find celibacy an impractical means of reducing sexual risk, many individuals may find changing other specific sex behaviors difficult or unacceptable. Although some sexual behaviors may be less “mainstream” than others, it is important to remember that participation in such behaviors does not necessarily reflect a lack of morals or willpower, but rather different perceptions of enjoyable and common sex behavior. Furthermore, sexually active women may not realize that they are practicing behaviors that put them at risk for HIV infection. Because of the heterogeneous nature of sexual practices, individual risk assessment is crucial in any attempt to reduce risk of HIV by changing sex behavior. In pre- and posttest HIV counseling, individual risk assessment provides a framework in which to conduct further behavioral intervention and identifies patients appropriate for HIV and STD screening. Guidelines for physicians and other care practitioners recommend that HIV and STD risk assessment be conducted for every patient; however, most primary care physicians do not routinely incorporate questions about sexual behavior into routine patient care.
  
• Clinician discomfort and fear of embarrassing or offending the patient when discussing sex are impediments to conducting effective risk assessment.
  In such circumstances, the clinician may find it more acceptable to “frame” the discussion by explaining the routine nature of such questions, thus demonstrating that the patient is not singled out because of mannerisms, appearance, or ethnicity. One approach may be to emphasize the importance of this information for patient care: “To be able to provide the best care for you today, we need to understand your risk for certain infections by talking about your sexual practices.” Another may be to allude to the universality of many concerns: “Many women find it difficult to get their men to wear condoms; has this been a problem for you?” (Curtis, 1999).
  
• As with any type of medical history taking, open-ended questions probably serve as the most effective means of eliciting information when taking a sexual history.
  Language should be clear, easy to understand, nonoffensive, and nonjudg-mental. Many clinicians prefer closed-ended questions when they are functioning under time pressures. In such cases, a questionnaire that the patient completes in the waiting room may be a preferred tool. Whenever possible, however, clinician-patient interaction serves as the ideal forum for sexual risk assessment.
  
• Many clinicians are not familiar with risk factors for HIV infection specifically relevant to women.
  Risk factors for HIV infection in male homosexuals and intravenous drug users have been well described. In contrast, factors that may increase risk in women, such as a history of unwanted pregnancy, or an incarcerated sex partner, are less specific and less well recognized. Although some risk factors for women can be derived from epidemiologic studies, such as history of “high-risk STDs” (i.e., gonorrhea or syphilis), crack cocaine use, and injection drug use, some women are at risk through monogamous partner relationships with their HIV-infected husbands. Therefore, identifying risk behaviors in women requires a careful and skilled clinician. In many cases, a low threshold for recommending HIV testing is necessary. Important risk topic areas to cover are listed in Table 3-1.

Screening strategies range from mandatory screening of pregnant women to selective screening of high-risk women.
Selective screening strategies have targeted intravenous drug users, STD clinic attendees, and economically disadvantaged individuals (Ades, 1999). The advantage of selective screening is cost-savings, particularly in low-prevalence parts of the world. Many experts favor a universal recommendation for HIV screening, at least for pregnant women. The advantage of universal screening is not only increased detection rates, but perhaps also increased test acceptance. Universal screening removes the stigma of HIV testing by eliminating any targeted testing based on sexual orientation, socioeconomic status, or race. When HIV testing is stigmatized, women in high-risk groups may be reluctant to identify themselves. On the other hand, the cost of universal HIV testing is significantly higher than voluntary, selective screening strategies, and there are both practical and ethical issues in implementing universal screening, even in perinatal care.

• The counseling that occurs before and after HIV testing has three principal goals (Celum, 1999):
  1. to provide counseling about risk reduction for HIV-negative persons, 
  2. to identify HIV-infected persons for clinical interventions, and 
  3. to provide counseling to HIV-positive persons about potential transmission.
  
• The components of HIV pretest and posttest counseling are outlined in Table 3-2
  Pretest counseling should include discussion about the basic facts of HIV infection, the acquired immunodeficiency syndrome (AIDS), and HIV testing. However, in most situations, emphasis should be placed less on didactic material than on individualized discussion of risk and risk-reduction unless the patient has very limited understanding of HIV/AIDS. Posttest counseling should reinforce these concepts in the context of the test result. Regardless of the test result, resources and referrals for the patient and/or her partner should be provided. For patients at risk for domestic violence, the potential domestic turmoil that a positive test result can elicit should be emphasized. This issue will be further addressed in the section on ethnic and gender considerations.

• Make use of an opportunity to provide client-centered counseling 
  Any time spent with the patient, however short, provides an opportunity for the clinician to conduct individualized counseling about recognizing and reducing high-risk sexual behaviors. Patients who present with concerns or symptoms of STDs are usually also at risk or concerned about risk for STD, including HIV. In the context of a negative HIV test, the posttest counseling session provides a valuable opportunity to develop a risk-reduction plan in a woman who has identified herself as someone who is concerned about risk and may be at high risk. Many clinicians may find it effective to deliver the negative test result in the context of a “second chance,” thus emphasizing that current behaviors are unsafe and can be changed.

B.  RAPID TESTS

• Rapid tests are a good alternative in certain circumstances.  
  After all, HIV testing is only of value if patients return for their test results and posttest counseling. Many testing programs in the United States use an initial enzyme-linked immunosorbent assay (ELISA) with confirmation through Western blot. In less developed areas, two ELISAs run in sequence are often used. With both protocols, the patient is required to return to clinic 1–2 wk after testing for results. In 1995, 25% of persons testing HIV-positive and 33% of persons testing HIV-negative at publicly funded HIV testing sites in the United States failed to return for test results (Centers for Disease Control and Prevention [CDC], 1998d). Similar low return rates have been described in Nairobi, Kenya, and other parts of the world.

     Rapid testing for HIV would result in substantial cost savings and circumvent patient no-show rates. At least 10 rapid tests, defined as tests requiring less than 2 hr, are currently available internationally, although only one test (Single Use Diagnostic System HIV-1 Test) is approved for use in the United States (see Chapter IV on Primary Care) (Kassler, 1997; Spielberg, 1996). The World Health Organization (W.H.O.) has developed alternative testing strategies using sequential rapid tests, thus obviating the need for expensive and delayed confirmatory testing. Some tests require as little as 5 min and are easy to perform in the field. Most tests are 95–100% sensitive and specific. In the United States, the CDC has published recommendations that clients receive the results of rapid HIV tests on the day of testing. Patients who test negative can be given a definitive negative result without a return visit. For patients who test positive, it is recommended that they be informed that their screening test was positive, and that they should return to receive a confirmed test result.

     In the United States, rapid testing is most appropriate in areas of high prevalence where clinic return rates are low (STD clinics, emergency departments) or an HIV diagnosis will influence immediate management decisions (postexposure prophylaxis, unknown HIV status in a pregnant woman presenting to Labor & Delivery). In many ways, rapid testing is most appropriate in economically disadvantaged countries where HIV seroprevalence is high, laboratory resources are limited, and patient travel to and from clinic may be very inconvenient.

• Rapid tests may result in unwanted test results
  Critics of rapid testing for HIV are concerned about the ability to provide appropriate counseling outside the framework of two visits for pre- and posttest counseling. Importantly, the prompt sequence of events associated with rapid testing may not give the patient enough time to digest counseling information. However, for many women in areas where rapid tests are likely to be used, rapid testing presents several difficulties. Women may find it difficult to decline an unwanted test, sometimes related to a cultural injunction against refusing a test offered by a health care worker perceived as an authority figure. Furthermore, women may fear that refusing HIV testing may result in not receiving other health care services offered by the clinic. Therefore, availability of rapid tests may result in subtle coercion of a woman to consent to HIV testing. Informal surveys in the context of HIV research in Kenya have revealed that many women feel that an interval of 1 wk between testing and results is ideal. In some cases, failure to return to clinic for HIV test results may reflect a desire not to have had the test in the first place.
  

