Human Immunodeficiency Virus and Sports

Robert J. Dimeff

PATHOPHYSIOLOGY

Definition

Human immunodeficiency virus (HIV) is a human retrovirus that targets and infects CD4⁺ T-helper cells. It replicates within the CD4 cells and causes cell death.
Acquired immunodeficiency syndrome (AIDS) is a chronic illness with an average natural history of > 10 years. It is the result of a progressively immunocompromised state due to quantitative and functional defects in CD4⁺ T-helper cells. The decline in CD4 cells results in decreased function of the immune system and the development of opportunistic infections and various malignancies (16).

Natural History

Following a 10- to 28-day incubation period after exposure to HIV, the individual may develop an acute and self-limited viral-like syndrome, followed by seroconversion.
Seroconversion may occur with the development of the viral syndrome.
After seroconversion, a clinical latency period occurs that may last over 10 years. During this time, the infected person has normal immune and exercise function.
As immunocompromise develops, the individual may experience otherwise unexplained fevers, fatigue, weight loss, and lymphadenopathy.
AIDS occurs as the immune system continues to fail, and opportunistic infections ranging from mild candidiasis to life-threatening Pneumocystis carinii pneumonia may occur. Malignancies such as lymphoma and Kaposi sarcoma may develop. Muscle wasting occurs through mechanisms that are still not completely understood (16).

EPIDEMIOLOGY

Worldwide (73)

33.3 million people were living with HIV/AIDS as of December 2009, compared with 42 million in 2002.
In 2010, it was estimated that there were 2.6 million new cases of HIV/AIDS and 1.8 million AIDS deaths.
Two-thirds of the total cases are in sub-Saharan Africa.
HIV testing and treatment of pregnant females has decreased the transmission of disease to newborns and infants.

United States (8,73)

According to the Centers for Disease Control and Prevention (CDC), there were 17,000 deaths from HIV in 2009, and there have been approximately 500,000 HIV-related deaths in the United States since the onset of the disease.
It is estimated that there have been approximately 48,000 new cases annually since 2006.
At the end of 2008, it was estimated that there were 1,178,350 persons over the age of 13 in the United States living with HIV infection, and this number continues to increase annually. It is estimated that 20% are unaware of their positive status.
Men having sex with men (MSM) account for 75% of the HIV cases in the United States. MSM represent 2% of the U.S. population but 50% of all new cases. MSM have a 44 times greater rate of HIV infection than men having sex with women.
African Americans represent 14% of the U.S. population and 44% of the new cases annually. The rate of infection in African Americans is three times greater than Hispanics and six times greater than Caucasians. African American females have a 15 times higher rate of infection than Caucasian females.

Athletics

The incidence and prevalence of HIV/AIDS in athletes are unknown, but there are several high-profile elite and professional athletes who have acquired HIV, including Earvin “Magic” Johnson in 1991 (competed in National Basketball Association [NBA] and 1992 Summer Olympics with HIV) and Greg Louganis (competed in 1988 Olympics with HIV), who attribute their infection to personal behaviors unrelated to sports participation.
Tommy Morrison (professional boxing) was banned from sports after testing positive for HIV in 1996. He was reinstated
in 2006 after apparently becoming HIV negative and has subsequently fought professionally. Controversy regarding his true testing and disease status continues to exist.
Several professional athletes have died from AIDS contracted from nonsports activities including sexual activity, drug abuse, and blood transfusion. Prominent HIV-positive athletes include Bill Goldsworthy (National Hockey League [NHL]), Jerry Smith (National Football League [NFL]), Alan Wiggins (Major League Baseball [MLB]), Esteban DeJesus (boxing), Tim Richmond (NASCAR driver), Robert McCall and Rudy Galindo (figure skating), and Arthur Ashe (professional tennis).
HIV-infected athletes have participated in professional American-style football in the United States as well as Canada (26).
Fears of the widespread dissemination of HIV throughout professional sports have been fueled by reports such as in 1991 when two Canadian physicians announced a woman who had died of AIDS had disclosed that she had sexual intercourse with 30-70 different hockey players in the NHL (33).
HIV-positive athletes have participated in intercollegiate sports and the 2011 Ironman World Championship (36,43).

