Library

Resource

Adherence

What is the role of adherence in HIV treatment?

Why is adherence important?

The introduction of highly active antiretroviral therapy (HAART) has extended and improved the quality of life for people living with HIV by reducing viral load, often to undetectable levels. However, the initial enthusiasm for these drugs has been dampened somewhat by the discovery that they require near perfect adherence to prevent virus replication and mutation. Studies have shown that 95% adherence is needed for viral suppression and that even a small decrease in adherence can greatly increase viral load.¹ If the virus is allowed to mutate into drug resistant strains, the treatment regimen can become ineffective, which reduces treatment options both for the non-adherent individuals and for any partners they may infect with these strains.²

How do you measure adherence?

Adherence is usually measured through self-report, pill count, electronic pill bottle caps (MEMS caps) and laboratory tests.³ Self-report through doctor’s office visits, questionnaires, structured interviews or diaries provides a simple and practical way of determining the self-perceived level of adherence.⁴ However, many individuals forget whether or not they took all their pills or may forget to complete their diary every day, and others may misrepresent their adherence in order to please the interviewer or clinician. Diaries may also not be feasible in settings where literacy is an issue. Pill count, particularly if unannounced, may provide a more accurate assessment of adherence rates than self-report. However, it is labor intensive and may be perceived as intrusive, especially if conducted during unannounced home visits. In such situations, in-clinic pill count may work better. MEMS caps record each time the bottle cap is removed by the patient. They have been found to correlate highly with concurrent viral load. However, they are expensive to use and may under-report adherence in patients who remove more than one dose at a time for using medi-sets pill organizers.⁶ All of these methods assume that patients have actually taken all missing pills. Laboratory tests, an indirect measure of adherence, can include viral load, CD4 counts, and blood levels of drug metabolites. These measures are less commonly used and very expensive. The results give no specific information about number of doses missed or adherence to medication schedule. They can also be influenced by other factors, such as the presence of drug resistant virus. Still, lab measures are often considered a useful adherence measure when combined with patient self-report and/or pill counts.

What are barriers?

Adhering to medications is hard to do. Most people have a problem finishing even a 5-day dose of antibiotics. Adherence is even more difficult when taking multiple drugs with different dosing requirements and severe, unpleasant side effects such as diarrhea, nerve damage and changes in body composition. Many people with HIV also have other complicating factors in their lives, including mental health issues, economic worries, lack of stable housing and alcohol or drug use, making it difficult to prioritize adherence. Adherence barriers are often divided into regimen-specific, social/psychological and institutional. Regimen-specific issues, such as the complexity of the treatment and taking many pills at different times, as well as side effects of the medication, can lead persons to miss doses.⁸ Scheduling demands such as work, travel and mealtimes can also be barriers. Social and psychological factors influence adherence. Mental health issues (such as depression or psychological distress), attitudes toward treatment and toward HIV, and support from health care workers, family and friends are key to adherence.⁹ Positive responses promote adherence and negative responses (lack of support, pessimism, etc.) can make it more difficult to adhere to treatment regimens. Institutional factors such as incarceration, clinic setting and access to reliable health care and medication affect adherence. Factors that promote adherence are pleasantness of the clinic, convenience of scheduling, confidentiality and availability of transportation and childcare.¹⁰

What’s being done?

Action Point, a storefront drop-in center in San Francisco, CA, offers adherence support for the urban poor with active drug or alcohol addiction. Located in an area of high rates of drug-related arrests and deaths, Action Point is open 6 days a week and operates on a harm reduction principle that encourages any positive change in health. The program offers adherence case management, prescription dispensing, nursing care, acupuncture and referrals to mental health and substance abuse services. After one month of enrollment, clients are offered a pager that receives e-mail messages to remind clients to take their medications. After six months, 61% of Action Point clients were taking HAART and 81% reported greater than 90% adherence.¹¹ In New York, patients who had not previously been on HAART were offered an individualized, three-module program on basic understanding of HIV, adherence and regimen options. Counselors discussed with each patient in detail potential adherence barriers, anticipated toxicities, pill burdens, dosing intervals and drug preferences. These were evaluated, reported to their provider and used to select an individualized regimen. Patients were given tools such as pillboxes, dose cards and beepers, if needed. They also provided intensive coaching and a dedicated phone line for patients. The program increased adherence and enhanced virologic response.¹² One promising new adherence strategy is directly observed therapy (DOT) for antiretrovirals, or DAART. Based on DOT for tuberculosis, DAART has been used in settings where patients have frequent interactions with health care workers, such as prisons and methadone maintenance clinics. Some complications of using DAART include the fact that medications need to be taken for a lifetime and dosing is usually more than once a day.¹³

What can we do?

Because adherence to HAART is a complex process, interventions to improve adherence are best designed to be multifaceted. Factors to consider include regimen complexity, side effects, patient-related factors and even the patient-health care worker relationship, each of which affects adherence to medications. Overall, the better that a regimen “fits” with a patient’s lifestyle, the greater adherence is likely to be.¹⁴ Health care workers can help increase adherence by: involving the patient in selecting a regimen with tolerable dosing schedules; preparing for and managing side effects; addressing and treating mental health and drug use issues; addressing concrete issues such as lack of transportation and homelessness; providing memory aids and anticipating treatment fatigue.¹⁵ Patients can help by: learning about HIV disease and anti-HIV drugs and what they do; finding treatment goals that are not HIV-related (seeing children grow up, remaining healthy and looking good); recruiting friends or family to act as adherence monitors and anticipating changes in routine such as travel.¹⁵

What needs to be done?

Everyone can be adherent with proper support. HIV+ persons may combat not just HIV disease, but drug addiction, homelessness and/or incarceration. Many of the barriers to adherence can be overcome with treatment and the right tools. For example, depression and other mental health problems that get in the way of optimal adherence are often treatable and should be diagnosed and treated. Because adherence is complex, it often requires an “adherence team.” Collaboration between the patient, physician, nurse, case manager, social worker, pharmacist, counselor and family or friends is essential.

Says who?

