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HIV and Disability: Updating the Social Security Listings 6 HIV-Associated Conditions With Listings Elsewhere As discussed in Chapter 2, a new set of medical conditions associated with HIV infection has emerged in recent years. These conditions are also seen in the general population and include cardiovascular disease and malignancies. In the United States, these and other conditions have become the leading cause of morbidity and mortality for persons living with HIV infection. Chapter 5 reviewed HIV-associated conditions currently not covered elsewhere in the Listing of Impairments. In contrast, some comorbid conditions occurring with increased frequency or at an earlier age among people living with HIV are already mentioned elsewhere in the Listings. In these instances, the Social Security Administration (SSA) has processes in place to deal with claimants affected by multiple conditions. One procedure called cross-referencing allows claims to be decided based on the specific requirements of an existing listing. CONDITIONS COVERED ELSEWHERE IN THE LISTINGS The prevalence of disabling chronic conditions already included in the Listing of Impairments separately from the HIV Infection Listings (see Box 6-1) is growing among HIV-infected populations and will likely increase as people live longer with HIV infection. Although HIV infection increases the risk for developing these conditions and in some instances accelerates the rate of disease progression, the comorbid conditions in Box 6-1 are generally not clinically distinct and can be evaluated adequately using the current listing criteria.
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HIV and Disability: Updating the Social Security Listings BOX 6-1 List of HIV-Associated Conditions With Current Listings Elsewhere in the Listing of Impairments HIV-associated conditions that have current listings in the Listing of Impairments, not covered in the HIV Infection Listings, include the following, but are not limited to: Cardiovascular disease; Chronic kidney disease, including HIV-associated nephropathy; Diabetes; Hepatitis; and Malignancies, not otherwise specified in the report. Cardiovascular Disease An increased risk for cardiovascular disease in HIV-infected populations as compared with HIV-negative populations has been well documented (Currier et al., 2008). Cardiovascular disease is the leading cause of death of Americans. It is also a leading cause of death in those infected with HIV, with an analysis of the Data Collection on Adverse Events of Anti-HIV Drugs Study finding that 11 percent of HIV-positive people die from a cardiovascular condition (Smith and the D:A:D Study, 2009). The risk factors for cardiovascular disease in HIV-infected populations are the same as those in the general population, including smoking, older age, diabetes, male gender, and other prior cardiovascular conditions (Currier et al., 2008; Glass et al., 2006). Increasingly, HIV infection itself is considered a cardiovascular disease risk factor, probably as or more important than the conventional ones. The exact mechanisms and extent of the relationship between HIV and cardiovascular disease are not well understood. Hypotheses suggest increased cardiovascular disease can be related to HIV infection and, to a lesser extent, combination antiretroviral therapies. A review of cohort studies indicated that HIV-infected adults are at higher risk of cardiovascular disease than adults without HIV (Currier et al., 2008). The presence of HIV can lead to changes in lipid profiles that are themselves cardiovascular disease risk factors, such as low HDL-C and high triglyceride levels (Aberg, 2009). HIV is also implicated in chronic inflammation, which can be a cause of endothelial dysfunction, a risk factor for atherosclerosis (de Saint Martin et al., 2007). While the risk of developing cardiovascular disease is elevated in conjunction with HIV infection, the disease profile and impact on disability is similar to that in uninfected individuals.