TRANSMISSION

HIV is found in all body fluids of the infected individual including blood, semen, vaginal and cervical secretions, breast milk, and amniotic fluid. The highest concentration of HIV is in the cerebrospinal fluid. The virus is also found in low concentrations in tears, sputum, saliva, and urine, but it is not considered to be infectious in these forms unless they are blood tinged. HIV has not been found in sweat (38).
The primary routes of transmission are through sexual contact; parenteral exposure to blood, blood products, or blood-containing body fluids; and maternofetal transmission at birth.
HIV is not transmissible through casual contact, swimming pools, mosquitoes, saliva, sweat, tears, urine, feces, or inanimate object (13).
With the advances in diagnoses and treatment, the transmission rate has dropped from 92% in the early 1980 to 5% in 2008. This means that at the onset of the epidemic in the 1980s, 92 of 100 HIV-positive patients transmitted the disease to uninfected individuals; the rate is now less than 5 per 100 HIV-positive patients (73).
There are currently no reports of transmission of HIV from an athlete to a health care provider on the sidelines or in the training room. The theoretical risk to the athletic health care provider is based on data on health care professionals exposed to HIV by needlestick and is estimated at 0.3%. There have been several reports of health care workers who have contracted HIV from infected blood splashed onto their mucous membranes. This is extremely rare and requires prolonged exposure to large amounts of blood; the risk has been estimated at approximately 0.1%. The risk of transmission following exposure to nonintact skin of HIV-infected blood is less than 0.1%, and small amounts of blood on intact skin pose no risk (25,73).
No transmission of HIV during sports has ever been documented. However, two reports of transmission of HIV during bloody fistfights have been verified by the CDC (19). In determining theoretical risk of on-field HIV transmission, the following are necessary: (a) the presence of an infected athlete; (b) a bleeding wound or exudative skin lesion in the infected athlete; (c) a skin lesion or exposed mucous membrane on a susceptible athlete; and (d) sustained contact between the portal of entry on the susceptible athlete and the infective material (13,43).
The potential risk of HIV transmission during professional football has been estimated at less than 1 per 85 million game contacts (4).
Athletes are more at risk of contracting HIV from nonathletic activities. Off-of-the-field situations in which athletes may more commonly put themselves at risk for contracting HIV include: sexual contact, use of injectable steroids or other drugs with shared needles or paraphernalia, tattoos, and body piercings.
There is a higher proportion of risky lifestyle behaviors among intercollegiate male athletes compared to nonathletes. These include number of sexual partners, sexual activity, intravenous drug use, and episodes of sexually transmitted diseases (51). Although female intercollegiate athletes also show high levels of risky health behaviors, this is less than nonathlete peers (35).
In the realm of the professional athlete, the rate of risky behavior is unknown, but anecdotal evidence suggests that their celebrity status may lead to higher risks (33).

TESTING

Screening Test

HIV antibodies are low or absent in the first few weeks of infection but are usually present within 6 weeks. However, antibody production may not be detectable until 6 months after infection. Therefore, antibody testing following possible exposure is recommended at 6 weeks, 3 months, 6 months, and 1 year (16).
The most common screening test is the enzyme-linked immunosorbent assay (ELISA), which can identify HIV antibodies in the blood with a sensitivity of up to 99.5%. If the ELISA test is positive, it is automatically repeated. If the second screen is positive, infection is confirmed by the Western blot analysis, which identifies antibodies to proteins of a specific molecular weight. It is only after these confirmatory tests are positive that an HIV antibody test should be reported as being positive.
The U.S. Food and Drug Administration recently approved four rapid HIV antibody tests (28). The OraQuick Advance Rapid test of oral fluid and blood has a sensitivity of 99.6% and specificity of 99.8%-100.0%. The Reveal G-2 Rapid HIV-1 test of serum or plasma has a sensitivity of 99.9% and specificity of 98.6%-99.1%. The Uni-Gold Recombigen test of serum, plasma, and whole blood has a sensitivity of 100.0% and specificity of 99.8%. The Multispot HIV-1/HIV-2 test of serum and plasma has a sensitivity of 100.0% and specificity of 99.93%.
Detection of p24 core antigen is possible 1-3 weeks after exposure. It is only present for a short interval and thus has been largely replaced by HIV RNA or DNA viral load to determine recent HIV exposure.

