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What the Primary Care Physician Needs to Know About HIV
Jonathan Z. Li, MD, Clinical and Research Fellow, Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Paul E. Sax, MD, Clinical Director, Division of Infectious Diseases, Brigham and Women's Hospital, Associate Professor of Medicine, Harvard Medical School, Boston, MA
Dean L. Winslow, MD, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center, Clinical Professor of Medicine and Pediatrics, Stanford University, CA.
Although the treatment of HIV disease has become quite complex and typically beyond the scope of most PCPs, PCPs play an important role in the co-management of patients, new diagnoses, and postexposure prophylaxis.
There have been impressive success stories in the field of HIV over the past decade. Most notably, these include the near-elimination of mother-to-child HIV transmission in the United States and the dramatic improvement in survival both the result of potent combination antiretroviral therapy (ART), which is now standard of care. However, these successes have been accompanied by ongoing challenges. Approximately 1 in 5 people with HIV in the United States is unaware that they carry the virus, but making HIV testing a routine part of medical care remains a controversial strategy. Increased options for HIV therapy bring with them a greater number of potential adverse event profiles and drug-drug interactions, as well as increasingly complex drug resistance profiles. Prolonged survival of patients with HIV has led to an aging population now dealing with the consequences of both long-standing HIV infection and medication-associated toxicities. HIV vaccine studies have demonstrated limited efficacy at best, and thus far standard ART cannot cure this chronic infection.
Because of these complexities, the treatment of HIV infection should be under the direction of an HIV specialist. However, the primary care physician continues to play an important role in the diagnosis of new infections and co-management of the patient with HIV, who will increasingly have non-infectious complications common to an aging general medical population. This article will provide an overview of HIV epidemiology, testing guidelines, key information to be elicited during the history and physical examination, and initial and follow-up laboratory evaluations. In addition, the basic principles of HIV therapy, both for treatment and for prevention, will be reviewed.
Epidemiology of HIV in the United States
As of 2006, approximately 1.1 million individuals were estimated to be living with HIV in the United States.1 During the earliest years of the epidemic, HIV/AIDS primarily affected white men who have sex with men (MSM). Since then, the burden of disease has broadened to affect an increasing number of women and minorities.2,3 Despite this change, the majority of new infections still are in men (73%).2 African Americans account for 45% of new infections; since they are 12% of the U.S. population, they are clearly disproportionately affected by the epidemic. Caucasians make up 35% and Hispanics 17% of new infections. Individuals aged 20-49 years account for the vast majority of new cases. The most common risk factor for transmission is MSM (53%). Heterosexual transmission accounts for 31% of new infections, and intravenous drug users (IDU) account for 12%. While overall incidence of HIV/AIDS leveled off between 1999 and 2006, there were increasing numbers of new infections among MSM in men and through high-risk heterosexual transmission in women, predominantly among racial and ethnic minorities. Certain regions have particularly high HIV prevalence, similar to that seen in sub-Saharan Africa. For example, 1 in 16 black men in Washington, D.C. are infected, and in some urban centers, the prevalence of HIV among MSM is close to 30%.4
Patient Selection. Earlier diagnosis of HIV infection is important not only for optimal clinical outcomes, but also for limiting the spread of the epidemic.5 However, an estimated 21% of individuals living with HIV in the United States do not know their status.1 Those who are diagnosed often are found late in their disease. It is estimated that an average of 7-9 years has elapsed before most are diagnosed, and almost 40% of those newly diagnosed with HIV progress to end-stage AIDS within 1 year of the test.6,7 Early diagnosis of HIV not only improves survival, but those who are aware of their status are less likely to transmit HIV to others.8 In 2006, these numbers led the Centers for Disease Control (CDC) to recommend routine HIV testing for all individuals aged 13 to 64 years, except those living in areas with extremely low HIV prevalence (<0.1%) who have no sexual contact or other HIV risk factors.7 The CDC further recommended annual screening for those at high risk for HIV infection specifically, gay men, injection drug users, and seronegative sexual partners of those known to be HIV-infected. While the American College of Physicians also endorses routine HIV testing,9 the American Academy of Family Physicians (AAFP) and the U.S. Preventive Services Task Force (USPSTF) continue to recommend testing for those with known risk factors and in high-risk clinical settings (e.g., emergency departments, STD clinics, correctional facilities, homeless shelters, and primary care clinics in high-prevalence areas).10,11 All guidelines recommend routine HIV testing of pregnant women in the first trimester, as HIV therapy initiated during pregnancy virtually eliminates the risk of transmission of HIV to the newborn. The CDC also recommends a repeat test in the third trimester for women with HIV risk factors and those in high-prevalence settings.7
