HIV-Associated Conditions Without Listings Elsewhere
The course of HIV and the compounding effects of its comorbidities and treatment are sometimes difficult to predict, complicating decisions about whether people are able to work and for what period of time. A number of potentially severe HIV-associated conditions can be disabling, even though they are not imminently fatal. These impairments can be the result of the disease itself, adverse effects of HIV treatments, comorbid diseases, or from the treatment of those conditions.
Some concurrent conditions are covered in the Listing of Impairments, but others are not. The committee considered the two groups separately because a current listing provides these claimants with a path to being deemed disabled. If a current listing does not exist for conditions that can be truly disabling, a path to receive disability benefits will need to be identified. HIV-associated conditions without listings mentioned elsewhere in the Listing of Impairments are discussed in this chapter. Conditions covered elsewhere in the Listing of Impairments are discussed in Chapter 6.
THE IMPORTANCE OF FUNCTIONING IN DETERMINING DISABILITY
As discussed later in this chapter, the committee believes that in the era of potent antiretroviral therapy, the presence of an opportunistic infection or a manifestation of HIV alone is insufficient to declare a person unable to work. For instance, adverse effects of treatment can affect one’s ability to work (e.g., interferon therapy for hepatitis C leads to malaise and fever), but the extent to which these residual conditions impair functioning is
unknown. Therefore, even though the literature is unclear, the committee believes, based on its expertise, the combination of clinical severity and limited functional capacity can allow for an appropriate determination of disability to be made. The severity of the conditions in Box 5-1 can be more appropriately determined by coupling objective tests of medical impairment with an assessment of functioning.
The committee examined the literature for widely accepted, valid measures of functioning to determine which measures of functioning should be used (see Appendix D). As discussed in Chapter 1, few such measures were identified, none of which are commonly found in a claimant’s medical record. The current 14.08K sublisting, as well as other listings in the immune and mental disorders body systems, incorporates three measures of functioning: (1) limitation of activities of daily living; (2) limitation in maintaining social functioning; and (3) limitation in completing tasks in a timely manner due to deficiencies in concentration, persistence, or pace. The committee found disability examiners to be familiar with the requirements, generally to like this sublisting, and to be fairly comfortable using it. This is supported by the fact that sublisting 14.08K provides the second most
List of HIV-Associated Conditions Without Current Listings Elsewhere in the Listing of Impairments
Comorbidities induced by HIV and its treatment currently without listings elsewhere include, but are not limited to:
These conditions should be considered in the HIV Infection Listing when diagnosed in a person with established HIV infection and marked limitation in functioning in one or more of the following areas:
Symptoms such as fatigue, malaise, and pain also should be considered if found to limit functioning.
allowances in the HIV Infection Listing (see Figure 1-2). In the absence of a single, widely used measure of functioning for people living with HIV/ AIDS, the committee believes these three measures should be retained in a revised listing.
RECOMMENDATION 3. SSA should continue to include measures of functional capacity in the HIV Infection Listings and update these measures with research advances.
Although opportunistic infections now occur, albeit at a lower rate, they can still be associated with early mortality. Based on data received from the NA ACCORD and EuroSIDA databases (Justice et al., 2010; Mocroft and the EuroSIDA Study Group, 2010), the committee believes that the majority of HIV-infected people with severe opportunistic infections would be captured by a CD4 ≤ 50 cells/mm3 listing, as discussed in Chapter 3. Disability assessment could also be triggered by poor functional status based on the above three measures of functioning; such allowances could “equal” a listing or be determined at a later stage.
CONDITIONS CURRENTLY WITHOUT LISTINGS
Advances in treatment have reduced the frequency of many opportunistic infections and manifestations currently in the HIV Infection Listings. These infections and manifestations are generally less common, no longer necessarily permanently debilitating, or less predictive of disability than they were in 1993 when the HIV Infection Listings were developed. It is now uncommon for patients to present with these manifestations to the point that they are both unresponsive to standard therapy and completely disabled. For example, diarrhea attributed to HIV infection that is resistant to treatment and lasting for more than 12 months is extremely uncommon today. These manifestations can become persistent as a result of late-stage AIDS that is untreated or unresponsive to treatment due to increased drug resistance or nonadherence with persistent viremia. The committee assumes that allowances for these conditions would be made based on the notion that HIV-associated conditions would be chronic, as the SSA definition of disability requires that the impairment last for a minimum of 12 months or result in death. Other unlisted conditions could conceivably be considered as medically equaling the Listings.
