This section provides brief summaries of current research related to HIV/AIDS, particularly in low-resource settings. Because a wealth of high-quality HIV/AIDS information is available through other online resources, we encourage readers to review the resources listed on RHO's HIV/AIDS Links page as well.
Overcoming stigma and discrimination
HIV thrives in an atmosphere of silence and secrecy. The stigma, real or feared, of HIV/AIDS often is a barrier to HIV-prevention programs. If people are uncomfortable discussing their risk of infection with health care providers due to concerns about discrimination or a lack of confidentiality, they may avoid HIV testing and treatment of symptoms. Those who suspect they are infected may choose to hide their disease from friends and family for fear of abandonment (Busza 2001). Several recent studies demonstrate how stigma and discrimination are fueled, resulting in prejudicial treatment of people living with HIV/AIDS. In Nigeria, a survey found that one in ten doctors and nurses admitted having refused care to patients with HIV/AIDS or having denied hospital admission to these patients. Twenty percent of those surveyed believed that people with HIV/AIDS were guilty of immoral behavior and were reaping their just dessert. In the Philippines, 50 percent of respondents to a recent survey conducted among people with HIV/AIDS reported having suffered discrimination by health care workers. In India, a study found that 70 percent of people living with HIV/AIDS had experienced discrimination, most often by family members or health care workers (UNAIDS, 2003).
Community leaders and health care professionals can help decrease the stigma of AIDS by avoiding discriminatory policies and practices, messages of fear, and implications that HIV/AIDS is a shameful disease. Communities also must encourage acceptance, compassion, and understanding of infected individuals. Programs can help decrease stigma by increasing knowledge and promoting discussion about HIV/AIDS through the involvement of people living with HIV/AIDS, media campaigns, and educational interventions in schools, police departments, and worksites. Community mobilization and involvement of groups most affected by stigma (such as injecting drug users, sex workers, and people living with HIV/AIDS) also are important (PATH/Outlook 2001; UNAIDS 2001).
A recent article reviewed 22 studies that tested several strategies for reducing AIDS-related stigma among a variety of population groups. Many of the studies were conducted in the United States, but other sites included Canada, England, Nigeria, Scotland, South Africa, Thailand, and Uganda. Among other things, the authors found that information alone was insufficient in changing deep-seated fears about HIV/AIDS. One of the most successful strategies for reducing AIDS-related stigma appears to be contact with people living with HIV/AIDS, particularly those who disclose their status during educational sessions (Brown et al. 2003). Other innovative strategies include a community-centered approach adopted in Zambia, whereby chiefs in the district of Lundazi had themselves tested for HIV, an act that encouraged other community members to follow suit. In Brazil, the Volkswagen company adopted a policy that guaranteed the right to confidentiality of workers living with HIV/AIDS and prohibited mandatory testing and firing of workers with HIV/AIDS. The Philippines HIV/AIDS Control and Prevention Act also includes strong measures to protect people living with the virus (UNAIDS, 2003).
Communication for behavior change
Communication activities aimed at changing behavior have been a critical component of efforts to address health issues such as child survival, reproductive health and family planning, and HIV/AIDS. Theoretically, communication activities aimed at changing behavior fall along a continuum that balances the number of clients reached with program impact. Positive, sustained impacts on attitudes, social norms, and behavior change are best achieved through programs that use a mix of communication activities and interventions at both the individual and community levels (PATH/Outlook 2001). In the context of prevention efforts in general, activities that use communication to help change behavior benefit from local political support and social marketing for condoms and STI treatment packages (Taguiwalo 2000).
Interpersonal communications—such as peer education, counseling, and small group discussions—reach fewer people but tend to have a greater impact on promoting behavior change (Kerrigan 1999). Interventions such as street-theater performances or community-mobilization efforts reach broader audiences with messages that can be tailored to meet the community's norms and needs. An evaluation of a street-theater program in several inner-city communities in India's Tamil Nadu State reported an increase in audience members' knowledge about HIV and improvements in self-reported attitudes toward people living with HIV/AIDS (Valente and Bharath 1999).
Macro-level interventions encompass print material and mass media (radio and television talk shows, dramas, and popular songs). In Mozambique, a radio campaign led 97 percent of those who heard it to report the intention of changing their sexual behavior, and 86 percent of those who recalled the campaign's message to effect an actual change in their behavior (Karlyn 2001).
Information, education, and communication (IEC) programs for HIV/AIDS are most effective when they create an environment conducive to HIV/AIDS prevention by working with key political, religious, and community leaders; addressing sensitive issues; and changing community norms. For example, work with barangay (village) officials in the Philippines helped to alter local attitudes and norms that prevented communities from confronting the health aspects of commercial and casual sex (Taguiwalo 2000). Another study, conducted in Kenya, Uganda, and Zambia, found that knowing someone who died of AIDS was an important behavior change determinant for men (MacIntyre et al. 2001). Because behavior change is a gradual process, such programs must maintain a sustained effort and involve their target audience in the design of effective messages.
