COMPLICATIONS
Selected Endocrine Topics in HIV: Osteoporosis and Adrenal Insufficiency
The care of HIV-infected patients has become increasingly complex. Endocrine problems, such as osteoporosis and AI, have been frequently reported in the HAART era. Additional considerations may be required regarding the etiologies, diagnosis, and treatment compared with the general population. Further research is required to understand the intricacies of these problems in HIV-infected patients in order to provide optimal care.
Selected Neurologic Complications of HIV and Antiretroviral Therapy
Despite the marked benefits of highly active antiretroviral therapy (HAART), up to 70% of patients with HIV develop neurologic complications of the central or peripheral nervous system (Sacktor, 2000). Neurologic consequences of HIV can be divided into primary and secondary disorders. The primary neurologic complications include HIV dementia in adults, encephalopathy in children, HIV-associated (vacuolar) myelopathy, and distal peripheral polyneuropathy. Secondary disorders are due to opportunistic infections resulting from HIV immunosuppression. The focus of the presentation and this article is limited to complications in adults.
Update on the Neurological Manifestations of HIV
With the continued widespread use of combination antiretroviral therapy, the incidence of various neurological complications remains low. However, some complications continue to have a serious impact on the lives of HIV-infected patients. The diagnosis of these neurological complications has become even more complex in recent years. Adverse events, stemming from the long-term use of antiretroviral therapy, can lead to neurological complications. And as HIV-positive people continue to live longer because of antiretroviral therapy, the risk of neurological complications stemming from comorbidities increases.
Restorative Treatment Approaches for HIV-Associated Lipoatrophy
For numerous HIV-infected patients, facial lipoatrophy has become a frustrating reality. While not typically life-threatening, it can lead to comorbidities and is one of the most stigmatizing complications of HIV. And because facial lipoatrophy is believed to be an adverse effect of antiretroviral therapy, it can significantly affect a patient’s “relationship” with his or her regimen, potentially resulting in poor adherence or termination of therapy altogether, even if the regimen is achieving a desired effect on viral load and CD4+ cell counts.
Managing Depression in HIV Disease, Viral Hepatitis, and Substance Abuse
Dr. Ferrando began his September 2005 PRN lecture by explaining that depression is the most common psychiatric disorder for which HIV-infected patients receive treatment. “A number of epidemiological studies have been conducted,” he said. “However, the rates of depression vary greatly. This has a lot to do with variations in the studies themselves. The studies have been conducted in different settings and involved different risk groups.” Some studies assessed depression using screening instruments in clinic settings. While screenings are efficient, they tend to overestimate prevalence rates. Others involved highly structured psychiatric clinical diagnostic interviews in research cohorts. Regardless of the settings and methods of assessment, Dr. Ferrando explained, rates of depression and other psychiatric disorders are elevated in HIV-positive patients.
Methamphetamine, HIV, and the Human Brain
Nearly all primary care providers in the United States, especially those with sizeable HIV practices, are aware of the very real dangers of crystal methamphetamine use. It has been a pervasive concern among many Physicians’ Research Network members—indeed, a hot topic during several question-and-answer sessions—and an issue that PRN has been struggling to adequately address.
Use of Androgens in HIV-Infected Men and Women
Endocrine abnormalities—specifically androgen deficiency—are nothing new among HIV-positive patients. Their significance came to light in the earlier days of the AIDS epidemic, particularly as a leading contributor to AIDS-related weight loss and wasting syndrome. While these complications are much less common today, thanks to the restorative benefits of antiretroviral therapy, androgen deficiency is still an issue that many HIV-positive individuals continue to grapple with. Fortunately, there have been a number of studies reported in recent years evaluating the safety and effectiveness of androgen replacement therapy in both men and women. Dr. Steven Grinspoon has played no small role in many of these studies, and thus was considered to be the ideal candidate to address the PRN membership at a recent meeting.
Lipodystrophy: What’s Going On?
The etiology and pathogenesis of antiretroviral therapy-associated morphologic complications—most notably loss of subcutaneous fat and truncal obesity—remain something of a mystery. However, research continues to move forward. To bring PRN members up to date on the various work that is being done to better understand and manage the fat redistribution that is synonymous with HIV-associated with lipoatrophy, Dr. Donald Kotler took the podium at the November 2004 PRN meeting to review some of the newest, most important data that will likely guide clinical research in this arena in the months and years to come.
Restorative Treatment for HIV-Associated Lipoatrophy: A Report from the 6th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV
If HIV infection is to be recognized as a chronic, manageable condition, researchers and clinicians still have an enormous undertaking ahead of them: coming up with tangible strategies to prevent and treat the adverse events associated with antiretroviral therapy. Numerous treatment-related adverse events have been documented and have been shown to have serious clinical consequences that can ultimately have a profound effect on the durability of treatment.
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Mechanisms of HIV Drug Resistance: A Primer
Resistance of HIV to antiretroviral drugs is one of the most common causes for therapeutic failure in people infected with HIV. Sadly, the emergence of drug-resistant HIV variants is a common occurrence—even under the best of circumstances—given that no antiretroviral drug combination studied as of yet is completely effective in shutting down viral replication. And there is no shortage of data indicating that the emergence of HIV drug resistance is clearly associated with adverse treatment outcomes.
