HIV Infection: Recognition, Risk Stratification, and Post-Exposure Prophylaxis in Emergency Medicine - Part 1
HIV Infection: Recognition, Risk Stratification, and Post-Exposure Prophylaxis in Emergency Medicine
Part I: Primary Infection, Acute Retroviral Syndrome, and Current Treatment Protocols for Occupational and Non-Occupational Exposure
Authors: Dawn Demangone, MD, FAAEM, Assistant Professor of Medicine, Assistant Residency Director, Co-Director, Graduate Medical Education, Tem- ple University Hospital and School of Medicine, Philadelphia, PA; and Betsy Schrader, MD, Division of Emergency Medicine, Temple University Hospital, Philadelphia, PA.
Peer Reviewer: Sid M. Shah, MD, FACEP, Assistant Residency Director of Research, Sparrow/Michigan State University Emergency Medicine Residency Program, Ingham Regional Medical Center, Lansing, MI.
The AIDS epidemic in the United States has changed in ways that affect the practice of emergency medicine. With newer antiretroviral regimens, the length of time for progression from human immunodeficiency virus (HIV) infection to acquired immunodeficiency syndrome (AIDS), and from AIDS to death, has increased.1 Individuals infected with HIV are living longer, healthier lives. Both the number of AIDS cases and deaths from AIDS decreased in the United States in 1996 for the first time. Yet, the incidence of new HIV infections continues to grow, but at a slower rate than was seen in earlier years.1
Consequently, as the prevalence of persons living with HIV continues to increase in the United States, it is likely that an increased number of patients with HIV will seek emergency department (ED) care at some point during their illness. Accordingly, it is imperative that emergency physicians remain abreast of variable presentations of this illness, side effects of polypharmacy drug regimens, and drug interactions characteristic of current treatment protocols.
In addition, emergency physicians may be involved in counseling and evaluation of health care workers at risk for acquiring HIV and other blood-borne disease transmission following exposure to potentially contaminated fluids. At times, prompt initiation of antiretroviral therapy may be required. As the public becomes more informed regarding post-exposure prophylaxis, patients may present to the ED requesting evaluation and treatment following non-occupational exposure. These post-exposure prophylaxis assessments present an opportunity for emergency physicians to have a significant affect on disease progression in those with recently acquired HIV infection.
Given the evolving changes in transmission and treatment recommendations in HIV infection, this review will first outline the epidemiology of HIV infection. The pathophysiology of HIV infection will be described, with an emphasis on disease manifestations, prognostic factors, and treatment objectives. The acute retroviral syndrome associated with recent HIV acquisition and its potential effect on emergency medicine practice will be explored. Current treatment medications, side effects, and drug interactions will be presented. Finally, the current recommendations for post-exposure evaluation and prophylaxis (both occupational and non-occupational) will be discussed in detail.
— The Editor
Epidemiology
Worldwide, as of December 1999, it has been estimated that 33.6 million people are living with HIV. The majority of these individuals live in the developing world, with almost 70% living in sub-Saharan Africa. Most of these individuals are expected to die within the next 10 years, adding to the 16.3 million who have already died as a result of AIDS.2 The worldwide prevalence rate in 1998 was estimated at 1.1%, that is, 1.1 out of every 100 people in the world were infected with HIV. Sub-Saharan Africa had a prevalence rate of 8% during this period.2
In the United States, approximately 900,000 Americans were living with HIV in 1998, giving North America a prevalence rate of 0.56%.1-3 Approximately 417,000 Americans had died as result of AIDS by this time.3 The number of AIDS cases and deaths due to AIDS steadily increased in the United States until a decline was first noted in 1996.1 However, the number of Americans infected with HIV continues to rise, with approximately 40,000 new infections reported every year.1 The groups with the highest rates of new HIV diagnoses include African-Americans, women, Hispanics, and individuals between the ages of 13 and 24.1 Prevention efforts should be aimed at these high-risk subgroups.