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HIV and Disability: Updating the Social Security Listings Studies of the effects of antiretroviral agents on cardiovascular disease risk are mixed. A literature review concluded that combination antiretroviral therapy has only a modest effect on increased cardiovascular risk (Aberg, 2009). The association of protease inhibitors with metabolic disturbances is complex—effects might be attributed to the specific drug and might not be applicable to the entire drug class. For example, indinavir and lopinavir-ritonavir have been shown to increase risk of myocardial infarction in 12 and 13 percent of patients, respectively (Worm et al., 2010), whereas the whole class of protease inhibitors was found to affect 16 percent of patients (The D:A:D Study Group, 2007). The nucleoside reverse transcriptase inhibitors abacavir and didanosine were also associated with an increased risk of myocardial infarction (Worm et al., 2010). One study found an increased risk of hypertension in patients taking nonnucleoside reverse transcriptase inhibitors as compared to HIV-positive patients not on antiretroviral treatment (Wilson et al., 2009). Cardiovascular disease is a significant cause of disability among Americans and is covered by SSA’s Listing of Impairments under the Cardiovascular System (Listings 4.00 and 104.00). Cardiovascular disease is also a significant comorbidity of HIV infection. The committee concludes that HIV-infected claimants with disability due to cardiovascular disease should be considered under the Cardiovascular System Listings. Chronic Kidney Disease, Including HIV-Associated Nephropathy Chronic kidney disease includes HIV-associated nephropathy and end-stage renal disease (Gupta et al., 2005; Lucas et al., 2007; Szczech et al., 2004a; Winston et al., 2008). About 30 percent of HIV patients experience abnormal kidney functioning. Defined in Listing 6.00 as kidney damage or a glomerular filtration rate ≤ 60 mL/min for 3 or more months (National Kidney Foundation, 2002), chronic kidney disease can leave people at greater risk for faster progression to AIDS-defining illnesses and death (Szczech et al., 2004b). The disease is similar between seropositive and seronegative populations. Although the literature about the relationship between chronic kidney disease and HIV and its treatment is still developing, the incidence of chronic kidney disease appears to be slowing. Incidence of chronic kidney disease decreased significantly after the introduction of combination antiretroviral therapy. Although prevalence increased, this increase is potentially due to longer survival times (Lucas et al., 2007). Chronic kidney failure is diagnosed through screening urine analysis, calculated estimates of renal function (e.g., creatinine clearance, glomerular filtration rate), and kidney biopsy. These tests are recommended by the Infectious Disease Society of America’s Guidelines for the Management of Chronic Kidney Disease in HIV-Infected Patients (Gupta et al., 2005).
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HIV and Disability: Updating the Social Security Listings In addition to HIV infection, renal functioning can be impaired by diabetes and hypertension. Hepatitis C is also a risk factor for chronic kidney disease. Nephrotoxicity can be induced by HIV treatments, such as indinivir and tenofovir (Izzedine et al., 2005; Szczech et al., 2004a; Winston et al., 2008). Renal failure in HIV patients is also known as HIV-associated nephropathy, which is characterized by significant proteinuria and quick advancement to end-stage renal disease due to scarring of blood vessels in the kidneys. Today, HIV-associated nephropathy remains an aggressive disease, especially when it advances to the point of requiring dialysis. One-year survival has increased from 25 to 75 percent (Winston et al., 2008). While one study found the overall prevalence of HIV-associated nephropathy to be 6.9 percent (Shahinian et al., 2000), the true prevalence is unknown. HIV-associated nephropathy is definitively diagnosed only by kidney biopsy, but they are performed relatively infrequently. Kidney biopsies have shown that the condition is present in approximately 40 to 60 percent of specimens taken from HIV-infected individuals (Szczech et al., 2004a). Disability due to impaired renal functioning is described in and adjudicated based on the Genitourinary Impairment Listings (6.00 and 106.00), although the more current term is chronic kidney disease. Because HIV and its treatments do not result in a form of chronic kidney disease distinct from the Genitourinary Impairment Listings, it ought to be cross-referenced to those listings. HIV-associated nephropathy is not specifically mentioned in the Genitourinary Impairment Listings, but because it has the same end result as renal failure it is adequately covered by those listings. Furthermore, SSA may wish to consider adopting changes to the aforementioned guidelines for managing chronic kidney disease in HIV patients in the future as a method of keeping up with advances in treatment. Diabetes Diabetes is a metabolic disease characterized by high blood glucose levels and leading eventually to multisystem complications, such as kidney failure, cardiovascular disease, retinopathy, and neuropathy. Diabetes is diagnosed through blood glucose tests. The American Diabetes Association has set diagnostic standards that include the following as meeting the definition of diabetes: 2-hour plasma glucose ≥ 200 mg/dL, fasting glucose ≥ 126 mg/dL, or hemoglobin A1C ≥ 6.5 percent (American Diabetes Association, 2009; The International Expert Committee, 2009). The number of people with concomitant diabetes and HIV has increased since the introduction of combination antiretroviral therapy. The prevalence of diabetes among men infected with HIV in the Multicenter AIDS Cohort Study was 14 percent, significantly greater than among un-