Confirmatory Testing

HIV viral load is performed via polymerase chain reaction or branched DNA testing and is useful at detecting recent exposure as well as monitoring response to treatment.
It is suggested that a baseline measurement be obtained at the time of diagnosis and then rechecked within 2-8 weeks of initiating or changing treatment. Viral loads are then followed every 3-4 months.
Viral genotype and phenotypic resistance assays may be used to guide specific antiretroviral therapy.
T-cell tests can identify the total CD4 count and the CD4:CD8 ratio in the blood, which can assist with HIV diagnosis, management, and treatment and the initiation of prophylaxis therapy for opportunistic infections (24). Normal CD4 cell counts range from 500-1,600 cells · µL⁻¹. CD4 levels ranging from 200-500 cells · µL⁻¹ are considered low, and levels below 200 cells · µL⁻¹ are considered extremely low and diagnostic of AIDS. Most experts recommend initiation of antiretroviral therapy if the CD4 level is below 350 cells · µL⁻¹. The normal CD4:CD8 ratio is 30%-60%; if the ratio is less than 14%, it is considered diagnostic of AIDS.

Mandatory Testing in Sports

The American College of Sports Medicine, National Collegiate Athletic Association (NCAA), Canadian Academy of Sport and Exercise Medicine, CDC, International Federation of Sports Medicine, International Olympic Committee, and the World Health Organization do not recommend mandatory screening of athletes for HIV. Any testing that is performed must be accompanied by pre- and posttest counseling, incorporate confidentiality measures, address the frequency of testing, and adhere to local and federal law.
The 1993 survey of NCAA institutions concerning HIV/AIDS policies found that routine HIV testing for athletes occurred in 4% of institutions and only two were mandatory (44).
None of the four major professional sports leagues in North America (NFL, NBA, MLB, or NHL) have adopted mandatory HIV testing, but they do recommend routine screening for athletes engaging in high-risk behaviors. In the NFL, the New York Giants and the Philadelphia Eagles reportedly tested players and personnel in 1991 and 1992 despite some of the players being unaware of the testing (33).
In 1988, the Nevada Boxing Commission mandated HIV testing for all boxers fighting in Nevada, and a positive result would disqualify a boxer from fighting. Numerous boxing commissions followed the lead, and currently boxers with a positive HIV test are not allowed to box in the United States, although several have fought in other countries (19).

TREATMENT

General Recommendations

Treatment regimens of HIV-positive patients focus on improving overall general health and slowing the disease progression. Treatment goals should include suppression of viral replication and evolution of resistant strains, increased CD4 cell counts, prevention of disease progression, improved energy levels, maintenance of a healthy weight, improvement in quality of life, and prolongation of overall survival.
In addition to engaging in a regular exercise program, other general health measures should be reinforced. Eating a healthy, well-balanced diet with high carbohydrates and moderate protein and avoidance of saturated fats and cholesterol is recommended. The HIV-positive patient should be encouraged to obtain adequate sleep, stop smoking, use alcohol in moderation, lose weight if obese, and treat other medical diseases such as hypertension and diabetes.