Two major causes of diarrhea are associated with HIV: opportunistic infections (e.g., cryptosporidiosis, microsporidiosis) and adverse reactions
to medications. HIV infection complicated by the opportunistic infections that were causes of debilitating diarrhea in the era prior to combination antiretroviral therapy are now relatively rare as a result of this therapy. Now the more common cause of diarrhea is adverse reactions to medicines, which show variable rates depending on the drug.
Severe cases of diarrhea can lead to dehydration and malnutrition, and have been found to significantly reduce quality of life in areas such as physical functioning, social functioning, and fatigue (Siddiqui et al., 2007). The Nutrition for Healthy Living Cohort found 28 percent of 671 patients had chronic diarrhea. This was more common in those with an AIDS-defining illness than HIV-positive patients in earlier stages of disease (Knox et al., 2000). The current incidence of chronic diarrhea is higher in the HIV-infected population than the general population, but can often be managed by changes in the anti-HIV regimen or by symptomatic treatment using diphenoxylate, loperamide, curcumin, or mesalamine.
Despite these advances, a small number of patients still have chronic and sometimes debilitating diarrhea from an opportunistic infection that cannot be effectively treated or diarrhea as an adverse reaction to antiretroviral agents that cannot be changed due to limited options (Esser et al., 2007; Monkemuller et al., 2000; Siddiqui et al., 2007; Tinmouth et al., 2007; Tramarin et al., 2004).
Although acute diarrhea continues to be a serious ailment affecting the lives of many infected with HIV, it usually resolves spontaneously or with treatment. Acute diarrhea does not meet the statutory definition of disability where a condition must last for 12 months or result in death. Chronic diarrhea is defined by the committee as a change in bowel habit with at least three loose or watery stools (i.e., take the form of the container) lasting for at least 3 weeks and unresponsive to standard treatment. Treatment protocols vary based on the cause of diarrhea and the stage of HIV infection. Many microbial pathogens can be treated with antibiotics, and some require combination antiretroviral therapy with immune recovery. Some patients benefit from “nonspecific therapy” such as loperamide.
Diarrhea is not specifically mentioned in other parts of the Listing of Impairments. Although cases of HIV patients with diarrhea that lasts for at least 12 months or result in death are rare, some do exist in late presenters or as a result of toxicity to HIV treatment. Therefore, the committee determined diarrhea should be included in the HIV Infection Listings when associated with marked limitation in functioning.
Distal Sensory Polyneuropathy
Peripheral neuropathy is a disease of the peripheral nervous system, associated with pain, weakness, and sensations such as burning and numb-
ness. This can lead to nerve damage and can reduce quality of life. For example, patients may have difficulty walking, persistent pain, and absence of sensation. Many forms of HIV-associated peripheral neuropathy exist, with the most common among HIV patients being distal sensory polyneuropathy.
Prevalence is increasing, with more than one-third of HIV patients having symptomatic distal sensory polyneuropathy, and up to an additional one-third without symptoms (Gonzalez-Duarte et al., 2007; Schifitto et al., 2005); another study found 58 percent of HIV-infected patients with signs of peripheral neuropathy (Ellis et al., 2008). Symptoms include sensations of burning, hypersensitivity to touch, and tingling and various types of pain, mostly in the extremities, which compromise quality of life, cause decline in everyday function, and can lead to unemployment (Ellis et al., 2010). Incidence has been shown to both decrease and remain the same with the use of combination antiretroviral therapy (Gonzalez-Duarte et al., 2007; Lichtenstein et al., 2005). More advanced HIV disease, exposure to combination antiretroviral therapy, and older age all contribute to increased frequency of neuropathy (Ellis et al., 2008). The drugs that were most frequently implicated (ddI, d4T, and ddC) are now used infrequently (ddI and d4T) or no longer made (ddC). This condition is generally irreversible and sometimes requires aggressive pain management, including use of narcotics.