1. Paterson DL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Annals of Internal Medicine. 2000;133:21-30. 2. Bangsberg DR, Deeks SD. Is average adherence to HIV antiretroviral therapy enough? Journal of General Internal Medicine. 2002;17:812-813. 3. Fogarty L, Roter D, Larson S et al. Patient adherence to HIV medication regimens: a review of published and abstract reports. Patient Education and Counseling. 2002;46:93-108. 4. Chesney MA, Ickovics JR, Chambers DB, et al. Self-reported adherence to antiretroviral medications among participants in HIV clinical trials: The AACTG Adherence Instruments. AIDS Care. 2000;12:255-266.https://pubmed.ncbi.nlm.nih.gov/10928201/ 5. Samet JH, Sullivan LM, Traphagen ET, et al. Measuring adherence among HIV-infected persons: is MEMS consummate technology? AIDS and Behavior. 2001;5:21-30. 6. Wendel CS, Mohler MJ, Kroesen K, et al. Barriers to use of electronic adherence monitoring in an HIV clinic. The Annals of Pharmacotherapy. 2001;35:1010-1015. 7. Ickovics JR, Meade CS. Adherence to HAART among patients with HIV: breakthroughs and barriers. AIDS Care. 2002;14:309-318. 8. Altice FL, Mostashari F, Friedland GH. Trust and acceptance of and adherence to antiretroviral therapy. Journal of Acquired Immune Deficiency Syndromes. 2001;28:47-58. 9. Gordillo V, Del Amo J, Soriano V, et al. Sociodemographic and psychological variables influencing adherence to antiretroviral therapy. AIDS. 1999;13:1763-1769. 10. Ciccarone D, Bangsberg D. , Bamberger J, et al. HIV-Related hospitalization before and during participation in ‘Action Point’ an adherence case management program. Presented at the American Public Health Association Conference. 2003. 11. Bamberger JD, Unick J, Klein P et al. Helping the urban poor stay with antiretroviral HIV drug therapy. American Journal of Public Health. 2000;90:699-701. 12. Esch L, Hardy H, Wynn H, et al. Intensive adherence interventions improve virologic response to antiretroviral therapy (ART) in naive patients. Presented at the 8th Conference on Retroviruses and Opportunistic Infections, Chicago, IL. 2001. Abst #481. 13. Lucas GM, Flexner CW, Moore RD. Directly administered antiretroviral therapy in the treatment of HIV infection: benefit or burden? AIDS Patient Care and STDs. 2002;16:527-535. 14. Chesney MA, Malow RM. Adherence in Chronic Diseases: Lessons learned from HIV/AIDS. World Health Organization volume on Adherence in Chronic Diseases. in press 15. Bartlett JA. Addressing the challenges of adherence. Journal of Acquired Immune Deficiency Syndromes. 2002;29:S2-S10. For information on how this affects prevention, please see Fact Sheet #27 “Do new HIV drugs affect HIV prevention?”

Prepared by Maria Ekstrand, Michael Crosby and Pamela DeCarlo, CAPS January 2003. Fact Sheet #47E Special thanks to the following reviewers of this Fact Sheet: Margaret Chesney, Linda Fogarty, Celia Friedrich, Jeanette Ickovics, James L. Sorensen.

Reproduction of this text is encouraged; however, copies may not be sold, and the Center for AIDS Prevention Studies at the University of California San Franciso should be cited as the source of this information. For additional copies of this and other HIV Prevention Fact Sheets, please call the National Prevention Information Network at 800/458-5231. Comments and questions about this Fact Sheet may be e-mailed to [email protected]. © January 2003, University of California

Resource

Effect of treatment on prevention

What is the effect of HIV treatment on HIV prevention?

revised 9/03

Why HIV treatment and prevention?

Traditionally, HIV prevention efforts have focused on uninfected persons at risk, encouraging them to adopt and maintain safer sex and drug-using behavior that would keep them uninfected. Less attention was paid to prevention among persons who were already infected, where the priority was maintaining their health in the face of a devastating disease. Providers and programs for prevention and care were distinct and separate. While such a division was always short-sighted (naturally the behavior of both HIV+ and HIV- persons influence transmission), in today’s era of more effective treatment for HIV, it is even more important that prevention and care be permanently linked. More effective treatment, also known as highly active anti-retroviral therapy or HAART, can have differing effects on HIV prevention. On the one hand, HAART has dramatically improved the length of survival and the physical well-being of persons living with HIV/ AIDS, and with it has increased the opportunities for transmission of the virus to others. On the other hand, treatment may decrease the opportunity for HIV transmission by lowering the amount of HIV virus shed through blood and genital secretions. The availability and use of HAART also may have produced changes in attitudes that can help or hinder HIV prevention. Prevention efforts must therefore carefully weigh and address the potential positive and negative effects of HAART on HIV transmission.

Can treatment benefit prevention?

There is a variety of evidence supporting HAART’s beneficial effect on HIV prevention, both in the acquisition of infection among HIV- persons and in the transmission of infection from HIV+ persons to others. First, the provision of anti-retroviral treatment to HIV+ women and their infants around the time of delivery has been shown to reduce mother-to-child transmission.¹ Treatment is thought to work by reducing the mother’s infectiousness and/or by blocking the establishment of infection in the infant. Second, follow-up of healthcare workers exposed to HIV through needlestick injuries or other accidental contact with body fluids found that persons taking anti-retroviral post-exposure prophylaxis (PEP) were less likely to become infected compared to those who did not.² The concept has been extended to the provision of PEP to prevent HIV infection resulting from episodes of unprotected sex or needle-sharing.³ A third argument is indirect. HAART can dramatically reduce the levels of virus in the blood, often to the point of becoming undetectable by current tests. Although not a one-to-one relation, lower blood levels of virus tend to correlate with lower genital fluid levels of virus.^4,5 At least one study in Africa observed that low blood viral load translated to low likelihood of sexual transmission; no HIV transmissions were observed among discordant couples when the partner’s blood viral load was under 1500 copies per ml.⁶ If treatment can reduce blood levels of virus to below this level, the reasoning goes, then it can prevent HIV transmission. This conclusion, while appealing, has not been proven. Even in patients on HAART, virus remains in many tissues of the body, inside cells and in the blood despite being undetectable with tests.⁷ While it is probably true that a low viral load makes someone less infectious, viral loads fluctuate over time due to changes in adherence, the development of drug resistance or the natural history of infection. While the evidence suggests treatment can reduce infectiousness, it does not eliminate it at all points in time. Until the conditions when someone is not infectious are well-defined, it is safest to assume that an HIV+ person remains potentially infectious for life. On a different level, HAART can help prevention by providing hope to persons affected by AIDS. There is greater incentive to seek HIV testing (and therefore risk reduction counseling) when effective HIV treatment is available and greater disincentive when it is not, especially where high stigma of HIV exists. Moreover, communities devastated by friends and families getting sick and dying may view HIV infection as inevitable and self care and prevention take low priority. A study in Baltimore, MD, found that informal caregivers were more likely to promote prevention messages in the community when their friends and family had access to HIV treatment, giving them hope for the future.⁸

Can treatment harm prevention?