C.  IMPACT OF HIV COUNSELING AND TESTING ON PREVENTION

What is the evidence that HIV testing may change risk behavior? The literature in this area is difficult to synthesize, largely because of evolving counseling practices, varying lengths of follow-up, and lack of a well-defined endpoint. In one large prospective study the incidence of STDs was determined for patients who received HIV testing and counseling at a public STD clinic in Baltimore. Both HIV-positive and HIV-negative patients demonstrated high rates of STDs 6–23 mo after receiving HIV test results and posttest counseling (Zenilman, 1992). In another study, the incidence of gonorrhea was measured after receipt of HIV result and posttest counseling. HIV testing and counseling was associated with a moderate decreased in gonorrhea infection among patients who tested positive for the virus, but with a slight increase in incidence in patients who tested negative (Otten, 1993). These findings suggest that learning of a positive HIV test result may have a modest effect on sexual risk-taking. The studies also raise important concerns about the effectiveness of HIV testing and counseling in impacting sexual risk-taking, and about potential disinhibition after receiving a negative test result.

     Results from a study of discordant couples in Zaire were more promising; among 149 discordant couples who voluntarily attended an HIV counseling center, HIV testing and posttest counseling resulted in an increase in consistent condom use from less than 5% to more than 70% (Kamenga, 1991). During 100 person-years of follow-up, incidence of new HIV infections was only 3%. The difference between these results and the results obtained in Baltimore and Miami may reflect varying levels of baseline HIV knowledge, the differences between individuals in long-term relationships vs. casual relationships, and cultural and geographic influences.

IV. BEHAVIORAL INTERVENTION MODELS

• The Health Belief Model, the Social Cognitive Theory, the Theory of Reasoned Action, and the Stages of Change Theory (Bandura, 1996; Fishbein, 1999) have been developed to explain determinants of human behavior change. These models all have in common the theory that perceived risks and benefits of behavioral change predict the likelihood of behavior change and can guide the approach to behavioral interventions. These models are described and contrasted in Table 3-3.
  
• The AIDS Risk Reduction Model integrates the concepts of the above-mentioned theoretical models into a framework providing information, motivation, and behavioral skills specific to AIDS risk reduction (Catania, 1990; Fisher, 1992). With this model, counselors help patients to identify sexual behaviors that put them at risk for acquiring HIV, formulate plans to change these behaviors, and take action to realize these plans.
  
• The Stage of Change (SOC) behavioral theory proposes that the process of behavioral change occurs along a continuum of five fundamental stages (Table 3-3) (Coury-Doniger, 1999). The stages can be used to tailor the counselor’s approach to an individual by assessing where an individual is on that continuum for a specific behavior. For example, an individual with multiple partners who sees no need to use condoms consistently would be in the Precontemplative stage. In contrast, a woman in a mutually monogamous relationship who sees the need to know her partner’s HIV status, but fears angering her partner by this request, would be in the Action stage. A counselor’s approach to these two patients would be different. For the first individual, counseling directed at recognition of risk would be most appropriate, whereas for the second woman, communication and goal-setting skills should be emphasized. Importantly, individuals do not always move forward linearly along this continuum, but may “relapse” and move forward and backward between the stages. At the Rochester STD clinic, clinicians who have formally incorporated the SOC in their risk assessment and counseling of STD clients report a high degree of satisfaction with the SOC model as a diagnostic tool that guides their specific counseling interventions with a client.
  

V. PUBLISHED BEHAVIORAL INTERVENTION TRIALS

Several well-designed randomized controlled trials have been conducted to assess the efficacy of various behavioral intervention strategies, and most conclude that such interventions result in decreased sexual risk-taking (primarily unprotected sex) and, in some studies, STD and HIV incidence. In contrast to didactic education sessions, behavioral interventions focus on recognizing risk and formulating effective risk reduction strategies. Knowledge alone does not motivate change. To translate this concept into an issue many of us have experienced, consider the issue of weight reduction and diet modification. Despite widespread knowledge about the adverse health effects of eating fatty foods, adhering to a diet is notoriously difficult. Similarly, knowledge about STDs and HIV is not enough to implement change in sexual behavior.

     Randomized controlled studies using STD incidence as an outcome provide objective evidence of health-related endpoints, thus representing the most valid measurement of an intervention’s efficacy. Five such trials have been published in the past few years examining the efficacy of behavioral intervention strategies using STD incidence as an outcome measure (Table 3-4). All five studies used similar intervention approaches incorporating education, motivation, and development of a concrete plan for behavioral change. Sessions were structured as individual or group counseling.

• Behavioral interventions can lead to lower rates of STD acquisition
  As shown in Table 3-4, results of these studies varied. The discrepancy in reported outcomes may be related to several factors. The sample sizes of the National Institute of Mental Health (NIMH) study (NIMH, 1998) and CDC-funded Project RESPECT (Kamb, 1998) study were large, providing excellent ability to detect even a modest effect of the intervention. In the San Francisco study (Boyer, 1997), for example, the sample size provided only 45% power to detect the approximate 20% change in STD incidence detected in the RESPECT study. However, an appreciable effect of the intervention was detected in the San Antonio study (Shain, 1999) despite a sample size of only 617. In this study, ethnic-specific tools and counselors were used, thus perhaps enhancing the effect of the intervention. Indeed, in this study, a 49% decreased STD incidence was detected after 12 mo, compared with a 20% decrease reported in the RESPECT study. Finally, adherence to behavioral session schedule and follow-up with STD exam are crucial elements affecting study validity. The NIMH, RESPECT, and San Antonio studies all reported higher adherence rates and follow-up rates compared to the Houston (Branson, 1998) and San Antonio studies, thus providing increased ability to measure the effectiveness of the intervention. 
  
• Even brief (two 20-min) counseling sessions can result in lower STD rates and can be incorporated into clinical settings 
  The  20-min Project RESPECT counseling sessions may be most applicable to busy practitioners interested in conducting effective behavioral counseling. This study demonstrated that individual ģbrief ī counseling, involving two sessions of 20 min each, was as effective in reducing STD incidence as four ģenhancedī 1-hr sessions. Both intervention arms, the two 20-min and four 1-hr counseling sessions, were superior to a didactic message. The first of the two brief 20-min sessions focused on recognizing HIV risk and barriers to risk reduction. After working with the client to agree on an achievable risk reduction plan, the counselors concluded the sessions by identifying a small risk reduction step that could be achieved before the second session. At the second session, counselors reviewed progress and barriers in achieving the behavioral goal, and helped to clients to arrive at a long-term risk reduction plan. Although the four 1-hr “enhanced” sessions also included recognizing risk and formulating risk reduction plans, more energy was focused on key theoretical behavioral elements such as self-efficacy, attitudes, and social norms underlying risk behavior. The fact that the brief two 20-min counseling sessions demonstrated equivalent efficacy to 4 hr of counseling is encouraging to practitioners who would like to integrate effective HIV counseling into busy clinical settings.

VI. PRACTICAL ASPECTS OF COUNSELING PATIENTS

ABOUT SEXUAL RISK REDUCTION

All of this information may seem overwhelming to the health care provider who has no special training in behavioral theory. However, the underlying principle is one that can be applied by any practitioner in any setting: counseling should be individualized to the person receiving the counseling. Any attempt to accomplish individualization of approach would be superior to simply providing a didactic message. Some practical aspects of counseling are listed in Table 3-5 and discussed below.