Fortunately, the availability of drug-resistance testing has improved the ability of clinicians to deal knowledgeably with HIV drug resistance head on. On the research front, drug-resistance testing has enabled investigators to more effectively develop and study both novel and older therapeutics for the sake of tailoring treatment for patients with varying resistance profiles. In this respect, therapy can now be individualized, based on our evolving knowledge of drug resistance, drug-resistance testing, and state-of-the-art treatment approaches.
HIV Drug Resistance: New Insight and Updated Practices
Over the past 18 months, significant amounts of data presented at scientific conferences have shed additional light on the mechanisms and clinical significance of antiretroviral drug resistance. These include new reports from studies evaluating the incidence and lingering consequences of transmitted drug-resistant HIV, the significance of the K65R mutation in reverse transcriptase, the persistence of minor HIV variants harboring drug-resistance mutations, the selection of TAM pathways, as well as some heartening data indicating that lamivudine retains some activity against HIV carrying the M184V mutation. To discuss these and other emerging data, Dr. Daniel Kuritzkes graciously accepted PRN’s offer to speak at the May 2004 meeting, the proceedings from which are reviewed here.
Diagnosis and Management of HPV-Associated Anogenital Dysplasia in HIV-Infected Men and Women
Antiretroviral therapy continues to have a positive impact on both the incidence and prevalence of many AIDS-related diseases. At the same time, the life-extending benefits of antiretroviral therapy have paved the way for infections with long latency periods to fulfill their pathogenic potential and fulminate into life-threatening complications. A prime example of this is human papillomavirus (HPV) and its sinister sequelae: squamous intraepithelial lesions and invasive cervical or anal carcinoma.
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Buprenorphine and the Treatment of Opioid Addiction
Illicit opioid addiction, which is no stranger to the HIV-infected population, is a complex illness. It is characterized by compulsive, at times uncontrollable drug craving, seeking, and use that persist even in the face of extremely negative consequences. For many people, opioid addiction becomes chronic, with relapses possible even after long periods of abstinence.
Because opioid addiction has so many dimensions and disrupts so many aspects of an individual's life, treatment for this illness is never simple. Effective drug abuse and addiction treatment programs typically incorporate many components, each directed to a particular aspect of the illness and its consequences.
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Bioterrorism and Smallpox Vaccination: Experience and Considerations
Smallpox, which is believed to have originated over 3,000 years ago in India or Egypt, is one of the most devastating diseases known to humanity. For centuries, repeated smallpox epidemics swept across continents, decimating populations in their wake. The disease, for which no effective treatment was ever developed, killed as many as 30% of those infected. Between 65% and 80% of survivors were marked with deep-pitted pockmarks, most prominent on the face. Blindness was another complication. In 18th century Europe, a third of all reported cases of blindness were because of smallpox.
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Mitochondrial Toxicity in HAART
Damage to cellular mitochondria has snowballed into one of the most feared toxicities of antiretroviral therapy. Yet its incidence and prevalence among patients being treated with various nucleoside reverse transcriptase inhibitors (NRTIs)-believed to be the most likely culprits-have not been elucidated and the precise role, if any, of drug-induced mitochondrial damage in the development of hallmark NRTI-related side effects remains unclear. Needless to say, a great deal of research is still needed to better understand the link between antiretroviral treatment and mitochondrial damage and the ways this toxicity can be monitored, managed, and if possible, avoided completely.
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Lymphoma in the Setting of HIV Disease
Lymphomas have long been some of the most devastating and complex opportunistic diseases of HIV infection. Their epidemiologies, both before and after the widespread use of HAART, have not been fully elucidated, and their various treatments, both in the setting of underlying immune suppression and used concurrently with antiretroviral therapy, have not been officially standardized. As for their etiologies and pathogeneses, there is still much to understand, including the role of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) and the Epstein-Barr virus (EBV) in the transformation of B-cells into lymphomas in the setting of HIV disease. But this much is clear: Lymphomas remain the most lethal complications of HIV disease (Chaisson, 1998). Yet it is also true that the incidence of HIV-related lymphoma has decreased in recent years. What’s more, the immune recovery associated with antiretroviral treatment has enabled many more patients to better tolerate chemotherapy and to live longer, healthier, and cancer-free lives after receiving what is potentially a grim diagnosis.
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Liver Disease in HIV: An Update
In the United States, it is estimated that 30% of the 800,000 people living with HIV are coinfected with the hepatitis C virus (HCV). Similar rates have been documented in Western Europe, although the actual number of HIV-infected individuals in some countries is not well defined. The magnitude and potential ramifications of HIV/HCV-coinfection is even more alarming in Spain, where Dr. Vincent Soriano suggested that at least half of the 130,000 HIV-positive people in the country are coinfected with HCV (Soriano, 2000). In turn, Spain has become a hotbed for coinfection research and has yielded studies that have helped to address some of the most important questions regarding follow up and treatment facing clinicians today.
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The Plot Thickens: KSHV and Molecular Piracy
Perhaps the greatest advance in the area of AIDS-related malignancies has been the identification of human herpesvirus-8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus (KSHV). Since its discovery by Drs. Yuan Chang and Patrick Moore and their colleagues almost eight years ago, KSHV has been identified in virtually all AIDS- and non-AIDS-related KS lesions. At the same time, several research teams have identified the virus in a subset of other less common pathologic conditions, including primary effusion lymphomas (PEL) and multicentric Castleman’s disease (MCD). But while a definitive link exists between KSHV and these specific malignancies, the precise role that it plays in their development is just now coming into focus.
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