HIV+ persons and HIV- persons have been having sex and/or injecting drugs since the beginning of the epidemic, before the advent of HAART. In the past few years, however, there have been increases in sexually transmitted diseases (STDs) and sexual risk behavior in the US and across the developed world.^9-12 These increases might be a sign of upcoming increases in HIV infection. It is difficult to determine if this is due to improved treatment or not. Outbreaks of syphilis among men who have sex with men (MSM) have occurred in several cities across the US. Around half of the men in these outbreaks were HIV+, with many receiving treatment. In San Francisco, CA, acquiring an STD after AIDS diagnosis was associated with the use of HAART.¹⁰ STDs can promote HIV transmission by increasing HIV infectiousness in HIV+ persons and increasing susceptibility to HIV in HIV- persons.¹³ Internationally, increases in sexual risk behavior and STDs have been documented among both HIV- and HIV+ MSM in the last few years. In London, Manchester and Brighton, England, Amsterdam, the Netherlands and Sydney, Australia, high-risk sexual behavior increased since 1996, especially among MSM.¹⁴ These increases in sexual risk behavior in recent years have led to heated discussion on the role of “treatment optimism” in HIV transmission. Treatment optimism means that people are more likely to engage in sexual risk behavior because they believe treatment will make them or their partners less infectious or they believe that HIV is less serious a disease than before. In fact, a recent review of studies on treatment optimism in three continents found few gay men were optimistic overall and the association between optimism and sexual risk behavior was inconsistent.¹⁴ That is, treatment optimism may be causing an increase in sexual risk behavior among some communities or segments of communities of gay men, but not among others. The trade-offs between the potential benefits of HAART in reducing the likelihood of HIV transmission and potential harm resulting from increased risk behavior have been included in many complex mathematical models of the epidemic. The models suggest that HIV transmission can increase in a community where greater than 50% of infected persons are on HAART if risk behavior increases on the order of 10% or more.¹⁵

What needs to be done?

HIV care programs provide opportunities for treatment and prevention to work together. Health care providers can take a greater role in HIV prevention, making prevention activities an expected part of medical care. Key prevention components can include regular risk reduction counseling and STD screening. Training and support are needed for HIV care providers unfamiliar with these roles. Programs outside medical care settings are needed to help HIV+ and HIV- persons avoid transmission.¹⁶ These prevention programs should incorporate a variety of strategies, including counseling and training on when and how to disclose HIV status, how to maintain consistent condom use in the absence of disclosure, how to address HIV-related stigma, and how to keep intimacy in serodiscordant and seroconcordant relationships. This should be available for HIV+ and HIV- persons in the context of managing a healthy sex life. Communities impacted by HIV need better understanding of and access to research on when and how persons are infectious and how to best use HIV treatment to reduce the risk of transmission, so that they can make appropriate informed decisions. Persons who know they are HIV-, know they are HIV+, or do not know their serostatus all need community-level prevention messages that address sexual and drug-related behavior. New HIV tests that are easier to use and give faster results should facilitate increased testing for those who do not know their status. HIV testing should be made more widely available through as many outlets as possible, including anonymous and confidential test sites and home collection kits. The fight against the HIV/AIDS epidemic should not be divided into treatment for HIV+’s and prevention for HIV-’s. Treatment will not eliminate the epidemic in the absence of prevention programs for HIV- and HIV+ persons; prevention will not work unless relevant to those infected and uninfected.

Says who?

1. Mofenson LM. Technical Report: Perinatal Human Immunodeficiency Virus Testing and Prevention of Transmission. Pediatrics. 2000;106:E88. 2. Cardo DM, Culver DH, Ciesielski CA, et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. New England Journal of Medicine. 1997;337: 1485-1490. 3. Kahn JO, Martin JN, Roland ME, et al. Feasibility of postexposure prophylaxis (PEP) against human immunodeficiency virus infection after sexual or injecting drug use exposure: the San Francisco PEP study. Journal of Infectious Diseases. 2001;183: 707-714. 4. Barroso PF, Schechter M, Gupta P, et al. Adherence to antiretroviral therapy and persistence of HIV RNA in semen. Journal of Acquired Immune Deficiency Syndromes. 2003;32:435-440. 5. Goulston C, McFarland W, Katzenstein D. Human immunodeficiency virus type 1 RNA shedding in the female genital tract. Journal of Infectious Diseases. 1998;177:1100-1103. 6. Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and risk of heterosexual transmission of HIV-1 among sexual partners. Presented at the Conference on Retroviruses and Opportunistic Infections. Jan 30-Feb 2;2000. Abst# 193. 7. Zhu T, Wang N, Carr A, et al. Genetic characterization of human immunodeficiency virus type 1 in blood and genital secretions: evidence for viral compartmentalization and selection during sexual transmission. Journal of Virology. 1996;70:3098-3107. 8. Knowlton AR. Social network approaches to HIV prevention and care: theoretical and methodological considerations of intervention. Presented at the International AIDS Conference, Barcelona, Spain. 2002. ThOrE1501. 9. Valdiserri RO. Preventing new HIV infections in the US: what can we hope to achieve? Presented at the 10th Conference on Retroviruses and Opportunistic Infections, Boston, MA. February 10-14, 2003. 10. Scheer S, Chu PL, Klausner JD, et al. Effect of highly active antiretroviral therapy on diagnoses of sexually transmitted diseases in people with AIDS. Lancet 2001 Feb 10;357(9254):432-5. 11. Katz MH, Schwarcz SK, Kellogg TA, et al. Impact of highly active antiretroviral treatment on HIV seroincidence among men who have sex with men in San Francisco. American Journal of Public Health. 2002;92:388-394. 12. Stolte IG, Coutinho RA. Risk behaviour and sexually transmitted diseases are on the rise in gay men, but what is happening with HIV? Current Opinions in Infectious Diseases. 2002;15:37-41. 13. Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sexually Transmitted Infections. 1999;75:3-17. 14. Elford J, Bolding G, Sherr L. HIV optimism: fact or fiction? FOCUS. 2001;8:1-3. 15. Blower S, Schwartz EJ, Mills J. Forecasting the future of HIV epidemics: the impact of antiretroviral therapies and imperfect vaccines. AIDS Reviews. 2003;5:113-125. 16. Collins C, Morin SF, Shriver MD, et al. Designing Primary Prevention for People Living with HIV. Monograph published by the AIDS Policy Research Center & Center for AIDS Prevention Studies. March, 2000.prevention.ucsf.edu/uploads/publications/pozmono.pdf (Accessed 4/20/06)