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HIV and Disability: Updating the Social Security Listings infected controls, and was associated with a nadir CD4 cell count under 300 cells/mm3 (Winston et al., 2008). In the Swiss HIV Cohort Study, the risk for developing diabetes was associated with protease inhibitors and nucleoside reverse transcriptase inhibitor therapy (Ledergerber et al., 2007). In contrast, the Women’s Interagency HIV Study failed to document increased risk for diabetes associated with HIV infection, although among HIV-infected women, longer duration of nucleoside-based therapy was associated with greater risk (Tien et al., 2007). This finding contrasts with an earlier analysis of data from the same cohort, which concluded that protease inhibitors were associated with a three-fold increased rate of self-reported diabetes (Justman et al., 2003). Although the complete picture of metabolic dysfunction in the setting of HIV infection remains to be described, clearly people with HIV infection are at risk for developing diabetes as a result of preexisting factors such as diet, environment, and genetics, in addition to the effects of HIV and its treatment. Diabetes is listed as part of the Endocrine System in the Listing of Impairments (specifically Listing 9.08), which lists neuropathy, acidosis, and retinitis proliferans as the conditions under which allowances should be made. Listing 109.08 requires recurrent acidosis, hypoglycemia, retarded growth, and reduced renal functioning for juvenile diabetes. Claimants with both HIV and diabetes should be cross-referenced to Listings 9.08 and 109.08. Hepatitis Hepatitis is a general term referring to a variety of diseases leading to inflammation of the liver cells, the hepatocytes. Hepatitis ranges from an asymptomatic, self-limited condition to a fulminant, rapidly fatal disease. Chronic hepatitis can lead to liver fibrosis called cirrhosis, hepatocellular carcinoma, and chronic impairment of liver function. Hepatitis can be caused by infections, drugs, and collagen-vascular diseases, but the most common causes of HIV infection follow coinfection with the hepatitis B or C viruses (HBV and HCV, respectively). Also important are cases of liver injury from drugs used in HIV management either as a direct drug toxicity or as part of an inflammatory response to the restored immune system following the introduction of antiretroviral drugs. Hepatitis B is most commonly diagnosed through blood tests for the hepatitis B surface antigen, hepatitis B virus DNA, and hepatitis B early antigen. Tests to detect the presence of hepatitis C viral RNA are used to diagnose hepatitis C. Findings indicate that HIV has been shown to accelerate progression to cirrhosis and hepatocellular cancer in hepatitis C-coinfected patients and that coinfected patients may not respond as well to treatment of hepatitis
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HIV and Disability: Updating the Social Security Listings C (Soriano et al., 2002; Sulkowski, 2004). Whether combination antiretroviral therapy improves liver function in those coinfected with either HBV or HCV remains unclear, but it does slow hepatitis progression. Coinfection is also an indication to initiate HIV therapy at an early stage of HIV infection. Hepatitis is discussed in the Digestive System Listings (specifically, chronic liver disease is covered in Listings 5.05 and 105.05). The committee suggests editorial changes be made within 5.00 and 105.00, the introductory text that describes chronic viral hepatitis infections (specifically 5.00D4 and 105.00D4), to better reflect the current state of hepatitis care. This includes stating that HIV infection may accelerate the clinical course of viral hepatitis infection and patients infected with HIV may have a poorer response to treatment instead of simply stating that it may affect the clinical course of disease; including hepatitis B virus DNA as a method of diagnosing hepatitis B infection; revising “hepatitis B envelope antigen” to “hepatitis B early antigen” or “hepatitis B ‘e’ antigen”; adding “hepatocellular carcinoma” to end-stage liver disease and cirrhosis as a condition with increased risk of progression; and removing “combination of interferon injections” as a method of suppressing hepatitis B virus. Because HIV and hepatitis coinfection does not necessarily redefine the level of disability but instead causes people to reach the same level of disease severity more quickly, cross-referencing to Listings 5.05 and 105.05 is appropriate for HIV-infected claimants also living with hepatitis. Malignancies Not Otherwise Specified Cancers in people living with HIV/AIDS can be fatal and can lead to high levels of morbidity. These conditions have been classified into two groups: AIDS-defining cancers and non-AIDS–defining cancers. AIDS-defining cancers, as identified by the Centers for Disease Control and Prevention, are Kaposi’s sarcoma, invasive cervical cancer, and non-Hodgkin’s lymphoma, both those arising within the central nervous system (CNS) and ones arising peripheral to that site. Non-AIDS–defining cancers are all other cancers that manifest in HIV-infected persons. Some malignancies are specifically discussed in prior chapters—primary CNS lymphomas (Chapter 4), Kaposi’s sarcoma (Chapters 4 and 5), and primary effusion lymphoma (Chapter 4)—because of the aggressive nature of the condition or because they are still relatively common clinical conditions despite the wide use of antiretroviral therapy. Since the development of potent combination antiretroviral therapy, the incidence of AIDS-defining cancers has dramatically decreased (Brodt et al., 1997; Buchacz et al., 2010; Grulich et al., 2001; Rabkin et al., 1993). However, non-AIDS–defining cancers are increasingly common, whether