Voluntary counseling and testing (VCT)
While it is widely agreed that people have the right to know their HIV status, HIV testing can be emotionally devastating for people who must cope with the news of a positive result without appropriate counseling. Combined voluntary counseling and HIV testing has been effective in encouraging people to protect themselves and their partners (whether the test result is positive or negative), preventing mother-to-child transmission, and helping people adjust to the knowledge that they are infected (Painter 2001; UNAIDS 2002). One of the most comprehensive studies of VCT found that VCT has the potential to significantly reduce unprotected intercourse with both steady and casual partners (VCT Efficacy Study Group 2000).
Programs considering the addition of a VCT component need to carefully consider the attitudes of the community in which their clients live; they also should be equipped to provide adequate and confidential medical, psychological, and social-support services to people infected with HIV (WHO/UNAIDS 2001). HIV testing and subsequent knowledge of HIV status can bring emotional distress, stigma, discrimination, abandonment, and violence, especially for women. However, physical and sexual violence toward women is also a significant risk factor for HIV infection through their male partners (Maman et al. 2002).
The Joint United Nations Programme on HIV/AIDS (UNAIDS) has developed a set of tools to evaluate HIV voluntary testing and counseling services. A team from South Africa and the United Kingdom used the tools to conduct a study of the VCT services available to mineworkers employed by a company in the Free State region of South Africa. Based on interviews with nurse counselors, community volunteers, and clients, the team found that the nurse counselors were more successful than community volunteers in establishing communication with clients, and more confident in giving information and answering questions. Clients generally felt that they had benefited from the counseling, for example, by learning about risk factors and possible treatment options, as well as calming their fears about losing their jobs. One barrier that caused clients to hesitate to accept VCT was concern about confidentiality. The recommendations of the study team included tailoring counselor training to the type of counselor in question; providing more medical information when training community volunteers; and providing anonymous testing through a numeric identification system to encourage more people to be tested (Ginwalla et al. 2002).
An evaluation of the work of the Groupe Haitien d’Etude du Sarcome de Kaposi et des Infections Opportunistes (Haitian Study Group for Kaposi Sarcoma and Opportunistic Infections), or “GHESKIO,” documented the group’s success in integrating primary care services into HIV voluntary counseling and testing. Primary care services sought by GHESKIO’s clients included care for tuberculosis and HIV infection; sexually transmitted infection treatment; and reproductive health services, including family planning, condom use, and prenatal care (Peck et al., 2003).
Reproductive health programs can help
As the magnitude and consequences of HIV/AIDS and other sexually transmitted infections (STIs) become more widely recognized, especially among women, integrating HIV-prevention strategies into reproductive health and primary care facilities (including family planning and antenatal care services that target women) becomes critical. Integrating HIV/AIDS-prevention services with family planning is an attractive option since family planning clients—generally women—often need HIV/AIDS-prevention services, and those seeking methods to prevent HIV acquisition or transmission often need family planning services as well (PATH/Outlook 2001).
In any prevention effort, the dual goals are to prevent people from being infected with HIV and to prevent those who are infected from transmitting the virus to others. Family planning programs can counsel people on contraceptive methods that prevent transmission of HIV and provide information on relevant issues such as mother-to-child HIV transmission as well as treatment of other reproductive tract infections. Some programs also provide HIV testing and appropriate counseling, which can help reduce high-risk behaviors. Expanding the effectiveness of integrated services may be linked to acknowledging that not only married women, but also men and young, single people need both reproductive health and HIV/STI services (Lush 2002). Despite the benefits of linking HIV prevention with reproductive health services, some argue that not all services should be integrated in all situations (Fleischman Foreit et al. 2002).
The clear linkages between HIV/AIDS and sexual and reproductive health have not led to widespread efforts to integrate services in most parts of the world. In many cases, separate ministries address HIV/AIDS and reproductive health. These ministries may compete for funding and may also have to contend with bilateral and multilateral donors who maintain separate departments for the two health-related issues, further complicating efforts to integrate services (Berer, 2003). One author characterizes the national HIV/STI and maternal-child health/family planning programs in Tanzania, for example, as being, “entrenched and separate,” and unable to meet women’s needs. Yet she avers that the solution is not to simply insert the issue of HIV/AIDS “into existing family planning programmes, renamed reproductive health programmes.” Rather, new and creative paradigms will be necessary to respond to the dual challenges of HIV/AIDS and reproductive health (Richey, 2003). These paradigms, as regards strengthening the capacity of sexual and reproductive health services to respond to HIV/AIDS, will need to involve better infrastructure, updated equipment and supplies, improved staff training and supervision, and stable drug supplies. Some of the methods that may serve the dual purpose of preventing HIV infection and ensuring reproductive health—possibly under the aegis of “sexual health services”—include education on unsafe sex; promotion of dual protection (e.g., using condoms to prevent HIV and unwanted pregnancies); education on STIs; detection and management of STIs; ensuring access to contraception and sterilization for those with HIV to prevent pregnancy; counseling and testing pregnant women for HIV and other conditions; and preventing mother-to-child HIV transmission (Askew and Berer, 2003).
For more information about condoms and other contraceptive methods, please see RHO's Contraceptive Methods section.
Reducing mother-to-child transmission
Since the beginning of the HIV/AIDS pandemic, millions of children have contracted HIV through mother-to-child transmission, including more than 800,000 in 2002 alone. Currently, approximately 1,600 newborn infants acquire HIV through perinatal transmission each day. Ninety percent of these children are born in Africa (Sullivan, 2003; UNAIDS 2002). Mother-to-child HIV transmission (also called perinatal or vertical transmission) can occur during pregnancy, delivery, or breastfeeding, and is influenced by multiple factors such as maternal viral load and the type of delivery method (Fowler et al. 2002).