Prepared by Willi McFarland* and Pamela DeCarlo** *San Francisco Department of Public Health, **CAPS September 2003. Fact Sheet #27ER Special thanks to the following reviewers of this Fact Sheet: Angela Kashuba, Mitch Katz, Jeffrey Klausner, Kimberly Page-Shafer, Jack Summerside, Dan Wohlfeiler.

Resource

Healthcare workers

Can Healthcare Workers Help in HIV Prevention?

revised 4/99

Are healthcare providers important in prevention?

Yes. Healthcare providers have many opportunities to help foster the behavior changes needed to stem the spread of HIV infection. In the US in 1996, the average adult visited a physician 3 times a year. Overall, 82% of visits were in physician offices and 10% in emergency departments.¹ Visits with healthcare providers or other encounters with the healthcare system are “teachable moments”-opportunities for discussing sexual and drug-use risks in a manner relevant to individual patients’ lives. Healthcare providers in environments with large numbers of high-risk patients such as emergency departments, sexually transmitted disease (STD) clinics, methadone maintenance clinics and prison or jail clinics, can be crucial for HIV prevention. For example, men, women and adolescents who have been incarcerated have high rates of HIV, STDs and tuberculosis, as well as substance abuse problems, and would benefit from preventive information and medical services.² In a nationwide survey of adults, only 20% of patients had discussed HIV risks with their doctors in the previous five years. Only 21% of those who did talk to a physician said the physician initiated the discussion. And only 23% of those who reported a behavioral risk for HIV had spoken to their physician about AIDS.³

What are barriers to discussing HIV?

HIV prevention requires the ability to talk about sexuality and drugs in an open manner, which may be uncomfortable. Healthcare providers need training in initiating discussions, negotiating awkward moments, responding to fears and expectations, encouraging patient feedback and being empathic. Ways to help foster these skills include instructors acting as patients for role-play and videotaped feedback on clinical performance.⁴ Lack of time can be a huge barrier to discussing HIV risks for healthcare providers. Many hospitals, clinics and health maintenance organizations (HMOs) require healthcare providers to address prevention in many other areas such as diet and exercise, smoking, depression, diabetes, heart disease and cancer. With a limited amount of time allotted each patient, healthcare providers may feel there is not enough time to also discuss sensitive issues such as sexuality and drug use.

What can healthcare providers do?

Assessing HIV risk behaviors should be a standard part of new patient intake. In-depth AIDS prevention education is not necessary for each and every patient. However, healthcare providers should ask all patients about condom use, number of sexual partners, sexual orientation and injection drug use to assess a patient’s risk for HIV. These quick questions may lead to longer discussions and counseling about safer sex or drug use practices. Healthcare providers who don’t have the time or comfort for these discussions can refer patients to toll-free hotlines or community-based public health programs. Healthcare providers can provide HIV counseling and testing to patients who request it, and recommend testing to patients at high risk for HIV. These include patients with STDs, especially adolescents, injection drug users (IDUs), women whose partners may be IDUs and patients who are unsure of their partner’s HIV status.⁵ Helping patients get into drug treatment can be an effective HIV prevention tool. Healthcare providers can have a profound effect on patients’ lives by showing an interest in drug-using patients and encouraging willing patients to enter a drug or alcohol treatment program. Because relapse is common in treating addictions, healthcare providers should use a non-judgmental attitude.⁶ Healthcare providers who work with HIV+ patients can help prevent HIV transmission by assessing patients’ risky sexual and needle-use behaviors and counseling them to reduce those unsafe behaviors.⁷ This is especially important with the advent of more effective treatments for HIV. For example, HIV+ patients may believe that if they have a low or undetectable viral load, they cannot transmit HIV. Opportune moments for counseling are: at diagnosis, at onset of symptoms and when beginning drug treatment.⁸

Can treatment promote prevention?

Yes. Diagnosing and treating STDs such as syphilis and gonorrhea can help protect against HIV transmission. Early detection and treatment of STDs can be crucial, as STD infections make it easier to both get HIV and transmit it to others. In areas and populations with high rates of STDs and low rates of HIV infection, treating STDs is an effective means to prevent HIV infection.⁹ In recent years, great advances have been made in preventing HIV transmission from mother to infant. Healthcare providers should offer HIV testing to all pregnant women. Treating HIV+ mothers and their babies with AZT has been shown to reduce transmission by two-thirds. HIV+ mothers should also be counseled on the risk of breastfeeding and provided with alternates to breast milk if needed.¹⁰ Post-exposure prophylaxis (PEP) is a method for potentially preventing HIV transmission by administering AZT and other anti-HIV drugs within 72 hours of an accidental exposure to HIV. Studies of occupational PEP have found that HIV transmission can be prevented by post-exposure treatment, and PEP is now recommended by the Centers for Disease Control and Prevention (CDC) for occupational exposure among healthcare workers.¹¹ PEP is currently being piloted for exposure via sexual or drug use activities, including sexual assault. The CDC has not yet endorsed this due to lack of research data directly from drug and sexual exposure.¹²

What’s being done?

