Overview and Risk Factors
Worldwide, more than 40 million people are infected with human immunodeficiency virus (HIV). About 40,000 new infections occur yearly in the United States.
HIV is a retrovirus that infects and destroys cells containing the CD4+ antigen, particularly CD4+ T-helper cells. The virus enters the body through disrupted mucosal barriers and rapidly infects CD4+ cells, ultimately disabling the immune system. Over time, morbidity and mortality occur due to opportunistic infections and malignancies that result from compromised immunity.
Acquired immunodeficiency syndrome (AIDS) is defined as the presence in an HIV-infected person of a CD4+ helper T cell count of less than 200 cells/mL, or the presence of any AIDS-defining illness, usually an opportunistic infection. Examples include: candidiasis of the esophagus or respiratory tract; cryptosporidiosis with persisting diarrhea; cytomegalovirus (other than of the liver); Herpes simplex virus with a mucocutaneous lesion that persists beyond 1 month; Kaposi's sarcoma; Mycobacterium avium complex infection; Pneumocystis carinii pneumonia; or toxoplasmosis of the brain. A complete listing is downloadable (PDF) at http://www.aidsinfo.nih.gov/other/cbrochure/english/01_en.pdf.
Transmission of HIV occurs by sexual intercourse, intravenous drug use, perinatal infection, breast-feeding, blood products, and open wound-fluid interchange. Transmissibility rises in direct proportion to the HIV viral load.
Upon seroconversion, the initial presentation is a flu-like or mononucleosis-like syndrome (headache, fever, chills, cough, myalgias, adenopathy) with a rash that occurs within 4 to 14 days of infection and lasts less than 3 weeks. Patients then return to their baseline state of health for 2 to 10 or more years, while the virus replicates within T cells and the CD4+ cell count declines.
As the number of CD4+ T cells declines, patients become more susceptible to infection and neoplasm. Once the CD4+ cells are sufficiently depleted, patients experience multiple opportunistic infections and malignancies that may affect any organ system. These include:
- Pulmonary: Upper respiratory infections, sinusitis, pneumonia, tuberculosis.
- Neurologic: Bell's palsy, dementia, meningitis, cerebritis, spinal cord dysfunction, peripheral neuropathy.
- Gastrointestinal: Esophagitis, diarrhea, liver disease.
- Rheumatologic: Arthritis.
- Dermatologic: Kaposi's sarcoma, herpetic lesions, molluscum contagiosum, abscess.
- Hematologic: Lymphoma, thrombocytopenia.
Risk Factors
High-risk sexual intercourse. This includes heterosexual and homosexual contact. Nearly 90% of cases occur through heterosexual transmission. Condom use reduces, but does not eliminate, the risk. Factors associated with increased risk of transmission include male-male sexual intercourse, lack of circumcision (female-to-male transmission),1 and sexual intercourse during menses (female-to-male transmission).
Blood transfusion. Since 1985 the screening of blood products has significantly decreased the HIV transmission rate. The risk of transmission due to blood transfusion is now about 1 in 2 million.
Injection drug use. Drug injection is a particularly important source of the HIV epidemics in Eastern Europe, Asia, and the Middle East.
Perinatal transmission. Children are at risk while in utero, during delivery, and postnatally via breast-feeding. Perinatal transmission rates can be as high as 40%. However, the combination of antiretroviral therapy, elective cesarean delivery, and avoidance of breast-feeding in HIV-positive mothers has reduced perinatal transmission significantly.
Occupational exposure. Risk of transmission after an accidental needle stick exposure is less than 1%.
Diagnosis and Treatment
Diagnosis
Early diagnosis is important, because early antiretroviral treatment enhances immunologic responses to HIV and likely delays progression to AIDS.
Several tests are available to identify HIV infection:
- HIV RNA viral load is the most sensitive test for identifying primary HIV infection and is also used to follow disease progression. During acute infection, the viral load can be greater than 500,000, but it then falls significantly.
- HIV enzyme-linked immunosorbent assay (ELISA) is positive in 95% of cases within 6 weeks of infection.
- Western blot to identify HIV viral proteins has better than 99% specificity for HIV infection and is generally used for confirmation of a positive ELISA test.
- Assay for the p24 antigen is rarely used because it is less sensitive than testing for HIV RNA.
- CD4+ count is used to monitor the progression of HIV infection: the lower the value, the greater the risk for opportunistic infections. Abnormal complete blood count (CBC) is common and may reveal leukopenia, lymphocytosis, thrombocytopenia, or anemia.
After diagnosis, the CD4+ count and viral load are followed every 3 to 6 months to evaluate the progression of infection and the need for prophylaxis of opportunistic infections.