• Focus the counseling session
  The cornerstone of the counseling session is to focus the session on the patient’s recent sexual activities, their perception of their risk, and motivation to reduce their risk of HIV/STD exposure, redirecting the patient to this topic whenever necessary. Clinicians and counselors may become distracted by providing excessive information about scientific data and principles in response to patient questioning. Such information is probably more effectively dispensed in pamphlet form or by referral to other patient information sources. In addition, women at risk for STDs including HIV frequently come to clinic with multiple complicating issues, including poverty, domestic violence, substance abuse, and child care problems. Often the counselor begins to feel responsible for addressing all of these issues and discouraged by the fact that many of them seem so insurmountable. Furthermore, the patient may be uncomfortable discussing her own risk, and may therefore be emotionally invested in distracting the counselor from that subject. For these reasons, it is important for the counselor to remember that the goal during the limited interaction period with the woman is to directly address, and hopefully impact, risky sexual behavior. Some appropriate topics are listed in Table 3-6. Other longstanding issues may not be easily solvable, and may be more appropriately referred to a social worker, substance abuse counselor, or mental health counselor.
  

• Listen and react
  At the same time, it is important to listen and react to the patient. It is a human quality that we enjoy talking and thinking about ourselves. A counseling technique of summarizing a patient’s descriptions and viewpoints about her risk is an extremely effective communication tool. In an effort to be nonjudgmental, counselors may find themselves nodding supportively to just about any statement that the patient may make. Instead, sometimes direct and clear feedback from the counselor about self-destructive behavior may communicate more effectively the importance of reducing risk (Figure 3-1). For example, if a patient is describing an evening during which she had sex with multiple men while using crack cocaine, it may be more appropriate for the counselor to respond with emphasis that such behavior is dangerous. It would also be important to explore the emotional or physical needs leading to such risky sexual behavior and to identify potential alternatives to fulfilling such needs.

• Don’t stick to a practiced script
  In an effort to focus, some counselors may restrict themselves to a practiced script and thus squander opportunities to effectively impact risk behavior. Specific counseling scenarios a provider might encounter are described below: ! references to suicide: “I could have killed myself ” ! self-deprecating comments: “I was so stupid” ! overacceptance of risk: “Even if I would have known he was HIV-positive, I wouldn’t have used a condom” ! inappropriate behavior: giggling, putting feet up on the table Such statements are usually pleas from patients for a direct and honest response, and taking such opportunities to acknowledge and problem-solve risky behavior is important in establishing the objectives of the session. Inappropriate patient behavior such as excessive giggling, angry postures, or demonstrations of boredom, should also elicit comment and questions from the counselor. Overlooking such behavior in an effort to be professional, polite, or focused detracts from the ability to communicate.
  
• Avoid overambitious risk reduction plans
  The most common error made by counselors is to develop an overambi-tious risk reduction goal, particularly during sessions in which good rapport has been developed. In many cases, counselors may convince themselves that the woman has acknowledged her risk to such a degree that she is now ready to eliminate any subsequent episodes of unprotected sex. Such goals are likely unrealistic. Behavioral specialists favor extremely concrete goals, such as “On Friday night I am going to ask my partner to wear a condom.” Even modest goals, such as stopping at a drug store and purchasing condoms on the way home from the session, may be suggested. Other possible goals are listed in Table 3-7.
  
• Put it in writing
  Furnishing written documentation of patient goals reinforces verbal instructions and provides additional motivation.
  
• Use time wisely
  The question then remains: what amount of time is necessary to effect a behavioral intervention? The Project RESPECT study demonstrated successful intervention with two 20-min sessions within 10 days of each other. An ongoing follow-up study, RESPECT 2, compares a single 1-hr visit with rapid HIV testing to the two 20-min sessions. In busy clinics, where care for genital tract infections and other medical problems may be occurring simultaneously with patient counseling, clinicians may not feel that they have sufficient time to counsel effectively. However, in many cases, patients spend much more time waiting in the reception area or in the exam room than they actually do with the clinician. Optimizing use of patient time by providing educational materials during waiting periods may allow the clinician to limit the amount of didactic information dispensed in clinic and to spend more time in interactive behavioral modification. A self-assessment of the counseling session will allow clinicians to measure their counseling skills. Goals for the counseling session include exploring behaviors most associated with risk, identifying a reasonable risk reduction plan, and assessing the patient support system. A reasonable checklist for a behavioral intervention session is shown in Table 3-8.

FIGURE 3-1: LISTEN AND REACT TO THE PATIENT

React to what a woman tells you. Use words and body language to express yourself.

TABLE 3-7: EXAMPLES OF CONCRETE INDIVIDUALIZED RISK
REDUCTION PLANS

TYPE OF PLAN

1.  Patient will talk about HIV/STD concern/risk to partner/friends
2.  Patient plans to get herself tested or have partners tested for HIV/STDs before to having sex
3.  Patient plans to reduce, change, or eliminate at-risk partner(s)
4.  Patient will change the type of partners she has
5.  Patient plans to change use of alcohol and drugs
6.  Patient plans to increase condom use or increase situations that she uses condoms
7.  Patient plans to change the kind of sex she will have
8.  Patient plans to make changes in the situations she is in that are associated with risk behavior

DESCRIPTION

• Disclosure or communication with partner
• Disclosure or communication with peers
• Disclosure or communication with others
• Patient will test herself again to ensure uninfected
• Have partner tested for HIV/STD
• Use condoms until partner tested for HIV/STD
• Abstain from sex until partner tested for HIV/STD
• Break up with high-risk partner(s)
• Eliminate a particular type of high-risk partner (prostitute, anonymous partner)
• Patient will have fewer partners
• Patient will get to know partners better before having sex
• Patient will remain monogamous with one partner for 3 mo
• Patient will abstain from sex for 3 mo
• Decrease/eliminate alcohol/drug use when having sex
• Generally decrease/eliminate a specific drug/alcohol
• Change venue where needles/drugs/alcohol used
• Do not share needles (exchange or obtain new)
• Clean needles or only share with known HIV-negative partner
• Talk to partner(s) about using condoms
• Buy condoms or have them more available
• Sex with condoms more often
• Use condoms with all partners (vaginal/anal sex)
• Use with all non-main partner (vaginal/anal sex)
• Use condoms with main partner (vaginal/anal sex)
• Have oral sex instead of vaginal or anal sex
• Have mutual masturbation or petting (no penetrative sex)
• Eliminate going to particularly risky place (bar, park)
• Reduce number of times going to particularly risky place
• Substitute behavior; go to gym, movies, etc.

Source: Adapted from Kamb ML, 1998, and from Beth Dillon, Project RESPECT training materials.

TABLE 3-8: A CHECKLIST FOR THE BEHAVIORAL INTERVENTION
COUNSELING SESSION

• Explored behaviors most associated with risk
• Identified behaviors most amenable to change
• Identified reasonable change step
• Developed the change step into a plan for action
• Problem-solved obstacles to the plan
• Confirmed with patient that the plan is reasonable
• Assessed patient’s support system
• Identified referral resource, if necessary and available
• Reviewed date, time, and goals for next visit
• Recognized behavior change as a challenge

Source: Adapted from Kamb ML, 1998, and from Beth Dillon, Project RESPECT training materials.

VII. ETHNIC AND GENDER CONSIDERATIONS IN RISK REDUCTION COUNSELING

• Language, visual materials, and descriptive terms sensitive to specific cultures and ethnicities may be important in improving communication techniques.
  Ethnographic data from the San Antonio study found that African Ameri-can women in their study population displayed an emphasis on infectious disease prevention, referring to sharing eating utensils as “eating behind” and sharing needles as “fixing behind.” The authors suggested that use of terms such as having sex “behind” someone might be an effective means of communicating the concept of unsafe sexual practices in their study population. In contrast, people of Asian background often conceptualize the human body of being made up of “hot” and “cold” components and may think of disease processes such as STDs as “hot.” Referring to a condom as “cold” may emphasize the effectiveness of such preventative measures. Finally, some studies have shown that the use of visual tools enhances verbal communication in Spanish. It is important to recognize, however, that such colloquialisms or cultural preferences may vary between regions, socioeconomic strata, and religions. If used in the wrong setting, approaches designed for one ethic group may offend another, and detract from the counselor’s ability to communicate. In the absence of a validated communication tool, the counselor should take their cues from the patient.
  