Healthcare providers need access to training and medical updates. One program trained rural healthcare providers in HIV/AIDS information, how to conduct risk assessments, advances in treatments, and sensitivity to diverse populations. The most effective training was achieved with a self-study booklet which helped increase prevention, early intervention and health promotion among rural health care providers. This booklet is now available free of charge on the Internet. Interactive teleconference training and personal training from visiting educators were also effective.¹³ Healthcare providers need to address the multiple needs of patients. In Bangalore, India, the Well Woman Clinic was established as part of an HIV control program. Poor women, especially commercial sex workers, had been underserved, had high rates of STDs and were at high risk for HIV. Because women are conditioned to ignore or tolerate health problems, patients at the Clinic are automatically screened for STDs without having to admit to any symptoms.¹⁴ Healthcare providers need to take advantage of community-based services. Children’s Hospital Los Angeles teamed with community-based prevention organizations to provide an integrated care model for youth with and at high risk for HIV infection. The model offers a general medical clinic for youth and psychosocial services such as counseling and case management. Peer educators also conduct extensive street outreach where high-risk youth congregate. The program developed a computerized referral system for local youth services available on the Internet.¹⁵

Will enhancing healthcare providers’ involvement be enough?

Enhancing healthcare providers’ involvement is only one aspect of a broad prevention policy. A comprehensive HIV-prevention strategy uses multiple elements to protect as many people at risk of HIV infection as possible. HIV prevention is not a “one-shot” effort; it is an ongoing process that demands the involvement of many sectors of society. This includes the physicians, nurses, health educators, therapists, dentists and other healthcare providers to whom people look for advice on how to stay healthy.

Says who?

1. Schappert SM. Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departments: United States, 1996 . Vital and Health Statistics. 1998;134:1-37. 2. Hammett TM, Gaiter JL, Crawford C. Reaching seriously at-risk populations: health interventions in criminal justice settings . Health Education and Behavior. 1998;25:99-120. 3. Gerbert B, Bleecker T, Bernzweig J . Is anybody talking to physicians about acquired immunodeficiency syndrome and sex? A national survey of patients. Archives of Family Medicine. 1993;2:45-51. 4. Epstein RM, Morse DS, Frankel RM, et al. Awkward moments in patient-physician communication about HIV risk. Annals of Internal Medicine. 1998;128:435-442. 5. American Medical Association. Physician Guide to HIV Prevention. June 1996. 6. Herman M, Gourevitch MN. Integrating primary care and methadone maintenance treatment: implementation issues . Journal of Addictive Diseases. 1997;16:91-102. 7. Gerbert B, Brown B, Volberding P, et al. Physicians’ transmission assessment and counseling practices with their HIV-seropositive patients. AIDS Education and Prevention. In press. 8. Gerbert B, Love C, Caspers N et al. “ Making all the difference in the world”: how physicians can help HIV-seropositive patients become more involved in their healthcare . AIDS Patient Care and STDs. 1999;13:29-39. 9. Centers for Disease Control and Prevention. HIV prevention through early detection and treatment of other sexually transmitted diseases-United States . Morbidity and Mortality Weekly Report. 1998;47(RR-12):1-25. 10. Centers for Disease Control and Prevention. Update: perinatally acquired HIV/AIDS-United States, 1997 . Morbidity and Mortality Weekly Report. 1997;46:1086-1092. 11. Centers for Disease Control and Prevention. Management of health-care worker exposures to HIV and recommendations for postexposure prophylaxis . Morbidity and Mortality Weekly Report. 1998;47(RR-7):1-33. 12. Centers for Disease Control and Prevention. Management of possible sexual, injecting drug-use, or other non-occupational exposure to HIV, including considerations related to antiretroviral therapy . Morbidity and Mortality Weekly Report. 1998;47(RR-17):1-14. 13. Martin SJ. HIV/AIDS prevention, early intervention and health promotion: results of training for rural health care providers. Presented at the 9th National AIDS Update Conference, San Francisco, CA. March 19, 1997. 14. Baksi CM, Harper I, Raj M. A `Well Woman Clinic’ in Bangalore: one strategy to attempt to decrease the transmission of HIV infection . International Journal of STDs & AIDS. 1998;9:418-423. 15. Schneir A, Kipke MD, Melchior LA, et al. Children’s Hospital Los Angeles: a model of integrated care for HIV-positive and very high risk youth. Journal of Adolescent Health. 1998;23(2Suppl):59-70. Computerized referral system:www.caars.net

Prepared by Pamela DeCarlo*, Barbara Gerbert, PhD** and the Center for Health Improvement and Prevention Studies** *CAPS, **Division of Behavioral Sciences, UCSF April 1999. Fact Sheet #6ER

Resource

Hepatitis C

Can hepatitis C (HCV) transmission be prevented?

Prepared by Alice Asher RN, MS, CNS and Kimberly Page PhD MPH Fact Sheet: 46 September 2010

What is the hepatitis C virus (HCV)?

Hepatitis C virus is blood borne virus affects the liver. It is principally acquired and transmitted by blood-to-blood contact, most commonly among injection drug users (IDU). Other common infectious viruses that affect the liver are Hepatitis A and B which have other routes of infection. Unlike hepatitis A and B, there is no vaccine for HCV. About 3.2 – 4 million Americans are estimated to be infected with HCV.¹ In the US, 8,000 to 10,000 deaths per year are attributed to HCV-associated liver disease and that is expected to triple in the next 10-20 years.

Who’s at risk for HCV?

The population at highest risk for HCV are people who inject drugs; principally through sharing of syringes directly or through sharing of drug preparation equipment. Among newly reported HCV cases with known risk factors, 50%-60% are attributable to injecting drugs. However, this may be underestimated due to underreporting both due to the illicit nature of IDU and lack of HCV surveillance in high risk groups.² HCV is usually acquired rapidly after a person first starts injecting drugs. As a result, prevalence of HCV among IDU is very high, ranging from 40-90%, depending on a person’s age and number of years injecting.³ Persons who received blood transfusions or an organ transplant before 1992 and hemophiliacs who received clotting factor concentrates before 1987 are also at risk for HCV. At moderate risk are persons receiving continual care (hemodialysis) for kidney failure. Others at risk include healthcare workers exposed to needlesticks with HCV+ blood.and, rarely, infants born to infected mothers. Sexual transmission of HCV is uncommon, although recent studies of HIV+ gay men show that it does occur.⁴Rough sex, fisting, sex with multiple partners and having a sexually transmitted disease (STD) or HIV appear to increase a person’s risk of HCV.⁵ This is likely due to blood contact during sex.

What does HCV infection look like?