Pathophysiology
As would be expected, understanding the pathophysiology of HIV infection is critical for identifying the natural history of this condition and the distinct phases of the illness that are amenable to intervention. HIV is classified as a retrovirus (more specifically a lentivirus), which contains its genetic information in a single strand of RNA. The virus is contained within a lipid bilayer, and a protein "core" structure encloses the genetic information and other enzymes essential to its life cycle.
As is characteristic of retroviruses, HIV shows a propensity for mutation. Two main types, HIV-1 and HIV-2, have been identified, with several groups and subgroups also identified within viral types. HIV-1 infection predominates worldwide, and is the type generally referred to as "HIV." HIV has a predilection for cells that express the CD4 molecule on their surface, but it also may infect other mononuclear or glial cells.4
Infection begins with binding of the viral envelope (env) protein to the CD4 molecule, followed by fusion of the virus and host cell membranes. The viral contents then enter the host cell cytoplasm, and eventually its nucleus. Viral reverse transcriptase is activated and a DNA copy of the viral RNA information is produced. The new, viral-derived DNA is incorporated into the host cell genome. The infection of the host cell is now complete, and permanent. Targeting the virus for elimination without injury to the host cell now becomes much more difficult. All progeny cells will carry the viral genes.4
After insertion into the host cell genome, the viral DNA information may remain quiescent for future activation, or it may be reproduced immediately. When activated, the viral DNA information is translated into novel, viral-derived proteins using host resources. The viral proteins are packaged into virions, which are released into the extracellular space to infect more susceptible cells. This active replication is highly toxic to the host cell, and eventually leads to its death.4 It has been estimated that each infected host cell will result in the infection of 19 more host cells through its viral progeny.5
Following exposure, epidermal dendritic cells acquire the virus and "present" it to cells of the immune system so that systemic dissemination can begin. This does not occur immediately; it has been estimated that dissemination requires several hours to days.6,7 During early HIV infection, the viral burden is concentrated in the hematopoietic and lymphatic systems, where uninfected immune system cells frequently migrate and gain exposure to the virus. The immune cells respond to the virus with the production of cytokines, which can contribute to the damage of the immediate surrounding host tissues.4,8 HIV infection eventually destroys the microstructure of the lymph nodes, further compromising immune functions and the immune system as a whole.4
Table 1. Source Factors that Increase the Risk of HIV Transmission9,10 |
• High viral titer |
Primary HIV infection |
Advanced or pre-terminal AIDS |
• Menstruation |
• Other vaginal bleeding |
• Presence of inflammatory or ulcerative genital lesions |
Transmission
Transmission: Blood and Body Fluid Source Factors. The likelihood of HIV transmission has been linked with specific, "source patient" characteristics. (See Table 1.) Individuals with high HIV viral titers (i.e., those with primary HIV infection, advanced HIV disease, or pre-terminal AIDS) are more likely to transmit the virus than those with lower levels of circulating HIV.9 One occupational exposure study demonstrated that HIV transmission is more likely if the source patient dies within two years following the exposure incident.10 Menstruation, other sources of vaginal bleeding, and the presence of inflammatory or ulcerative genital lesions also have been associated with an increased likelihood of transmission.9
HIV can be transmitted through several mechanisms: transfusions, sexual contact, perinatal transmission, occupational, and non-sexual/non-occupational vectors. Currently, the most frequent transmission route worldwide is sexual activity. The risks of transmission based on exposure type are listed in Table 2.9-16
Table 2. Risk of Transmission Per Episode of Contact9-16 |
Blood Transfusion |
(recipient of 1 unit) 95% |
Non-sexual, non-occupational |
IV drug abuse/needle sharing/other percutaneous 0.67% |
Occupational |
(Percutaneous) < 0.5% |
Sexual |
Penile—anal contact (receptive partner) 0.1-3% |
Penile—anal contact (insertive partner) 0.03% |
Penile—vaginal contact (receptive partner) 0.1-0.2% |
Penile—vaginal contact (insertive partner) 0.03-0.09% |