Highly Active Antiretroviral Therapy

Highly active antiretroviral therapy (HAART), including nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and protease inhibitors, is the cornerstone of treatment of HIV-infected patients. Many drug protocols have been developed, and there are a number of combined medications available to decrease the number of pills that must be consumed. The ultimate goals of HAART are to optimize the immune system and decrease viral load while minimizing the toxicity and development of drug-resistant HIV strains. The main effect of these agents is to suppress viral replication. This allows the immune system to recover and delays and protects the infected individual from developing AIDS (66).
Treatment regimens are constantly changing to achieve these goals, and thus consultation with HIV experts is necessary.
Current guidelines now recommend initiation of HAART when CD4 counts drop to 350 cells · µL⁻¹ and may be given with counts of 350-500 cells · µL⁻¹ (66). Earlier treatment may improve immunologic and virologic outcomes but may also increase drug toxicity and the rate of development of drug resistance. Only 20%, 26%, and 46% of those starting
HAART with CD4 counts of less than 50, 50-200, and 200-350 cells · µL⁻¹, respectively, achieved cell counts over 800 cells · µL⁻¹ 7 years after initiation of therapy. If CD4 cell counts were 350-500 or over 500 cells · µL⁻¹, the rates improved to 73% and 87%, respectively (27).
Treatment may also be considered in those with high viral loads, rapidly decreasing CD4 cell counts, or low CD4 percentage. Deaths from non-AIDS causes are increased with lower CD4 cell counts. Those on intermittent HAART had higher rates of cardiovascular, renal, hepatic, and pancreatic disease than those on continuous HAART. Patients must adhere to antiretroviral regimens to obtain optimum outcome (1,65,66).
Drug toxicities include myopathy, neuropathy, pancreatitis, cardiomyopathy, bone marrow suppression, nephrotoxicity, lactic acidosis with hepatic steatosis, osteonecrosis, osteoporosis, insulin resistance, hyperglycemia, hyperlipidemia, and lipodystrophy. All of these, even in their mildest forms, could have adverse effects on athletic performance (9,61,63,70).
The fusion inhibitors enfuvirtide, maraviroc, cenicriviroc, and ibalizumab may prove to be a tremendous advancement in HIV therapy. These attach to cell surface proteins of the CD4 cells or HIV to prevent the virus from entering the immune system. This may be especially beneficial in the treatment of drug-resistant HIV. Current drawbacks include subcutaneous administration, cost, and experimental status (61).

Other Medications and Supplements

Testosterone supplementation (transdermal or injection) has been used to improve hypogonadism, loss of lean body mass and muscle wasting, and increased visceral fat in HIV-positive males. Injection of 300 mg of testosterone enanthate for 16 weeks resulted in significant increase in lean body mass, strength, mental health, and quality-of-life scores compared to placebo; however, walking speed, stair climbing ability, fatigue, and mood scores were no different between the groups (34,48).
Growth hormone and the growth hormone analog tesamorelin have been shown to decrease visceral fat and increase lean mass in HIV-positive patients suffering from lipodystrophy associated with use of antiviral therapies (2,48). Glutamine and arginine are amino acids essential for immune system function. Both are used during exercise, and deficiencies may have a detrimental effect on tissue recovery and immune function. Supplementation may improve cytokine profile and immunologic function in HIV-positive patients. High-dose arginine supplementation (12 g · d⁻¹) may increase weight gain in HIV-positive patients and may benefit those suffering from chronic or acute infection (20). Preliminary studies have shown that cysteine supplementation in HIV-positive individuals may slow disease progression and prevent muscle wasting, but further research is needed before recommendations can be made (14).
Creatine supplementation during a 14-week resistance exercise program in HIV-positive patients resulted in nonsignificant increase in lean body mass but no difference in strength gains compared to placebo. Both groups had improved muscle size, strength, and overall function. Creatine supplementation may be considered in HIV-positive patients engaged in resistance training (67).
Oral nutritional supplementation may increase protein synthesis, body weight, and fat mass in HIV-positive individuals (39).
Future therapy for HIV treatment and prevention will focus on the development of new antiretroviral agents, genetic engineering, stem cell research, immunotherapy, and vaccine therapy (62).