Two years ago, while revisiting the quality and durability of highly active antiretroviral therapy-linked immune reconstitution, I noted that the incidence of certain non-AIDS-defining malignancies associated with sexually transmitted viruses in immunosuppressed persons, including penile, oral, and anal cancers, have continued to increase among HIV-infected persons despite the use of highly active antiretroviral therapy
Oral cavity lymphoma occurs frequently in HIV-positive patients, often with a poor prognosis.1 Ortega and colleagues2 present an enlightening case of a destructive oral plasmablastic lymphoma in a 43-year-old HIV-positive man. Similar to another recently reported case,3 this lymphoma was their patient's first manifestation of his underlying HIV infection.
Thinking about the potential use of a vaccine to control or eliminate the spread of HIV has been present since the earliest days of the epidemic.
Tens of thousands of persons with HIV/AIDS have seen their treatment interrupted by the worldwide recall of Roche Pharmaceuticals’ protease inhibitor Viracept (nelfinavir).
We conducted a survey of 154 inmates of the Rhode Island Department of Corrections jail regarding HIV risk, HIV testing experiences, and attitudes toward rapid HIV testing in the correctional setting.
Treatment of HIV infection reduces the risk of transmission and can significantly improve patients’ quality of life. For these reasons, the CDC has recommended routine screening for HIV in all health care settings.1 HIV testing access in correctional facilities is the weakest link in the fight against HIV infection in the United States; increasing access to testing would improve the identification of HIV-positive inmates as they pass through prisons and jails, providing an opportunity to integrate them into the public health infrastructure of HIV care. However, numerous logistical and cost-related barriers to such testing must be addressed when determining how and when it should be conducted.
Two girls, aged 10 and 17 years, both with perinatally acquired HIV infection, participated in a 12-week, hospital-based exercise rehabilitation program of progressive resistance exercise training with an aerobic component.
Miller1 reports the results of a 3-month program of progressive resistance and aerobic exercise training in 2 perinatally HIV-infected girls: a normal-weight 10-year-old and an overweight 17-year-old. By the end of the program, both had decreases in body mass index (BMI); lost fat, including visceral fat, by at least some measures; and gained significant muscle strength. One had improved cardiovascular fitness, and both showed further improvements after completing a home-based program after the initial 12-week program.
Acute mastoiditis, an infectious inflammatory process in the temporal bone, is an uncommon complication of otitis medi
We evaluated admissions of HIV-positive persons to an inner-city hospital from 2000 to 2005. There was a decline in the number of substance abusers, homeless persons, injection drug abusers, and African Americans, and there was an increase in patients older than 50 years.
Many of the comments made since the arrival of highly active antiretroviral therapy-the HAART era-relate to the number of those with HIV infection able to return to work or remain active in the community, living with the virus as a chronic disease rather than as an acute, life-ending infection. Looking inside an inner-city hospital to consider the changes, if any, in hospitalizations over the period of rapid implementation of effective antiretroviral therapy makes sense. We expect changes, we think we know what they are, but without verification we would be making policy based on our best wishes or worst fears and not on reality.Hospitals matter and clearly so in inner cities where a public hospital may be the only door open to an uninsured or underinsured population with few resources. In our best post–HAART era dream, HIV-related hospitalizations evaporate as medication puts all symptoms at bay; the HIV-positive person is occasionally an inpatient, but for unrelated problems, such as injuries from an athletic event. In our post–HAART era nightmare, the number of hospitalizations remains high and even rises higher as the adverse effects of drugs and the resistance of HIV to treatment both take their toll on an already vulnerable population.The article by Pulvirenti and colleagues1 reporting on the experiences of one hospital in inner-city Chicago suggests that elements of both are true, and it points toward at least a dozen more studies. Is the drop in admissions of those with substance abuse problems the result of the success of our outreach and syringe exchange programs, or the continuing denial of the very existence of these people? Is the increase in the white population admitted part of a new shift in demographics in the epidemic, or of the demographics of those attracted to or welcome at this hospital? Is the increase of admissions of those older than 50 the result of the successful aging of those infected years ago, or are these new infections in an older population? Is the increase in internal medicine admissions the result of conditions that would have appeared anyway as folks aged, or is this increase an indication of complex, subtle problems caused by antiretroviral therapy over time?What about the push to keep people out of the hospital? Or to shorten length of stay? What are the predictable or planned changes in admissions when a new facility is built as a neighborhood changes? If those plans leave out some of those previously served, is there an organized attempt to ensure continuity of care?Finally, the focus on hospitals in isolation may well mislead policy makers. The early days of the epidemic taught us how important home- and community-based services were. Without a critical analysis, it is impossible to say whether this need has increased or decreased and whether something about other services is behind the reported changes in hospitalization.The arrival of the HAART era let some policy makers stop worrying about HIV, but this article shows us that the availability of effective antiretroviral therapy has not made the HIV policy options any easier. In fact, it leads to even more questions and more concerns about needed services and support, especially for those vulnerable populations most at risk for HIV infection and most likely to turn to public resources for their care.