HCV infection can range of in severity from a mild illness lasting a few weeks to a serious, lifelong illness that damages the liver.5 The majority of people infected with HCV do not experience symptoms related to their infection. Because of this, testing is the only way to confirm HCV infection. The first period after HCV infection is referred to as the “acute” period. Acute HCV infection generally lasts about 6 months after someone is infected with the virus. About 25% of people who become infected with HCV will spontaneously clear the virus on their own in the first 6 months. Studies have shown that women are more likely to spontaneously clear the virus than men. Even for those who have cleared HCV, re-infection can occur. While many who become re-infected will clear the virus again, this is not guaranteed, and a subsequent infection may become chronic. Those who do not clear or resolve their HCV infection are considered chronically infected. Most people with chronic infection remain asymptomatic for 20-30 years, and some will never develop symptoms of advanced disease. However, 60-70% of people with chronic HCV ultimately will develop some degree of liver disease.⁵ People with chronic infection whose liver disease has started to progress often report increasing levels of fatigue and stomach pain. The symptoms of chronic HCV are often are vague and unspecific and may go undiagnosed. This again underlines the importance of testing for anyone at risk of HCV. Chronic HCV infection causes liver damage that can turn into cirrhosis (scarring of the liver) and liver cancer.⁵ Up to 20% of chronically infected individuals will develop cirrhosis and 5% will develop liver cancer. Alcohol and drugsincluding marijuana and even tobaccocan speed up the rate of liver damage significantly.

Can HCV be treated?

The short answer is yes, there is a treatment for HCV, but currently available treatments will not work for everybody. Before starting a treatment regimen, it is important to stabilize any mental or other health problems. Undergoing antiviral treatment for HCV is a long, difficult and expensive process, so determining whether treatment is the right choice is a decision that should be made between a patient and a care provider. There are two approved antiviral medications used for the treatment of HCV: pegylated interferon alpha (often referred to as “peg”) and ribavirin. Peg interferon is taken by injection once a week. Ribavirin is an oral tablet that is taken daily. When taken together, the medications are effective in clearing the HCV virus 40-80% of the time, depending on the genotype of the virus.⁷ Hepatitis C has 6 chemical types (1-6), called genotypes, and they differ in how they respond to treatment. People of color, especially African-Americans and Latinos, have lower response rates to treatment, compared to other groups.⁷ New drugs are being developed that may be more effective than currently available treatments and may be available in the very near future. Treatment during the acute phase of infection is significantly more likely to be effective⁸, so identifying HCV early can be beneficial. While herbal remedies are popular among people living with HCV, none have been proven effective at clearing the HCV virus or in improving liver health.⁹ HCV treatment can be successful for active drug users. Nonetheless, daily drug and alcohol use can adversely affect treatment eligibility and completion. Engaging in drug or alcohol treatment programs while being treated for HCV can be helpful.

How does HCV affect HIV?

About one-quarter of all people in the US living with HIV are also infected with HCV. Persons who are both HIV+ and HCV+ (coinfected), can experience a much faster progression of liver disease and have higher HCV viral loads and higher rates of cirrhosis than do people who have HCV but not HIV.¹⁰ Liver damage from HCV infection also can increase the toxicity of medications used to treat HIV. As persons living with HIV who are on effective medications lead longer lives, liver disease has become the leading cause of non-AIDS-related deaths among HIV+ persons, due to HCV and HBV infection.¹¹ Treatment for HCV infection in an HIV+ person can be effective. Side effects and drug interactions, however, can be hard to manage. It is important the coinfected person be on well-managed HIV treatment before starting treatment for HCV.

How can HCV be prevented?

HCV prevention can take many forms.¹² Currently, targeted prevention strategies and harm reduction programs, including increased availability of clean syringes and increased access to drug treatment programs have the greatest potential to slow transmission of HCV. Educating those at risk, especially about the risks associated with shared injecting and ancillary equipment is very important. Encouraging the use of condoms, lubrication and gloves during high-risk sexual practices also can help reduce HCV transmission. Behavioral risk reduction prevention programs have had mixed results in decreasing risks associated with HCV transmission. Two peer-led interventions were effective in reducing injection risk behaviors in HIV negative and positive IDUs. The Study to Reduce Intravenous Exposures (STRIVE) and Drug Users Intervention Trials (DUIT) both provided information, enhanced risk-reduction skills, and motivated behavior change through peer education training. Although participants in these programs reported decreases in sharing syringes and drug preparation equipment,^13,14 rates of new HCV infections among HCV negative participants in the DUIT Study did not decrease (neither did HIV infections). The UFO Study conducts HCV-related research and provides hepatitis, HIV and STD prevention services including testing, counseling, support and education tailored to young adult IDUs under age 30 in San Francisco, CA. Young injection drug users comprise a group for whom few health-related resources or programs are targeted.¹⁵ For persons who are infected with HCV or at risk of becoming infected with HCV, it is important to get regular healthcare. A healthcare provider can help monitor HCV infection and liver health and make important decisions about prevention and treatment. Support and education groups are valuable in learning more about HCV infection and about the experience of living with HCV, treating HCV and preventing HCV transmission to others. People infected with HCV should be screened and vaccinated for HBV and should be strongly encouraged to stop or decrease alcohol use.

What needs to be done?

Over the next 15 years, the global costs associated with HCV infection are projected to increase from $30 billion to $85 billion.¹⁶ Development of an HCV vaccine will significantly decrease rates of new HCV infections. Research is needed on the development of a vaccine and effective models for delivery. Increasing access to HCV testing and screening, HCV treatment, drug treatment, clean syringes and effective behavioral interventions is crucial.

Says who?