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HIV and Disability: Updating the Social Security Listings simply reflecting the now aging cohort of HIV-infected persons benefiting from HIV therapy or growing at an increased rate caused by HIV infection and immune deficiency or inflammation or even as an adverse effect of antiretroviral drugs. The standardized incidence rate for all non-AIDS–defining cancers is about twice that of the general population, although this is an area of active, ongoing investigation (Powles et al., 2009; Shiels et al., 2009). The most common non-AIDS–defining cancers include cancers of the anus, liver, lung, oropharynx, and Hodgkin’s lymphoma (Nguyen et al., 2010; Patel et al., 2008; Powles et al., 2009). Generally, the severity of these cancers is not increased as a result of HIV coinfection and they respond comparably to chemotherapeutic management. One exception is Hodgkin’s lymphoma, which may be more aggressive in HIV/AIDS patients (Powles et al., 2009). The risk factors for these cancers depend on the type of malignancy. For example, smoking is a major risk factor for lung cancer, both in the general population and in the HIV-positive population; this can be attributed in part to higher smoking rates in the HIV-positive population and longer duration of tobacco exposure (Nguyen et al., 2010). Interestingly, most cancers that appear to have an increased incidence in HIV-infected persons have a second viral infection as a potential cause, including oropharyngeal cancer (Epstein-Barr virus), anal cancer (human papillomavirus), and hepatocellular cancer (HBV, HCV). The effect of combination antiretroviral therapy on the increased risk of non-AIDS–defining cancers is unclear. Nonnucleoside reverse transcriptase inhibitors may be associated with an increased risk of Hodgkin’s lymphoma (Powles et al., 2009), and an increase in cancer was reported with an early CCR5 inhibitor, but the literature is limited about the effects of specific classes of antiretroviral therapy on developing malignancies. Combination antiretroviral therapy may improve survival for some types of cancers, but this is not yet well supported in the literature (Nguyen et al., 2010). Malignancies not otherwise specified in this report can be disabling and are important to consider in the management of HIV/AIDS. These malignancies are generally not unique from malignancies in noninfected individuals. These conditions follow the same standard treatment regimens as in the general population. Therefore, the committee concludes that malignancies should be considered under the Malignant Neoplastic Diseases Listings (13.00 and 113.00). COMORBIDITY IN THE LISTINGS SSA has specific processes in place to deal with claimants affected by multiple conditions. A process called cross-referencing can be used at the Listings step, where the claim is “referred” to an existing listing and the
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HIV and Disability: Updating the Social Security Listings decision is made based on the specific requirements of that listing. For example, a claimant coinfected with HIV and hepatitis can currently be adjudicated under either Listing 5.05, chronic liver disease, or Listing 14.08K, repeated manifestations of HIV. If the primary impairment is hepatitis and the claimant does not meet the 14.08K listing, the claim can be referred to 5.05. In this case, the claim is adjudicated in the same way as a hepatitis claim without HIV is, regardless of the claimant’s HIV diagnosis, unless the condition is also part of the HIV Infection Listings. Upon assessment of the criteria currently in the Listing of Impairments for these other infections, the committee determined that these were appropriate for assessing disability for individuals with HIV coinfection. Because the condition is not usually clinically distinct and can be captured adequately by other disability listings, the committee concluded that HIV coinfection with one of the conditions listed in Box 6-1 should be cross-referenced to other listings. RECOMMENDATION 5. SSA should cross-reference the following HIV-associated conditions to existing listings: Cardiovascular disease (Listings 4.00 and 104.00); Chronic kidney disease, including HIV-associated nephropathy (Listing 6.00 and 106.00); Diabetes (Listings 9.08 and 109.08); Hepatitis (Listings 5.05 and 105.05); and Malignancies (Listings 13.00 and 113.00), not otherwise specified in the report. This recommendation differs from Recommendation 4 in two ways. First, the duration of these allowances should follow the durations identified by the other sublistings. However, if the literature is found to show that HIV coinfection causes changes to the disease not effectively captured in other disability listings, SSA may want to consider adding the disease to the HIV Infection Listings. Second, unlike conditions in Recommendation 4, the conditions discussed in this chapter are not linked to functional criteria to allow for the conditions to be easily cross-referenced. REFERENCES Aberg, J. A. 2009. Cardiovascular complications in HIV management: Past, present, and future. Journal of Acquired Immune Deficiency Syndromes 50(1):54–64. American Diabetes Association. 2009. Standards of medical care in diabetes—2009. Diabetes Care 32(Suppl 1):S13–S61. Brodt, H. R., B. S. Kamps, P. Gute, B. Knupp, S. Staszewski, and E. B. Helm. 1997. Changing incidence of AIDS-defining illnesses in the era of antiretroviral combination therapy. AIDS 11(14):1731–1738.
