III. Prevention Of HIV

Jared M. Baeten, MD, PhD,
Chia Wang, MD, MS, and
Connie Celum, MD, MPH

I. Introduction  TOP

Two d/ecades 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 preventive 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 infections (STIs) and HIV.

Many of the measures that women can take to prevent acquisition of STIs 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 are 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/WHO, 2003). 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 STIs 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 STI 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 STI/HIV Infections  TOP

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 STI screening. Guidelines for physicians and other care practitioners recommend that HIV and STI risk assessment be conducted for every patient (Phillips, 2003); 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 nonjudgmental. 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 STIs” (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. A rare case of female-to-female sexual transmission of HIV, possibly through sharing sex toys, was recently reported (Kwakwa, 2003). 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.

III. HIV Counseling and Testing  TOP

There are clear benefits to HIV testing.

For a woman, knowledge of her serostatus is essential to prevent vertical transmission to her infant and horizontal transmission to her partners, and to seek medical care for herself. With the proven efficacy of several peri-partum antiviral regimens to reduce vertical transmission rates and medical therapy to improve survival among HIV-infected individuals, including in resource-poor settings, there are even stronger reasons to urge sexually active women to seek HIV testing for themselves and their partners. Unfortunately, most women at risk for HIV infection remain unaware of their HIV status (Kitahata, 2002).

Routine provision of HIV testing may be most effective.

Selective screening strategies have targeted intravenous drug users, STI clinic attendees, and economically disadvantaged individuals (Phillips, 2003). 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. Screening using an opt-out approach, under which testing is done routinely unless actively declined, significantly increases HIV testing rates among pregnant women (Stringer, 2001). Opt-out testing at antenatal clinics in Africa is being promoted as a key strategy to increase uptake of interventions, such as short-course antiretrovirals, for prevention of mother-to-child HIV transmission (Bassett, 2002). In the United States, the Centers for Disease Control and Prevention (CDC) has recently recommended that HIV-1 screening of all pregnant women become part of routine care (CDC, 2003). 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. Thus, for the general population, current U.S. guidelines recommend routine offering of voluntary testing in all settings where HIV prevalence is >1% or where there is increased risk of acquiring or transmitting HIV, regardless of setting prevalence (CDC, 2003). Offering routine HIV testing is cost-effective under certain circumstances and could lead to earlier identification of infected individuals and linkage to HIV treatment. However, routine offering of HIV testing in high-prevalence areas to hospitalized patients and those presenting to emergency care settings has not been widely adopted. 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.

A. PRE- AND POSTTEST HIV COUNSELING

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 STIs are usually also at risk or concerned about risk for STI, 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 many settings.

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 the 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 (CDC, 1998a). Similar low return rates have been described in many developing-country settings.

Rapid testing for HIV would result in substantial cost savings and circumvent patient no-show rates (Spielberg, 1996). A number of rapid tests, defined as requiring less than 2 hr, are available. The World Health Organization (WHO) has developed alternative testing strategies using sequential rapid tests, thus obviating the need for expensive and delayed confirmatory testing (UNAIDS, 2002). Some tests require as little as 5 min, use blood obtained from a finger-stick, and can be performed easily by clinical staff using only minimal laboratory facilities. Most tests are 95–100% sensitive and specific. One rapid test (OraQuick Rapid HIV-1 Antibody Test) has been approved by the FDA with a waiver from the Clinical Laboratory Improvements Amendments (CLIA) regulations, allowing it to be used outside of traditional laboratory settings. Thus, HIV rapid testing is expected to become more feasible and widely-adopted in the United States. The CDC is currently conducting demonstration projects to promote the use of rapid testing outside of usual clinical settings, including in correctional facilities, non-medical venues, and during labor and delivery for women who did not receive antenatal testing (CDC, 2003). 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 (STI 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). Rapid and other alternative testing methods (e.g., home testing, oral fluid and urine testing, telephone collection of test results) are being explored as strategies to increase HIV testing among high-risk populations. 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. The use of rapid tests has increased substantially over the past few years and has become a key component of HIV prevention and treatment programs in many developing countries (e.g., initiatives for prevention of mother-to-child transmission and general population voluntary counseling and testing).

Rapid tests may result in unwanted test results

Some have expressed concern that rapid HIV testing may not offer patients sufficient time to digest counseling information and to decide whether they truly desire to know their HIV status. In some settings, women in particular may find it difficult to decline unwanted HIV testing, in part due to cultural injunctions against refusing a test offered by a health care worker perceived as an authority figure. Thus, the principal components of HIV testing must remain the same for rapid testing as for traditional screening programs. Regardless of how HIV testing is done, patients must be informed of the nature of the test and the risks and benefits of knowing their HIV status. They should consent voluntarily to the testing procedures, be informed that they can refuse testing, and have their confidentiality strictly preserved. Finally, they should be told that refusal of testing will not lead to denial of usual clinical services.