With a wide range of symptoms, peripheral neuropathy is difficult to diagnose, requiring a neurologic examination. The exact etiology of distal sensory polyneuropathy is unknown, but as indicated above, it is associated with HIV infection, antiretroviral therapy, or possibly comorbid conditions such as hepatitis C coinfection (Ellis et al., 2008).
Peripheral neuropathy is assessed under Listing 11.14 of the neurologic body system. However, this Listing refers to motor functioning, as opposed to sensory functioning, which is found to afflict HIV patients. For this reason, distal sensory polyneuropathy that is associated with marked functional impairment should be considered as part of revised HIV Infection Listings.
HIV-Associated Neurocognitive Disorders
HIV infection frequently results in neurological complications, some of the most frequent of which are neurocognitive. HIV-associated neurocognitive disorders (HAND) are characterized by a decline in cognitive functioning affecting multiple domains (see Box 5-2).
Despite modern combination antiretroviral therapies, HAND has been reported in approximately 40 percent of those with HIV infection (Antinori et al., 2007; Heaton et al., 2010). HAND is prevalent in more advanced
Most Commonly Affected Domains of Cognitive Functioning
stages of HIV disease (e.g., in approximately 50 percent of those individuals who meet the criteria for AIDS) and tends to be more severe in those with the greatest immune compromise (e.g., current CD4 less than 50 cells/mm3, nadir CD4 less than 200 cells/mm3, and high viremia) (Heaton et al., 2010). HAND outcomes vary, with some cases improving, especially with long-term viral suppression and immune reconstitution. Other cases manifest static impairment, and others develop a fluctuating or declining course. Periodic reassessments of status are therefore desirable.
Three levels of HAND have been defined (Antinori et al., 2007):
HIV-associated dementia (HAD), introduced in Chapter 4, refers to severe impairment in at least two cognitive domains (see Box 5-2) that markedly or extremely affect everyday functioning. Commonly the individual is unable to carry out more than the most basic activities of daily living independently (e.g., eating, bathing, dressing). Typically the diagnosis can be made by a clinician based on a mental status evaluation, assessing the domains of cognitive functioning. If neuropsychological testing is carried out, HAD can be identified by performance that falls 2 standard deviations or more below expected in at least two cognitive functioning domains.
HIV-associated mild neurocognitive disorder (HIV MND) refers to presentations with at least two areas of neurocognitive compromise, but the severity is less than with HAD. The effect on everyday functioning is less severe than with HAD; typically the individual manages basic activities of daily living, but needs some assistance or accommodation in more demanding activities. These include most forms of employment and schooling. Assistance or accommodation is also needed in more complex home tasks such as financial management. If neuropsychological testing is performed, HIV MND is defined by performance between 1 and less than 2 standard deviations below the mean in at least two cognitive functioning domains.
HIV-associated asymptomatic neurocognitive impairment (HIV ANI) exists when mild cognitive decline, ascertained by neuropsychological performance 1 to less than 2 standard deviations below expectation, is documented, but there is no documentation of impairment in everyday functioning. Some cases report exerting greater effort to maintain performance, but do not require other accommodation. This category is listed for completeness, but HIV ANI does not qualify for Social Security disability.
In the case of MND, which may be observed in about 25 percent of HIV-infected persons (Heaton et al., 2010), there is not total disability. However, mild to moderate disability of MND may combine with other sources of functional impairment (e.g., severe neuropathy, marked mood change, severe fatigue due to treatment, or comorbid conditions such as hepatitis C) to produce an overall picture of severe functional impairment. Because these conditions are specific to HIV, HIV-associated mild neurocognitive disorder should be included in the HIV Infection Listings when marked functional limitations can be demonstrated.
HIV-Associated Wasting Syndrome
“HIV wasting” is an AIDS-defining condition that is defined as an involuntary loss of more than 10 percent baseline body weight that is accompanied by chronic fever, fatigue, or diarrhea for at least 30 days (CDC, 1992). Although this is the definition most often used in the literature, it may lead to underreporting of AIDS in the more recent era of combination antiretroviral therapy (Siddiqui et al., 2009).
Involuntary weight loss in patients with HIV infection has shown a consistent correlation with morbidity and mortality. This weight loss has been reported in patients treated with combination antiretroviral therapy, including patients who have HIV suppression and CD4 counts above 200 cells/mm3, although this combination is unusual (Mangili et al., 2006; Tang et al., 2002; Uhlenkott et al., 2008).