Most mother-to-child HIV transmission (more than 75 percent) takes place during or following delivery. HIV-infected mothers who have a high plasma viral load while pregnant have a greater probability of transmitting the virus to the fetus or infant during the in utero or intrapartum periods, especially if seroconversion occurs during pregnancy. Prolonged breastfeeding further increases the risk of transmission. Damaged breast tissue also facilitates viral transmission from a mother to her breast milk, and then to her infant (Sullivan, 2003).
The risk of mother-to-child transmission can be reduced through antiretroviral therapy for the mother and infant, and by reducing the exposure of the infant to HIV during delivery and breastfeeding (Petra Study Team 2002). Ideally, programs aimed at preventing mother-to-child transmission should not end with therapy directed at the infant; they should be part of care for the mother after delivery that includes treatment and prevention of illnesses related to HIV, palliative care, nutritional advice, and links to organizations that can ease the social and psychological challenges confronting the HIV-infected mother (UNAIDS 2000; WHO 2001). In South Africa, a pilot program to reduce mother-to-child HIV transmission in the Western Cape region in the context of routine prenatal care demonstrated a high level of acceptance among women for both HIV testing and subsequent perinatal HIV-transmission prevention measures (Etiebet et al., 2004).
Mother-to-child HIV transmission rates have decreased dramatically in developed countries, largely due to the use of zidovudine (formerly known as AZT) to prevent perinatal transmission and highly active antiretroviral therapy for women living with HIV/AIDS. In Europe, transmission rates are now under ten percent, while in the United States rates have fallen to less than two percent (Sullivan, 2003).
In trials conducted in developing countries, drug therapy has reduced mother-to-child transmission by about 37 percent among women who breastfeed and by 50 percent or more among women who do not breastfeed (Guay 1999; Marseille et al. 1998). Over the past 10 to 15 years, several antiretroviral regimens consisting of zidovudine alone and zidovudine combined with lamivudine have been used (Culnane et al. 1999; Petra Study Team 2002). The national program to prevent mother-to-child HIV transmission in Thailand, initiated in 2000, has produced evidence that a short course of zidovudine for HIV-infected women and their infants may reduce the rate of transmission from 30 percent to 10 percent (Kanshana and Simonds 2002). In a study conducted in Côte d’Ivoire from 1996 to 1998, however, results showed that zidovudine prophylaxis given to HIV-positive pregnant women (but not to their infants) from 36 weeks of gestation until delivery decreased the risk of perinatal HIV transmission only for those women with low viral loads at enrollment (Jamieson et al., 2003).
Nevirapine has also proven effective in reducing mother-to-child transmission; nevirapine regimens are shorter, simpler, and less expensive than zidovudine regimens (Guay 1999). Some researchers have proposed universal treatment with nevirapine for all pregnant women prior to or at the time of delivery in areas where HIV prevalence is known to be high and access to HIV testing is low. Mass treatment with nevirapine—at the onset of labor for mothers and within 72 hours of birth for infants—may constitute a simple and inexpensive way to greatly increase access to antiretroviral drugs among pregnant women. In the Dominican Republic, a one-year project evaluation that began in 2000 indicated that a single-dose nevirapine regimen for mothers and infants—reinforced when possible by voluntary counseling, cesarean section delivery, and alternative feeding methods—could reduce the risk of mother-to-child HIV transmission by 50 percent, preventing an average of 1,000 infant HIV infections per year (Perez-Then et al., 2003). In a study conducted in Uganda, this regimen reduced the rate of mother-to-child transmission of HIV from 21 percent to 12 percent among infants aged six to eight weeks (Basset 2002; Hashimoto et al. 2002; Kiarie et al. 2003). In Cameroon, a short-course nevirapine regimen prevented HIV infection in 87 percent of 123 children born to HIV-infected mothers and tested at six to eight weeks of age. Despite the successes recorded in studies of the use of short-course nevirapine regimens to prevent perinatal HIV infection, concern has arisen about the incidence of nevirapine-resistant virus present in both mothers and infants, even in the case of a single dose of the drug (Ayouba et al., 2003a; Sullivan, 2003).
Recent studies conducted in Cameroon and Uganda indicate that co-infection with malaria may increase the risk of perinatal HIV transmission in pregnant women infected with the virus. In the Uganda study, results showed mother-to-child transmission in 40 percent of HIV-positive women with malaria and in 15 percent of women without malaria, with maternal viral load as a significant cofactor in HIV transmission. The increased risk of mother-to-child HIV transmission in the presence of maternal malaria infection may be linked to the inflammation that results from malaria infection. In HIV-positive pregnant women, this inflammation may damage the placenta, “increasing the exchange of maternal and fetal blood and facilitating in-utero HIV transmission” (Ayouba et al., 2003b; Brahmbhatt et al., 2003).
Researchers have suggested that partner involvement and support, increased knowledge about the use of antiretrovirals to prevent mother-to-child transmission of HIV, and positive attitudes of service providers may be key elements in ensuring compliance with drug regimens for pregnant women living with HIV (Kiarie et al. 2003).