1. Armstrong GL, Wasley A, Simard EP, et al. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Annals of Internal Medicine. 2006;144:705-714. 2. Hagan H, Snyder N, Hough E, et al. Case-reporting of acute hepatitis B and C among injection drug users. Journal of Urban Health. 2002;79:579-585. 3. Hagan H, Pouget ER, Des Jarlais DC, et al. Meta-regression of hepatitis C virus infection in relation to time since onset of illicit drug injection: the influence of time and place. American Journal of Epidemiology. 2008;168:1099-1109. 4. Urbanus AT, van de Laar TJ, Stolte IG, et al. Hepatitis C virus infections among HIV-infected men who have sex with men: an expanding epidemic. AIDS. 2009;23:F1-7. 5. Hepatitis C Fact Sheet. Prepared by the Centers for Disease Control and Prevention. 6. Page K, Hahn JA, Evans J, et al. Acute hepatitis C virus infection in young adult injection drug users: a prospective study of incident infection, resolution, and reinfection. Journal of Infectious Diseases. 2009;200:1216-1226. 7. Ghany MG, Strader DB, Thomas DL, et al. Diagnosis, management, and treatment of Hepatitis C: An update. Hepatology. 2009;49:1335-1374. 8. Kamal SM. Acute hepatitis C: a systematic review. American Journal of Gastroenterology. 2008;103:1283-1297 9. Liu JP, Manheimer E, Tsutani K, et al. Medicinal herbs for hepatitis C virus infection. Cochrane Database of Systematic Reviews. 2001;4. 10. Verucchi G, Calza L, Manfredi R, et al. Human immunodeficiency virus and hepatitis C virus coinfection: epidemiology, natural history, therapeutic options and clinical management. Infection. 2004;32:33-46. 11. Tuma P, Jarrin I, Del Amo J, et al. Survival of HIV-infected patients with compensated liver cirrhosis. AIDS. 2010;24:745-753. 12. Page-Shafer K, Hahn J, Lum PJ. Preventing hepatitis C virus infection in injection drug users: risk reduction is not enough. AIDS. 2007;21:1967-1969. 13. Latka MH, Hagan H, Kapadia F, et al. A randomized intervention trial to reduce the lending of used injection equipment among injection drug users infected with hepatitis C. American Journal of Public Health. 2008;98:853-861. 14. Garfein RS, Golub ET, Greenberg AE, et al. A peer-education intervention to reduce injection risk behaviors for HIV and hepatitis C virus infection in young injection drug users. AIDS. 2007;21:1923-1932. 15. Lum PJ, Ochoa KC, Hahn JA, et al. Hepatitis B virus immunization among young injection drug users in San Francisco, Calif: the UFO Study. American Journal of Public Health. 2003;93:919-23. 16. Shah BB, Wong JB. The economics of hepatitis C virus. Clinics in Liver Disease. 2006;10:717-34.

Special thanks to the following reviewers of this Fact Sheet: Laura Mae Alpert, Orlando Chavez, Myrna Cozen, Richard Garfein, Holly Hagan, Judy Hahn, Emalie Huriaux, Steve Livingston, Megan Mahoney, Brian McMahon, Jay Ryan, Jim Stillwell, Leslie Tobler, Anouk Urbanus. Reproduction of this text is encouraged; however, copies may not be sold, and the University of California San Francisco should be cited as the source. Fact Sheets are also available in Spanish. To receive Fact Sheets via e-mail, send an e-mail to [email protected] with the message “subscribe CAPSFS first name last name.” ©September 2010, University of CA. Comments and questions about this Fact Sheet may be e-mailed to [email protected].

Resource

HIV vaccine

Can an HIV Vaccine make a Difference?

why do we need an HIV vaccine?

Vaccines are among the most powerful and cost-effective disease prevention tools available. A vaccine that could prevent HIV infection or stop progression of the disease would greatly help in the fight against the AIDS pandemic. Vaccines have been pivotal in worldwide smallpox elimination efforts, have nearly eliminated polio and have drastically reduced the incidence of infectious diseases like measles and pertussis in the US. A crucial question is whether a vaccine based on one strain of HIV would be effective for populations in which a different strain is predominant. There are also questions about how an HIV vaccine would protect individuals: the vaccine might not be able to actually prevent infection, but could prevent or delay progression to disease, or simply reduce the infectiousness of people who do become infected with HIV. HIV prevention education and counseling are important components of vaccine programs. Even after the release of a vaccine, there will be an ongoing need for effective behavioral prevention programs. An HIV vaccine will not be a “magic bullet” but it could play an extremely powerful role as part of a package of prevention interventions.

has progress been made?

Twenty-two years into the epidemic, researchers are still struggling with the daunting scientific challenges involved in HIV vaccine research: 1) traditional approaches to vaccine design (i.e. use of inactivated or attenuated viruses) are considered too dangerous with HIV; 2) the virus is highly variable and mutates rapidly; 3) the viral infection is permanent, full recovery from HIV has not been documented, and thus, it is unclear how the body could mount an effective immune response and 4) there is no perfect animal model for use in AIDS vaccine research.¹ There is still no HIV vaccine that has been tested and found to be effective. There have been over 70 small-scale human clinical trials of over 35 different candidate HIV vaccines, but only one product, AIDSVAX, produced by VaxGen, has been tested in a large-scale (Phase III) trial. Unfortunately, two separate trials of AIDSVAX conducted in 1) North America, Puerto Rico and the Netherlands² and 2) Thailand, found that the vaccine did not prevent HIV infection in the overall study populations and did not slow progression of disease among participants who became HIV-infected during the trial.³ A successful HIV vaccine would train the immune system to recognize HIV before it does extensive damage. Vaccine concepts now in development use a variety of methods to train the immune system to recognize parts of HIV without exposing people to HIV itself. Early AIDS vaccine research focused on developing bio-engineered vaccines that represent a portion of HIV’s outer surface (envelope) protein. Different vaccine approaches are currently in development, none of which include the actual virus (HIV) and none of which can cause a recipient to acquire HIV from the vaccine itself.

what is the impact on HIV prevention?

An effective HIV vaccine cannot take the place of HIV prevention efforts, any more than prevention efforts can take the place of a vaccine. The best way to address the HIV pandemic is using multiple interventions at multiple levels, and the protective power of a vaccine could one day be of enormous benefit in HIV prevention. There have been increases in sexual risk behavior in men who have sex with men (MSM) since the advent of ART (antiretroviral treatment).⁴ There is concern that when a vaccine becomes available there could be similar increases in risk behavior among people who receive the HIV vaccine because they feel they can’t become infected with HIV. In the VaxGen efficacy trial in North America, younger participants and MSM who believed they had received the actual vaccine rather than a placebo were more likely to report unprotected anal intercourse during the trial. Overall, self-reported risk behavior did not increase throughout the trial.⁵ In the VaxGen efficacy trial in Thailand, injecting drug users reported decreases in injection drug use and needle sharing during the first 12 months of the trial.⁶ This may have been due to the prevention education and risk-reduction counseling received.

what are the ethical issues?