HIV-associated wasting syndrome is defined by the committee as an involuntary weight loss of 10 percent and a body mass index (BMI) less than 18.5 (the BMI that is the standard metric used to define malnutrition). The use of a 10 percent involuntary reduction in body weight is based on multiple reports that consistently show a correlation between death and this level of weight loss. These include reports in the postcombination antiretroviral therapy era.
The causes of involuntary weight loss are not specified, but they have been studied extensively and appear to be “multifactorial.” The main causes are inadequate caloric intake and altered metabolism. Contributing
factors include: HIV that is untreated or unresponsive to treatment (the precombination therapy experience), opportunistic infections and tumor, malabsorption due to “AIDS enteropathy,” depression, gastrointestinal adverse reactions to antiretroviral agents or other treatments (including decreased intake and lipoatrophy), hypogonadism, protein energy dysmetabolism, and cytokine dysregulation (Mangili et al., 2006).
Outside of the HIV Infection Listings, weight loss due to any digestive disorder is described under Listings 5.08 and 105.08 in the Digestive System. Because of the increased risk of mortality and a potential impact on quality of life and functioning, the committee concludes that HIV wasting syndrome should be included in the HIV Infection Listings to the extent that they cover substantial involuntary weight loss that markedly impairs functioning.
In HIV-infected persons, Kaposi’s sarcoma (KS) is uniformly associated with coinfection with human herpesvirus-8 (HHV-8). KS is definitively diagnosed by biopsy, and histologically KS is characterized by vascular proliferation and a vigorous inflammatory reaction. In early stages, it is debated whether KS is a true malignancy, but this seems clearer in more advanced disease. It arises from endothelial tissues and can affect any region of the body except the central nervous system. KS is especially common in some body regions and organs. Areas commonly affected include the skin, the oral pharynx, the conjuctiva, and the gastrointestinal tract. Some patients have lymphatic obstruction with chronic leg edema. Lesions in the digestive system can occasionally bleed; involvement of the pulmonary parenchyma, often with associated pleural effusions, is symptomatic and rapidly fatal (see Chapter 4). Advanced Kaposi’s sarcoma in any region can cause death, although this is very uncommon with the availability of antiretroviral therapy, except when there is pulmonary involvement.
It is important to note that there is increased social stigma because the lesions are visible. The lesions can cause particular difficulty in the workplace for the person who has them. Additionally, larger lesions can cause chronic pain. For these reasons the committee specifically identified KS and not other opportunistic infections.
The risk of morbidity and mortality of Kaposi’s sarcoma has been reduced dramatically since the beginning of the epidemic, largely as a result of combination antiretroviral therapy (Bower et al., 2009; Grabar et al., 2008; Mocroft et al., 2004). In one study, the percentage of KS in HIV-infected Americans fell from 1980 to 1989 (63.9 percent) and from 1996 to 2002 (30 percent) (Engels et al., 2006). An 85 percent decline in risk of death was found between precombination antiretroviral therapy (1993 to 1995) and
postcombination antiretroviral therapy (2001 to 2003) eras in a large cohort of men in France (Grabar et al., 2008). In the postcombination therapy era, the overall 5-year survival for Kaposi’s sarcoma patients on combined therapy was 91 percent in one British report (Bower et al., 2009).
Cutaneous KS is typically a treatable condition that responds to the initiation of antiretroviral therapy, usually completely. With more advanced-stage disease, or in those with incomplete response to antiretroviral therapy, systemic chemotherapy can be helpful to control the condition, and some topical agents occasionally are used as well. KS can, however, remain a serious and disabling condition despite treatment, especially in cases exhibiting visceral disease or bulky cutaneous involvement.
Based on the expertise of the committee, it was determined that Kaposi’s sarcoma (currently Listings 14.08E2 and 114.08E2) and the social stigma attached to it can be disabling. Squamous cell carcinoma and lymphomas are part of the Malignant Neoplastic Diseases Listings (13.00 and 113.00), which include recurrent disease following antineoplastic therapy. These Listings do not address Kaposi’s sarcoma, which can respond to antiretroviral therapy. KS that severely limits an individual’s ability to work should therefore be included in the HIV Infection Listings.