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 randomized trials with well-defined endpoints. Older studies from the United States did not demonstrate a substantial effect. In one observational study from Baltimore from the early 1990s, both HIV-positive and HIV-negative patients had high rates of STIs 6–23 mo after receiving HIV test results and posttest counseling (Zenilman, 1992). A second study found HIV testing was associated with a moderate decrease in gonorrhea incidence among patients in Miami who tested HIV-positive but with a moderate increase among those testing HIV-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. However, guidelines and training for HIV-1 counseling have improved over the past decade, and thus it is difficult to know the impact that current counseling procedures may have on subsequent sexual behavior.

A more recent large study conducted in Kenya, Tanzania, and Trinidad randomly assigned individuals and couples to either HIV voluntary counseling and testing or basic health information (Voluntary HIV-1 Counseling and Testing Efficacy Study Group, 2000). This trial found that counseling and testing resulted in a significant decline in unprotected intercourse with non-primary partners by both male and female study participants. Newly-identified HIV-infected participants were more likely than HIV-uninfected participants to reduce episodes of unprotected intercourse. Among couples, unprotected intercourse reduced more in those in which one or both members were diagnosed with HIV compared with those in which both members were HIV-uninfected.

Other studies of HIV counseling and testing among couples have demonstrated similarly encouraging results. Among 149 HIV-discordant couples in Zaire, HIV counseling and testing was followed by a dramatic increase in consistent condom use (from <5% to >70%) and a low rate of HIV transmission (3% after 100 person-years of follow-up) (Kamenga, 1991). A recent study of 963 discordant couples from Zambia reported a sustained increase in condom use from <3% to >80% after joint voluntary counseling and testing (Allen, 2003). The authors concluded that couples’ counseling and testing should be a top HIV prevention priority. Overall, modeling studies suggest that voluntary counseling and testing is a highly cost-effective HIV prevention strategy (Creese, 2002).

IV. Behavioral Intervention Models  TOP

Over the past 20 years, there has been a growing appreciation that behavioral interventions should be based on deterministic models of sexual behavior. These models provide us with guidance on the determinants of high risk sexual behavior, and allow us to develop interventions and measurements for those key determinants. A number of behavioral models are used in HIV/STI prevention research and interventions, including those listed below.

• 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 STI clinic, clinicians who have formally incorporated the SOC model in their risk assessment and counseling of STI clients report a high degree of satisfaction with the SOC model as a diagnostic tool that guides their specific counseling interventions with a client (Coury-Doniger, 1999).

V. Published Behavioral Intervention Trials  TOP

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, STI 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 STIs and HIV is not enough to implement change in sexual behavior.

Randomized controlled studies using STI 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, all conducted in the United States, examined the efficacy of behavioral intervention strategies using STI 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.

Table 3-4: Results of Large Randomized Trials of Behavioral Interventions Conducted in the United States

Behavioral interventions can lead to lower rates of STI 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 STI 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 STI 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 STI 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 STI 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 “brief” counseling, involving two sessions of 20 min each, was as effective in reducing STI incidence as four “enhanced” 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. A follow-up study of the efficacy of a brief counseling intervention in the context of rapid HIV testing is being conducted by the CDC (Respect II) which will be relevant given the increased use of rapid testing both in the U.S. and in resource-poor settings.

Behavioral intervention studies in resource-poor settings

Several early studies among female commercial sex workers in developing country-settings demonstrated that condom promotion activities were accompanied by reduced high-risk sexual activity and a decrease in HIV and STI incidence. More recently, sustained reductions in HIV incidence among sex workers, paralleled by changes in sexual behavior, have been noted in several countries. Encouragingly, a few countries (e.g., Thailand, Uganda) have reported reduced HIV prevalence in the general population as well during the last few years, accompanied by secular changes in sexual behavior. Unfortunately, very few controlled trials of sexual behavior interventions to prevent HIV and STI transmission have been conducted in resource-poor settings. Recently, a large community randomized trial examined the effects of behavioral intervention or behavioral intervention coupled with improved STI services compared with routine government health services on HIV and STI transmission in the Masaka district of rural Uganda (Kamali, 2003). Behavioral interventions focused on knowledge acquisition, skill and attitude development, and motivational support and were accomplished through community-level approaches including public meetings, drama productions, informational leaflets, and individual discussions.