HIV Tests. In order to decrease barriers to testing, the CDC guidelines do not mandate either pre-test counseling or a separate written consent,7 although providers should be still follow their state and local laws on counseling and consent. The standard test for diagnosis of HIV infection is detection of antibodies by either a rapid HIV test or an enzyme-linked immunoassay (EIA) followed by a confirmatory Western blot or immunoflourescent assay.12 A number of rapid tests for HIV are FDA-approved and can provide results within 20 minutes: Clearview HIV 1/2 STAT-PAK Assay, Clearview Complete HIV1/2, Multispot HIV-1/HIV-2 Rapid Test, OraQuick Advance Rapid HIV-1/2 Antibody test, Reveal G3 Rapid HIV-1 Antibody Test, and Uni-Gold Recombigen HIV Test. The OraQuick test can be used on both plasma and oral fluid specimens, but is not approved for children younger than 13 years. Screening enzyme immunoassays have been reported to have a 99.7% sensitivity and 98.5% specificity.13 Given the high sensitivity and slightly lower specificity of screening HIV tests, all positive samples must be confirmed by either a Western blot or indirect immunofluorescence assay; laboratories will do this confirmatory testing following standard EIAs as part of their routine testing procedures. With a confirmatory Western blot, the chance of a false-positive test in a low-prevalence setting is 1 in 250,000.13 In most cases, a positive screening test and negative or indeterminate Western blot should prompt repeat testing 4 weeks after the initial test, along with measurement of HIV viral load, as in rare circumstances this pattern of HIV antibody testing may occur during HIV seroconversion. Similarly, individuals with HIV risk factors who have signs and symptoms of acute retroviral syndrome (fever, rash, pharyngitis, lymphadenopathy, aseptic meningitis) may present in the 2- to 8-week window period when antibodies to HIV have not yet fully developed. To avoid false-negative results, these patients should be offered HIV viral RNA testing in addition to serologic testing. If acute HIV infection is present, the HIV RNA level generally will be greater than 500,000 copies/mL. HIV RNA testing should not be generally used for diagnosis of chronic HIV infection since low copy number false-positive results commonly occur.
Primary Care and Prevention of Opportunistic Infections
Initial and Follow-up Evaluations. The initial patient evaluation should include a comprehensive assessment of behavioral risk factors, medical history, physical examination, and a detailed laboratory evaluation.14 The complete guidelines to the initial evaluation are available from guidelines issued by the Infectious Disease Society of America12 and the DHHS.15 Patients living with HIV are often dealing with concurrent social, psychiatric, substance abuse, and medical issues. The initial evaluation should include an assessment of medical and psychiatric comorbidities, high-risk behaviors including substance abuse and sexual history, economic situation (e.g., housing), social support, and the patient's knowledge of HIV. Health care providers also should provide HIV education including HIV risk factors and strategies for preventing HIV transmission to others.
Recommended laboratory testing provides baseline immune and HIV status, as well as organ function and the risks of co-infections. (See Table 1.) In general, HIV patients should have a follow-up evaluation every 3-4 months. However, the frequency of follow-up evaluations can vary depending on the immune status of the patient and the rate of immunologic change. In the event of an antiretroviral medication change, safety labs and immunologic/virologic response to therapy should be monitored at earlier intervals (2-4 weeks). The recommended follow-up laboratory and health care maintenance evaluations are also shown in Table 1. In addition to the HIV-specific primary care considerations, HIV-infected patients should undergo many of the same health care screening evaluations as HIV-negative patients, including tests for colorectal, breast, and prostate cancers. Hyperlipidemia should be managed according to the National Cholesterol Education Program guidelines, but lipid-lowering agents must be chosen carefully, as there are significant drug-drug interactions between certain statins and protease inhibitors.14 For example, simvastatin levels increase significantly when co-administered with HIV protease inhibitors, and hence should not be used; safer choices include rosuvastatin, pravastatin, or low-dose atorvastatin.