• Some counseling concerns are particularly relevant to women.
  In many economically disadvantaged areas of the world, poverty engenders oppression of women. When education and jobs are scarce, many economies preferentially educate and employ men, thus leaving women financially dependent on their husbands, vulnerable to “sugar daddies,” and bartering sex for food and clothing either in informal relationships or in a structured brothel setting. Many cultures sanction a family structure in which the mother of the husband lives in the home and is responsible for directing household activities and ensuring the well-being of her son. Many cultures also may place more value on men than on women, and may mythologize male prowess and discourage condom use. Finally, many societies do not recognize the legal rights of women in custody battles, thus leaving women tied to their husbands if they wish to remain with their children. In conditions in which women are economically and emotionally dependent on men, women often neglect their basic human rights. Such barriers may be extremely daunting to counselors, and the temptation may be to attempt to debunk societal inequalities or to degenerate into a “male-bashing” session. In such cases, the basic tenets of behavioral counseling should be recalled; focus on risk and tailor the session to the readiness of the woman for behavioral change. Clear, feasible risk reduction plans should be formulated, usually involving self-education about risk and recognition of responsibility to reduce risk.
  
• Domestic violence may need to be addressed.
  Domestic violence continues to be a prevalent problem, affecting 20–30% of households in the United States and possibly even higher numbers in other parts of the world. A study of HIV testing of women in Nairobi, Kenya, has produced some disturbing results. Out of 243 women informed that they were HIV-positive, only 66 (27%) informed their partner of their result. Of these 66, 11 (17%) were chased from the home, 7 (11%) were beaten, and 1 (1%) committed suicide. When the testing protocol was changed to informing women that returning for HIV test results was optional, only one third of women returned for their results (Temmerman, 1995).
  Fear of domestic violence may also impede a woman’s ability to assert her rights in a relationship to reduce her risk of HIV infection. Counselors must realize that such fear may be entirely reasonable, and that counseling patients about domestic violence may be beyond their area of expertise. Whenever possible, appropriate patients should be referred to domestic violence centers. At the same time, counselors can help patients formulate risk reduction plans in the setting of domestic violence. The counselor must approach the issue of HIV testing while mentioning and indeed, when appropriate, emphasizing the possibility of domestic violence and social stigma. Although counselors must encourage disclosure in order to avoid the potential of infecting an uninfected partner, they must remember that the safety of the patient is their first priority. Unfortunately, only initiation of widespread testing and recognition of seroprevalence will succeed in destigmatizing HIV infection. Meanwhile, on the individual level, care must be taken to help the woman identify ways to reduce her risk of physical harm and excessive emotional stress while at the same time initiating the process of recognizing and reducing risk behavior.
  

VIII. SEXUALLY TRANSMITTED DISEASES AND THE RISK OF HIV INFECTION

• Genital tract infections increase susceptibility to HIV infection
  The fact that STDs are important cofactors for HIV infection has been well established by prospective studies examining risk factors for seroconversion in high-risk populations. In such studies, the increased risk for HIV-1 acquisition in women with genital ulcer diseases and gonococcal and chlamydial cervicitis has been estimated at two to four above baseline. Women with Candida and trichomonal vaginitis have been estimated to have an approximately 2–3-fold increased risk above baseline (Laga, 1993).
  
• Bacterial vaginosis may also increase susceptibility to HIV infection
  In an important recent study in Malawi, bacterial vaginosis was shown to be a significant risk factor for HIV seroconversion in pregnant women attending an antenatal clinic. In this study, bacterial vaginosis (defined by vaginal pH > 4.5, homogeneous vaginal discharge, absence of other etiologic agents of cervicitis or vaginitis, presence of clue cells, and positive amine odor) was a prevalent condition, affecting 30% of women. Presence of bacterial vaginosis at the enrollment exam was associated with a 3–4-fold increased risk of HIV seroconversion over the median 2.5 yr of follow-up (Taha, 1998). An association between bacterial vaginosis and HIV-1 sero-conversion has also been reported in a study of nonpregnant women; women with bacterial vaginosis in the 60 days before HIV testing were 1.4 times more likely to have incident HIV infection than women without genital infections (multivariate p=.07) (Martin, 1998).
  
• Syndromic management of STDs decreased HIV acquisition rates, but mass treatment of STDS did not in two different community randomized trials
  From these studies, one can conclude that a healthy genital tract reduces a woman’s susceptibility to HIV infection. This conclusion was further solidified by the results of a community-based randomized trial conducted in Mwanza, Tanzania, demonstrating that syndromic management of STDs resulted in a 40% reduction in HIV-1 seroconversion in the intervention communities (Hayes, 1995; Mayaud, 1997). In contrast, a randomized controlled trial of mass antibiotic treatment conducted during almost the same time period in Rakai, Uganda, failed to demonstrate a reduction in HIV seroincidence (Wawer, 1999). The reason for the difference in findings in these two trials testing an STD intervention is likely related to the stage of the epidemic in the two locations. In Mwanza, the baseline prevalence of HIV was only 4%, indicating an early phase of the epidemic. In comparison, the Rakai study was conducted in a population with a baseline prevalence of 16%, indicating a more mature epidemic. Experts feel that the core group of high-risk individuals crucial to epidemic transmission was already saturated in Rakai, thus minimizing the impact of the intervention. The Rakai intervention also did not address genital herpes, which was the most common cause of genital ulcer disease in the Rakai communities. The disparate findings of these studies emphasize the complexities of the association between HIV and cofactors affecting transmission.
  
• How should we counsel women at risk for STDs and HIV?
  Important issues in counseling women at risk for STDs and HIV are presented in Table 3-9. Reducing the prevalence and incidence of STDs should reduce the susceptibility to HIV transmission. Measures to reduce STDs include female and male condom use, seeking early diagnosis and treatment of genital tract symptoms, and frequent STD screening and should be a part of HIV prevention in the United States as well as in developing countries (CDC, 1998b). Infections such as yeast vaginitis and bacterial vaginosis are not sexually transmitted, but arise from disruption of a woman’s genital tract flora. For this reason, these infections are often underemphasized in programs to diagnose and treat genital tract infections. However, these are prevalent conditions, and studies have shown that both yeast vaginitis and bacterial vaginosis may increase risk of HIV acquisition. Clinicians should diagnose and have a low threshold to treat both bacterial vaginosis and Candida vaginitis in women with high-risk sexual behavior. Douching may increase the risk of developing bacterial vaginosis or pelvic inflammatory disease. Douching has no therapeutic benefit and should be strongly discouraged. Preventable risk factors for Candida vaginitis include uncontrolled diabetes mellitus, antibiotics, and high-estrogen oral contraceptives. Other possible risk factors that are less well documented include wearing poorly ventilated clothing, use of low-estrogen oral contraceptives, frequent swimming, feminine hygiene sprays, and use of spermicidal jelly.

TABLE 3-9: MEASURES TO REDUCE STDS

• Encourage male and female condom use
• Encourage seeking medical care early for diagnosis and treatment of genital tract symptoms
• Routine screening for genital tract infections, including chlamydia cervicitis, yeast vaginitis, and bacterial vaginosis among sexually active women
• Discourage douching
• Educate women about risk factors for yeast vaginitis
• Teach how to recognize genital herpes recurrences and prodromes and offer antiviral treatment to shorten or suppress recurrences
  

     Finally, many studies have shown that genital ulcer diseases (i.e., syphilis, chancroid, and genital herpes) are important cofactors for HIV transmission. Women with a history of genital herpes or with serologic evidence of herpes simplex virus type 2 infection should be taught how to recognize prodromes and recurrences. Suppressive herpes antiviral therapy should be considered in women with frequent recurrences who report high-risk sexual behavior (CDC, 1998a).

