Lisa M. Chirch

Treatment of HIV infection with raltegravir

Background: Raltegravir, an inhibitor of the HIV-1 integrase enzyme, is now available for the treatment of drug-resistant virus. Objective: To establish raltegravir as an effective addition to the existing antiretroviral armamentarium by reviewing pharmacokinetics, efficacy, safety and tolerability. Methods: Data from pharmacokinetic, Phase II and III clinical trials were reviewed. Results/conclusions: Results from clinical trials indicate that raltegravir is safe and highly effective in the treatment of both antiretroviral-naïve and -experienced patients.

Cerebral toxoplasmosis in AIDS.

Publisher Summary This chapter focuses on the epidemiology—both in developed and developing countries—pathogenesis, clinical manifestations, diagnosis, and treatment of central nervous system (CNS) toxoplasmosis in HIV-infected individuals. Toxoplasma gondii , an obligate intracellular protozoan parasite in human beings, has the potential to cause disease in both immunocompetent and immunocompromised individuals. Cerebral toxoplasmosis is a frequent cause of neurological pathology in HIV-infected patients. Toxoplasmic encephalitis (TE) is a life-threatening CNS infection observed in advanced HIV infection, particularly in patients with CD 4 cell counts of 100 cells/mm 3 or fewer. Cerebral toxoplasmosis in immunocompromised hosts most likely occurs as a result of the reactivation of latent infection. It is characterized pathologically by the necrosis and thrombosis of involved vessels with perivascular inflammation, and with frank vasculitis in extreme cases. There may be a microglial response with the formation of nodules, and tachyzoites or toxoplasmic antigens have been associated with these nodules.

Proactive infectious disease approach to dermatologic patients who are taking tumor necrosis factor–alfa antagonists: Part I. Risks associated with tumor necrosis factor–alfa antagonists

Tumor necrosis factor-alfa levels are linked to disease severity in patients with inflammatory conditions, such as psoriasis. Inhibitors of this cytokine are commonly used with significant success in the treatment of such inflammatory disorders. Their use, however, can be plagued by infectious complications. An awareness of potential infections associated with these therapies is critical in order to maximize preventive efforts both before and during therapy. This review provides a guide for dermatologists caring for patients in need of this type of biologic therapy to preemptively address the infectious risks. Part I of this continuing medical education article reviews background information on the various infectious risks associated with tumor necrosis factor inhibitor therapy and appropriate historical data to obtain in the context of pretherapy evaluations.

HIV and aging: a clinical journey from Koch's postulate to the chronic disease model and the contribution of geriatric syndromes.

PURPOSE OF REVIEW With the discovery and widespread use of antiretroviral therapies, growing numbers of individuals with HIV are now able to live into advanced age. Nevertheless, growing evidence indicates that these dramatic gains in longevity have also resulted in increased prevalence among the survivors of non-AIDS morbidity and disability, together with acceleration of many underlying aging processes. As a result, individuals involved in HIV care, policy, and research have increasingly had to refocus their efforts from a traditional infectious disease emphasis toward conceptual models grounded in the management of common chronic diseases and geriatric syndromes. RECENT FINDINGS It has been estimated that by 2015, one-half of all Americans with HIV will be 50  years or older. Such individuals are likely to develop chronic diseases typically seen in their older HIV-negative counterparts. Moreover, the presence of multiple coexisting chronic conditions together with polypharmacy and acceleration of varied age-related physiological changes renders many older HIV-positive individuals more vulnerable to becoming disabled or dying from conditions that are not immediately linked to HIV. SUMMARY As growing numbers of individuals confront the prospect of a life with HIV, both they and their providers will need to shift their focus toward a broader and more encompassing perspective that considers the impact of multiple coexisting conditions and age-related changes on outcome measures associated with function, independence, and quality of life. To that end, there is an urgent need for increased dialog between different disciplines, ensuring that the care of older HIV-positive individuals is guided by research that incorporates relevant functional outcome measures.

Nontuberculous mycobacterial infections: a potential complication of cosmetic procedures

Interest in surgical and non-surgical cosmetic procedures has increased significantly over the last few decades. Billions of dollars are spent on these procedures annually. Although the associated risk is generally low, multiple cases of skin and soft tissue infections have been reported. Nontuberculous mycobacteria (NTM), in particular M. chelonae, M. fortuitum, and M. abscessus, have been increasingly identified as causative of numerous cosmetic procedure–related infections worldwide. This has therefore become a public health concern. Delays in diagnosis and appropriate management may occur given subtleties in diagnostic methods. The purpose of this review is to highlight the NTM-related skin and soft tissue infections associated with more common cosmetic procedures, describe methods of identification, and outline best treatment practices.

HIV/HCV Antiviral Drug Interactions in the Era of Direct-acting Antivirals.

Abstract Therapy for human immunodeficiency virus (HIV) and chronic hepatitis C has evolved over the past decade, resulting in better control of infection and clinical outcomes; however, drug-drug interactions remain a significant hazard. Joint recommendations from the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America regarding drug-drug interactions between HIV antiretroviral agents and direct-acting antiviral agents for treatment of hepatitis C virus (HCV) infection are reviewed here. This review is oriented to facilitate appropriate selection of an antiviral therapy regimen for HCV infection based on the choice of antiretroviral therapy being administered and, if necessary, switching antiretroviral regimens.