Labor and Delivery Care
Interventions to prevent HIV transmission during labor and delivery have focused on reducing infants' exposure to HIV-infected blood and vaginal secretions (UNAIDS 2000). Health care providers can reduce the risk of transmission during birth by avoiding invasive procedures such as amniotomies or episiotomies. Although vaginal lavage to disinfect the vagina before birth was once thought to have some potential in preventing transmission during delivery, available data show no reduction in HIV transmission. Some reports from observational studies conducted in the United States and Europe show reductions in HIV transmission to infants born by elective cesarean section. Along with safety concerns, the cost and availability of elective cesarean section make it an impractical intervention in low-resource settings (Gibb and Tess 1999).
Although breastfeeding can result in mother-to-child HIV transmission, failure to breastfeed also can lead to significant health risks to the infant in some settings. The World Health Organization (WHO) has issued guidelines in order of priority for pregnant women with HIV infection. These include:
- using formula if it is affordable and can be safely prepared (animal milk also may be used if it is safely prepared);
- breastfeeding exclusively only for the first three to six months;
- expressing breastmilk and heating it to kill HIV, and feeding the infant with a cup rather than a bottle or nipple; and
- engaging a wet nurse who does not have HIV.
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WHO recommends breastfeeding for women who do not know if they are infected (WHO 2001).
Programs must consider these and related issues before reaching an appropriate decision. Women who do not breastfeed lose the contraceptive effect of breastfeeding and will need counseling to choose another contraceptive method (Fowler et al. 2002). Infants also lose the protective effects and nutritional value of breastmilk. In addition, the stigma of HIV/AIDS works against WHO recommendations to use alternative feeding methods: the majority of women in developing countries breastfeed, and not breastfeeding often is interpreted as a sign of HIV infection or child neglect.
Caring for Infants
Under ideal circumstances and in the presence of considerable resources, a number of procedures can help in caring for infants who have been exposed to HIV. These include:
- Performing a thorough medical history and physical exam.
- Carrying out routine infant immunizations.
- Assessing growth, nutrition, and development.
- Offering psychosocial support.
- Providing a regimen of zidovudine from birth to six weeks, then PCP prophylaxis from 4–6 weeks until HIV infection can be reasonably excluded (Siberry et al., 2003).
Care and support for people with HIV/AIDS
As the number of people living with HIV/AIDS continues to increase, strategies to control the epidemic need to incorporate a care continuum that includes counseling, clinical care, community- and home-based care, and social support services (UNAIDS 2001). Palliative care is a term used to describe an approach to care that does not attempt to directly treat HIV/AIDS, but instead seeks to improve patients’ quality of life by relieving physical, emotional, and spiritual pain for patients and their caregivers (UNAIDS, October 2000). Palliative care is ideally provided by a team that includes professional health care providers along with the patient and family. The provision of care and support must extend from the individual/home to the hospital, with the various levels of care linked by referral networks (Nsutebu 2001). Early entry into the continuum ensures opportunities for improving quality of life and educating infected individuals about ways to avoid HIV transmission. People with HIV/AIDS, particularly those in rural settings, face many barriers that prevent them from receiving important life-care services (UNAIDS 2001).
Part of the care continuum includes relief of pain. People living with AIDS often suffer from pain, diarrhea, weight loss, shortness of breath, fatigue, fever, skin problems, and depression (UNAIDS, October 2000). Children with HIV/AIDS require routine well-child medical care and immunizations, and appropriate management of diseases such as pneumonia, diarrhea, measles, malaria, malnutrition, and other common health problems (Lepage et al. 1998). While direct treatment of HIV and opportunistic infections can be costly, relief of these symptoms can be relatively simple and inexpensive. For example, treatment for constipation or diarrhea can include dietary advice, increased fluid intake, or inexpensive medication (UNAIDS, October 2000). People living with HIV can live longer, fuller lives when these physical symptoms are addressed.
Counseling is an important component of HIV/AIDS care. Counseling can help infected individuals better cope with their disease, assist them obtaining early medical intervention, and help them make decisions about family planning and contraceptive use (UNAIDS 2001). Counseling can be clinic-based, school-based, and/or community-based, and can involve doctors, nurses, support groups, and home-care workers, as well as church leaders (Kaleeba 1997; Krabbendam et al. 1998). An evaluation of the counseling, social, and medical services provided by a Ugandan organization known as TASO has shown that these care and support services were able to bring about positive behavior change and family and community support (Kaleeba 1997). A number of studies underscores the importance of training and motivation in maximizing the ability of health care workers to provide care and support services to people living with HIV. Kaleidoscope, a five-year action research project aimed at nurses caring for HIV/AIDS patients in India, found that quality training increased nurses’ confidence and knowledge and reduced their fear of contagion. Participation in the training course inspired many nurses to become local leaders in advocacy for care and support (Horizons Program 2002; Pratt et al. 2001). A questionnaire administered to female patients from HIV/AIDS referral clinics in São Paulo, Brazil, however, revealed several unmet needs linked to care and support. These included psychological support, nutrition care and oral health. Most of the women did not receive counseling prior to HIV testing, and not all received post-test counseling (Segurado et al. 2003).