Communities randomized to the behavioral intervention experienced a lower incidence of HSV-2, and those randomized to STI services as well had reduced transmission of gonorrhea and syphilis. In both intervention arms, an increase in condom use was noted. Disappointingly, however, neither intervention arm saw a reduction in HIV incidence compared with the control arm, though HIV incidence in both the intervention and control communities was lower than the investigators expected, likely related to the secular change in HIV transmission that appears to be occurring in Uganda.

Some on-going studies are examining sexual behavior among adolescents, among whom HIV incidence is particularly high in many countries. Additionally, in light of gender differences in sexual decision making in many settings, other intervention trials are targeting behavioral change in men as a way to reduce heterosexual HIV spread. Given the high incidence of HIV in many developing countries, behavioral interventions to prevent heterosexual HIV transmission continue to be desperately needed.

VI. Practical Aspects of Counseling Patients ABout Sexual Risk Reduction  TOP

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/STI 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 STIs 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 overambitious 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.

Figure 3-1: Listen and React to the Patient

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

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 the 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.

VII. Ethnic and Gender Considerations in Risk Reduction Counseling  TOP

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 American 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 STIs 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. Younger women and those with or at-risk for HIV may be particularly likely to experience domestic violence (Maman, 2002). One study from the early 1990’s from Kenya found that only 66 (27%) of 243 HIV infected pregnant women informed their partners of their results, of whom 11 were subsequently chased from their home, 7 were beaten, and 1 committed suicide (Temmerman, 1995). Only one third of women in that research setting returned to receive their HIV results when the testing protocol was later changed to allow women the option of not knowing their HIV status. As voluntary HIV counseling and testing programs become more available in many part of the world, support must be given to women living in abusive relationships so that they can negotiate choices that will have positive effects on their health and that of their children. Anecdotal reports from voluntary counseling and testing centers in several African countries suggest that HIV testing of couples is associated with less partner violence, especially in recent years as HIV testing has become more common.

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 increased availability and acceptance 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 Infections and the Risk of HIV Infection  TOP

Sexually transmitted infections (STIs) increase susceptibility to HIV infection

The fact that STIs are important cofactors for HIV acquisition has been well established by prospective studies from a variety of populations examining risk factors for seroconversion. In such studies, women with genital ulcer disease, gonococcal or chlamydial cervicitis, or trichomoniasis were at 2–4-fold increased risk for HIV infection. However, study design issues, including small sample sizes and potential confounding by sexual behavior, have limited the ability of these observational studies to fully determine the magnitude of risk that STIs pose for HIV acquisition (Røttingen, 2001). Moreover, even the best-designed prospective studies have been unable to separate STIs acquired at the same time as HIV (perhaps reflecting increased infectiousness of an HIV-infected partner) from those present prior to HIV acquisition that could increase susceptibility. Because of obvious ethical limitations, randomized trials that deny individuals STI treatment cannot be conducted. Thus, as detailed below, community intervention trials of improved STI services or mass STI treatment have been conducted to determine the impact of STIs on population-wide HIV transmission.

Vaginal infections may also increase HIV susceptibility

Several studies, including well-controlled prospective investigations, have demonstrated that disturbances in the normal microbial flora of the vagina may increase HIV risk. One study among women attending an antenatal clinic in Malawi found that those with bacterial vaginosis (defined by vaginal pH >4.5, homogeneous vaginal discharge, presence of clue cells, and positive amine odor) were 2–4 times more likely to acquire HIV during pregnancy and postnatally over an average follow-up of more than 2.5 years (Taha, 1998). A second prospective study from Kenya found that HIV incidence was 2-fold higher among nonpregnant women with abnormal flora on Gram’s stain of vaginal fluid or with negative vaginal cultures for Lactobacillus species, which are the hydrogen peroxide–producing gram-positive rods that dominate the normal vaginal ecosystem (Martin, 1999). An earlier report from this same cohort of Kenyan women found that Candida vaginitis also increased HIV risk ~2-fold (Martin, 1998).

Genital herpes may contribute substantially to HIV spread

A number of recent studies have highlighted the possible role of genital herpes infection (primarily due to HSV-2) in facilitating HIV transmission worldwide. As noted above, genital ulcer disease has long been regarded as a strong risk factor for HIV acquisition. Over the last two decades, HSV-2 has become the major cause of genital ulcer disease in many populations, and HSV-2 seroprevalence has increased substantially as well. A meta-analysis found chronic HSV-2 infection to be associated with a 2-fold increase in the risk of HIV acquisition among the best designed studies (Wald, 2002). Recent studies suggest that primary HSV-2 infection may be associated with even greater HIV risk (del Mar Pujades Rodriguez, 2002). Compellingly, one large survey study from Africa concluded that country-to-country differences in the prevalence of HSV-2 may be one of the principal causes of differential HIV spread across that continent (Auvert, 2001). Studies of suppressive antiviral therapy against HSV-2 to prevent HIV transmission are underway and may provide a relatively inexpensive and simple intervention to decrease HIV acquisition, infectiousness, or both.