Transfusions. Blood and/or blood product transfusion remains the most efficient manner of HIV transmission. Individuals receiving a single unit of infected blood have approximately a 95% chance of acquiring the virus.11 All blood donated in the American Red Cross system is screened for HIV via donor self-disclosure questionnaires and antibody testing.17 However, the possibility does exist of an individual who has been infected but is not yet antibody positive donating blood. One group has estimated the risk of blood donation during the antibody negative period of HIV infection as being one in 493,000. They concluded that adding viral nucleic acid testing to routine blood bank testing for antibody to virus potentially would identify only up to 19 more HIV-infected donations per 12 million units collected annually.17
Occupational Exposure. The overall risk of acquiring HIV through percutaneous occupational exposure has been identified as less than 0.5% per exposure episode.10,15 However, certain circumstances associated with percutaneous exposure increase the risk of disease acquisition. (See Table 3.) They include: deep injury; exposure to a visibly bloody device; exposure to a needle previously inserted in the source patient’s vein or artery; and terminal illness or AIDS in the source patient.10 One study reviewed 94 reported cases of occupationally acquired HIV infection. Eighty-two (or 91%) of these cases followed a single percutaneous exposure, eight cases (8.5%) followed mucocutaneous exposure alone, two cases (2%) followed simultaneous percutaneous and mucocutaneous exposure, and one case (1%) occurred after two separate percutaneous exposures.10 Additional, detailed information regarding occupational HIV exposure and transmission will be presented in a section covering occupational post-exposure evaluation and prophylaxis in the second part of this two-part series.
Table 3. Factors that Increase HIV Transmission Risk after ccupational Percutaneous Exposure10 |
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Sexual Transmission. The most common mechanism of HIV transmission is through sexual contact.18 A number of source and recipient factors increase the likelihood of transmission and influence the risk of acquiring the virus through sexual activity.9 (See Table 4.) Individuals with ulcerative/inflammatory genital lesions, cervical ectopy, or those who are not circumcised have a higher risk of acquiring HIV.9,19 Risks for transmission have been estimated based on participative sexual activity and are listed in Table 2.9-16
| Table 4. Factors that Increase Risk of HIV Acquisition Through Sexual Activity9 |
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Although probably less efficient as a transmission mechanism than other forms of sexual activity in HIV transmission, oral-genital contact should be considered a potentially important vector.20 One study found that patients with primary HIV infection had participated in oral-genital contact 10 times more frequently than in anal-genital contact. In addition, participants used condoms during only 3-4% of their oral-genital contacts, compared with 42% of their anal-genital contacts.20 It appears that the public perceives this behavior as less "risk-linked" than other sexual activities. Even though the risk has not yet been estimated, oral-genital contact appears to carry a substantial risk for HIV transmission based on the high frequency of unprotected encounters.20
Non-Sexual/Non-Occupational Exposure. Non-sexual/non-occupational exposures occur in many situations. Potentially significant percutaneous exposures can occur via needle sharing in intravenous drug use, body piercing or tattooing, or other cuts with sharp objects or inadvertent needlesticks with discarded needles. Skin or mucous membrane contact with blood or other body fluids is especially concerning when exposed areas are chapped, abraded, affected by dermatitis, or cover large regions of the skin.21 Oral mucous membrane contact with contaminated blood has been associated with occupationally acquired infection, and this has been suggested as the source of transmission in one reported case of infection of a woman by her HIV-infected husband.10,22
Transmission through human bites is rare, but has been reported. One such case involved a man who came to the aid of his neighbor, an end-stage AIDS patient. The victim was not aware of his neighbor’s HIV status and attempted to maintain an open airway during a grand mal seizure. The man was unintentionally bitten, producing a small wound near his fingernail. Later, he noticed blood in the mouth of the seizing man. Despite starting post-exposure prophylaxis with zidovudine (AZT) 10 hours after the bite, the victim developed symptoms consistent with a mild acute retroviral syndrome 33 days following the incident, and seroconverted to HIV antibody positive two weeks later.23 Although this case demonstrates transmission via oral secretions, it was more likely that the viral source was the blood contamination of the saliva, and not the saliva itself.23 One investigator cited findings suggesting that saliva is actually a poor vector for transmission, as it inhibits the infectivity of HIV, and the virus only infrequently has been identified in saliva.23