People living with HIV/AIDS must pay particular attention to their consumption of food and water. Illnesses contracted through food and water can cause diarrhea, nausea, vomiting, and weight loss. The application of several precautions can help reduce the incidence of food- and water-borne illnesses among people living with HIV/AIDS. These include:
- Avoiding raw or undercooked meat, poultry, fish, or shellfish.
- Reheating sauces, soups, marinades, and gravies to a boil, and leftovers to at least 165°F.
- Avoiding raw or partially cooked eggs.
- Keeping hot foods hot (140°F or above) and cold foods cold (40°F or below).
- Freezing fresh meat, poultry, fish, and shellfish that cannot be used in a few days.
- Avoiding cross-contamination of foods.;
- Avoiding water drawn directly from lakes or rivers.
- Boiling water for at least one minute (Hayes et al. 2003).
Often, when a family member suffers from HIV/AIDS, a mother or other female family member becomes the primary caretaker. Frequently this caretaker does not have appropriate skills for addressing the infected person’s physical needs or for helping the family to deal with emotional turmoil. The unique factors surrounding HIV/AIDS—including stigmatization, power shifts in the family, and the inevitability of death—increase the need for early intervention at the family level to ensure that the support system can provide the necessary care. Programs can support caretakers by providing them with training in both emotional and physical. Mildmay Center for Palliative HIV/AIDS Care in Uganda, for example, offers workshops for care providers covering topics such as basic nursing, nutrition, positive living, and income-generating activities (UNAIDS 2001). The South African Hospice Association, which functions at seven sites, uses the Integrated Community-based Home Care model to link people living with HIV/AIDS and their families, community caregivers and hospices, clinics, and hospitals. Many people involved in the issue of increasing care and support for people living with HIV/AIDS in developing countries feel that part of the solution lies in strengthening the capacity for home-based care (Uys 2002). For more information about caretaking by older family members, see RHO's Older Women section.
HIV weakens the immune system, leaving people living with HIV/AIDS vulnerable to infections and illnesses they would normally be able to resist. These illnesses are referred to as opportunistic infections and are the main cause of death in patients with HIV/AIDS. Common opportunistic infections include many different types of bacterial infections, protozoal diseases, fungal infections, viral diseases, and malignancies (UNAIDS, October 1998).
Co-infection with hepatitis B is one problem that has been gaining momentum in people living with HIV/AIDS. As many as 10 percent of HIV-infected people also have chronic hepatitis B (CHB). Clinicians responsible for the care of patients co-infected with HIV/CHB must confront the issues of preventive care, which patients to treat, and choosing between available treatment options. Although several options are possible, combination treatment (for example, with lamivudine and tenofovir) seems to be most effective in treating hepatitis B infection in HIV-infected people (Thio 2003).
Although women are susceptible to the same opportunistic infections as men, they face the additional risk of gynecological infections and cancers. HIV/AIDS contributes to the frequency and severity of many gynecological infections, including vaginal candidiasis, herpes simplex, pelvic inflammatory disease, and genital warts. Women living with HIV are ten times more likely to have abnormal Pap smears and cervical dysplasia than those without HIV. They are also more likely to be infected with human papillomavirus (HPV, the primary cause of cervical cancer). Women with HIV/AIDS who do develop invasive cervical cancer tend to present at more advanced stages, have metastases in unusual locations, respond less successfully to treatment, and have higher rates of recurrence and death (Abularch and Anderson 2001). (See RHO's Cervical Cancer Prevention section for more information.)
There is evidence that primary treatment of opportunistic infections can help extend the life of those infected with HIV/AIDS (Chaisson et al. 1998). For example, the WHO Reproductive Health Library includes a summary of a meta-analysis of the effectiveness of preventive therapy with anti-tuberculosis drugs in HIV-infected patients. This review found that preventive therapy with anti-tuberculosis drugs appears to benefit HIV-infected patients with positive tuberculosis skin tests by reducing the incidence of active tuberculosis. Although the use of drugs to treat opportunistic infections has become relatively common in the developed world, drug use is not as common in low-resource settings, where the issues of access to and affordability of medical care and pharmaceuticals remain a challenge (UNAIDS 1998). As a response to the HIV/AIDS pandemic, particularly in Africa, a number of experts on opportunistic infections recommend primary HIV prevention and care programs, increased efforts to control and treat other infectious diseases (including malaria and tuberculosis), and primary prevention for opportunistic infections (such as diarrhea and pneumococcal infections) (Corbett et al. 2002; Maartens 2002; Holmes et al. 2003).
Drugs and treatment for HIV/AIDS
In developed countries, drug treatment allows many people living with HIV/AIDS to live long and active lives. The first drug therapies were single-drug treatments introduced in the late 1980s. These drugs were initially successful, but within months patients began developing immunity to them. Since that time, pharmaceutical companies have developed combination-drug therapies commonly referred to as highly active antiretroviral therapy (HAART). With HAART, several antiretroviral drugs (usually three or more) such as saquinivir, ritonavir, lamivudine, zalcitabine, indinavir, or zidovudine are used together.