Community randomized trials of STI treatment offer conflicting results

Observational studies have demonstrated clear and consistent evidence that STIs and other genital tract infections increase HIV susceptibility. This conclusion was supported by the results of a trial conducted in the Mwanza region of Tanzania that randomly allocated communities to improved syndromic management of STIs or to routine government health care services (Grosskurth, 1995). Syndromic STI management resulted in a 40% decrease in new HIV infections in the intervention communities. In contrast, in the Rakai district of Uganda, a community randomized trial of mass antibiotic treatment for STIs, given at 10-month intervals, failed to demonstrate a reduction in HIV seroincidence (Wawer, 1999). One principal reason for the disparate results of these two trials is likely related to the stage of the epidemic in the two locations (Grosskurth, 2000). In Mwanza, the baseline HIV prevalence was 4%, indicating an early phase of the epidemic. In Rakai, the epidemic was at a more mature phase, with a baseline prevalence of 16%. Experts concluded that the core group of high-risk individuals, who are crucial to epidemic transmission and who are most likely to have concurrent STIs, was already HIV-saturated in Rakai, thus minimizing the impact of the intervention. Recently, a third trial, from the Masaka district of Uganda, demonstrated no effect of syndromic STI management on HIV incidence in the context of a mature HIV epidemic (Kamali, 2003). These results confirm that it is not the type of intervention but rather the stage of the epidemic in an area that permits a community-wide impact of better STI services. Subsequent analysis suggested that an important difference between the three studies was the prevalence of curable STIs, which was significantly higher in Mwanza than in Rakai or Masaka, which may explain the larger impact that STI treatment had on HIV transmission in that study (Orroth, 2003). In all the studies, the effect of herpes treatment was not assessed, since medications against genital herpes were not part of the interventions, though a large proportion of STI episodes in all three trials were likely a result of herpes outbreaks. Nevertheless, STIs clearly increase individual-level risk of HIV acquisition, and STI treatment should remain an important part of reducing HIV risk for individuals and populations, even in areas where HIV is already well-established. STI treatment remains one of the most cost-effective HIV prevention strategies for resource-poor settings (Creese, 2002).

How should we counsel women at risk for STIs and HIV?

Important issues in counseling women at risk for STIs and HIV are presented in Table 3-9. Reducing the prevalence and incidence of STIs should reduce the susceptibility to HIV transmission. Measures to reduce STIs include female and male condom use, seeking early diagnosis and treatment of genital tract symptoms, and frequent STI 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 relatively common conditions, and thus they may be responsible for a substantial fraction of HIV infections in some populations. Clinicians should diagnose and have a low threshold to treat both bacterial vaginosis and Candida vaginitis in women with high-risk sexual behavior. Vaginal douching, which has no therapeutic benefit, may increase the risk of developing bacterial vaginosis and pelvic inflammatory disease 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.

Finally, 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, 2002).

IX. Condoms and Prevention of HIV Infection  TOP

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, polyurethane 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.

A. MALE CONDOMS

Male condoms prevent transmission of many STIs

The literature on the role of barrier contraception as protection against STIs is vast and the reported degree of protection against specific STIs 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 STIs, and are currently the most reliable protective measure. In a workshop reviewing the scientific evidence on condom effectiveness, the U.S. National Institutes of Health concluded that consistent condom use reduces a woman’s risk of HIV by at least 85% (NIAID, 2001). Moreover, some studies have reported no seroconversions at all among consistent condom users despite repeated coital exposure (Carlin, 1995). A significant increase in condom use, and a lower than anticipated rate of new HIV infections, followed voluntary HIV counseling and testing of HIV discordant couples in one African study (Allen, 1992). In terms of other STIs, 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 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 STI 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 STIs, 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 STIs 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 or STIs 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 STI 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. A recent study found that the female condom acts as an effective barrier for the vast majority of uses, and exposures to semen become less frequent with greater user experience (Macaluso, 2003).

Figure 3-2: The Female Condom


Source: The Female Health Company. Chicago, IL.

Figure 3-3: Female Condom Insertion and Positioning

Source: Adapted from Reality brand female condom literature.

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 STIs. 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 STIs and pregnancy. Many women have also strongly expressed a preference for a female-controlled device to prevent STIs. 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).