Vaccines. Recommended adult vaccinations are listed in Table 2 with differences in those recommended for healthy, HIV-uninfected adults.16 In general, it is best to avoid live-attenuated intranasal influenza and oral polio vaccines in HIV-positive patients with low CD4 cell counts. Patients with AIDS, CD4 cell count < 200 cells/mL or < 15% should not receive the MMR, varicella, zoster, intranasal influenza, and yellow fever vaccines. As vaccine responses are more robust in patients with higher CD4 cell counts, deferring vaccinations until after initiating ART is recommended in most situations.
Prevention of Opportunistic Infections (OIs). The CD4 T-cell count (or CD4 count) is the main marker of immune function and the primary measure by which HIV disease progression is monitored. During acute HIV infection, there is an initial peak in plasma viral load and drop in the CD4 cell count. The CD4 cell count rebounds around 3-6 months after the primary infection.17 Without treatment, the CD4 count will generally decline at a rate of 25 to 100 cells/µl per year,18 with wide variability between patients. As the CD4 cell count declines, patients are at increased risk of OIs, which are the principal causes of morbidity and mortality in advanced HIV disease. The key recommendations for the primary prophylaxis of common OIs are shown in Table 3 and reflect the changing risk based on CD4 cell count, prior exposure, and the geographic distribution of the pathogens. Comprehensive guidelines on the prevention and treatment of HIV-related OIs were updated in 2009.19 The importance of OI prophylaxis has diminished since the introduction of effective ART, as HIV therapy can in most cases reverse immunosuppresion sufficiently to make specific antimicrobial prophylaxis unnecessary.
When to Start and Why. When to start ART in patients without HIV-related symptoms remains one of the most controversial areas in the clinical care of HIV patients. Since the first antiretroviral agent (ARV) became available more than two decades ago, multiple new medications have been developed, with reduced short- and long-term adverse effects and lower pill burden. When combination ART became widely available in the late 1990s, some advocated a "hit early, hit hard" strategy in the hopes that early treatment could potentially eradicate the infection.20 During the next few years, the pendulum swung toward delaying therapy as it became apparent that eradication of HIV infection was not possible and that ART would be limited by adverse effects, especially disfigurement due to lipodystrophy, painful peripheral neuropathy, and other effects and leading to a sharply reduced quality of life. In addition, some patients reported that these complex regimens fostered treatment fatigue and suboptimal adherence, eventually leading to drug resistance.
During the past few years, however, there has once again been a shift toward earlier initiation of therapy, even in patients with no symptoms and relatively high CD4 cell counts.21 Simpler drug regimens, including the one-pill once-a-day formulation of tenofovir, emtricitabine, and efavirenz (Atripla), have led to improved drug adherence and are associated with fewer side-effects. In addition, there is evidence that antiretroviral treatment reduces morbidity and mortality even at higher CD4 cell counts,22 likely through the prevention of "non-AIDS" complications such as cardiovascular disease and malignancies. Several studies have shown that CD4 counts < 500 cells/µl are associated with increased risk of AIDS-defining and non-AIDS-defining malignancies23,24 and that ART can decrease inflammation and immune activation thought to contribute to cardiovascular and other complications in HIV-positive patients.15,25,26 ART also lowers viral load, which decreases the rate of HIV transmission and has important public health implications.27,28
Current guidelines issued by the Department of Health and Human Services recommend starting therapy with a CD4 count of ≤ 500 cells/µl, and that treatment can be considered in those with even higher CD4 counts.15 In addition, ART should be initiated in pregnant women, patients with HIV-associated nephropathy, and those needing treatment for HBV co-infection regardless of CD4 count. Patients initiating therapy should be counseled regarding the risks and benefits of treatment, the importance of adherence, and the likely need for life-long therapy.
There are now six FDA-approved classes and more than 20 antiretroviral agents and co-formulations available. Recommended regimens consist of three active agents from at least two drug classes. Recommended regimens use two nucleoside reverse transcriptase inhibitors (NRTIs) (generally a one-pill daily co-formulation of tenofovir/emtricitabine [Truvada] or abacavir/lamivudine [Epzicom]) with either a non-nucleoside reverse transcriptase inhibitor (NNRTI), a protease-inhibitor (PI), or an integrase inhibitor. Most protease inhibitors are optimally given with low doses of ritonavir, which acts as a pharmacokinetic booster but not as an antiviral; as a result, patients receiving PI-based treatments are usually on 4 drugs, with only three of them given for antiviral activity.