Increased access to new and effective antiretroviral combination therapies has contributed to the decline in the number of HIV/AIDS cases and AIDS-related deaths in developed countries. For example, in the United States, AIDS deaths declined by nearly 50 percent in from 1996 to 1997. (For more information on antiretroviral treatment, see www.worldbank.org/aids-econ/arv/index.htm.) The availability of treatment may help prevention efforts, as it gives people an incentive to be tested and helps reduce stigmatization of the illness. Treatment also lowers viral load in those who are already infected, limiting the chances of transmission. In addition, antiretroviral treatment reduces the need for palliative care and treatment of opportunistic infections. In Brazil, universal access to therapy has reduced AIDS-related hospitalizations by three-quarters, saving the Ministry of Health an estimated US$422 million between 1997 and 1999 (Rosenberg 2001).
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In developing countries, access to HAART is rare. For example, of the 25 million people reported to be living with HIV in sub-Saharan Africa in 2001, only about 10,000 individuals were receiving treatment (Harvard 2001). Factors preventing access to HAART include poor health infrastructure, the complexity of the regimens, and, most significantly, the high price of drug therapy. In a major effort to make HIV treatment more accessible in developing countries, WHO released the first treatment guidelines for HIV/AIDS in low-resource settings and added 12 antiretroviral drugs to its Essential Medicines List, including nevirapine and zidovudine, recommended for reducing mother-to-child transmission and also for treating adults and children with HIV. The inclusion of drugs for HIV treatment on the Essential Medicines List is intended to support governments' efforts to make HIV treatments broadly available in countries that are the most impacted by the HIV pandemic (WHO 2002).
Effective treatment programs require that patients observe strict adherence to sometimes-complicated drug regimens. Despite the challenges inherent to weak health infrastructures, evidence suggests that programs in developing countries have achieved adherence levels equal to those in industrialized countries (Farmer et al. 2001; Rosenberg 2001). Pilot programs have been successful in distributing HAART in low-resource communities. For example, use of Direct Observation Therapy (DOT), a system that requires patients be observed when taking medication, has been successful in trials in Haiti, Senegal, and Thailand (Farmer et al. 2001; Harvard 2001). DOT is largely inexpensive and can employ existing DOT tuberculosis treatment infrastructures. This is a particularly useful overlap of systems, as tuberculosis is a leading opportunistic infection in developing countries (Farmer et al. 2001).
The question most commonly raised is whether drug treatment is cost-effective given a developing country's scarce resources. Cost-effectiveness may be measured in terms of cost per year of healthy life gained with the treatment, or the reduction in the incidence of HIV-infected children in the context of maternal-child transmission (Floyd et al. 1998). Although the cost of HIV drug therapies may be prohibitive in some countries, it has been suggested that antiretroviral therapy may be cost-effective if HIV prevalence is high, the therapies are proven effective, and drug prices are reduced (Marseille et al. 1998). One possible approach to addressing the numerous health challenges in developing countries (including tuberculosis, STIs, and opportunistic infection) is to deliver highly active antiretroviral therapy within a comprehensive HIV/AIDS management strategy (Harries et al. 2002).
Antiretroviral therapies are becoming more affordable as drug companies reduce their prices by up to 90 percent for some developing countries (Harvard 2001). In the near future, this trend may continue as bulk-purchase arrangements become commonplace; partnerships between international agencies, countries, and drug companies are established; and drug regimens become more manageable (Floyd et al. 1998). Treatment may also become more widely available in light of the recent World Trade Organization statement redoubling their commitment to making drugs available to the poorest countries, in addition to the World Health Organization announcement of its intention to make HIV treatment accessible to at least three million people in developing countries by 2005 (WTO 2001; WHO 2002). However, even when HAART becomes available for less than US$400 per year, as is now the case in India and parts of Africa, it can cost as much as US$1,000 per year to monitor antiretroviral therapy based on CD4 count testing and HIV plasma viral load. The development of simpler, less costly methods to monitor treatment may be a solution to this challenge (Kumarasamy et al. 2002).
Although antiretroviral therapy has prolonged millions of lives since the mid-1990s, drug resistance has emerged as cause for concern among people living with HIV/AIDS and following a HAART regimen. In recent years, studies have suggested that there is a “bell-shaped” relationship between adherence and resistance. Under this hypothesis, “the greatest risk of drug resistance results from only marginally sub-optimal adherence.” A study conducted at the Johns Hopkins Moore Clinic among patients receiving HAART revealed that adherence of 70 to 89 percent more than tripled the risk of drug mutation as compared to patient adherence of less than 70 percent or more than 90 percent. These findings present a challenge to HIV clinicians, who must counsel patients to adhere as closely as possible to their HAART regimen, with the knowledge that low levels of adherence may be less dangerous than medium adherence to the regimen. At the same time, “even perfect adherence may not prevent resistance,” while non-adherence “is associated with virologic failure, immunologic failure, and clinical disease progression” (Sethi, 2004).