D. SPECIAL CONSIDERATIONS FOR WOMEN WHO HAVE SEX WITH WOMEN

Discussion of recommendation of protective sexual practices should not be limited to exclusively heterosexual women. Sexual transmission of HIV between women has been described. The use of barriers such as dental dams should be recommended for oral-genital contact, particularly in HIV discordant relationships. Sexual activity should be avoided during menstruation or when there are symptoms of genital tract infection. The sharing of sex toys contaminated with blood was implicated in a recently described case of female-to-female sexual transmission of HIV (Kwakwa, 2003).

Table 3-11: Factors Associated with Condom Use and Non Use

Aspect	Important to Men	Important to Women
Condoms in General
Negative image of condom use associated with disease, promiscuity, and distrust of sex partner
Actual and perceived social norms governing condom use
Perceived ability to protect against sexually transmitted infections
Ease of obtaining or purchase
Ease of putting on or in
Slippage during intercourse
Adequate lubrication
Sensation during intercourse
Male Condoms
Normal appearance and feel
Lack of odor
Reservoir tip
Spermicide coating
Interruption of foreplay
Inferior contraceptive method
Perception that partner may believe user is sensitive and caring
Female Condoms
Aesthetic appearance of external ring
Noise during intercourse
Polyurethane material
Interruption of foreplay
Female controlled device
Inferior contraceptive method

X. Other Forms of Contraception and the Risk of HIV Infection  TOP

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 prospective studies found that use of the injectable contraceptive depo-medroxyprogesterone acetate (Depo-Provera) was associated with increased risk of HIV infection. One, conducted among 779 commercial sex workers in Mombasa, Kenya, found women using Depo-Provera were at a 2-fold increased risk of acquiring HIV compared with women using no contraceptive method, after controlling for differences in sexual behavior, condom use, and STIs (Martin, 1998). Insufficient data exist on other hormonal contraceptive methods to reach a conclusion about the effect on a woman’s susceptibility to HIV. A large observational study currently being conducted among family planning clinic attenders in Zimbabwe, Uganda, and Thailand is examining the relationship between hormonal contraceptive use and HIV acquisition in a lower-risk population of women, with preliminary results expected in 2004.

Other contraceptive methods and HIV acquisition

Cervical barrier contraceptive devices, such as the diaphragm or cervical cap, have been postulated as potentially protective against HIV (Moench, 2001). Evidence supporting this hypothesis comes from laboratory investigations suggesting the cervical epithelium is particularly susceptible to HIV infection and observational studies that found lower rates of cervical STIs, like gonorrhea, among women who used the diaphragm. However, cervical barrier devices do not cover much of the vagina and thus still would result in significant mucosal exposure to HIV. A large randomized trial of the diaphragm to decrease HIV acquisition will be conducted in Africa. If successful, cervical barriers would be a discreet, easy, female-controlled method to prevent HIV infection.

The use of spermicides as a sole method for HIV prevention should be discouraged. The most well-studied vaginal spermicidal product is nonoxynol-9 (N-9). A large meta-analysis of several controlled trials concluded that N-9 provides no protection from HIV (summary relative risk 1.12, 95% confidence interval 0.88-1.42) or other STIs and slightly increases the risk of genital ulceration (Wilkinson, 2002). This last finding may be of particular concern to women at high risk of HIV. In the largest randomized trial of N-9, conducted among commercial sex workers in several developing countries, a nearly 2-fold increased HIV risk was seen among the subset of women who used the product several times per day (Van Damme, 2002). Overall, N-9 is not recommended for HIV prevention, especially among high-risk women.

Data on the relationship between the use of intrauterine devices (IUDs) and HIV acquisition is sparse. In general, IUDs are not recommended for women at high risk for STIs because of possible increased risk of pelvic inflammatory disease, though IUDs are a safe, long-lasting, and effective contraceptive method for lower-risk women. Like many other contraceptive methods, IUDs provide no barrier protection and thus would be unlikely to decrease HIV risk. A theoretical increase in HIV risk has been hypothesized due to the foreign body reaction and accompanying intrauterine inflammation associated with IUD use. In addition, use of non-progestin releasing IUDs are associated with longer and heavier menses, which may increase risk of transmission bidirectionally.