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HIV and Disability: Updating the Social Security Listings Buchacz, K., R. K. Baker, F. J. J. Palella, J. S. Chmiel, K. A. Lichtenstein, R. M. Novak, K. C. Wood, J. T. Brooks, and the HOPS Investigators. 2010. AIDS-defining opportunistic illnesses in US patients, 1994–2007: A cohort study. AIDS 24(10):1549–1559. Currier, J. S., J. D. Lundgren, A. Carr, D. Klein, C. A. Sabin, P. E. Sax, J. T. Schouten, and M. Smieja for Working Group 2. 2008. Epidemiological evidence for cardiovascular disease in HIV-infected patients and relationship to highly active antiretroviral therapy. Circulation 118(2):e29–e35. The D:A:D Study Group. 2007. Class of antiretroviral drugs and the risk of myocardial infarction. New England Journal of Medicine 356(17):1723–1735. de Saint Martin, L., E. Pasquier, O. Vandhuick, B. Arnaud, S. Vallet, J. Duchemin, V. Bellein, and L. Bressollette. 2007. Correlations between carotid IMT, Factor VIII activity level and metabolic disturbances: A cardiovascular risk factor in the HIV positive persons. Current HIV Research 5(3):361–364. Glass, T., C. Ungsedhapand, M. Wolbers, R. Weber, P. Vernazza, M. Rickenbach, H. Furrer, E. Bernasconi, M. Cavassini, B. Hirschel, M. Battegay, and H. Bucher. 2006. Prevalence of risk factors for cardiovascular disease in HIV-infected patients over time: The Swiss HIV cohort study. HIV Medicine 7(6):404–410. Grulich, A. E., Y. Li, A. M. McDonald, P. K. Correll, M. G. Law, and J. M. Kaldor. 2001. Decreasing rates of Kaposi’s sarcoma and non-Hodgkin’s lymphoma in the era of potent combination anti-retroviral therapy. AIDS 15(5):629–633. Gupta, S. K., J. A. Eustace, J. A. Winston, I. I. Boydstun, T. S. Ahuja, R. A. Rodriguez, K. T. Tashima, M. Roland, N. Franceschini, F. J. Palella, J. L. Lennox, P. E. Klotman, S. A. Nachman, S. D. Hall, and L. A. Szczech. 2005. Guidelines for the management of chronic kidney disease in HIV-infected patients: Recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clinical Infectious Diseases 40(11):1559–1585. The International Expert Committee. 2009. International expert committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 32(7):1327–1334. Izzedine, H., V. Launay-Vacher, and G. Deray. 2005. Antiviral drug-induced nephrotoxicity. American Journal of Kidney Diseases 45(5):804–817. Justman, J. E., L. Benning, A. Danoff, H. Minkoff, A. Levine, R. M. Greenblatt, K. Weber, E. Piessens, E. Robison, and K. Anastos. 2003. Protease inhibitor use and the incidence of diabetes mellitus in a large cohort of HIV-infected women. Journal of Acquired Immune Deficiency Syndromes 32(3):298–302. Ledergerber, B., H. Furrer, M. Rickenbach, R. Lehmann, L. Elzi, B. Hirschel, M. Cavassini, E. Bernasconi, P. Schmid, M. Egger, and R. Weber. 2007. Factors associated with the incidence of type 2 diabetes mellitus in HIV-infected participants in the Swiss HIV cohort study. Clinical Infectious Diseases 45(1):111–119. Lucas, G. M., S. H. Mehta, M. G. Atta, G. D. Kirk, N. Galai, D. Vlahov, and R. D. Moore. 2007. End-stage renal disease and chronic kidney disease in a cohort of African-American HIV-infected and at-risk HIV-seronegative participants followed between 1988 and 2004. AIDS 21(18):2435–2443. National Kidney Foundation. 2002. K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification, http://www.kidney.org/professionals/kdoqi/guidelines/doqi_upex.html (accessed March 2, 2010). Nguyen, M. L., K. J. Farrell, and C. J. Gunthel. 2010. Non-AIDS–defining malignancies in patients with HIV in the HAART era. Current Infectious Disease Reports 12(1):46–55. Patel, P., D. L. Hanson, P. S. Sullivan, R. M. Novak, A. C. Moorman, T. C. Tong, S. D. Holmberg, and J. T. Brooks. 2008. Incidence of types of cancer among HIV-infected persons compared with the general population in the United States, 1992–2003. Annals of Internal Medicine 148(10):728–736.