As noted above, one of the most popular HIV regimens is a single pill of co-formulated tenofovir, emtricitabine, and efavirenz. This treatment is not appropriate for all HIV patients, however, including those who have baseline resistance to any of its components due to acquisition of a drug-resistant virus. Because of the efavirenz, which has caused neural tube defects in primates, it is contraindicated in pregnant women during the first trimester or women of childbearing age who do not use reliable birth control. Efavirenz also induces distinctive central nervous system effects that may not be tolerated by some individuals, especially those with severe psychiatric comorbidities, although in controlled trials, worsening of pre-existing psychiatric disease was not observed.
Other "preferred" regimens for treatment-naïve individuals based on DHHS guidelines include the co-formulated tenofovir/emtricitabine in conjunction with either the protease inhibitors ritonavir-boosted atazanavir or ritonavir-boosted darunavir, or the integrase inhibitor raltegravir.15 These recommendations take into account efficacy as demonstrated in prospective clinical trials, ease of dosing, and safety history. When initiating or changing ART regimens, it is also important to note that many antiretroviral agents, especially the ritonavir-boosted protease inhibitors, have significant interactions with other commonly used drugs such as statins, anti-seizure medications, psychiatric drugs, treatments for erectile dysfunction, and inhaled corticosteroids.15
The goal of ART is to suppress HIV-1 replication and to lower the viral load to undetectable levels (< 50 copies/mL). With a successful regimen, this usually occurs within 3-6 months and is accompanied by a rise in CD4 cell counts.14 Virologic "blips" are occasional low viral loads (< 500 copies/mL) that do not persist and are usually representative of laboratory artifact (proviral DNA leaking out of cells is falsely measured as RNA in PCR-based viral load assays) or residual virus released from long-lived reservoirs. These "blips" do not constitute virologic treatment failure, which is defined as persistently detectable viremia suggestive of viral replication. Treatment failure is usually indicative of medication non-adherence and/or the presence of drug resistance mutations. With the potency of currently available drugs, by far the most common cause of virologic failure is that the patient has stopped taking the medications. In clinical cohorts today, the vast majority of patients treated for HIV are successfully treated, with only 10-20% experiencing treatment failure.29
Recent studies have shown that 6-16% of treatment-naïve individuals harbor HIV with drug resistance mutations.15 This baseline resistance can impair the efficacy of antiretroviral therapy, and hence a resistance test is recommended at the time of HIV diagnosis. The other main indication for resistance testing is at the time of virologic failure. In both settings, the goal of resistance testing is to avoid using drugs with limited or no antiviral activity.
There are currently two main types of drug resistance assays, genotype and phenotype. Genotype assays detect mutations in the virus known to confer resistance to specific antiretroviral agents. Phenotype assays measure the ability of HIV to grow in different concentrations of HIV drugs. While the phenotypic assays are more intuitive (and closer to susceptibility testing done for bacteria), in most situations genotypic testing is preferred. This preference is based on lower cost, wider availability, better sensitivity of detecting mutations present in mixtures, and a faster turnaround time. Phenotype assays are most useful in patients with complex patterns of drug resistance mutations (especially to HIV protease inhibitors) that may be difficult to interpret. In general, interpretation of HIV resistance testing is a skill reserved for clinicians who have extensive experience caring for patients with HIV; the primary care provider's role will usually be to order a genotype test in a newly diagnosed patient or in someone experiencing virologic failure.12,15
Antiretroviral therapy has been linked to a number of chronic health conditions including insulin resistance, subcutaneous lipo-atrophy, regional fat accumulation, lipid abnormalities, and cardiac disease.12,30 The multicenter AIDS Cohort Study found a higher risk of insulin resistance with increased exposure to nucleoside reverse transcriptor exposure,31 while other trials have shown a modest impact of certain protease inhibitors on insulin sensitivity.12 The spectrum of HIV lipodystrophy encompasses both fat accumulation (lipohypertrophy) and fat loss (lipo-atrophy).32 Fat accumulation primarily occurs centrally in the viscera, but can also manifest as enlarged dorsocervical fat pad ("buffalo hump"), chin fat ("horse collar"), or increased breast tissue. Fat loss, on the other hand, generally occurs in the face, extremities, and buttocks. These fatty changes are associated with an increased risk of diabetes, coronary artery disease, hyperlipidemia, and osteoporosis. Both lipodystrophy and hyperlipidemia are most commonly associated with older NRTIs and protease inhibitors no longer in wide use.32-35 The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study is a collaboration of 11 prospective cohorts from Europe, Australia, and the United States. Analysis of this combined cohort suggests that several antiretroviral agents (indinavir, ritonavir-boosted lopinavir, ddI, and abacavir) may be associated with increased risk of myocardial infarctions.36 Given the potential complications of HIV therapy and the likelihood that HIV itself induces increased cardiovascular risk through inflammatory mechanisms, aggressive reduction of traditional CV risk factors is an emerging critical role of the primary care physician.