HIV vaccines can only be tested for safety and effectiveness if thousands of individuals are willing to participate in clinical trials. These trials raise concerns about the potential harm to trial participants. Certain HIV vaccines may cause trial volunteers to test HIV+ on standard HIV antibody tests, even though they are not infected with the virus. A positive HIV test result could expose individuals to discrimination in health insurance, employment and immigration, or lead to social stigma. The simple act of participating in an HIV vaccine trial may result in someone being labeled as a “high risk” individual, a gay person or a drug user, and discrimination against these and other groups is a very real issue in many places. It is the responsibility of researchers to ensure that vaccine trial participants receive assistance to alleviate the risks of discrimination or other harm that may result.⁷ Communities must be closely involved in clinical trial design and implementation. Researchers also need to ensure that true informed consent is acquired before individuals are enrolled in a vaccine trial. Community members and potential volunteers need to be fully informed about the vaccine trial process and must understand such concepts as “placebo,” “randomization” and “blinding” to be able to truly evaluate whether participation is right for them. Using community educators and peers to help with the community education that accompanies HIV vaccine research will also help increase participants’ understanding and acceptance of vaccine trials.⁸

what are barriers?

Much of the expertise to develop and manufacture HIV vaccines rests in private-sector pharmaceutical and biotechnology companies. Yet industry commitment to HIV vaccines has not matched the enormity of the public health need.^9,10 An HIV vaccine will only bring the pandemic under control if it is widely available in the developing world, where more than 95% of new HIV infections are occurring. People in resource-poor countries have often had to wait a decade or more for vaccines after they have been licensed for use in industrialized nations.^11,12 There are numerous challenges to HIV vaccine access in addition to price. Marginal health care infrastructures in some developing countries may make it difficult to distribute a vaccine. Even countries that can afford vaccines may not see them as a high priority and may not allocate adequate resources to fund research or vaccine purchase. Vaccination programs generally focus on children. With HIV, it is sexually active adolescents and adults who will need a vaccine most immediately, necessitating new approaches to immunization. Vaccine acceptance may be problematic in communities where there is a distrust of government or stigma in being associated with HIV/AIDS.

what needs to be done?

Public sector funding for research on HIV vaccines has increased in recent years, and additional resources are needed. The private sector must be encouraged to invest in HIV and other priority vaccines through a range of incentives, including direct funding, public support for clinical research infrastructure and product manufacture, and through public/private partnerships.⁹ Wealthy governments should commit in advance to purchase AIDS vaccines for people in the developing world. Continued political leadership is needed to prioritize resources for vaccines. Vaccine trials conducted to date have included HIV prevention education and risk reduction counseling. Vaccine trials can further benefit participants by offering drug treatment services and STD screening and treatment. Combining medical, behavioral and psychological efforts as part of a vaccine initiative can be a powerful tool for combatting the HIV pandemic. Vaccines are an integral part of an effective disease prevention strategy, and vaccine development is critical in arresting the spread of HIV. Yet, a vaccine alone will not eliminate the social and structural conditions that created and fuel the epidemic. Even when HIV vaccines are available, communities will continue to need quality behavioral interventions to control the HIV epidemic and policies that ensure access to vaccines. Prepared by Chris Collins, MPP, AIDS Vaccine Advocacy Coalition

Says who?

1. National Institute of Allergy and Infectious Diseases. Challenges in designing AIDS vaccines. May 2003. www.niaid.nih.gov/factsheets/challvacc.htm 2. AIDS Vaccine Advocacy Coalition. Understanding the results of the AIDSVAX trial. May 2003. https://www.avac.org/sites/default/files/resource-files/understanding_a… 3. VaxGen Announces Results of its Phase III HIV Vaccine Trial in Thailand: Vaccine Fails to Meet Endpoints. Press release from VaxGen. www.vaxgen.com/pressroom/ 4. Valdiserri RO. Preventing new HIV infections in the US: what can we hope to achieve? Presented at the 10th Conference on Retroviruses and Opportunistic Infections, Boston, MA. February 10-14, 2003. 5. Bartholow B. Risk behavior and HIV seroincidence in the US trial of AIDSVAX B/B. Presented at the AIDS Vaccine 2003 Conference, New York, NY. September 2003. 6. Vanichseni S, van Griensven F, Phasithiphol B, et al. Decline in HIV risk behavior among injection drug users in the AIDSVAX B/E vaccine trial in Bangkok, Thailand. Presented at the XIV International AIDS Conference, Barcelona, Spain. July 2002. 7. UNAIDS. Guidance Document on Ethical Considerations in HIV Preventive Vaccine Research. June 2002. 8. van Loon KV, Lindegger GC, Slack CM. Informed consent: A review of the experiences of South African clinical trial researchers. Presented at the XIV International AIDS Conference, Barcelona, Spain. July 2002. Abst #TuOrG1170. 9. AIDS Vaccine Advocacy Coalition. https://www.avac.org/avac-report 10. Klausner RD, Fauci AS, Corey L, et al. The need for a global HIV vaccine enterprise. Science. 2003;300:2036-2039. 11. Public health considerations for the use of a first generation HIV vaccine: Report from a WHO-UNAIDS-CDC Consultation, Geneva, 20-21 November 2002. AIDS. 2003;17:W1-W10. 12. International AIDS Vaccine Initiative. AIDS Vaccines for the New World: Preparing Now to Assure Access. July 2000. www.iavi.org Resources AIDS Vaccine Advocacy Coalition (AVAC) 101 West 23rd St. #2227 New York, NY 10011 212/367-1021 www.avac.org HIV InSite: Vaccine Overview http://hivinsite.ucsf.edu/InSite?page=kb-08-01-11 HIV Vaccine Trials Network http://www.hvtn.org International AIDS Vaccine Initiative (IAVI) 110 William Street New York, NY 10038-3901 212/847-1111 www.iavi.org National Institute of Allergy and Infectious Diseases (NIAID) Division of AIDS Vaccines www.niaid.nih.gov/aidsvaccine NIAID Vaccine Research Center https://www.niaid.nih.gov/about/vrc

January 2004. Fact Sheet #38ER Special thanks to the following reviewers of this Fact Sheet: Barbara Adler, Emily Bass, Mark Boaz, Susan Buchbinder, Jose Esparza, Jorge Flores, Paula Frew, Ingelise Gordon, Ashraf Grimwood, Margaret McCluskey, Catherine Slack, Robert Smith, Steven Tierney, Steven Wakefield, Doug Wassenaar, Sandra Wearins, Dan Wohlfeiler.