A new report shows that persons with HIV/AIDS and transplant patients are much more likely to contract about 20 different cancers than those in the general population (McLean T. Australian Associated Press. June 6, 2007). Conducted by the University of New South Wales, the study found that immune deficiency-a problem common to the 2 groups-makes them more vulnerable to infections and cancers, including those in the liver, stomach, skin, lung, cervix, eye, lip, mouth, and penis.
Lichen myxedematosus, or papular mucinosis, is a skin disorder characterized by accumulation of mucin in the dermis. We present the case of a patient with HIV infection and lichen myxedematosus whose skin condition completely resolved with antiretroviral therapy. [AIDS Reader. 2007;17:418-420]
Both HIV and its treatment, particularly protease inhibitors, can cause dyslipidemia similar to that seen with the metabolic syndrome. The most notable effects are elevated triglyceride levels and decreased high-density lipoprotein cholesterol levels, with or without elevated low-density lipoprotein cholesterol (LDL-C) levels.
Elevated fasting triglyceride levels and low levels of high-density lipoprotein cholesterol (HDL-C) are the hallmarks of HIV-associated dyslipidemia. Despite the perception of many HIV-infected patients and their clinicians, low-density lipoprotein cholesterol (LDL-C) levels among persons infected with HIV-even those receiving antiretroviral therapy––tend to be lower than those in uninfected controls.1,2 During antiretroviral therapy, increases in all lipid parameters are common; however, it is dramatic rises in triglyceride levels that for a number of reasons can be of the most concern.
One of the 2 feature articles this month in The Aids Reader is a review of the literature on the management of dyslipidemia. In this article, Dr Craig E. Metroka of Columbia University and colleagues focus on the use of fish oil to reduce elevated triglyceride levels, an independent risk factor for cardiovascular disease and a hallmark of antiretroviral-related dyslipidemia.
Drug-resistant HIV strains that pass from mother to infant can go undetected in the baby’s immune system cells and remain there for years, according to a study by Deborah Persaud, MD, of Johns Hopkins University School of Medicine and colleagues (Reuters. April 30, 2007).
Much has been written over the years about the prevalence of HIV drug resistance mutations and about the fitness and transmissibility of resistant strains of virus and their present and potential impact on the HIV pandemic.
We report the case of an HIV-positive patient with preexisting bone disease who developed tenofovir-induced Fanconi syndrome and subsequently sustained pathologic fractures. We suggest that tenofovir treatment may have contributed to the patient’s pathologic fractures through its effects on phosphorus balance and vitamin D metabolism.
Although it bears his name, Guido Fanconi only defined the “syndrome” after it was first described by Lignac in 1924.1 Fanconi described children with rickets, glucosuria, and growth retardation.1 Fanconi syndrome now includes multiple disorders, with the common pathologic mechanism of proximal tubular dysfunction. This syndrome is a rare disorder, making it conspicuous when it does occur. Most cases in children are linked to inherited disorders, while those in adults are usually acquired, most commonly from multiple myeloma2 (due to immunoglobulin light chains in the urine) or drug-related toxicity.1 Recently, much attention has been paid to the occurrence of Fanconi syndrome as a result of exposure to the NRTI class of antiretroviral agents.3-5 In HIV-infected persons, Fanconi syndrome was initially associated with adefovir nephrotoxicity.3 Therefore, when the closely structurally related NRTI tenofovir was introduced, there was concern about a risk of nephrotoxicity similar to that of adefovir. Although no nephrotoxic events were reported in clinical trials,6,7 subsequent use in clinical practice revealed tenofovir-associated renal side effects. A recent review by Sax and colleagues8 details the renal effects of this agent, which include acute renal failure from acute tubular necrosis and isolated Fanconi syndrome. Although most of the case reports of acute renal failure in HIV-infected patients exposed to tenofovir have been described with Fanconi syndrome,9 this is possibly a result of publication bias. Because Fanconi syndrome was a well-recognized feature of tenofovir’s predecessor adefovir3 and because the syndrome is otherwise relatively rare, tenofovir was generally easy to identify as the culprit. The presence of Fanconi syndrome certainly confirms a diagnosis of tenofovir-induced injury. However, when acute renal failure is present without Fanconi syndrome, tenofovir still needs to be considered as the cause. The findings of the case reported by Brim and colleagues10 can be best appreciated through an understanding of proximal tubular function. Proximal tubular epithelial cells are the workhorses of the nephron; they have the highly important role of reabsorbing the electrolytes and small molecules that are filtered at the glomerulus. For example, the proximal tubule reabsorbs almost all of the 0.5 kg of filtered sodium daily-the equivalent amount of sodium in 2.5 pounds