Lipoatrophy or Lipohypertrophy
Disabling disorders involving adipose tissues in people living with HIV/AIDS are collectively known as lipodystrophy and present as either lipoatrophy or lipohypertrophy. Lipoatrophy (fat wasting) refers to the reduction of subcutaneous body fat, particularly in the face and distal extremities. Although less disabling, lipohypertrophy refers to an increase of body fat in the central abdomen, breasts in women, and the dorsoclavicular fat pad (buffalo hump) (Cabrero et al., 2010; Fichtenbaum, 2009). These disorders are primarily cosmetic; however, in rare instances they can result in permanent disfigurement and pain, or both, and can reduce a person’s ability to walk, stand, or sit if they manifest on the pads of feet or the buttocks. Importantly, they can also negatively impact the quality of a patient’s life due to depression, fears of stigma, and reduced social functioning. This is particularly true if the disorder occurs in the face (Crane et al., 2008; Guaraldi et al., 2008).
Although the etiology of lipoatrophy and lipohypertrophy are not well understood, lipoatrophy is thought to be caused by thymidine nucleoside reverse transcriptase inhibitors. The most frequent cause is stavudine (d4T), which is no longer commonly used. Nevertheless, once the characteristic changes in the face have occurred, they are generally irreversible except with cosmetic surgery. Lipohypertrophy may be caused by protease inhibitors or a refeeding process. As with lipoatrophy, discontinuation or change
in treatments has not been shown to be very effective in reversing changes that have already taken place (Cabrero et al., 2010).
No consensus definition or standard, objective measure defining lipoatrophy or lipohypertrophy exists. Both are diagnosed on a clinical basis, often through patient self-reports confirmed by clinicians. As a result, the prevalence of both lipoatrophy and lipohypertrophy in HIV-infected people is difficult to measure and ranges widely. Contrast-enhanced computed tomography (CT) scans and magnetic resonance imaging (MRIs) can be used to quantify the amount of fat reduction or development, although these procedures are costly. One study suggests that more than 45 percent of HIV-positive people have experienced lipoatrophy and more than 25 percent have experienced lipohypertrophy (Cabrero et al., 2010). Another found the prevalence of fat atrophy and central fat deposition to be 30 and 44 percent, respectively (Jacobson et al., 2005). However, many of these cases may not be disabling. Furthermore, an analysis of the Swiss HIV Cohort Study suggests that the prevalence of lipodystrophy has decreased continuously since 2003 (Nguyen et al., 2008).
Both lipoatrophy and lipohypertrophy are conditions specific to the treatment of HIV/AIDS and are not found in other sections of the Listing of Impairments; therefore, they should be considered under the HIV Infection Listings when associated with marked functional limitation, including stigma that can be limiting in the workplace.
First documented in the late 1990s, the etiology of osteoporosis in HIV/AIDS patients remains poorly understood today. Osteoporosis is a disease characterized by the loss of bone mass over time and can lead to fragility and a high risk of fracture. This is of particular concern for bones in the hips and spine, which have the potential to cause pain and affect a person’s ability to ambulate.
Evidence shows that osteoporosis occurs at a higher rate in HIV-infected populations as compared to seronegative populations. Additionally, a review of the literature suggests the prevalence of osteoporosis ranges from 3 to 21 percent (Paccou et al., 2009); another study found a prevalence of 33 percent (Cazanave et al., 2008). Although a higher percent of HIV-infected patients suffer from osteopenia (characterized by a less severe level of bone loss), osteoporosis (the more severe condition) can ultimately lead to a reduction in quality of life.
Defined by the World Health Organization (WHO), osteoporosis occurs when bone density is 2.5 standard deviations below average, also known as having a T-score of less than –2.5. Bone density is commonly determined through dual X-ray absorptiometry (DEXA) and WHO’s Fracture
Risk Assessment Tool. Hypothesized to be caused both by the virus and antiretroviral treatments (Brown et al., 2009; Fichtenbaum, 2009), there is no conclusive evidence in the literature about the true etiology of osteoporosis. Nonetheless, HIV-induced bone loss has been ascribed to reductions in lymphocyte activity and increases in bone-absorbing cytokines, among others. Other risk factors include low body weight, smoking, vitamin D deficiency, and living for long periods of time with HIV (Fichtenbaum, 2009). Osteoporosis also has been theorized to result from antiretroviral treatment.