Female sterilization by tubal ligation has no effect on male-to-female HIV transmission. Additionally, HIV has been acquired vaginally by women who have had hysterectomies. 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 HIV-infected 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 STIs, including HIV, are separate considerations. Regardless of which method women choose for pregnancy prevention, counselors must emphasize that male and female condoms are the only methods proven to prevent STI 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

Method	May Increase Risk*	No Effect or Insufficient Data*	Protective – Strong Evidence
Male condom
Female condom
Intrauterine device
Diaphragm
Cervical cap
Tubal ligation
Vasectomy
Early penile withdrawal
Oral contraceptives
Depo-Provera

XI. New Approaches to HIV and STI Prevention: Microbicides, Vaccines, and Postexposure Prophylaxis  TOP

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). Unfortunately, as reviewed in section X, N-9 is unlikely to provide significant protection from HIV or STIs and may increase the likelihood of HIV transmission to high-risk women (Van Damme, 2002; Wilkinson, 2002). Policy organizations such as the CDC and WHO have recently circulated advisories to discourage use of N-9 for STI and HIV prevention.

Although the concept of topical microbicides is promising, the process of developing and testing new microbicidal products for safety and ultimately efficacy in preventing HIV in clinical trials will take a number of years

A number of new topical microbicidal products are in early clinical trials, and many more are in preclinical development (McCormack, 2001). These include agents with broad-spectrum activity (acidic buffers such as BufferGel, surfactants such as C31G, and natural Lactobacillus suppositories), inhibitors of viral entry (such as PRO2000, carrageenan, and dextrin sulfate), and inhibitors of viral replication (such as gel formulations of antiretroviral medications, including tenofovir). Efficacy trials of topical microbicides face many challenges, including issues of compliance, product safety and acceptability, and the potential for sexual behavior to change as a result of product use. Moreover, microbicide studies have faced difficulty in the development of biologically inert but physically identical placebos for use in efficacy trials, as even inactive gel placebos may provide some degree of HIV protection simply as a result of their physical or barrier properties.

Vaccines hold the most promise for preventing the largest number of HIV infections transmitted sexually, perinatally, or through drug use

Only one HIV prophylactic vaccine has completed efficacy testing. This vaccine, which used a recombinant HIV subtype B gp120 protein developed by the VaxGen corporation, provided essentially no reduction in HIV acquisition in a large trial conducted in North America and Europe (McCarthy, 2003). A similar trial of a bivalent HIV subtype B/E construct among Thai injection drug users also failed to prevent HIV acquisition. Overall, the necessary components of an immunogen that could induce protection against infection are not yet completely understood. Clues have emerged from dissecting the properties of immunity that offer protection against other pathogens, and also those that arise in individuals infected with HIV. Primate studies, using the related simian immunodeficiency virus (SIV) or SIV/HIV chimeric virus constructs, have provided important information about how the virus establishes itself during early infection as well as about the immunologic potential of candidate vaccines. In addition, studies of persons demonstrating unusual control of HIV infection (e.g., who remain uninfected despite repeated HIV exposure or who demonstrate long-term nonprogression although infected with HIV) suggest there are unique host defense characteristics, particularly cellular immunity, that might be able to be replicated by a vaccine.

Our understanding of the mechanism of action of other effective viral vaccines and of HIV pathogenesis is guiding HIV vaccine development. Most licensed vaccines prime host immunity to control initial infection more efficiently, rather than 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. However, HIV preferentially targets T helper cells and often establishes latent infection within them. Thus, a vaccine must induce sufficient immunity to block such HIV “seeding” or prevent viral reemergence from latently infected cells. Unfortunately, HIV is not easily neutralized by antibody, so vaccine strategies that use recombinant proteins, like in the effective hepatitis B vaccine, are unlikely to be successful for HIV (as demonstrated by the unsuccessful HIV recombinant gp120 subunit vaccine). Most experts believe that regimens priming both the cellular and humoral immune arms are the best candidates for protection. Considerable research into cellular immunity against HIV has been conducted over the past few years, and vaccine constructs that induce cell-mediated responses, at least in a moderate proportion of individuals, have been developed. These generally consist of poorly replicating viral or bacterial vectors (e.g., vaccinia, canarypox, adenovirus, salmonella) expressing a selection of HIV gene products, such as gag, pol, env, nef, or a variety of isolated T-cell epitopes. Alternative strategies include naked DNA vaccines, which can induce some degree of cellular and antibody-mediated immunity and have the advantage of being considerably more stable in tropical climates.

The development of an effective HIV vaccine faces several additional challenges. The remarkable ability of HIV to undergo genetic change suggests that vaccines based on individual viral strains, especially laboratory adapted strains, may not induce immunity with sufficient flexibility to prevent a new infection. The predominance of distinct HIV subtypes in different regions of the world may complicate development of a single universal HIV vaccine, although cross-clade cellular immune responses have been demonstrated in human immunogenicity trials. Moreover, since HIV transmission occurs predominantly by sexual contact, protection will likely require mucosal as well as systemic immunity. Finally, a number of logistic and ethical considerations relevant to the conduct of HIV vaccine research have been raised, including the need for unbiased counseling towards risk reduction for vaccine participants, the obligation to provide HIV care to individuals infected during a trial, and the commitment to rapidly provide vaccine to at-risk communities should an effective candidate be found.