The role of RTIs in HIV transmission
The presence of ulcerative or inflammatory conditions caused by reproductive tract infections (RTIs) increases susceptibility to HIV acquisition and the likelihood of transmission. A large-scale study of the impact of RTI treatment on HIV transmission in Mwanza, Tanzania, found that using a syndromic management protocol to treat symptomatic RTIs helped reduce HIV incidence by approximately 40 percent in a community in the early stages of the HIV epidemic, when the HIV prevalence was approximately 4 percent (Grosskurth 1995). A second study in Rakai, Uganda—a community with a mature HIV epidemic and an HIV prevalence of 16 percent—found that using periodic mass treatment of RTIs with antibiotics showed no impact on reducing HIV incidence. In addition to higher baseline HIV prevalence, the high prevalence of genital herpes (known to be a cofactor in the spread of HIV) may help explain the seemingly contradictory results of the two studies (Grosskurth 2000). There is considerable evidence that genital ulcers facilitate a large proportion of HIV transmission among heterosexuals and that this effect has been underestimated (O'Farrell 2002). Research has suggested that prior infections by certain types of HPV also increase the risk of sexual transmission of HIV, and are strongly associated with cervical cancer and its precursor lesions (dysplasia) (McClelland et al. 2001; Pisani et al. 1997; Levine 1998). (See RHO's Cervical Cancer Prevention section for more information.)
Improved RTI/STI services, syndromic management, and periodic mass treatment may help prevent HIV transmission (Dallabetta and Feinberg 2001). A study in Cote d’Ivoire, for example, provided clinical examinations, screening and testing for STIs, and counseling and testing for HIV infection for 542 female sex workers. The study participants then reported once a month to a confidential clinic where they received health education, condoms, and STI treatment, as necessary. The HIV-1 seroincidence rate for participants was considerably lower during the study (6.5 per 100 person-years) than before the study (16.3 per 100 person-years) (Ghys et al. 2001). Women's encounters with health care providers for prenatal care or other reproductive health concerns provide opportunities for HIV testing and diagnosis (MacDonald et al. 1998). It is important to note that RTIs often are asymptomatic in women, which complicates RTI and HIV control efforts. (Please see RHO's Reproductive Tract Infections section for more information about RTIs.)
Male circumcision and HIV
Since 1989 researchers have had evidence that circumcised men are at lower risk for acquiring HIV infection than uncircumcised men. A recent meta-analysis found that uncircumcised men in sub-Saharan Africa are approximately two times more likely to be infected with HIV than circumcised men (Weiss et al. 2000). While more research is required, various biological mechanisms have been suggested for a possible protective effect of circumcision, for instance, susceptibility of the foreskin to fissures and ulcerative STIs (Bailey et al. 2001).
Promoting male circumcision as a programmatic prevention method remains controversial and involves a range of complex issues, including ethics, resources, culture, and safety (Bailey et al. 2001; Bailey et al. 2002; Bonner 2001). Some researchers caution that the available evidence is based on observational studies where behavioral factors related to religion, ethnicity, and culture are potential confounders and make interpretations of the data complicated. With the first randomized, controlled trial recently approved, some researchers urge the public health community to wait for the completion of such trials to evaluate the evidence of the safety and effectiveness of circumcision (Gray et al. 2002). Other critics of promoting male circumcision as a prevention strategy argue that it would be irresponsible to encourage men to undergo circumcision because they may consider it license to have unprotected sex. A study recently conducted among men and women in South Africa revealed that many participants had a positive perception of male circumcision; over 50 percent of non-circumcised men reported the intention of being circumcised in the future. The study also divulged the disturbing fact that circumcised participants tended to engage in riskier sexual practices with a higher number of partners, fueled in part by a belief that circumcision protected them from HIV (Lagarde et al. 2003). Promoting a surgical procedure that can have complications also raises concerns when noninvasive preventive methods exist (Cold and Young 2000) and may introduce confusing messages in communities trying to discourage female genital mutilation traditions.
Still, male circumcision for HIV prevention is gaining support. There are researchers who feel strongly that it would be wrong to delay developing programs that can offer safe circumcision services, and encourage efforts to begin informing and educating communities about the benefits and risks of this potential prevention strategy (Halperin et al. 2002). In fact, a recent article listed the lack of male circumcision as a key factor in heterosexual transmission, and included promoting male circumcision as a way to reduce transmission between heterosexuals (Lamptey 2002). Additional research on the acceptability of male circumcision in traditionally non-circumcising populations reveals that there is growing interest in the procedure due to its benefits of increased hygiene and decreased risk of transmission of HIV and other STIs; this research also indicates that groups would like more available services, as well as information and education on the benefits and risks (Bailey et al. 2001; Bailey et al. 2002).
For more information, read the Special Report from the September 2002 Male Circumcision Conference in RHO's Men and Reproductive Health section.
Future directions: Vaccines and microbicides
As the HIV/AIDS pandemic continues, researchers around the world are working to develop improved HIV/AIDS prevention and treatment measures. In addition to behavior change, the most promising prevention tools include vaccines against HIV and microbicides.
Vaccines against HIV would provide a significant boost to prevention efforts and are the most promising hope for eradicating HIV/AIDS. The difficulty of developing a vaccine is reflected by the 12 years that passed between the first laboratory test of an HIV vaccine and the first large clinical trial. Technical challenges include the existence of numerous subtypes of HIV as well as their broad geographic distribution. A vaccine against subtype B, for example, which is prevalent in the United States and Western Europe, may be less effective in southern Africa and India, where subtype C predominates (Esparza and Bhamarapravati 2000). Other technical obstacles to developing an effective HIV vaccine include the difficulty for antibodies to neutralize the virus (due in part to rapid virus evolution and the emergence of neutralization-resistant mutants); HIV genetic diversity; HIV infection of CD4+ T-cells that stimulate immune responses; and the limitations of non-human primate models for pre-clinical evaluation of HIV vaccines (Garber and Feinberg, 2003).