Pregnancy and HIV
One of the success stories of HIV treatment is the dramatic reduction in perinatal transmission when babies are born to HIV-infected mothers. It is currently estimated that fewer than 250 infected children are born yearly in the United States.37 The linchpin of the current strategy lies in the use of antiretroviral therapy both antepartum and intrapartum as well as infant postexposure prophylaxis and the avoidance of breast feeding. Women who wish to become pregnant should be on a stable ART regimen with maximal suppression of viral load. The risk of transmission is < 1% in women with undetectable HIV viral load on treatment.38 Antenatal and intrapartum ART not only reduces HIV viral load in both the blood and genital secretions, but also results in systemic drug levels in the infant at the time of birth.39 However, there is no known threshold of HIV RNA level at which there is no risk of transmission.40
Based on these observations, current recommendations are to begin ART in all pregnant women regardless of CD4 count and viral load, although delaying the initiation of therapy until after the first trimester can be considered.12,39 Antenatal counseling should include a discussion about the known benefits of ART (reducing perinatal transmission and benefits to maternal health) as well as the risks, including the limited long-term outcome data for infants with in utero ART exposure. Certain ART regimens should be avoided, in particular those containing efavirenz, which is a potential teratogen (when given in the first trimester). (Interestingly, the latest WHO guidelines on prevention of MTCT recommend EFV during the second and third trimesters.) Toxicities and recommendations for the use of specific ARVs can be found in Table 3 of the recently updated Public Health Service Task Force guidelines for the reduction of perinatal HIV transmission.39
Post-Exposure Prophylaxis (PEP)
The risk of HIV transmission per act is generally low, but varies substantially by mode of transmission and other mitigating factors. The estimated risk of infection for the most common modes of transmission are:12,41
Contaminated blood transfusion: 95 in 100;
Perinatal transmission from mother to child: 1 in 4;
Needle sharing: 1 in 150;
Occupational needle stick: 1 in 300;
Male to male receptive anal intercourse: between 1 in 10 to 1 in 1600;
Male to female vaginal intercourse: between 1 in 200 to 1 in 2000;
Female to male vaginal intercourse: between 1 in 700 and 1 in 3000.
The risk of an occupational HIV transmission varies with the type and severity of exposure. Studies have shown that with exposure to HIV-infected blood, percutaneous needlestick injury carries an approximately 0.3% risk of transmission and a mucous membrane exposure 0.09% risk. There have also been cases of HIV transmission through non-intact skin exposure. Potentially infectious body fluids include blood, CSF, genital secretions, breast milk, amniotic, pleural, peritoneal, pericardial, and synovial fluid. Unless visibly contaminated by blood, fluids such as urine, feces, nasal secretions, sputum, vomit, tears, and sweat are not considered infectious.42 The initial evaluation should include a medical history and current medications for the patient, determining the HIV/HBV/HCV status of both the source and patient, and the details of the exposure (e.g., timing, hollow- vs. solid-bore needle, type of body fluid, intact vs. non-intact skin). While an undetectable viral load in the source patient likely indicates a lower risk of infection, it does not eliminate the possibility of transmission.