of table salt. This function is dependent on the cells’ ability to generate large amounts of energy through a very rich concentration of mitochondria. It is not surprising that small defects in energy generation could result in significant wasting of substances. Indeed, Fanconi syndrome is an instance of this. One of the most important energy-requiring steps is the action of the adenosine triphosphate (ATP)–requiring basolateral (blood side) sodium-potassium (Na+-K+) pump. Through the function of sodium-potassium ion exchange, the epithelial cell maintains very low intracellular sodium concentration. This provides a gradient for sodium to move into cells from the lumen through various apical transporters. Sodium reabsorption driven by the gradient is coupled with reabsorption of phosphate, glucose, and amino acids and, with excretion of hydrogen ions (H+), allows bicarbonate reabsorption. If the Na+-K+ pump does not function adequately, as occurs with proximal tubular mitochondrial dysfunction, the sodium gradient is reduced, and there is a loss of the cotransported phosphate, glucose, amino acids, and bicarbonate in the urine. The result is a proximal renal tubular acidosis (usually hypokalemic) with hypophosphatemia, glucosuria, and aminoaciduria (ie, Fanconi syndrome). Hypouricemia has also been seen, although its genesis is not understood.1 The occurrence of Fanconi syndrome with mitochondrial disorders is well described. Based on evidence of mitochondrial defects in the proximal tubule with adefovir toxicity,11,12 one proposed theory is that the structurally related tenofovir may cause Fanconi syndrome by similarly affecting mitochondrial function in the proximal tubule. Tenofovir secretion and accumulation in proximal tubule epithelial cells is detailed in the above-mentioned review by Sax and colleagues.8 Important to note is that not all the features of Fanconi syndrome need to be present simultaneously, and the presence of a partial syndrome is not uncommon. Certainly, any appearance of glucosuria in patients without diabetes suggests the presence of Fanconi syndrome. Hypophosphatemia may take longer to evolve with ample bone stores providing a reservoir for repletion. It is the loss of phosphate through this mechanism that will result in osteomalacia, as described in the Case Report presented by Brim and colleagues.10 The role of tenofovir in isolated hypophosphatemia is unclear. Hypophosphatemia has not been attributed to tenofovir in major trials. Two retrospective studies have evaluated hypophosphatemia in tenofovir-treated patients.13,14 Buchacz and colleagues13 reported phosphate blood levels less than 2.4 mg/dL (normal 3.0 to 4.5) in 15.1% and 6.7% of patients treated with and without tenofovir, respectively. In another study, hypophosphatemia (phosphate level less than 2.5 mg/dL) developed in 30.7% of patients who received tenofovir, compared with 22.1% who did not receive tenofovir.14 These differences did not reach statistical significance in either study. Not surprisingly, an elevated level of urinary 2-microglobulin, a small protein usually reabsorbed by the proximal tubule, was noted in the case reported by Brim and associates.10 However, even in the absence of overt kidney dysfunction, recent studies have described high levels of 2-microglobulin associated with tenofovir treatment.15,16 This implies a possible subclinical tubular defect, but the clinical significance of this has yet to be established. Although not common, the presence of Fanconi-like features in a patient treated with tenofovir should be highly suggestive of a drug-related effect. Consideration should be given to drug discontinuation, regardless of the degree of renal impairment. In addition to frequent monitoring of kidney function by estimating glomerular filtration rates, those taking tenofovir should be assessed at the same time for proximal tubular dysfunction, by obtaining serum levels for phosphate and bicarbonate and urinary glucose and protein levels. While it is not always the case with associated renal failure, tenofovir-related tubular effects are reversible, and an early diagnosis will avoid complications, such as those seen in the case reported by Brim and colleagues.
On a daily basis, both patients and providers are confronted with the complicated problem of pain. Unfortunately, pain is prevalent among persons infected with HIV-1 and is undertreated.2 Metaphorically, pain can be likened to sound. At the same decibel level, different persons will perceive the same level of sound as pleasant or unpleasant. At either end of the spectrum (ie, no sound and extreme noise), all who are not hearing-impaired will agree on how the sound is perceived. Likewise, in pain, at the extremes (no pain and excruciating pain), everyone will agree on how the level of pain is perceived. Like sound, what complicates our assessment of pain is that pain typically falls in the middle range, where many different variables affect both the physiology of the pain and the psychosocial perception of that pain.
A49-year-old woman was referred to the emergency department by her primary medical provider for complaints of 3 weeks of cough, pleuritic chest pain, fever, and night sweats. The patient reportedanorexia and weight loss of 9 kg (20 lb) during the past 4 months.