Current HIV vaccine strategies include the use of selected viral proteins, live vectors that express HIV proteins, and naked DNA. Additional and not yet tested strategies include “novel vectors […], envelope-CD4 complexes, various DNA constructs, novel adjutants and non-living delivery systems, novel means of stimulating dendritic cells, and combinations thereof […]” The use of live-attenuated virus or whole-killed virus is not possible for HIV vaccine development, due to safety concerns. A possible innovation in the approach to HIV vaccine development would be to focus on protecting one gender with the goal of preventing transmission to and from both men and women. This approach would consist of boosting women’s immunity with the use of a vaccine-laced tampon during menstruation or colonizing the vagina with “naturally occurring, harmless organisms (e.g., lactobacillus) modified by recombinant technology to reduce HIV-specific immune responses in the female genital tract” (Idemyor, 2003; Tramont and Johnson, 2003).
The first vaccines may only be 40 percent effective (Lancet, 2000), but mathematical models suggest that even partially effective vaccines would save millions of lives in high-prevalence countries. However, the relationship between the efficacity of a vaccine and the severity of an HIV epidemic is critical to the potential success of a vaccine. In the context of a less severe epidemic, vaccination of less than 100 percent of the population with a vaccine that is less than 100 percent effective may eradicate the epidemic. In the case of a more severe epidemic, it might be necessary to vaccinate 100 percent of the population with a vaccine that is less than 100 percent effective to eradicate the epidemic. An increase in risky behavior could also decrease the effectiveness of an imperfect vaccine, even in the case of a less severe epidemic (Blower et al., 2003).
Some experts believe that the greatest hope for the immediate future lies in producing an HIV vaccine capable of slowing disease progression, while a preventive vaccine remains more difficult to develop (Letvin 2002; Mwau and McMichael 2002; Hu et al. 2003). Others have highlighted the need to combine widespread antiretroviral treatment of people living with HIV/AIDS in Africa with work to develop effective preventive vaccines (Weidle et al. 2002). The impetus for conducting vaccine research and trials in developing countries, particularly in Africa, is tied to the large number of infections occurring there; the need to carry out phase III efficiency trials in populations with a high incidence of HIV infection; the genetic and antigenic variability of the virus, necessitating the testing of candidate vaccines in different parts of the world; and the need to evaluate how varying transmission paths and cofactors impact on the protection provided by vaccines (Esparza et al. 2002).
Some results of the many years and resources devoted to vaccine research may soon be forthcoming. The efficacy evaluation of the "AIDSVAX" product of VaxGen yielded the disappointing conclusion that the preventive vaccine reduced the rate of new HIV infections among volunteers by only 3.8 percent, although the company has suggested that AIDSVAX may have provided a higher level of protection among non-white, non-Hispanic volunteers. At the level of recombinant viral vectors, in early 2003 Merck and the Vaccine Research Center of the National Institutes for Health were planning to move into Phase I/II trials of a product that uses adenovirus as a vector system for HIV antigen delivery. A large Phase III trial of an ALVAC prime followed by the VaxGen gp120 B/E boost (a prime boost strategy) was also scheduled to begin in Thailand in early 2003 (Beyrer 2003).
Public and private organizations are working to overcome the many technical, programmatic, and ethical issues posed by developing and testing vaccines among uninfected men and women. A number of organizations in the European community, the U.S. National Institutes of Health (NIH), and the International AIDS Vaccine Initiative (IAVI), are providing increased funding for HIV vaccine development. IAVI is coordinating a global initiative to accelerate scientific progress, mobilize community support, and encourage industrial participation in HIV/AIDS vaccine development (Esparza and Bhamarapravati 2000).
Microbicides are products that, when applied intravaginally, may destroy HIV and other microorganisms that cause STIs. Since microbicides would require little to no partner involvement or negotiation, they would provide women with a powerful new option for HIV prevention. Formulated in contraceptive and noncontraceptive varieties, microbicides also could fill a need for women who want constant protection against STIs but do not want a contraceptive.
One important issue in the development of microbicides has been the search for pharmacologic agents that will destroy viruses but not harm the vaginal mucosa. The ideal microbicide would also be colorless, odorless, tasteless, and enhance or at least not impede sexual pleasure. Several types of microbicide are currently under development. These include the “Invisible Condom”™, a thermoreversible gel that assumes a liquid form at room temperature and is solid at body temperature. Sulfated polymers are another type of microbicide under development. These include naphthalene sulfonate polymer, binding/fusion/entry inhibitors, and carrageenan (the Carraguard™ brand—derived from red seaweed and generally used as a thickening agent in ice cream and soups—currently the best known and most advanced microbicide candidate). The option of using microbicides for anal sex is also important. All potential microbicides must undergo in vitro and in vivo testing before proceeding to clinical trials (Johnston 2002; Stone 2002).
For more information on microbicides, please see the Research and Development page of RHO's Contraceptive Methods section. For more information on spermicides, please see the Spermicides page of RHO's Contraceptive Methods section.