IX. CONDOMS AND PREVENTION OF HIV INFECTION

Readers of history may know that decorative penile covers have been mentioned in Egyptian writings as far back as 1350 BC. In 1564, the Italian anatomist, Fallopius, described the concept of a penile barrier for the prevention of venereal disease. The famous romancer, Casanova, is said to have protected himself with sheets of sheep intestine. Since that time, technology has allowed the production of latex male condoms and, more recently, poly-urethane male condoms and female condoms. Important issues to discuss while counseling women on use of male and female condoms are listed in Table 3-10 and discussed below.

TABLE 3-10: IMPORTANT ISSUES FOR PATIENTS BEING COUNSELED ON
CONDOM USE

• Store in a cool, dry place, such as a bedroom drawer

• Avoid excessive humidity, such as in a bathroom

• Avoid excessive heat, such as in a wallet carried in a trouser pocket
• Avoid exposure to direct sunlight

• Use appropriate spermicide or lubricating jelly

• Mineral-oil-containing compounds, such as petroleum jelly, cooking oils, shortening, or lotions, can weaken latex

• Use male condom properly

• Use male condom at the onset of male arousal, even before penetration

• Make sure that the male condom is unrolled to extend completely to the penis base
• Use enough lubrication to prevent excessive friction that might lead to breakage
• Hold the male condom at the base during withdrawal to prevent slippage

• Use female condom properly

• The inner ring must be placed completely onto the cervix or the condom may twist

• Additional lubrication may be needed to prevent the condom from twisting

• The outer ring may need to be held in place to keep the condom from slipping into the vagina or anus

• Care must be taken not to insert the penis between the condom and vaginal wall

• The outer ring may need to be held in place to keep the condom from slipping into the vagina or anus

• During anal intercourse, the insertive partner may have to keep thrusts shallow, because the condom is not as long as the rectum. It also might be advisable to remove the inner ring for anal sex to reduce likelihood of rectal bleeding.

A.  MALE CONDOMS

• Male condoms prevent transmission of many STDs
  The literature on the role of barrier contraception as protection against STDs is vast and the reported degree of protection against specific STDs varies from paper to paper. A distillation of available data produces the conclusion that, of available barrier methods that have been adequately tested, latex male condoms provide substantial protection against infection with HIV and most other STDs, and are currently the most reliable protective measure. Most studies describe a 7–8-fold decrease in risk of HIV-1 seroconversion for people who use condoms consistently. Some have reported no seroconversions at all among consistent condom users despite repeated coital exposure (Carlin, 1995). In terms of other STDs, male condoms may be less reliably protective against transmission of herpes and human papilloma viruses.

• Latex male condoms must be stored and used properly
  Male condom failures are more likely caused by postmanufacture defects secondary to latex deterioration than to manufacturing defects. Latex male condoms have proved impermeable to HIV in vitro. In contrast, natural membrane (“skin”) condoms have been shown to be permeable to small amounts of HIV and other infectious agents, and are not recommended for disease prevention. Transmission of HIV that occurs with use of latex male condoms is likely due to technical failures or improper usage rather than to manufacturing defects. Since 1987, the Food and Drug Administration in the United States has maintained a high level of quality by limiting the number of defective condoms to four per 1000 count batch. Patients should be counseled that stored male condoms should be replaced often because temperature, light, and animal pests all can contribute to latex deterioration and decreased effectiveness. In clinical studies, breakage rates range from 0.5% to 7% (Stratton, 1993). Studies reporting higher breakage rates tended to include populations from underdeveloped areas or those who participated in anal intercourse.
  
• Male condoms must also be used properly to be effective.
  Using oil-based lubricating materials such as petroleum jelly, cooking oils, shortening, or lotions during intercourse weakens latex and promotes breakage. Common errors that patients should be cautioned about include delaying condom use until just before full penetration, failure to extend the condom all the way to the penis base, insufficient application of a water-based lubricant, and failure to hold the condom at the base during withdrawal.
  
• Polyurethane male condoms may be a future alternative
  Acceptability of male condom use is limited by complaints of decreased male sensitivity and limitation of sexual enjoyment by both men and women. Polyurethane has been hailed as an attractive alternative to latex because of increased tensile strength that should, theoretically, allow for a thinner condom wall translating into increased penile sensation. A male polyurethane condom, Avanti, has been popular since its introduction in late 1994, but after increasing numbers of complaints of condom breakage, the manufacturers have changed specifications to produce a thicker condom labeled “Intended for Latex Sensitive Condom Users Only.” Breakage rates, patient acceptability, and the ability of this product to protect against STD and HIV infection are yet to be demonstrated.
  

B. FEMALE CONDOMS

Also made of polyurethane, the female condom has been available for use in the United States since 1993 (Bounds, 1997) and offers women more control over use than with the male condom. The female condom is a sheath, closed at one end, with flexible rings at both ends (Figure 3-2). The device is inserted into the vagina by compressing the closed-end ring and pushing against the cervix, while the outer ring covers the labia (Figure 3-3). Only one female condom is currently available, marketed under the name “Reality” in the United States and Canada and “Femidom” in other parts of the world. Limited data are available on the efficacy of the female condom in preventing HIV and STDs, although most experts have extrapolated from the data on male latex and polyurethane condoms to conclude that, if used properly, female condoms would be impermeable to most viruses and other microorganisms. In a study sponsored by the United Nations Programme on HIV/AIDS (UNAIDS), female commercial sex workers in Thailand were randomized into a group instructed to consistently use male condoms, and a group given the option to use female condoms if the male refused to wear a condom (Fontanet, 1998). Both groups reported universal male or female condom use rates of approximately 97%, although 9% of the women in the “option group” used the female condom. Before introduction of the female condom, women in the study population were experiencing an average of two STDs per year (trichomoniasis, chlamydial infection, gonococcal infection, genital ulcer disease). This rate was surprisingly high, particularly given the high rate of reported condom use, and may be due to overreporting of condom use (given the Thai 100% condom use policy) or STDs acquired from their husbands or nonpaying partners. Nevertheless, the group randomized to the option to use either type of condom demonstrated a 24% decrease in the incidence of STD compared with the male condom only group. Importantly, female condoms were reportedly well accepted by both the women and their clients. Condom tears occurred less frequently with the female condom than the male condom.

C. ACCEPTABILITY OF MALE AND FEMALE CONDOMS

Factors influencing condom use are presented in Table 3-11. These factors are complex, and often differ between men and women. Surveys have shown that both men and women are influenced by perceived social norms and attitudes about condom use, and by the recognition that condoms may prevent STDs. Ability to obtain condoms without excessive cost or embarrassment, ease of using the condom, and preservation of pleasurable sexual sensation are clearly concerns for both men and women. Acceptability of the male condom for both men and women is increased by normal appearance and feel, lack of odor, lack of slippage, the presence of a reservoir tip, and spermicidal lubrication. Men may be more likely to use the male condom if they feel that the woman may perceive them as being more sensitive and caring if they do so. Women, on the other hand, have complained that the interruption of foreplay negatively affects the acceptability of the male condom. For the female condom, both men and women have complained about the aesthetic appearance of the external ring, and the noise during intercourse. The fact that the female condom is made of polyurethane and not latex may increase its acceptability, particularly among latex-allergic users. Women have reported that inserting the female condom interrupts foreplay. Interestingly, in several surveys, more women have said that they would be likely to use the female condom again than have said that they liked using it, suggesting that women may be willing to sacrifice comfort and pleasure during sex for protection against STDs and pregnancy. Many women have also strongly expressed a preference for a female-controlled device to prevent STDs. Finally, in surveys, pregnancy prevention is more important to women than to men, and most women feel that both the male and female condom may be inferior to other contraceptive methods (Grady, 1999).