Screening for other sexually transmitted diseases is necessary, including gonorrhea, chlamydia, syphilis, herpes, hepatitis B, and hepatitis C.
HIV genotype should be obtained to assess for drug resistance, which may be as high as 25%.
Routine follow-up is important, with CBC, creatinine, renal function tests, and liver function tests to evaluate for medication side effects.
Other diagnostic tests are indicated, as necessary, for diagnosis of opportunistic infections (eg, chest x-ray, viral titers).
Treatment
Antiretroviral therapy has significantly improved the prognosis for HIV, reducing progression to AIDS, opportunistic infections, hospitalizations, and mortality. Most patients will achieve full viral suppression within several months of beginning therapy. In general, antiretroviral therapy is initiated in symptomatic patients and in all patients once the CD4+ count falls below 200 cells/mL; therapy should at least be considered and discussed with patients once the CD4+ is less than 350 cells/mL. However, some evidence suggests that early initiation of antiretroviral therapy (within 1 year of seroconversion) regardless of CD4+ count will delay the onset of AIDS; this theory is currently under investigation. Physicians and patients should consider enrollment in a clinical trial to take advantage of experimental therapies.
Antiretrovirals
Classes of antiretroviral agents include nucleoside reverse transcriptase inhibitors (eg, zidovudine, didanosine, lamivudine, stavudine, abacavir), non-nucleoside reverse transcriptase inhibitors (eg, efavirenz, nevirapine, and delavirdine), and protease inhibitors, such as indinivir and ritonavir.
A regimen combining three antiretroviral medications-known as highly active antiretroviral therapy (HAART) or "triple therapy"-is used to avoid or delay drug resistance. Strict adherence is essential.
Once antiviral therapy begins, the CD4+ count and viral load should be assessed every 3 months, along with medication resistance studies.
Prophylaxis
Antimicrobial prophylaxis for opportunistic infections is based on following the CD4+ count to anticipate risk.
Pneumocystis carinii pneumonia: Prophylaxis is usually indicated when CD4+ count falls below 200 cells/mL. Agents include trimethoprim-sulfamethoxazole, dapsone, and pentamidine.
Mycobacterium avium complex: Prophylaxis is usually indicated when CD4+ count falls below 100 cells/mL. Agents include clarithromycin and azithromycin.
Long-Term Antimicrobial Suppression
Once Pneumocystis carinii pneumonia, cryptococcus, or cytomegalovirus retinitis develops, long-term antimicrobial suppression is recommended.
Exercise
Regular exercise can reduce some side effects of antiretroviral treatment. Aerobic exercise can help reduce total body and visceral fat and normalize lipid profiles in HIV-infected patients.2 Combinations of aerobic exercise and progressive resistive exercise (done for at least 20 minutes ≥ 3 times per week) may also lead to significant reductions in depressive symptoms and improvements in cardiopulmonary fitness.3
Psychological Treatment
Psychological approaches can provide benefits for persons with HIV. Although further research is needed to confirm initial findings, available evidence suggests that excessive psychosocial stress can reduce resistance to opportunistic infections in HIV-positive persons. In women with HIV, higher indications of psychosocial stress increased the odds of developing progressive, persistent HPV-related squamous intraepithelial neoplasia 7-fold, compared with women experiencing the least life stress.4 Greater stress also accounted for 46% of the variance in recurrence of genital herpes lesions.5 Various psychological approaches are significantly associated with decreased viral load,6 higher CD4+ cell counts,7 and greater adherence to antiretroviral therapy.8 HIV-positive men assigned to cognitive-behavioral stress management or active coping interventions were shown to have greater numbers of CD4+ cells.9
Nutritional Considerations
Nutritional issues in HIV infection relate to macronutrient and energy needs, lipid disorders, and micronutrient adequacy.
Macronutrient and Energy Needs
HIV infection can trigger a chronic-inflammation, wasting syndrome with increases in protein turnover and energy requirements. Studies of asymptomatic HIV-infected men showed elevated protein breakdown, protein synthesis, and resting energy expenditure, compared with non-HIV-infected individuals. Compensatory increased energy intake can help prevent wasting. Nonetheless, wasting is common, despite HAART.10
Protein intake is associated with decreased lean body mass, loss of which is strongly associated with disease progression and death in HIV-positive persons.11 A review of available evidence noted that protein requirements of 1.0 to 1.4 grams/kg are indicated for maintenance of lean mass, and 1.5 to 2.0 grams/kg for anabolism.12
Protein supplementation with amino acids (L-arginine, L-glutamine) and related compounds (e.g., beta-hydroxy beta-methylbutyrate, a metabolite of leucine) has a significant anticatabolic effect in HIV-positive persons.13-16 However, additional clinical trials are required before these supplements can be routinely recommended.