In a case-control study of healthcare workers (HCW) with occupational needlestick exposure to HIV-infected blood, the risk factors for seroconversion were: deep injury, injury with a device visibly contaminated with patient blood, a procedure that involved needle access to an artery or vein, and a source patient who died of AIDS within two months. Each of these correlates with a higher inoculum of virus in the exposure, either due to volume of blood or as a proxy for the viral load in the source patient. The prompt use of zidovudine was associated with an 81% decrease in risk of acquiring HIV.43
The recommended PEP regimen for needlestick and mucous membrane exposures depends on both the severity of exposure and the infection status of the source patient. (See Table 4.)42 Therapy should be started as soon as possible, preferably within 72 hours, and continued for 28 days. The theoretically increased efficacy of a three-drug PEP regimen should be carefully weighed against the frequent side-effects and poor adherence, especially in the setting of a low-risk exposure. Consider prescribing antiemetics and antimotility agents to be taken on a PRN basis as a significant proportion of patients starting PEP (which contains zidovudine) will experience gastrointestinal side-effects including nausea and vomiting. Safety labs (CBC, chemistries, and liver and renal function tests) should be performed at baseline and 2 weeks after initiating PEP. If the HCW has not been vaccinated for hepatitis B and there is a suspicion that the source patient is infected, then the hepatitis B vaccine and immunoglobulin can be provided up to 7 days after the initial exposure. Whenever possible, the source patient should be tested for HIV, and hepatitis B and C infection; postexposure prophylaxis can be stopped if the source patient tests HIV-negative. The HCW should have HIV testing at baseline, 4-6 weeks, and should be offered testing at 12 weeks and 6 months after exposure, although with current HIV EIAs, seroconversion will occur within 4 weeks in greater than 95% of cases if HIV infection occurs.42
Individuals may also seek care after possible non-occupational HIV exposure, which generally occurs through sexual contact. The initial evaluation should include the determination of the HIV status of the patient and source, the timing and characteristics of the exposure (e.g., type of intercourse, condom use, presence of trauma).44 Baseline HIV testing should be performed to determine whether the patient was infected prior to the exposure. When the HIV status of the source individual is unknown, ideally that individual should be tested. If the risk of HIV exposure is considered high, PEP should be initiated until testing of the source patient is complete. Both animal studies and observational studies show evidence supporting the use of post-exposure prophylaxis in patients with non-occupational HIV exposure.44 Patients who have had unprotected sexual contact, injection drug use, or other high-risk exposures should be considered for PEP if they seek treatment within 72 hours of exposure. Clinicians must evaluate the risks and benefits of antiretroviral therapy on a case-by-case basis.
For those receiving PEP, treatment should be started as soon as possible and continued for a 28-day course. The preferred regimen is a three-drug combination comprised of two NRTIs with a protease inhibitor.44 There is no evidence that any specific ART regimen is superior to others. The commonly used NRTI combinations are Truvada (tenofovir and FTC) or Combivir (AZT and 3TC), and the recommended protease inhibitor is ritonavir-boosted lopinavir (Kaletra). Efavirenz can also be used, but is teratogenic during the first trimester of pregnancy and generally should be avoided in women of child-bearing potential. Ritonavir is a potent inhibitor of cytochrome P450 and has a number of drug interactions that must be taken into account when initiating Kaletra. There is no clear evidence, though, that a three-drug ART regimen is superior to a two-drug regimen, but extrapolation from treatment of HIV-infected patients suggests that it should be used in very high-risk situations. A two-drug regimen (commonly Truvada or Combivir) can be considered for individuals at lower risk of transmission and for whom adherence and toxicity are major concerns. Consider prescribing antiemetics and antimotility agents to be taken on a PRN basis as a significant proportion of patients starting PEP will experience gastrointestinal side-effects including nausea and vomiting, especially if prescribed AZT-containing regimens. Testing and prophylactic treatment for other sexually transmitted diseases including gonorrhea, chlamydia, and hepatitis B (for those not vaccinated) should also be considered. All patients seeking care after a potential HIV exposure should undergo HIV testing at 4-6 weeks, 3 months, and 6 months after exposure.44
HIV and Aging. Antiretroviral therapy has dramatically increased the lifespan of those infected with HIV and caused a significant shift in the demographics. In 2005, 25% of all patients living with HIV/AIDS were older than age 50, but that figure is expected to rise to more than 50% by 2015.45,46 In addition to the complications of ART as described above, HIV infection appears to accelerate the aging process, bringing on more rapid onset of frailty, bone loss, and age-related cognitive, metabolic, cardiovascular, kidney, and liver disease.45,47 This likely occurs through the deleterious effects of chronic inflammation and immune activation.48 Given these findings, the primary care physician will play an even more important role in keeping the older HIV patients healthy through the aggressive optimization of comorbid conditions and lifestyle counseling.
Vaccines. After several negative phase III HIV vaccine studies,49,50 a recent study showed a significant protective effect of an HIV vaccine for the first time.51 In this trial of more than 16,000 healthy Thai volunteers, the use of a recombinant canarypox vector vaccine with a recombinant gp120 subunit booster showed a 31% efficacy in preventing new HIV infections. While there was a modest benefit, this particular vaccine will not be developed further due to the relatively limited protective effect demonstrated and the cumbersome vaccine dosing schedule. As a result, it is likely that it will be at a minimum several years before an effective vaccine is ready for routine use to prevent infection.