HIV Testing in the Emergency Department
Even when the emergency physician is not called upon to perform HIV testing, it is important to understand the testing protocol in order to counsel the patient and to recommend testing to those with occupational or other potential exposures. Standard HIV laboratory protocols are used when testing for HIV-specific antibodies. Most commonly, an enzyme-linked immunoassay (ELISA) is performed first, and if this is negative, further testing is not pursued on a routine basis since this patient is considered HIV negative. Of course, false-negative tests can occur, especially in primary HIV infection, during a period in which antibodies have not yet developed. If the ELISA test is positive for HIV antibodies, a confirmatory Western Blot is performed. The patient is considered HIV positive only if both the ELISA and Western Blot are positive for antibodies to HIV.24
Regardless of the time elapsed between acquisition of the virus and presence of clinical symptoms, a high index of suspicion for primary HIV infection should prompt further testing. Evaluation for the presence of viral components should be pursued. Testing for specific viral proteins, such as the p24 core antigen, may be indicated, or polymerase chain reaction for viral RNA and/or DNA may be helpful in identifying patients who have not yet produced antibodies to HIV. Rapid screening tests are available, but are limited by their sensitivities and specificities.24
Performance of HIV testing requires time, confidentiality, patient consent, and both pre- and post-test counseling. This is a formidable commitment for an already busy ED staff. However, one group of investigators has suggested that ED-based HIV screening is feasible, and can play a significant role in the early identification of HIV infection, particularly in regions with high HIV prevalence rates.25,26 In these studies, rather than adding another task to the responsibilities of the ED physicians and nurses, trained counselors performed HIV pre-test counseling in parallel with the patient’s ED course.25,26
Post-test counseling appointments were made at the time of the initial ED visits. A rapid screening test, conventional ELISA, and confirmatory Western Blot studies for HIV were coordinated through the ED program, as were post-test counseling, delivery of results, and arrangement of follow-up care. They demonstrated the effectiveness of an ED-coordinated HIV screening program for diagnosing a large number of new HIV-positive individuals in a high-risk population.25,26 Whether more hospitals caring for populations with a high HIV prevalence will begin offering HIV testing services to the public has yet to be determined. However, one group has found that HIV testing is already performed routinely in some academic EDs in cases of occupational exposures, rape, disease consistent with AIDS, and even in patients treated for sexually transmitted diseases.27
Primary HIV Infection
Primary HIV infection is defined as the period between initial HIV acquisition and the time of HIV specific antibody production.28 Primary infection symptoms can range from none to a severe acute retroviral syndrome (ARS) requiring hospitalization.
Pathophysiology of Primary HIV Infection. Massive viremia quickly follows initial infection with HIV because of rapid viral replication, with an estimated doubling time of 10 hours.5,28-30 However, absolute viral levels are variable among individuals throughout primary infection.5,29 Typically, viremia appears to peak somewhere between 21 days and one month after viral acquisition.5,29 Following this early peak, viral levels begin a rapid decline, and may even fall to undetectable levels, presumably in response to an activated immune system.19 This decline continues until about post-exposure days 54-120, at which time viral levels again begin to climb.5,29 Viral levels at this inflection point appear to be significant in predicting the subsequent disease course.29
Without therapy, the CD4+ T cell counts fall at a rapid rate shortly after infection until post exposure day 160, when the decline continues but at a slower rate.5,28,29 Like viral levels, CD4+ T cell counts vary greatly among individuals throughout primary infection.5 The immune system responds to HIV infection by producing large numbers of CD8 T cells and various cytokines.8,28 This initial immune response appears to be another important factor predicting the ultimate disease course.31