Numerous clinical studies of various HIV vaccine constructs have been conducted, are in progress, or are planned. On-line updated lists of trials of HIV vaccines are maintained by the International AIDS Vaccine Initiative (www.iavi.org) and the HIV Vaccine Trials Network (www.hvtn.org).

Postexposure prophylaxis (PEP) may reduce the likelihood of HIV infection after a high-risk exposure

Theoretically, PEP can prevent HIV transmission either by blocking initial viral infection of cells or by inhibiting viral dissemination, thus allowing for immune clearance of a small number of already infected cells. The data for efficacy of antiretrovirals as PEP comes primarily from a single case-control study of health care workers who experienced occupational HIV exposures, mostly though needlestick injuries. Those who received zidovudine had an 80% lower likelihood of becoming infected, though this study was limited by a small sample size, retrospective design, and other potential sources of bias. The rationale for PEP after sexual exposure is largely that the probability of infection after a single unprotected sexual exposure is similar to that after a needlestick exposure (i.e., ~0.1%, though slightly higher for receptive anal intercourse) (Katz, 1998; USPHS, 1998). Animal models suggest that PEP may be effective for mucosal and needle exposures, particularly when used within 24–48 hr. Ethical and pragmatic considerations make it unlikely that a randomized trial of PEP will be conducted. The effectiveness of PEP is likely to be influenced by time to initiation of treatment, duration of treatment, size of inoculum, and drug resistance profile of the virus in the source individual. While the risks and benefits of PEP for sexual exposure remain to be fully defined, studies suggest that provision of PEP for nonoccupational exposures is feasible (Kahn, 2001). Recently, some have suggested that routine antiretroviral chemoprophylaxis, with relatively safe agents such as nevirapine or tenofovir, be tested as an HIV prevention strategy for individuals at particularly high risk (e.g., commercial sex workers in high HIV prevalence settings) (Youle, 2003).

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. CDC guidelines recommend 2–3 antiretroviral medications, depending on the intensity of the exposure, for 4 weeks for occupational exposures having at least moderate HIV risk (CDC, 2001). A similar approach has been adopted by many providers when selecting a regimen for “sexual PEP.” 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 STIs, 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 especially 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) 448-1737 or http://www.hivpepregistry.org.

XII. Prevention Messages for HIV-Infected Women  TOP

While this chapter has largely focused on factors that may increase a woman’s risk of acquiring HIV, prevention messages are equally important for women who are already HIV-infected. Studies have shown that women with HIV are concerned about factors that may increase their infectiousness to their sexual partners and children. In general, the central messages for preventing sexual HIV transmission apply to HIV-infected women as well as to those who are uninfected and at risk through their or their partners’ behaviors. These include the importance of knowing one’s HIV status and that of one’s sexual partners, the ability for behavioral change to prevent transmission, and the potential for consistent condom use to significantly reduce HIV risk. Issues relevant to the prevention of mother-to-child transmission of HIV are covered in chapter VII.

Perhaps not surprisingly, many factors that increase the risk of HIV acquisition also appear to increase HIV infectiousness (reviewed in Baeten, 2003). Because of logistical limitations, relatively few studies have been conducted to assess the risk that HIV-infected women pose to susceptible sexual partners. However, numerous studies have now demonstrated that HIV shedding in genital secretions is likely a reliable marker of infectiousness, based on good biologic plausibility that factors that increase genital HIV shedding increase HIV transmission and on strong agreement between correlates of HIV transmission in epidemiologic studies and correlates of genital shedding of HIV. Thus, most studies of factors that influence the infectiousness of women with HIV have examined HIV shedding in the genital tract.

Plasma viral load is the strongest predictor of HIV infectiousness

In a large study of HIV-discordant couples from Uganda, HIV plasma viral load was the principal predictor of heterosexual transmission and demonstrated a clear dose-response effect (Quinn, 2000). The rate of transmission from female index cases to their uninfected male partners was similar to that from male index cases to uninfected female partners, suggesting that HIV-infected women are no less likely to transmit the virus than are infected men. The results of this study were not necessarily surprising—higher viral load is a strong risk factor for mother-to-child HIV transmission and HIV shedding in genital tract secretions. Epidemiologic studies suggest that individuals with primary HIV infection and advanced HIV disease, which are both characterized by high systemic and genital viral burdens, are more likely to transmit the virus to sexual partners. The only study to assess the effect of antiretroviral therapy on sexual HIV transmission found that men taking zidovudine monotherapy were at 50% decreased risk of transmitting HIV to female partners (Musicco, 1994). Given the dramatic reductions in plasma viral load and in the risk of mother-to-child HIV transmission that result from combination antiretroviral therapy, it is likely that effective regimens would significantly decrease a woman’s risk of transmitting HIV to sexual partners. However, studies have shown that genital HIV shedding may not be fully suppressed among individuals on therapy, even those with undetectable plasma viral loads, suggesting that antiretroviral therapy may not completely eliminate transmission risk.