Pre-Exposure Prophylaxis (PrEP). Community programs focused on behavioral change and HIV risk reduction have had a significant impact on the number of new infections, but rates of HIV transmission continue to be a challenge, especially among certain high-risk populations.3 As an effective HIV vaccine appears to be many years away, the use of ART as pre-exposure prophylaxis is under study. Several randomized clinical trials are underway testing either tenofovir or tenofovir co-formulated with FTC (Truvada).52 At this time, PrEP cannot be recommended for routine use as its efficacy, safety, and impact on drug resistance are still unknown.
1. HIV prevalence estimatesUnited States, 2006. MMWR Morb Mortal Wkly Rep 2008;57:1073-1076.
2. HIV/AIDS Surveillance Report, 2007. Atlanta: Centers for Disease Control and Prevention; 2009.
3. Hall HI, Geduld J, Boulos D, et al. Epidemiology of HIV in the United States and Canada: Current status and ongoing challenges. J Acquir Immune Defic Syndr 2009;51 Suppl 1:S13-20.
4. El-Sadr WM, Mayer KH, Hodder SL. AIDS in Americaforgotten but not gone. N Engl J Med 2010;362:967-970.
5. Mahoney MR, Fogler J, Weber S, et al. Applying HIV testing guidelines in clinical practice. Am Fam Physician 2009;80:1441-1444.
6. Bartlett JG, Branson BM, Fenton K, et al. Opt-out testing for human immunodeficiency virus in the United States: Progress and challenges. JAMA 2008;300:945-951.
7. Branson BM, Handsfield HH, Lampe MA, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep 2006;55:1-17; quiz CE1-4.
8. Marks G, Crepaz N, Janssen RS. Estimating sexual transmission of HIV from persons aware and unaware that they are infected with the virus in the USA. AIDS 2006;20:1447-1450.
9. Qaseem A, Snow V, Shekelle P, et al. Screening for HIV in health care settings: A guidance statement from the American College of Physicians and HIV Medicine Association. Ann Intern Med 2009;150:125-131.
10. Screening for HIV and Treatment of Acquired Immunodeficiency: American Academy of Family Physicians; 2007.
11. Screening for HIV: U.S. Preventive Services Task Force; 2007.
12. Aberg JA, Kaplan JE, Libman H, et al. Primary care guidelines for the management of persons infected with human immunodeficiency virus: 2009 update by the HIV medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2009;49:651-681.
13. Chou R, Huffman LH, Fu R, et al. Screening for HIV: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2005;143:55-73.
14. Gallant JE. What does the generalist need to know about HIV infection? Adv Chronic Kidney Dis 2010;17:5-18.
15. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. 2009; 1-161. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf
16. Recommended adult immunization schedule: United States, 2010. Ann Intern Med 2010;152:36-39.
17. Pantaleo G, Graziosi C, Fauci AS. New concepts in the immunopathogenesis of human immunodeficiency virus infection. N Engl J Med 1993;328:327-335.
18. Lang W, Perkins H, Anderson RE, et al. Patterns of T lymphocyte changes with human immunodeficiency virus infection: from seroconversion to the development of AIDS. J Acquir Immune Defic Syndr 1989;2:63-69.
19. Kaplan JE, Benson C, Holmes KH, et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 2009;58:1-207; quiz CE1-4.
20. Ho DD. Time to hit HIV, early and hard. N Engl J Med 1995;333:450-451.
21. Sax PE, Baden LR. When to start antiretroviral therapy ready when you are? N Engl J Med 2009;360:1897-1899.
22. Kitahata MM, Gange SJ, Abraham AG, et al. Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 2009;360:1815-1826.
23. Bruyand M, Thiebaut R, Lawson-Ayayi S, et al. Role of uncontrolled HIV RNA level and immunodeficiency in the occurrence of malignancy in HIV-infected patients during the combination antiretroviral therapy era: Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort. Clin Infect Dis 2009;49:1109-1116.
24. Monforte A, Abrams D, Pradier C, et al. HIV-induced immunodeficiency and mortality from AIDS-defining and non-AIDS-defining malignancies. AIDS 2008;22:2143-153.
25. Emery S, Neuhaus JA, Phillips AN, et al. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study. J Infect Dis 2008;197:1133-1144.
26. Calmy A, Gayet-Ageron A, Montecucco F, et al. HIV increases markers of cardiovascular risk: Results from a randomized, treatment interruption trial. AIDS 2009;23:929-939.