Eventually, the immune system stabilizes and a "set point" or equilibrium is achieved between the virus and the host, typically at 4-12 months following infection.29 This "set point"—and more specifically, the viral load—is an important predictor of the rate and severity of the subsequent disease course. Although there is no correlation between early viral loads and rate of CD4+ T cell count declines, higher viral levels at 120-365 days after infection are associated with a significantly faster fall in CD4+ T cell counts throughout disease.29 But prior to the "set point" (approximately postexposure day 120), disease progression or CD4+ T cell depletion cannot be estimated.29,31
Primary HIV infection ends with the appearance of HIV specific antibodies, which have been first detected in as little as eight days after infection and as long as one year after infection.8,28 About 95% of patients with primary infection will test positive for antibodies within six months following infection.32 It should be stressed that the overall disease course already may have been established 4-6 months following viral acquisition, and therefore, early recognition represents an opportunity for appropriate treatment and establishing follow-up care.19,20,29,31
Acute Retroviral Syndrome. A syndrome of clinical symptoms associated with primary HIV infection was first described in 1984, in association with an occupationally acquired infection.33 In 1985, several cases were reviewed by a group that described a mononucleosis-like illness in 11 of 12 patients with acute seroconversion.34 One group has defined ARS as the "development of high-level viremia accompanied by immunological activation in the presence of clinical manifestations" of HIV infection.28 In 1997, another group of investigators suggested that because only 20% of their patients with ARS experienced a mononucleosis-like illness, the term ARS should be applied to a more generalized acute febrile illness rather than limited to the earlier mononucleosis-like definition.35 In this regard, fever appears to be the most common symptom reported by several authors, while sore throat is much more variable.20,34-38
It is essential to recognize ARS because symptomatic seroconverters have been reported to progress to AIDS and death from AIDS more rapidly than asymptomatic seroconverters. One study reported that 27% of symptomatic converters progressed to AIDS and 26% to death within 48 months, compared to only 6.5% progressing to AIDS and 2.8% to death in asymptomatic seroconverters.37 Symptomatic patients also have faster rates of CD4+ T cell decline.37 While some studies found that patients whose ARS symptoms lasted longer have progressed to AIDS faster than those with a shorter duration of symptoms, others have not.29,37 Therefore, early recognition is imperative to identify patients who are likely to experience a more rapid disease course.
Why some individuals develop symptoms with acute infection and others do not is not understood. One study reported no demographic differences between symptomatic and asymptomatic converters.20 It has been theorized that ARS may represent greater disease dissemination or an inadequate immune response to recent HIV acquisition.29 Publications have reported that symptomatic seroconversion occurs in between 10% and 90% of acutely HIV-infected individuals.20,28,34-38
Symptoms can range from mild to a degree of severity warranting hospitalization. Indeed, ARS may even present as an AIDS-defining illness, or with a CD4+ T cell count less than 400.20,28,34-38 Typically, the onset of ARS symptoms has been reported between five and 30 days following exposure to the virus.19,20,28,35 Symptoms can persist from seven to more than 28 days, and then this phase may be followed by a prolonged asymptomatic period.2,5,7,28,34-37,67 There is no difference in CD4+ T cell counts during acute infection between symptomatic and asymptomatic seroconverters.37
The most common symptoms reported during ARS in six different studies are listed in Table 5. The more common complaints include: fever, fatigue, sore throat, lymphadenopathy, weight loss, myalgias, headache, nausea, vomiting, diarrhea, and rash.20,34-35,37-38 Two studies reported that symptoms were severe enough to require hospitalization in 17% and 42% of the symptomatic subjects, respectively.20,38 Obviously, these complaints commonly are evaluated in the ED and, therefore, present an opportunity for early recognition in high-risk patients.