Clinical implications of elevated HIV-1 viral load results obtained from samples stored frozen in vacutainer plasma preparation tubes

Studies have demonstrated that plasma samples collected and stored frozen using vacutainer plasma preparation tubes (PPT) may result in falsely elevated viral load (VL) values with the Roche COBAS TaqMan HIV-1 v1.0 test. At the University of Connecticut Health Center, a total of 349 samples from HIV-1-infected patients on HAART were collected and stored frozen in PPT. Viral load (VL) results were obtained using the Roche COBAS TaqMan HIV-1 v2.0 test (CTM v2.0) and Abbott RealTime HIV-1 assay (RealTime HIV-1). Of the 349 samples, 260 (74.5%) had VL values that differed by >0.5log10copies/mL; 64 of these were quantified by both assays. The remaining 196 samples were detected by CTM v2.0 but not detected in RealTime HIV-1: 62 of the most discordant samples in this category (CTM v2.0 detected/RealTime HIV-1 not detected) were further analyzed using two nested RT-PCR assays targeting pol integrase: full-length (864nt) and a highly conserved subregion (134nt). No HIV-1 RNA was detected in the discordant samples, confirming RealTime HIV-1 results. The increase in VL reactivity with the CTM v2.0 assay was presumably due to proviral DNA captured by the CTM total nucleic acid extraction chemistry but not the RNA-specific extraction procedure used in RealTime HIV-1. These results suggest that using CTM v2.0 with samples frozen in PPT could have significant clinical implications for HIV-1 patient management.

Lepromatous leprosy reversal reaction.

A 41-year-old Dominican-born man presented in 2001 with lesions on his nose and ears, and numbness in both legs; all had developed over 2 years. He also described nasal congestion for several months. On examination, there were painless nodular lesions on the dorsum of his nose and ear lobes. There was mildly diminished lighttouch sensation of the distal lower extremities. Skin biopsy showed acid-fast bacilli and no granulomas, consistent with lepromatous leprosy. He was started on treatment of dapsone, rifampicin, and clofazamine. The patient developed eruptions of subcutaneous nodules on both forearms (figure, A) and swelling of isolated fingers, 6 months to 1 year after beginning therapy. After 2 years of therapy, he presented with multiple painless subcutaneous lesions on the forearms. Over the ensuing months he intermittently developed swelling of bilateral hands and dorsal foot (figure, B— diffuse generalised oedema of the right foot in comparision with the left foot). Radiography showed soft-tissue swelling without erosion or deformity. Uric acid concentration was 5·2 mg/dL, with an ESR of 47 mm/h. A punch biopsy of one of the lesions showed superficial and deep lymphocytic perivasculitis, and no acid-fast bacilli or granulomas, consistent with reversal reaction. Reversal reaction is characterised by an abrupt increase in inflammation within previously quiescent skin lesions, resulting from effective treatment. New lesions usually appear, sometimes with associated neuritis or fever. If the reversal reaction is not treated promptly, irreversible nerve damage can result. The reaction is associated with a shift toward the tuberculoid end of the leprosy spectrum, with a Th1 cytokine profile (ie, interferon-γ, tumour necrosis factorα, and interleukin-2). Rheumatological manifestations are not uncommon (although more frequently described in association with erythema nodosum leprosum), and may include frank arthritis, subcutaneous nodules, or swollen hands or feet, as in our patient’s case. The patient’s dose of clofazamine was increased to 100 mg daily, and a short prednisone taper was prescribed with good response. He remains on dapsone monotherapy after years of multidrug therapy. Intermittent reactions have been successfully managed with prednisone tapers. Lepromatous leprosy reversal reaction

Ecthyma gangrenosum secondary to methicillin-sensitive Staphylococcus aureus

Ecthyma gangrenosum (EG) is a well-described skin manifestation of Pseudomonas aeruginosa septicemia in immunocompromised patients. However, it can be seen in association with other bacteria, viruses, and fungi. We report a case of a 54-year-old African American female with metastatic gastric adenocarcinoma and recent chemotherapy and neutropenia who developed EG-like lesions due to methicillin-susceptible Staphylococcus aureus. We also review the literature to evaluate all reported cases of S aureus-associated EG and their clinical presentation, diagnosis, and treatment.

Endocrinological aspects of HIV infection

AbstractPurpose Patients with human immunodeficiency virus (HIV) are living longer with effective antiretroviral therapies and are enjoying near normal life span. Therefore, they are encountering endocrine issues faced by the general population along with those specific to HIV infection. The purpose of this article is to review the common endocrine aspects of HIV infection, and the early detection and management strategies for these complications.MethodsRecent literature on HIV and endocrine disease was reviewed.ResultsHIV can influence endocrine glands at several levels. Endocrine glandular function may be altered by the direct effect of HIV viral proteins, through generation of systemic and local cytokines and the inflammatory response and via glandular involvement with opportunistic infections and HIV-related malignancies. Endocrine disorders seen in people with HIV include metabolic issues related to obesity such as diabetes, hyperlipidemia, lipohypertrophy, lipoatrophy and lipodystrophy and contribute significantly to quality of life, morbidity and mortality. In addition, hypogonadism, osteopenia and osteoporosis are also more prevalent in the patients with HIV. Although disorders of hypothalamic–pituitary–adrenal axis resulting in adrenal insufficiency can be life threatening, these along with thyroid dysfunction are being seen less commonly in the antiretroviral therapy (ART) era. ARTs have greatly improved life expectancy in people living with HIV but can also have adverse endocrine effects.ConclusionsClinicians need to have a high index of suspicion for endocrine abnormalities in people with HIV as they can be potentially life threatening if untreated. Endocrine evaluation should be pursued as in the general population, with focus on prevention, early detection and treatment to improve quality of life and longevity.