Although bone damage is considered under the Musculoskeletal System of the Listing of Impairments, it does not address osteoporosis. For this reason and because severe disability can result from HIV infection complicated by osteoporosis, the committee believes it should be included in the HIV Infection Listings when associated with marked functional limitation.
HIV-ASSOCIATED CONDITIONS IN THE LISTINGS
HIV/AIDS is no longer a nearly fatal disease, but a number of serious conditions can cause disability, even in the era of potent antiretroviral therapy. The committee suggests that a listing be developed that identifies the HIV-associated conditions currently without listings elsewhere in the Listing of Impairments. The committee concludes that an assessment of functioning should be completed in disability claims that present with (1) HIV-associated conditions; (2) adverse effects of treatment for HIV or co-morbid conditions; or (3) other significant, documented symptoms (e.g., fatigue, malaise, pain). To account for the unpredictable nature of HIV and its treatment, allowances made under these parameters should be considered a disability for 3 years following the last documentation of the manifestation, adverse effects, or symptoms. This time period reflects the fact that HIV is now viewed as a generally manageable chronic disease. The immunologic and functional status of many HIV claimants is likely to improve once they are engaged in care and are receiving therapy. It should be noted that the benefits of therapy may decrease as comorbidities continue to develop, therefore requiring regular reevaluation.
RECOMMENDATION 4. Comorbidities induced by HIV infection or adverse effects of treatment should be considered disabling if they markedly limit functioning in one or more of the following areas: ability to perform activities of daily living; maintenance of social functioning; or completion of tasks in a timely manner due to deficiencies in concentration, persistence, or pace. This includes, but is not limited to, the following conditions:
Distal sensory polyneuropathy;
HIV-associated neurocognitive disorders;
HIV-associated wasting syndrome;
Lipoatrophy or lipohypertrophy; and
Symptoms such as fatigue, malaise, and pain should also be considered if found to limit functioning. Periodically, SSA should reevaluate claims made using these comorbidities, consistent with the reevaluation of other disability allowances.
Antinori, A., G. Arendt, J. T. Becker, B. J. Brew, D. A. Byrd, M. Cherner, D. B. Clifford, P. Cinque, L. G. Epstein, K. Goodkin, M. Gisslen, I. Grant, R. K. Heaton, J. Joseph, K. Marder, C. M. Marra, J. C. McArthur, M. Nunn, R. W. Price, L. Pulliam, K. R. Robertson, N. Sacktor, V. Valcour, and V. E. Wojna. 2007. Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69(18):1789–1799.
Bower, M., J. Weir, N. Francis, T. Newsom-Davis, S. Powles, T. Crook, M. Boffito, B. Gazzard, and M. Nelson. 2009. The effect of HAART in 254 consecutive patients with AIDS-related Kaposi’s sarcoma. AIDS 23(13):1701–1706.
Brown, T. T., G. A. McComsey, M. S. King, R. B. Qaqish, B. M. Bernstein, and B. A. Da Silva. 2009. Loss of bone mineral density after antiretroviral therapy initiation, independent of antiretroviral regimen. Journal of Acquired Immune Deficiency Syndromes 51(5):554–561.
Cabrero, E., L. Griffa, and A. Burgos. 2010. Prevalence and impact of body physical changes in HIV patients treated with highly active antiretroviral therapy: Results from a study on patient and physician perceptions. AIDS Patient Care and STDs 24(1):5–13.
Cazanave, C., M. Dupon, V. Lavignolle-Aurillac, N. Barthe, S. Lawson-Ayayi, N. Mehsen, P. Mercié, P. Morlat, R. Thiébaut, F. Dabis, and Groupe d’Epidémiologie Clinique du SIDA en Aquitaine. 2008. Reduced bone mineral density in HIV-infected patients: Prevalence and associated factors. AIDS 22(3):395–402.
CDC (Centers for Disease Control and Prevention). 1992. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescent and adults. Morbidity and Mortality Weekly Report 41(RR–17).
Crane, H. M., C. Grunfeld, R. D. Harrington, K. K. Uldall, P. S. Ciechanowski, and M. M. Kitahata. 2008. Lipoatrophy among HIV-infected patients is associated with higher levels of depression than lipohypertrophy. HIV Medicine 9(9):780–786.