Unless they are obese, patients should not be encouraged to lose significant amounts of weight. Studies have consistently shown that HIV-infected patients with a body mass index (BMI) of >25 have higher CD4+ cell counts, decreased risk of viral progression, and decreased mortality compared with their thinner (BMI <25) counterparts. This relationship may be explained by the elevated leptin production in heavier persons, which supports CD4+ cell proliferation.17 Loss of excess weight may be helpful, however, for overweight patients on HAART whose risk factors for heart disease and diabetes have been elevated by the therapy.18
Diet and Lipid Disorders
A diet that addresses cardiovascular risk factors is appropriate for patients with HIV. Individuals with HIV were observed to have disturbances in lipid metabolism and insulin resistance prior to the advent of protease inhibitors. However, these medications appear to exacerbate this tendency, even in those without HIV infection. Medication-related decreases in the catabolism of both apoB and nuclear sterol regulatory element binding proteins in the liver and adipocytes bring about increases in fatty acid and cholesterol biosynthesis, insulin resistance, and lipodystrophy. As a result, 10% to 50% of patients on protease inhibitors have hypercholesterolemia, and 40% to 80% of these individuals have hypertriglyceridemia. Although prospective studies do not indicate that this situation leads to increased cardiovascular risk, retrospective analyses found significantly greater risk for myocardial infarction in users of protease inhibitors. Substitution with reverse transcriptase inhibitors does not appear to provide lipid-lowering benefits.19
Micronutrient Adequacy
Although further study is required, preliminary evidence reveals that higher intakes of fruits, vegetables, and juices increase T cell proliferation,20 or reduce CD38+/CD8+ count, a marker of disease progression.21 Fruits and vegetables also provide many nutrients that are deficient in persons with HIV and help reduce the oxidative stress that may occur as a side effect of HAART.22
Nutrient supplements may be helpful, but study findings are equivocal. Low blood concentrations of many micronutrients are common in HIV-positive individuals and are associated with disease progression and increased mortality.23 Although some reviews suggest that multivitamin supplements reduce morbidity and mortality,23 others have found no such advantage.24 Preliminary evidence suggests that selenium supplementation (200 mg/day) may reduce the need for hospitalization by lowering the frequency of opportunistic infections.25 Magnesium deficiency has also been found in roughly 60% of HIV-infected individuals.26 However, routine magnesium supplementation is not recommended except for persons on foscarnet, which frequently causes hypomagnesemia.27 Future clinical trials may determine the impact of micronutrient supplementation on HIV and disease outcome.
Orders
See Coronary Heart Disease chapter.
Nutrition consultation to assess protein requirements.
Exercise prescription.
What to Tell the Family
HIV infection is not currently curable, but progressive immunosuppression and life-threatening, opportunistic infections can be greatly diminished through a combination of medications and a healthful diet. Emotional support from family, friends, and community, and also psychotherapeutic treatments, may provide additional immune benefits for persons with HIV. Family members can encourage healthy lifestyle changes through diet, regular exercise, and abstinence from tobacco and alcohol.
References
1. Moses S, Plummer FA, Bradley JE, Ndinya-Achola JO, Nagelkerke NJ, Ronald AR. The association between lack of male circumcision and risk for HIV infection: a review of the epidemiological data. Sex Transm Dis. 1994;21:201-210.
2. Malita FM, Karelis AD, Toma E, Rabasa-Lhoret R. Effects of different types of exercise on body composition and fat distribution in HIV-infected patients: a brief review. Can J Appl Physiol. 2005;30:233-245.
3. Nixon S, O'Brien K, Glazier RH, Tynan AM. Aerobic exercise interventions for adults living with HIV/AIDS. Cochrane Database Syst Rev. 2005;(2):CD001796.
4. Pereira DB, Antoni MH, Danielson A, et al. Life stress and cervical squamous intraepithelial lesions in women with human papillomavirus and human immunodeficiency virus. Psychosom Med. 2003;65:427-434.
5. Pereira DB, Antoni MH, Danielson A, et al. Stress as a predictor of symptomatic genital herpes virus recurrence in women with human immunodeficiency virus. J Psychosom Res. 2003;54:237-244.
6. Ironson G, Weiss S, Lydston D, et al. The impact of improved self-efficacy on HIV viral load and distress in culturally diverse women living with AIDS: the SMART/EST Women's Project. AIDS Care. 2005;17:222-236.