27. Attia S, Egger M, Muller M, et al. Sexual transmission of HIV according to viral load and antiretroviral therapy: Systematic review and meta-analysis. AIDS 2009;23:1397-1404.
28. Jain V, Deeks SG. When to start antiretroviral therapy. Curr HIV/AIDS Rep;7:60-68.
29. Gill VS, Lima VD, Zhang W, et al. Improved virological outcomes in British Columbia concomitant with decreasing incidence of HIV type 1 drug resistance detection. Clin Infect Dis 2010;50:98-105.
30. Aberg JA, Ribaudo H. Cardiac risk: Not so simple. J Infect Dis 2010;201:315-317.
31. Brown TT, Li X, Cole SR, et al. Cumulative exposure to nucleoside analogue reverse transcriptase inhibitors is associated with insulin resistance markers in the Multicenter AIDS Cohort Study. AIDS 2005;19:1375-383.
32. Fuller J. A 39-year-old man with HIV-associated lipodystrophy. JAMA 2008;300:1056-1066.
33. Carr A, Workman C, Smith DE, et al. Abacavir substitution for nucleoside analogs in patients with HIV lipoatrophy: A randomized trial. JAMA 2002;288:207-215.
34. Calza L, Manfredi R, Colangeli V, et al. Substitution of nevirapine or efavirenz for protease inhibitor versus lipid-lowering therapy for the management of dyslipidaemia. AIDS 2005;19:1051-1058.
35. Saves M, Raffi F, Capeau J, et al. Factors related to lipodystrophy and metabolic alterations in patients with human immunodeficiency virus infection receiving highly active antiretroviral therapy. Clin Infect Dis 2002;34:1396-1405.
36. Worm SW, Sabin C, Weber R, et al. Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: The data collection on adverse events of anti-HIV drugs (D:A:D) study. J Infect Dis 2010;201:318-330.
37. Achievements in public health. Reduction in perinatal transmission of HIV infectionUnited States, 1985-2005. MMWR Morb Mortal Wkly Rep 2006;55:592-597.
38. HIV testing and prophylaxis to prevent mother-to-child transmission in the United States. Pediatrics 2008;122:1127-1134.
39. Perinatal HIV Guidelines Working Group. Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. 2009; 1-94. http://aidsinfo.nih.gov/ContentFiles/PerinatalGL.pdf
40. Ioannidis JP, Abrams EJ, Ammann A, et al. Perinatal transmission of human immunodeficiency virus type 1 by pregnant women with RNA virus loads <1000 copies/ml. J Infect Dis 2001;183:539-545.
41. Royce RA, Sena A, Cates W, Jr., et al. Sexual transmission of HIV. N Engl J Med 1997;336:1072-1078.
42. Panlilio AL, Cardo DM, Grohskopf LA, et al. Updated U.S. Public Health Service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep 2005;54:1-17.
43. Cardo DM, Culver DH, Ciesielski CA, et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group. N Engl J Med 1997;337:1485-1490.
44. Smith DK, Grohskopf LA, Black RJ, et al. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States: Recommendations from the U.S. Department of Health and Human Services. MMWR Recomm Rep 2005;54:1-20.
45. Effros RB, Fletcher CV, Gebo K, et al. Aging and infectious diseases: Workshop on HIV infection and aging: What is known and future research directions. Clin Infect Dis 2008;47:542-553.
46. Simone MJ, Appelbaum J. HIV in older adults. Geriatrics 2008;63:6-12.
47. Sax PE. Assessing risk for cardiovascular disease in patients with human immunodeficiency virus: Why it matters. Circulation 2010;121:620-2.
48. Kuller LH, Tracy R, Belloso W, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med 2008;5:e203.
49. Pitisuttithum P, Gilbert P, Gurwith M, et al. Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand. J Infect Dis 2006;194:1661-1671.
50. Buchbinder SP, Mehrotra DV, Duerr A, et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): A double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 2008;372:1881-1893.
51. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 2009;361:2209-2220.
52. Mansergh G, Colfax G, McKirnan D, et al. Use and Sharing of Antiretroviral Medications for Pre- and Post-exposure Prophylaxis to Prevent Sexual Transmission of HIV among High-risk, Substance-using Men Who Have Sex with Men in 4 US Cities. In: 17th Conference on Retroviruses and Opportunistic Infections; February 16-19, 2010, San Francisco; Abstract #957.