TABLE 3-11: FACTORS ASSOCIATED WITH CONDOM USE AND NON USE

X.  OTHER FORMS OF CONTRACEPTION AND THE RISK OF HIV INFECTION

• The role of hormonal contraceptives in HIV transmission is controversial
  The association between hormonal contraception and HIV infection has been the subject of controversy. Because of the unique considerations that contribute to contraceptive choice, a clinical trial randomizing a woman to contraception or placebo is probably not feasible. Thus, although many studies presenting data on the association have been published, all are population surveys or observational studies. The reported effects of oral contraceptives on HIV susceptibility are widely divergent, ranging from protective, to no effect, to an increased risk. A meta-analysis on the subject reported that the use of oral contraceptives may be associated with a small increased risk of HIV infection (Wang, 1999). When the results of all 28 published studies were combined, a pooled odds ratio of 1.2 (95% confidence interval 0.99–1.42) was found. This pooled risk estimate increased with increasing study quality, suggesting that a true association, albeit small, does exist. In addition, two cross-sectional studies and two prospective studies have reported that women using depo-medroxyproges-terone acetate (Depo-Provera) are at increased risk of HIV infection. In a study conducted in Mombasa, Kenya, commercial sex workers (n=779) were followed for a median of 224 days; in multivariate analysis, women using Depo-Provera demonstrated a 2-fold increased risk of HIV serocon-version (Martin, 1998). Insufficient data exist on other hormonal contraceptive methods to reach a conclusion about the effect on a woman’s susceptibility to HIV.

• Barrier contraceptives other than condoms
  Other forms of barrier contraception, such as the diaphragm and the cervical cap, do not cover the vagina, and therefore would not be expected to provide substantial protection against HIV infection, although the diaphragm with nonoxynol-9–containing spermicide has been associated with a modest decrease in bacterial STDs. Nonoxynol-9 spermicides alone provide modest protection against bacterial STDs but no apparent effect on HIV in randomized clinical trials despite evidence of in vitro activity against HIV. Furthermore, nonoxynol-9 spermicides have been associated with chemical irritation or epithelial disruption in the lower genital tract at higher doses of nonoxynol-9 or with frequent use, raising concerns that these women may be at increased risk for HIV transmission if they use spermicides only. The use of spermicides alone should be discouraged in at-risk women and the potential benefits (lubrication, possible increase in protection if the condom breaks) and risks of spermicide use with condoms should be discussed. Intrauterine devices (IUDs) have been associated with an increased risk of pelvic inflammatory disease, especially around the time of insertion. A 2–3-fold increased risk of HIV infection in women who use IUDs has been reported (Kapiga, 1994). The foreign body reaction induced in the endometrium by an IUD, with accompanying inflammation, ulceration, and thinning, as well as generally longer and heavier menses (which may increase risk bidirectionally), provide an easily conceived biologic basis for increased susceptibility to HIV infection.
  
• Sterilization and prevention of HIV infection
  Female sterilization by tubal ligation has no effect on male-to-female HIV transmission. Early penile withdrawal, while theoretically reducing the innoculum size, has not been studied and should not be recommended. Although the exact effect of vasectomy on the ability to transmit HIV from male to female is unknown, HIV has been cultured from the ejaculate of vasectomized men (Anderson, 1991).
  
• Contraception and prevention of infection are separate issues
  The issue of contraception for sexually active woman of reproductive age is obviously complex. The importance of preventing unwanted pregnancies is clear. Any counselor working with women is familiar with the issue of controlling and planning family size while taking into account economic factors, maternal health, and social pressures. Hormonal contraception is one of the most effective means to prevent pregnancy. The message conveyed to women must be that contraception and protection against STDs, including HIV, are separate considerations. For women who choose to use hormonal contraception, counselors must emphasize that male and female condoms are the only means to prevent STD transmission The effectiveness of various contraceptive methods in reducing risk of HIV infection is summarized in Table 3-12.
  

TABLE 3-12: CONTRACEPTION AND PREVENTION OF HIV-1 INFECTION

XI. NEW APPROACHES TO HIV AND STD PREVENTION: MICROBICIDES, VACCINES, AND POSTEXPOSURE PROPHYLAXIS

Given the difficulties that many women encounter in negotiating condom use, other prevention strategies under the control of women have been sought, such as topical microbicides. Although microbicides have generated considerable enthusiasm, progress in this area has been relatively slow. Most of the research in microbicides over the past 10 years has focused on safety and efficacy of nonoxynol-9 (N-9). The findings have not been consistent across all studies, complicated by different concentrations and formulations of N-9 used, insufficient sample size, and differing frequency of condom use by the women studied. Data on N-9 are well summarized in a recent metaanalysis (Elias, 1996; Letvin, 1998a; Roddy, 1998a, 1998b).

• Data from recent trials show that N-9 does not protect against HIV infection, and may increase risk of HIV infection
  Data from the UNAIDS trial were presented in Durban at the 2000 AIDS Conference, reducing hope that this microbicide will be an effective means of preventing HIV infection. In 999 women enrolled in four sites in Benin, Cote d’Ivoire, South Africa, and Thailand, HIV seroconversion rates were significantly higher in women randomized to use N-9 (Advantage S) than in women randomized to use lubrication only (Replens). Furthermore, genital ulcers occurred more frequently in women using N-9 than in controls, suggesting than N-9 may have local irritative effects on the vaginal mucosa. These data have caused UNAIDS to abandon plans for future trials using Advantage S (Altman, 2000).
  
• Although the concept of topical microbicides is promising, the process to developing and testing new microbicidal products for safety and ultimately efficacy in preventing HIV in clinical trials will take a number of years
  New topical microbicidal products in early clinical trials include broad-spectrum microbicides (such as natural lactobacilli, buffering products such as BufferGel, and surfactants such as C31G), inhibitors of viral entry and cell fusion (such as PC503 which has activity against HIV, herpes simplex virus, and Chlamydia trachomatis; and PRO2000), and inhibitors of HIV replication and entry. Many challenges face the study of topical microbicides, including the standardization of in vitro exposure assays for meaningful and consistent comparisons of activities of different compounds against HIV and other STDs and identification of placebos that have similar viscosity and pH to the active ingredient.
  
• Vaccines hold the most promise for protecting the largest number of HIV infections transmitted sexually, perinatally, or through drug use
  However, no HIV-1 vaccine with proven efficacy currently exists, and the necessary components of an immunogen that can induce protection against HIV-1 infection are poorly understood. Clues have emerged from dissecting the properties of immunity that correspond to protection against other pathogens, and more particularly in vaccine studies in the related simian immunodecficiency virus/HIV primate models. In addition, persons demonstrating unusual control of HIV-1 infection, e.g., those repeatedly exposed to HIV-1 without overt infection, HIV-1 long-term nonprogres-sors, and HIV-2-infected persons, may have acquired a unique host defense against HIV that merits induction by vaccination.
  
       Our understanding of the mechanism of action of other effective viral vaccines and HIV pathogenesis is guiding HIV vaccine development. Most licensed vaccines prime host immunity to control initial infection more efficiently, rather than to provide sterilizing immunity. Protection is commonly mediated by induction of antibodies that block infection, which allows time for antigen-specific T cells to mature and overtake any cells that do become infected. HIV-1 preferentially targets T helper cells, and either destroys them or establishes latent infection; a vaccine must restrict HIV-1 “seeding” and reemergence over time. HIV-1 is not easily neutralized by antibody, so that mimicking the largely safe recombinant protein strategy for hepatitis B virus vaccines is less apt to be successful with HIV-1. HIV-1 transmission occurs predominantly by sexual contact; thus, protection may require both mucosal as well as systemic immunity.
  