Table 5. Most Commonly Reported Symptoms in Patients with ARS | ||||||
| Reference number§ | 1 | 2 | 3 | 4 | 5 | 6 |
Fever | 95% | 100% | 77% | 87% | 92% | 96% |
Fatigue | 90% | 51% | 66% | 26% | * | 61% |
Sore throat | 70% | 43% | 16% | 48% | 75% | * |
Weight loss | 68% | 20% | * | 13% | * | * |
Myalgias | 60% | * | 18% | 42% | 92% | * |
Headache | 58% | * | 51% | 39% | 58% | 61% |
Nausea | 58% | * | * | 26% | 67% | * |
Cervical adenopathy | 55% | 80% | 16% | * | 75% | * |
Night sweats | 50% | 33% | * | * | 92% | * |
Diarrhea | 50% | 7% | * | 32% | 33% | * |
Vomit | 40% | * | * | 23% | 67% | * |
| Rash | 35% | 20% | 56% | 67% | 50% | 67% |
| Abdominal pain | * | * | * | 32% | * | * |
| Arthralgia | * | * | * | 29% | * | * |
| Cough | * | * | * | 26% | * | * |
| Oral ulcers | * | * | * | 13% | * | * |
* = Symptom/sign not reported | ||||||
§ = References | ||||||
1. Schacker T, Collier A, Hughes J, et al. Clinical and epidemiologic features of primary HIV infection. Ann Int Med 1996;125:257-264. | ||||||
2. Dorrucci M, Rezza G, Vlahov D, et al. Clinical characteristics and prognostic value of acute retroviral syndrome among injecting drug users. AIDS 1995;9:597-604. | ||||||
3. Vanhems P, Allard R, Cooper DA, et al. Acute human immunodeficiency virus type 1 disease as a mononucleosis-like illness: Is the diagnosis too restrictive? Clin Infect Dis 1997;24:965-970. | ||||||
4. Kinloch-de Loes S. Symptomatic primary infection due to human immunodefi ciency virus type 1: Review of 31 cases. Clin Infect Dis 1993;17:59-65. | ||||||
5. Cooper DA. Acute AIDS retrovirus infection. Definition of a clinical illness associated with seroconversion. Lancet 1985;1:537-540. | ||||||
6. Perrin LU, Balavoine JF, Schockmell GA, et al. Post-exposure prophylaxis and sexual HIV transmission between husband and wife. Int Conf AIDS 1998;12:630(abstract no. 33189). | ||||||
Findings on physical exam can include fever, rash, lymphadenopathy, oral manifestations, and postural hypotension.20,28,34,38 (See Table 6.) The average temperatures reported were 38.6°C and 38.9°C.20,38 The rash most commonly has been described as a maculopapular erythematous truncal rash (with or without an urticarial component), but also may present on the face and extremities or as ulcers involving the mouth or genitalia or urticaria.34,38 Adenopathy is most often observed in the cervical distribution, but also may be found in axillae, inguinal, and epitrochlear regions.38 Oral manifestations can include exudative pharyngitis, oral ulcers, and thrush.20,28,34 The differential diagnoses of ARS should be considered based on the presenting complaints and physical findings.18,19 Some diseases to consider in the differential diagnosis are listed in Table 7 and include several infectious diseases.18,19
| Table 6. Physical Exam Findings in ARS20,28,34,38 |
| • Fever |
| • Rash |
| • Lymphadenopathy |
| • Oral manifestations |
| • Postural hypotension |
| • Hepatomegaly |
| • Neurological disorders such as meningitis, radiculopathy |
| Table 7. Differential Diagnosis of ARS18,19 |
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Clinical Implications of ARS Recognition. As stressed earlier, individuals with ARS more quickly progress to AIDS and death due to AIDS than asymptomatic converters. Moreover, failure to recognize acute HIV infection may mean missing an opportunity for early treatment, which may substantially improve the course of the illness and prevent further transmission to others. Therefore, prompt recognition of ARS by health care professionals is crucial; unfortunately, this phase of the illness frequently is not recognized. One study demonstrated that a significant majority (88%) of patients sought medical evaluation during onset of ARS symptoms. One-half went to their primary care physician; the other half sought care in an ED or walk-in clinic. Importantly, among patients undergoing medical evaluation for their symptoms, ARS was considered in only 26%, despite awareness on the part of health care professionals of high-risk activities among these individuals.20
Another study reported that 32% of symptomatic patients presented to an ED for evaluation.38 These studies suggest a large number of patients with ARS seek medical evaluation during their symptoms, but that their diagnosis is frequently overlooked during the initial encounter. Seeking medical attention for symptoms of ARS may be another factor associated with faster disease progression, in addition to experiencing symptomatic seroconversion. One group reported that patients with ARS who sought medical attention had lower CD4+ T cell counts at six months and progressed to AIDS faster than those whose symptoms did not prompt them to seek care.20,29 Based on the significant number of patients presenting to the ED with ARS, an opportunity exists for emergency physicians to identify and have an effect on the symptomatic, acutely HIV-infected patient.