STIs and other genital tract infections increase the risk of HIV transmission

Numerous studies have demonstrated that genital ulcer disease, cervical infections, and vaginal infections increase HIV shedding in the female genital tract, and that successful treatment reduces shedding (Baeten, 2003). In areas where antiretroviral therapy is not available, control of STIs should be a primary intervention to decrease sexual HIV transmission. Moreover, in all settings, STI screening and treatment may reduce HIV infectiousness among persons who do not qualify for antiretroviral therapy (e.g., those with CD4 counts >200–350) or even among those who are on therapy, since these infections may stimulate genital viral replication even in the context of good systemic HIV suppression. Recent studies have found that genital herpes shedding is associated with increased HIV shedding, suggesting that suppressive therapy for HSV may reduce HIV infectiousness. Studies to determine the efficacy of HSV therapy to decrease HIV shedding and transmission are planned.

Contraception, menstruation, and HIV infectivity

Oral and injectable hormonal contraception were associated with increased genital HIV shedding in two cross-sectional studies from Kenya (Mostad, 1997). No published prospective studies have yet assessed the effect of initiation of hormonal contraception or duration of hormonal contraceptive use on genital HIV shedding over time. Very little information is available from epidemiologic studies on the relationship between hormonal contraceptive use and HIV transmission risk. Thus, there is no recommendation against use of hormonal contraception by HIV-infected women. Given the importance of preventing unintended pregnancies, effective methods of contraception should be strongly encouraged, and condom use should be promoted as well as an adjunct method to decrease HIV infectiousness.

The effect of the diaphragm or cervical cap on HIV shedding and transmission is unknown. Cervical secretions tend to have significantly higher viral concentrations than vaginal secretions, potentially suggesting that cervical barrier devices may decrease transmission risk. However, women who have had hysterectomies can shed significant amounts of virus in the vagina, so even complete removal of cervical secretions does not eliminate HIV risk. One study from Kenya demonstrated that IUDs are a safe method of contraception for some HIV-infected women (Sinei, 1998), and a secondary analysis found no increase in HIV shedding in cervical secretions after IUD insertion.

Several studies have now demonstrated that the quantity of HIV shed in the genital tract varies over the course of the menstrual cycle (Coombs, 2003). Shedding appears to be lowest during the peri-ovulatory period and highest near the time of menstruation, which is in agreement with epidemiologic studies that found increased transmission risk for male partners of infected women who had unprotected intercourse during menses. However, these results are difficult to translate into a prevention message since HIV is shed to some degree throughout the menstrual cycle, and some women may shed high quantities of virus at all times. Overall, recommendations to women with HIV should stress the importance of consistent condom use to decrease HIV transmission risk.

New interventions to decrease HIV transmission risk

There remains a great need for simple, inexpensive interventions to prevent and treat HIV among individuals living in resource-poor settings. Several observational studies suggested that micronutrient deficiencies increased HIV infectivity and accelerated disease progression. However, subsequent randomized trials of micronutrients, conducted among HIV-infected African women among whom the prevalence of nutritional deficiencies was high, failed to demonstrate any substantial benefit of supplementation with vitamin A or other vitamin and mineral preparations (Baeten, 2002; Baeten, 2003). Vaginal microbicides offer a potentially promising strategy to decrease HIV transmission risk, since these products may decrease the infectiousness of virus shed into the genital tract. An effective therapeutic vaccine against HIV (i.e., one that could reduce systemic and genital viral burden among infected individuals) could significantly slow the global spread of the epidemic. No therapeutic vaccine has yet demonstrated clinical efficacy, though research in this area is continuing.

XIII. Conclusions  TOP

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. STI treatment decreases individual-level risk of acquiring and transmitting HIV and has been shown to be an effective population-wide intervention in some settings. 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. Development of an effective HIV vaccine will likely be essential to controlling the global epidemic, and a number of candidate vaccines are undergoing clinical testing at this time. Lastly, postexposure 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, providers must continue risk assessments to identify women at risk for acquiring or transmitting HIV and assist them in reducing their risk through setting achievable risk reduction plans.

XIV. References  TOP

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