Ellis, R. J., J. Marquie-Beck, P. Delaney, T. Alexander, D. B. Clifford, J. C. McArthur, D. M. Simpson, C. Ake, A. C. Collier, B. B. Gelman, J. McCutchan, S. Morgello, and I. Grant. 2008. Human immunodeficiency virus protease inhibitors and risk for peripheral neuropathy. Annals of Neurology 64(5):566–572.
Ellis, R. J., D. Rosario, D. B. Clifford, J. C. McArthur, D. Simpson, T. Alexander, B. B. Gelman, F. Vaida, A. Collier, C. M. Marra, B. Ances, J. H. Atkinson, R. H. Dworkin, S. Morgello, and I. Grant for The CHARTER Study Group. 2010. Continued high prevalence and adverse clinical impact of human immunodeficiency virus-associated sensory neuropathy in the era of combination antiretroviral therapy: The CHARTER Study. Archives of Neurology 67(5):552–558.
Engels, E. A., R. M. Pfeiffer, J. J. Goedert, P. Virgo, T. S. McNeel, S. M. Scoppa, and R. J. Biggar for the HIV/AIDS Cancer Match Study. 2006. Trends in cancer risk among people with AIDS in the United States 1980–2002. AIDS 20(12):1645–1654.
Esser, S., D. Helbig, U. Hillen, J. Dissemond, and S. Grabbe. 2007. Side effects of HIV therapy. Journal der Deutschen Dermatologischen Gesellschaft 5(9):745–754.
Fichtenbaum, C. J. 2009. Metabolic abnormalities associated with HIV infection and antiretroviral therapy. Current Infectious Disease Reports 11(1):84–92.
Gonzalez-Duarte, A., K. Cikurel, and D. M. Simpson. 2007. Managing HIV peripheral neuropathy. Current HIV/AIDS Reports 4(3):114–118.
Grabar, S., E. Lanoy, C. Allavena, M. Mary-Krause, M. Bentata, P. Fischer, A. Mahamat, C. Rabaud, and D. Costagliola. 2008. Causes of the first AIDS-defining illness and subsequent survival before and after the advent of combined antiretroviral therapy. HIV Medicine 9(4):246–256.
Guaraldi, G., R. Murri, G. Orlando, C. Giovanardi, N. Squillace, M. Vandelli, B. Beghetto, G. Nardini, M. De Paola, R. Esposito, and A. W. Wu. 2008. Severity of lipodystrophy is associated with decreased health-related quality of life. AIDS Patient Care and STDs 22(7):577–585.
Heaton, R., D. Clifford, D. Franklin Jr., S. Woods, C. Ake, F. Vaida, R. Ellis, S. Letendre, T. Marcotte, J. Atkinson, M. Rivera-Mindt, O. Vigil, M. Taylor, A. Collier, C. Marra, B. Gelman, J. McArthur, S. Morgello, D. Simpson, J. McCutchan, I. Abramson, A. Gamst, C. Fennema-Notestine, T. Jernigan, J. Wong, and I. Grant for The CHARTER Study Group. 2010 (in press). HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy. Neurology.
Jacobson, D. L., T. Knox, D. Spiegelman, S. Skinner, S. Gorbach, and C. Wanke. 2005. Prevalence of, evolution of, and risk factors for fat atrophy and fat deposition in a cohort of HIV-infected men and women. Clinical Infectious Diseases 40(12):1837–1845.
Justice, A., S. J. Gange, J. P. Tate, L. P. Jacobson, K. Gebo, K. Althoff, M. Kitahata, M. Saag, M. Horberg, and R. Moore for the NA-ACCORD and VACS Project Teams. 2010 (unpublished). Report to the Institute of Medicine committee evaluating disability criteria for those with HIV infection.
Knox, T. A., D. Spiegelman, S. C. Skinner, and S. Gorbach. 2000. Diarrhea and abnormalities of gastrointestinal function in a cohort of men and women with HIV infection. American Journal of Gastroenterology 95(12):3482–3489.