While the emergency physician may not perform the HIV testing, or even begin antiretroviral treatment, alerting the patient to the possibility of acute HIV infection and advising appropriate follow-up testing and care may ultimately lead to an improvement in the patient’s quality and length of life. Without question, earlier identification ARS or primary HIV infection will permit earlier initiation of antiretroviral therapy. In this regard, some experts believe that early, aggressive treatment will inhibit viral replication during the critical stages of early infection.21 In addition, during initial stages of infection, the viral load is relatively homogenous, since the virus has had limited time to mutate; therefore, it is less likely to have developed antiretroviral resistance and may be more susceptible to treatment.21,39,40
One trial reported that using AZT alone during primary infection led to patients with higher CD4+ T cell counts and a delay in HIV-associated infections (zoster, thrush, oral hairy leukoplakia) compared to placebo-treated patients.41 In fact, AZT-treated patients displayed monthly gains in their CD4+ T cell counts, while the placebo group demonstrated a decline.41 However, no significant differences in viral loads existed between treated and placebo patients throughout the study.41 It is hoped that early treatment favorably will alter the initial "set point" following acute HIV acquisition, leading to lower viral loads and, potentially, to improvement in the course of the disease. Lower HIV viral titers 4-6 months after infection potentially could slow and make the disease course more indolent for those patients at risk for a rapid disease progression.21,28,40
More recent studies have used triple drug regimens (AZT, lamivudine, and either indinavir or didanosine) for treatment of primary HIV and found continually decreasing viral levels throughout treatment.39,42 One study reported that triple antiretroviral therapy successfully suppressed viral replication in all treated subjects to undetectable levels at 24 weeks.42 Subjects in that study also demonstrated CD4 T cell counts at levels close to normal during treatment.42 However, these studies followed patients a maximum of 36-44 weeks or eight months, and therefore, long-term benefits are unclear at present.39,42 Despite these encouraging reports, it should be noted that discontinuing therapy started during primary HIV infection might result in a rapid rebound of the virus and its effects, although at a slower rate of viral replication than the rate in primary infection.5
In addition to improving the health of patients infected with HIV, counseling them with regard to high-risk activities may prevent further transmission. It has been estimated that HIV transmission is 4-12 times more frequent during primary HIV infection than during the later seropositive stages.43-45 Both high viral loads typical of primary HIV infection and the patient’s lack of awareness of newly acquired HIV infection are likely to contribute to the increased frequency of transmission.43-45 Moreover, because symptomatic converters have higher viral titers than asymptomatic seroconverters, these patients present a greater risk for transmission—again reinforcing the need for early identification.20
Current Treatment Options. Three medication classes are currently approved for treatment of HIV. Table 8 contains the current classifications and names of medications recommended for the treatment of HIV.21,46 Monotherapy is contraindicated with any medication because of the development of resistance. The one exception is AZT, when used during pregnancy for patients with high CD4+ T cell counts and low viral load to prevent HIV transmission to the fetus.21 The most recent information regarding specific combination therapy recommendations are available as a living document on the Internet. (See Table 9.)