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HIV and Disability: Updating the Social Security Listings Powles, T., D. Robinson, J. Stebbing, J. Shamash, M. Nelson, B. Gazzard, S. Mandelia, H. Moller, and M. Bower. 2009. Highly active antiretroviral therapy and the incidence of non-AIDS–defining cancers in people with HIV infection. Journal of Clinical Oncology 27(6):884–890. Rabkin, C. S., R. J. Biggar, M. S. Baptiste, T. Abe, B. A. Kohler, and P. C. Nasca. 1993. Cancer incidence trends in women at high risk of human immunodeficiency virus (HIV) infection. International Journal of Cancer 55(2):208–212. Shahinian, V., S. Rajaraman, M. Borucki, J. Grady, W. M. Hollander, and T. S. Ahuja. 2000. Prevalence of HIV-associate nephropathy in autopsies of HIV-infected patients. American Journal of Kidney Diseases 35:884–888. Shiels, M. S., S. R. Cole, G. D. Kirk, and C. Poole. 2009. A meta-analysis of the incidence of non-AIDS cancers in HIV-infected individuals. Journal of Acquired Immune Deficiency Syndromes 52(5):611–622. Smith, C., and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study. 2009. Association between modifiable and non-modifiable risk factors and specific causes of death in the HAART era: The data collection on adverse events of anti-HIV drugs study. Paper presented at Conference on Retroviruses and Opportunistic Infections Montreal, Canada, February 8–11. Soriano, V., M. Sulkowski, C. Bergin, A. Hatzakis, P. Cacoub, C. Katlama, A. Cargnel, S. Mauss, D. Dieterich, S. Moreno, C. Ferrari, T. Poynard, and J. Rockstroh. 2002. Care of patients with chronic hepatitis C and HIV co-infection: Recommendations from the HIV–HCV international panel. AIDS 16(6):813–828. Sulkowski, M. S. 2004. Hepatitis C virus infection in HIV-infected patients. Current HIV/ AIDS Reports 1(3):128–135. Szczech, L. A., S. K. Gupta, R. Habash, A. Guasch, R. Kalayjian, R. Appel, T. A. Fields, L. P. Svetkey, K. H. Flanagan, P. E. Klotman, and J. A. Winston. 2004a. The clinical epidemiology and course of the spectrum of renal diseases associated with HIV infection. Kidney International 66(3):1145–1152. Szczech, L. A., D. R. Hoover, J. G. Feldman, M. H. Cohen, S. J. Gange, L. Goozé, N. R. Rubin, M. A. Young, X. Cai, Q. Shi, W. Gao, and K. Anastos. 2004b. Association between renal disease and outcomes among HIV-infected women receiving or not receiving antiretroviral therapy. Clinical Infectious Diseases 39(8):1199–1206. Tien, P. C., M. F. Schneider, S. R. Cole, A. M. Levine, M. Cohen, J. Dehovitz, M. Young, and J. E. Justman. 2007. Antiretroviral therapy exposure and incidence of diabetes mellitus in the Women’s Interagency HIV Study. AIDS 21(13):1739–1745. Wilson, S., G. Scullard, S. Fidler, J. Weber, and N. Poulter. 2009. Effects of HIV status and antiretroviral therapy on blood pressure. HIV Medicine 10(6):388–394. Winston, J., G. Deray, T. Hawkins, L. Szczech, C. Wyatt, and B. Young. 2008. Kidney disease in patients with HIV infection and AIDS. Clinical Infectious Diseases 47(11):1449–1457. Worm, S. W., C. Sabin, R. Weber, P. Reiss, W. El-Sadr, F. Dabis, S. De Wit, M. Law, A. D. Monforte, N. Friis-Møller, O. Kirk, E. Fontas, I. Weller, A. Phillips, and J. Lundgren. 2010. 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. Journal of Infectious Diseases 201(3):318–330.