• Most experts believe that regimens priming both the cellular and humoral immune arms are the best candidates for protection, based on strong evidence in both experimental and human viral infections
  HIV vaccines that can stimulate a cellular immune response include poorly replicating viral or bacterial vectors expressing HIV gene products, such as poxviruses, vaccinia, and avipox. These products (e.g., the canarypox vector with gag, nef, and env genes) can elicit CD8+ cytotoxic T cell responses in approximately one third of volunteers. Macaque studies suggest that the less virulent, modified vaccinia Ankara recombinant may induce even stronger T cell responses, and its safety profile from previous use internationally looks quite good. Other recombinant vectors containing HIV-1 gene inserts that hold promise for clinical testing include Venezuelan equine encephalitis virus, adenovirus, poliovirus, and bacterial vectors (e.g., salmonella or listeria), but these as yet have not reached phase I testing. DNA vaccines may have promise, based on studies in the macaque model for SIV in which CD4+ and CD8+ T cell immunity and low-level antibodies were elicited. DNA vaccines are stable and will not require continuous cold storage, and may be more readily altered as the pool of viruses in the infected transmitting populations evolve, but immunogenicity has not been optimal at up to 3-mg doses.
  
       Building upon these insights, vaccine development has ensued and several strategies have been tested in the phase I/II setting. Of the vaccine regimens tested thus far in HIV-1 high-risk populations, no single approach is devoid of “breakthrough” infections. Clinical trials to test vaccine efficacy are expensive and large scale and have not as yet been endorsed except by private industry (VaxGen), which is testing the efficacy of a bivalent gp120 vaccination approach in North America and Thailand. At present, among the agents available and demonstrating acceptable safety in phase II trials, the next vaccine candidates to move to efficacy trials are likely to be a multivalent vaccine regimen with a canarypox vector prime and subunit gp120 boost, which induce neutralizing and nonneutralizing antibodies primarily recognizing the variable envelope regions of strains closely similar to that of the immunogen and cytotoxic T cells. An intermediate-sized efficacy trial in the next several years may answer whether the potency of antibodies and frequency of antigen-specific T cells elicited by the canarypox prime gp120 boost is adequate for protection.
  
• Postexposure prophylaxis (PEP) may reduce the likelihood of HIV infection after a high-risk exposure
  Theoretically, PEP may either prevent establishment of infection or prevent new infection while allowing clearance of already infected cells. The rationale for PEP with sexual exposure is that the probability of infection after a single exposure was similar to needlestick exposures (i.e., 0.1–3% for unprotected receptive anal intercourse or 0.1–0.2% for vaginal intercourse) (Katz 1997, 1998; USPHS, 1998). Animal models indicate that PEP may be effective, particularly when used within 24–48 hr of exposure with potent anti-retroviral agents. The data for efficacy of antiretrovirals for occupational exposure primarily is derived from a case-control study, in which health care workers who took zidovudine after needlesticks had an 80% lower likelihood of being infected, but which may suffer biases due to the case-control design. This study has been criticized because of its retrospective nature, small number of cases, and other potential sources of bias. There are also reported cases in which zidovudine failed to prevent HIV infection in health care workers. However, no prospective studies have assessed the efficacy of PEP for either occupational or sexual exposures because of ethical and pragmatic considerations in conducting a randomized trial of PEP. Thus, the risks and benefits of PEP for sexual exposure remain uncertain. Efficacy of PEP is likely to be influenced by time to initiation of treatment, duration of treatment, size of inoculum, and drug characteristics.
  
       Individual providers who are approached by anxious patients who have recently had a high-risk sexual exposure must weigh the likelihood of HIV infection in the contact, antiretroviral treatment history if the contact is known to be HIV-infected, specific nature and timing of the exposure (since initiation of PEP within 48 hr may be important), and possible risks of drug toxicity or side effects in choosing whether to use PEP and which drugs to prescribe. The CDC guidelines recommend two drugs (generally zidovudine or stavudine and lamivudine) for 4 wk for most cases of occupational exposure, and this approach has been adopted by many providers when selecting a regimen for “sexual PEP” (CDC, 1998c). The source partner’s likelihood of resistant virus, based on treatment history, stage of disease, and viral load, can be factored into the choice of a PEP regimen. Other considerations should include evaluation for other STDs, emergency contraception when appropriate, and possible indication for hepatitis B vaccination. Informed consent is recommended when administering PEP.
  
       PEP should not be administered routinely, with exposures at low risk of transmission, or when care is sought after 72 hr from the time of exposure. Situations in which PEP should be considered include condom breakage with serodiscordant couples and sexual assault. PEP is not a substitute for risk reduction and should not be considered a form of primary HIV prevention. Individuals presenting for possible PEP should have reinforcement of the importance of initiating, resuming, or improving risk reduction activities. Providers are requested to report nonoccupational PEP use to a national registry maintained by the CDC at (877) 488-1737 or http://www.hivpepregistry.org.

XII. CONCLUSIONS

Prevention of HIV remains a critical priority, particularly amidst increasing complacency related to enthusiasm about more effective treatments for HIV. The most effective available strategies for prevention are HIV counseling and testing, behavioral interventions to become abstinent or to reduce risk-taking, and condoms. Syndromic STD treatment has been shown to reduce HIV incidence in a large community-randomized trial, and ongoing studies are assessing other STD interventions. Topical microbicides may provide a prevention strategy directly under the control of women, although N-9 has not been shown to have significant efficacy against HIV transmission in commercially available spermicidal concentrations. New microbicide products are early in preclinical and clinical trial testing. Several HIV vaccines are also currently in clinical trials, ranging from phase I safety and immunogenicity studies to phase III efficacy trials of a recombinant gp120 subunit HIV vaccine. Lastly, postex-posure prophylaxis is occasionally being prescribed for high-risk exposures, although there are very few data on safety and efficacy. While these new strategies are being tested for their efficacy to prevent HIV infection, providers must continue to conduct risk assessments to identify women at risk for HIV and assist women in reducing their risk through setting achievable risk reduction plans.

REFERENCES

Ades AE, Gupta R, Gibb DM, et al. Selective versus universal antenatal HIV testing: epidemiological and implementational factors in policy choice. AIDS 13: 271–8, 1999.

Altman LK. Hopes for anti-HIV treatment dashed. The New York Times on the Web, July 13, 2000. http://nytimes.qpass.com.

Anderson DJ, Politch JA, Martinex A, Van Voorhis BJ, Padian NS, O’Brien TR. White blood cells and HIV-1 in semen from vasectomised seropositive men. Lancet 338: 573–4, 1991.

Bandura A. Social Foundations of Thought and Action: A Social Cognitive Theory. Englewood Cliffs, NJ: Prentice-Hall, 1996.

Bounds W. Female condoms. Eur J Contracep Reprod Health Care 2: 113–6, 1997. 

Boyer CB, Barrett DC, Peterman TA, Bolan G. Sexually transmitted disease (STD) and HIV risk in heterosexual adults attending a public STD clinic: evaluation of a randomized controlled behavioral risk-reduction intervention trial. AIDS 11: 359–67, 1997.

Branson BM, Peterman TA, Cannon RO, Ransom R, Zaidi AA. Group counseling to prevent sexually transmitted disease and HIV: a randomized controlled trial. Sex Transm Dis 25: 553–60, 1998.

Carlin EM, Boag FC. Women, contraception, and STDs including HIV. Int J STD AIDS 6: 373–386, 1995.

Catania JA, Kegeles SM, Coates TJ. Towards an understanding of risk behavior: an AIDS risk reduction model (ARRM). Health Educ Q 17: 53–72, 1990. 

Celum C, Buchbinder S. Counseling and testing for HIV infection. In: Holmes KK, Sparling PF, Mardh PA, et al., eds. Sexually Transmitted Diseases. New York: McGraw-Hill,1999.