| Table 8. Medications Used for Treatment of HIV Infection21,46 | |
| generic | brand |
| NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTI) | |
| Zidovudine (AZT) | (Retrovir) |
| Stavudine (d4T) | (Zerit) |
| Didanosine (ddI) | (Videx) |
| Lamivudine (3TC) | (Epivir) |
| Zalcitabine (ddC) | (Hivid) |
| Zidovudine plus lamivudine | (Combivir) |
| Abacavir (ABC) | (Ziagen) |
| NON-NUCLEOSIDE REVERSE TRANSCRIPTASe INHIBITORS (NNRTI) | |
| Nevirapine | (Viramune) |
| Delavirdine | (Rescriptor) |
| Efavirenz | (Sustiva) |
| PROTEASE INHIBITORS (PI) | |
| Saquinavir | (Invirase, Fortovase) |
| Ritonavir | (Norvir) |
| Indinavir | (Crixivan) |
| Nelfinavir | (Viracept) |
| Amprenavir | (Agenerase) |
| Table 9. Web Sites of Interest |
| • Centers for Disease Control and Prevention: www.cdc.gov |
| • HIV/AIDS Treatment Information Service: www.hivatis.org |
| • HIV InSite (University of California at San Francisco): hivinsite.ucsf.edu |
| • Pediatric AIDS Clinical Trials Group: pactg.s-3.com |
| • AIDS Education and Research Trust: www.avert.org |
| • Joint United Nations Programme on HIV/AIDS: www.unaids.org |
Treatment regimens frequently require adjustment throughout the disease course due to failure, development of resistance, and/or clinical intolerance.21 Present thinking suggests that no regimen completely eliminates the virus from all locations, although strategic combinations can postpone AIDS-related complications and extend length of life by diminishing viral replication and promoting immune system function.21 Accordingly, the primary goal of therapy is to suppress viral replication for as long as possible. Current recommendations support offering treatment to all symptomatic and asymptomatic patients with: CD4+ T cell counts less than 500; viral loads (HIV RNA) greater than 10,000 (6DIUA) or more than 20,000 copies (RT-PCR); ARS; recent, documented seroconversion (within 6 months); and symptoms of illness related to HIV infection.21
References
1. Center for Disease Control and Prevention. Trends in the HIV and AIDS Epidemic 1998. http://www.cdc.gov/nchstp/hivaids/stats/trends98.pdf (accessed 1/9/2000).
2. Joint United Nations Programme of HIV/AIDS. AIDS epidemic update: December 1999. http://www.unaids.org/publications/documents/epidemiology/surveillance/wad1999/Una99c53.doc (accessed 1/9/2000).
3. Centers for Disease Control and Prevention. United States HIV and AIDS Statistics. http://www.avert.org/usastaty.htm (accessed 1/9/2000).
4. Terwilliger, FF. Biology of HIV-1 and treatment strategies. Emerg Med Clin North Am 1995;13:27-41.
5. Little S, McLean A, Spina CA, et al. Viral dynamics of acute HIV-1 infection. J Exp Med 1999;190:841-850.
6. Jochimsen EM. Failures of zidovudine postexposure prophylaxis. Am J Med 1997;102:52-55.
7. Centers for Disease Control and Prevention. Guidelines for treatment of sexually transmitted diseases. MMWR Morb Mortal Wkly Rep 1998;47:109-111.
8. Daar ES. Virology and immunology of acute HIV Type 1 infection. AIDS Res Hum Retroviruses 1998;14:S229-S234.
9. Dong B. Prophylaxis after nonoccupational exposure to HIV. Am J Health Syst Pharm 1999;56:1011-1016.
10 Ippolito G, Puro V, Heptonstall J, et al. Occupational human immunodeficiency virus infection in health care workers: Worldwide cases through September 1997. Clin Infect Dis 1999;28:365-383.
11. Center for Disease Control and Prevention. Management of possible sexual, injecting drug use, or other nonoccupational exposure to HIV, including considerations related to antiretroviral therapy: Public Health Service statement. MMWR Morb Mortal Wkly Rep 1998;47(RR-17):1-14.
12. Katz MH, Gerberding JL. The care of persons with recent sexual exposure to HIV. Ann Int Med 1998;128:306-312.
13. Katz MH, Gerberding JL. Postexposure treatment of people exposed to human immunodeficiency virus through sexual contact or injection drug use. N Engl J Med 1997;336:1097-1100.
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