7. Antoni MH, Cruess DG, Klimas N, et al. Stress management and immune system reconstitution in symptomatic HIV-infected gay men over time: effects on transitional naive T cells (CD4(+)CD45RA(+)CD29(+). Am J Psychiatry. 2002;159:143-145.
8. Weber R, Christen L, Christen S, et al. Effect of individual cognitive behaviour intervention on adherence to antiretroviral therapy: prospective randomized trial. Antivir Ther. 2004;9:85-95.
9. Antoni MH. Stress management effects on psychological, endocrinological, and immune functioning in men with HIV infection: empirical support for a psychoneuroimmunological model. Stress. 2003;6:173-188.
10. Crenn P, Rakotoanbinina B, Raynaud JJ, Thuillier F, Messing B, Melchior JC. Hyperphagia contributes to the normal body composition and protein-energy balance in HIV-infected asymptomatic men. J Nutr. 2004;134:2301-2306.
11. Williams SB, Bartsch G, Muurahainen N, Collins G, Raghavan SS, Wheeler D. Protein intake is positively associated with body cell mass in weight-stable HIV-infected men. J Nutr. 2003;133:1143-1146.
12. Coyne-Meyers K, Trombley LE. A review of nutrition in human immunodeficiency virus infection in the era of highly active antiretroviral therapy. Nutr Clin Pract. 2004;19:340-355.
13. Rathmacher JA, Nissen S, Panton L, et al. Supplementation with a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine, and glutamine is safe and could improve hematological parameters. JPEN J Parenter Enteral Nutr. 2004;28:65-75.
14. Schon T, Elias D, Moges F, et al. Arginine as an adjuvant to chemotherapy improves clinical outcome in active tuberculosis. Eur Respir J. 2003;21:483-488.
15. Clark RH, Feleke G, Din M, et al. Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and arginine: a randomized, double-blind, placebo-controlled study. JPEN J Parenter Enteral Nutr. 2000;24:133-139.
16. Shabert JK, Winslow C, Lacey JM, Wilmore DW. Glutamine-antioxidant supplementation increases body cell mass in AIDS patients with weight loss: a randomized, double-blind controlled trial. Nutrition. 1999;15:860-864.
17. Jones CY, Hogan JW, Snyder B, et al. Overweight and human immunodeficiency virus (HIV) progression in women: associations [between] HIV disease progression and changes in body mass index in women in the HIV epidemiology research study cohort. Clin Infect Dis. 2003;37(suppl 2):S69-S80.
18. Gerrior JL, Neff LM. Nutrition assessment in HIV infection. Nutr Clin Care. 2005;8:6-15.
19. Calza L, Manfredi R, Chiodo F. Dyslipidaemia associated with antiretroviral therapy in HIV-infected patients. J Antimicrob Chemother. 2004;53:10-14.
20. Winkler P, Ellinger S, Boetzer AM, et al. Lymphocyte proliferation and apoptosis in HIV-seropositive and healthy subjects during long-term ingestion of fruit juices or a fruit-vegetable-concentrate rich in polyphenols and antioxidant vitamins. Eur J Clin Nutr. 2004;58:317-325.
21. Gil L, Lewis L, Martinez G, et al. Effect of increase of dietary micronutrient intake on oxidative stress indicators in HIV/AIDS patients. Int J Vitam Nutr Res. 2005;75:19-27.
22. Tang AM, Lanzillotti J, Hendricks K et al. Micronutrients: current issues for HIV care providers. AIDS. 2005;19:847-861.
23. Lanzillotti JS, Tang AM. Micronutrients and HIV disease: a review pre- and post-HAART. Nutr Clin Care. 2005;8:16-23.
24. Irlam JH, Visser ME, Rollins N, Siegfried N. Micronutrient supplementation in children and adults with HIV infection. Cochrane Database Syst Rev. 2005;(4):CD003650.
25. Burbano X, Miguez-Burbano MJ, McCollister K, et al. Impact of a selenium chemoprevention clinical trial on hospital admissions of HIV-infected participants. HIV Clin Trials. 2002;3:483-491.
26. Singhal N, Austin J. A clinical review of micronutrients in HIV infection. J Int Assoc Physicians AIDS Care (Chicago, Ill). 2002;1:63-75.
27. Huycke MM, Naguib MT, Stroemmel MM, et al. A double-blind placebo-controlled crossover trial of intravenous magnesium sulfate for foscarnet-induced ionized hypocalcemia and hypomagnesemia in patients with AIDS and cytomegalovirus infection. Antimicrob Agents Chemother. 2000;44:2143-2148.