Lichtenstein, K., C. Armon, A. Baron, A. Moorman, K. C. Wood, and S. Holmberg. 2005. Modification of the incidence of drug-associated symmetrical peripheral neuropathy by host and disease factors in the HIV outpatient study cohort. Clinical Infectious Diseases 40(1):148–157.
Mangili, A., D. H. Murman, A. M. Zampini, and C. A. Wanke. 2006. HIV/AIDS: Nutrition and HIV infection: Review of weight loss and wasting in the era of highly active antiretroviral therapy from the nutrition for healthy living cohort. Clinical Infectious Diseases 42(6):836–842.
Mocroft, A., and the EuroSIDA Study Group. 2010 (unpublished). The incidence and probability of death in HIV-infected persons pre- and post-cART. University College London. Mocroft, A., O. Kirk, N. Clumeck, P. Gargalianos-Kakolyris, H. Trocha, N. Chentsova, F. Antunes, H.-J. Stellbrink, A. N. Phillips, and J. D. Lundgren. 2004. The changing pattern of Kaposi sarcoma in patients with HIV, 1994–2003. Cancer 100(12):2644–2654.
Monkemuller, K. E., S. A. Call, A. J. Lazenby, and C. M. Wilcox. 2000. Declining prevalence of opportunistic gastrointestinal disease in the era of combination antiretroviral therapy. American Journal of Gastroenterology 95(2):457–462.
Nguyen, A., A. Calmy, V. Schiffer, E. Bernasconi, M. Battegay, M. Opravil, J.-M. Evison, P. Tarr, P. Schmid, T. Perneger, and B. Hirschel. 2008. Lipodystrophy and weight changes: Data from the Swiss HIV cohort study, 2000–2006. HIV Medicine 9(3):142–150.
Paccou, J., N. Viget, I. Legrout-Gérot, Y. Yazdanpanah, and B. Cortet. 2009. Bone loss in patients with HIV infection. Joint Bone Spine 76(6):637–641.
Schifitto, G., M. P. McDermott, J. C. McArthur, K. Marder, N. Sacktor, D. R. McClernon, K. Conant, B. Cohen, L. G. Epstein, K. Kieburtz, and the NEAD Consortium. 2005. Markers of immune activation and viral load in HIV-associated sensory neuropathy. Neurology 64(5):842–848.
Siddiqui, J., A. L. Phillips, E. S. Freedland, A. R. Sklar, T. Darkow, and C. R. Harley. 2009. Prevalence and cost of HIV-associated weight loss in a managed care population. Current Medical Research & Opinion 25(5):1307–1317.
Siddiqui, U., E. J. Bini, K. Chandarana, J. Leong, S. Ramsetty, D. Schiliro, and M. Poles. 2007. Prevalence and impact of diarrhea on health-related quality of life in HIV-infected patients in the era of highly active antiretroviral therapy. Journal of Clinical Gastroenterology 41(5):484–490.
Tang, A. M., J. Forrester, D. Spiegelman, T. A. Knox, E. Tchetgen, and S. L. Gorbach. 2002. Weight loss and survival in HIV-positive patients in the era of highly active antiretroviral therapy. Journal of Acquired Immune Deficiency Syndromes 31(2):230–236.
Tinmouth, J., G. Tomlinson, G. Kandel, S. Walmsley, H. A. Steinhart, and R. Glazier. 2007. Evaluation of stool frequency and stool form as measures of HIV-related diarrhea. HIV Clinical Trials 8(6):421–428.
Tramarin, A., N. Parise, S. Campostrini, D. D. Yin, M. J. Postma, R. Lyu, R. Grisetti, A. Capetti, A. M. Cattelan, M. T. Di Toro, A. Mastroianni, E. Pignattari, V. Mondardini, G. Calleri, E. Raise, and F. Starace for the Palladio Study Group. 2004. Association between diarrhea and quality of life in HIV-infected patients receiving highly active antiretroviral therapy. Quality of Life Research 13(1):243–250.
Uhlenkott, M. C., S. E. Buskin, E. M. Kahle, E. Barash, and D. M. Aboulafia. 2008. Causes of death in the era of highly active antiretroviral therapy: A retrospective analysis of a hybrid hematology–oncology and HIV practice and the Seattle/King County adult/ adolescent spectrum of HIV-related diseases project. The American Journal of the Medical Sciences 336(3):217–223.