Centers for Disease Control and Prevention. 1998 Guidelines for Treatment of Sexually Transmitted Diseases. MMWR 47(RR-1): 1–111, 1998a.

Centers for Disease Control and Prevention. HIV prevention through early detection and treatment of other STDs-United States: Recommendations of the advisory committee for HIV and STD prevention. MMWR 47(RR-12): 1–111, 1998b. 

Centers for Disease Control and Prevention. Public Health Service guidelines for the management of health-care worker exposures to HIV and recommendations for postexposure prophylaxis. MMWR 47(RR-7): 1–34, 1998c.

Centers for Disease Control and Prevention. Update: HIV counseling and testing using rapid tests — United States, 1995. MMWR 47: 211–215, 1998d.

Courey-Doniger P, Levenkron JC, Knox KL, Cowell S, Urban MA. Use of Stage of Change (SOC) to develop an STD/HIV behavioral intervention: phase 1. A system to classify SOC for STD/HIV sexual risk behaviors — development and reliability in an STD clinic. AIDS Patient Care 13: 493–502, 1999.

Curtis JR, Holmes KK. Individual-level risk assessment for STD/HIV infections. In: Holmes KK, Sparling PF, Mardh PA, et al., eds. Sexually Transmitted Diseases. New York: McGraw-Hill,1999.

Elias CJ, Coggins C. Female-controlled methods to prevent sexual transmission of HIV. AIDS 10 (Suppl 3):S43–51, 1996.

Fishbein M, Wolitski RJ, Doll LS. Behavioral interventions for sexually transmitted disease prevention at the individual level. In: Holmes KK, Sparling PF, Mardh PA, et al., eds. Sexually Transmitted Diseases. New York: McGraw-Hill,1999.

Fisher JD, Fisher WA. Changing AIDS-risk behavior. Psych Bull 111: 455–474, 1992. 

Fontanet AL, Saba J, Chandelying V, et al. Protection against sexually transmitted diseases by granting sex workers in Thailand the choice of using the male or female condom: results from a randomized controlled trial. AIDS 12: 1851–9, 1998. 

Grady WR, Klepinger DH, Nelson-Wally A. Contraceptive characteristics: the perceptions and priorities of men and women. Fam Plann Perspect 31: 168–75, 1999.

Hayes BF. HIV vaccines: where we are and where we are going. Lancet 348: 933–7, 1996. Hayes R, Mosha F, Nicoll A, et al. A community trial of the impact of improved sexually transmitted disease treatment on the HIV epidemic in rural Tanzania: 1.  Design. AIDS 9: 919–26, 1995.

Kamb ML, Fishbein M, Douglas JM, et al. Efficacy of risk-reduction counseling to prevent human immunodeficiency virus and sexually transmitted diseases: a randomized controlled trial. Project RESPECT Study Group. JAMA 280: 1161–7, 1998. 

Kamenga M, Ryder RW, Jingu M, et al. Evidence of marked sexual behavior change associated with low HIV-1 seroconversion in 149 married couples with discordant HIV-1 serostatus: experience at an HIB counselling center in Zaire. AIDS 5: 61–67, 1991.

Kapiga SH, Shao JF, Lwihula GK, Hunter DJ. Risk factors for HIV infection among women in Dar-es-Salaam, Tanzania. J Acquir Immune Defic Syndr 7: 301–9, 1994. 

Kassler WJ. Advances in HIV testing technology and their potential impact on prevention. AIDS Educ Prev 9 (Suppl 3): 27–40, 1997.

Katz MH, Gerberding JL. Postexposure treatment of people exposed to the Human Immunodeficiency virus through sexual contact or injection drug use. N Engl J Med 336: 1097–1100, 1997.

Katz MH, Gerberding JL. The care of persons with recent sexual exposure to HIV. Ann Intern Med 128: 306–12, 1998.

Laga M, Manoka A, Kivuvu M, et al. Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study. AIDS 7: 95–102, 1993.

Letvin NH. Progress in the development of an HIV-1 vaccine. Science 280: 1875–80, 1998.

Martin HL, Nyange PM, Richardson BA, et al. Hormonal contraception, sexually transmitted diseases, and risk of heterosexual transmission of human immunodefi-ciency virus type 1. J Infect Dis 178: 1053–9, 1998.

Mayaud P, Mosha F, Todd J, et al. Improved treatment services significantly reduce the prevalence of sexually transmitted diseases in rural Tanzania: results of a randomized controlled trial. AIDS 11: 1873–80, 1997.

NIMH Multisite HIV Prevention Trial: reducing HIV sexual risk behavior. The National Institute of Mental Health (NIMH) Multisite HIV Prevention Trial Group. Science 280: 1889–94, 1998.

Otten MW, Zaidi AA, Wroten JE, Witte JJ, Peterman TA. Changes in sexually transmitted disease rates after HIV testing and posttest counseling, Miami, 1988 to 1989.  Am J Public Health 83: 529–533, 1993.

Roddy RE, Schulz KF, Cates W. Microbicides, meta-analysis, and the N-9 question. Where’s the research? Sex Transm Dis 25: 151–3, 1998a.

Roddy RE, Zekeng L, Ryan KA, et al. A controlled trial of nonoxynol-9 film to reduce male-to-female transmission of STDs. N Engl J Med 339: 504–10, 1998b. 

Shain RN, Piper JM, Newton ER, et al. A randomized, controlled trial of a behavioral intervention to prevent sexually transmitted disease among minority women. N Engl J Med 340: 93–100, 1999.

Spielberg F, Kassler WJ. Rapid testing for HIV antibody: a technology whose time has come. Ann Intern Med 125: 509–511, 1996.

Stratton P, Alexander NJ. Prevention of sexually transmitted infections; physical and chemical barrier methods. Infect Dis Clin N Am 7: 841–59, 1993.

Taha TE, Hoover DR, Dallabeta GA, et al. Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV. AIDS 12: 1699–706, 1998. Temmerman M., Ndinya-Achola J, Ambani J, Piot P. The right not to know HIV-test results. Lancet 345: 969–70, 1995.

UNAIDS. Facts and figures: 1999 world AIDS campaign. Geneva: Joint United Nations Programme on HIV/AIDS (UNAIDS), 1999.

USPHS. Management of possible sexual, injecting-drug-use, or other non-occupational exposure to HIV, including considerations related to antiretroviral therapy. MMWR 47(RR-17) September 25, 1998.

Wang CC, Kreiss JK, Reilly M. Risk of HIV infection in oral contraceptive pill users: a meta-analysis. J Acquir Immune Defic Syndr 21: 51–8, 1999.

Wawer MJ, Sewankambo NK, Serwadda D, et al. Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Rakai Project Study Group. Lancet 353: 525–35, 1999.

Zenilman JM, Erickson B, Fox R, Reichart CA, Hook EW 3d. JAMA 267: 843–5, 1992.

We need YOUR HELP to make the NEXT EDITION as useful as possible!

Please send your comments criticisms corrections suggested changes, and other guidance to one of the addresses below. Be sure to include in your letter/note an address (fax, e-mail, or postal) where you can be reached for follow-up.

Translation Partners Needed
Write to us if you can help us find partners to help us have this Guide translated into your native language. For instance, provide us with a contact who works with translation in your country’s Ministry of Health, or tell us about a group at a medical school that translates medical texts.

Send Us Your Comments
E-mail: womencare@hrsa.gov
Fax to the attention of “Womencare”: 301-443-0791 (USA)
Postal address: Womencare Parklawn Building, Room 11A-33
5600 Fishers Lane Rockville, Maryland 20857 USA

Note that this and subsequent editions of
A Guide to the Clinical Care of Women with HIV will be available online.
Go to the HIV/AIDS Bureau Web site and click on the publication Women’s Guide: http://www.hab.hrsa.gov/