Overview

Management of HIV infection in the past year has continued the trends evident in the latter part of the previous decade. The availability of potent therapy has continued the dramatic decrease in opportunistic infections and in deaths from AIDS. In many patients, considerable recovery of previously damaged immune function has been possible. However, the success of treatment has been tempered by recognition of its limitations. The need for life-long therapy has made many question the risk-benefit associated with early initiation of treatment. Concerns about long-term side effects, especially metabolic and liver dysfunction, have grown. The need for strict adherence, with the cost of non-adherence being loss of effect and/or drug resistance, has led to a search for more simple regimens. Indeed, the concerns about the problems with therapy sometimes seem to outweigh the clear benefits of treatment. This should not be the case because untreated HIV infection is still a lethal disease, as is only too obvious in those parts of the world where access to therapy remains very limited. Joseph Eron and Pietro Vernazza discuss new drug treatments and emerging strategies for the management of HIV infection. As well as reviewing new reverse transcriptase and protease inhibitors, they discuss new classes of drugs in development, such as the fusion inhibitors, and inhibitors of the viral entry process. Some of these agents are in advanced clinical development and should be in wider use in the next year. Eron and Vernazza also provide a valuable review of the use of planned treatment interruption as a strategy in management. They contrast the promising results in acute early infection with those seen in chronic infection, and offer some thoughts on future studies in this area. One of the challenging questions when using available therapy is whether measurement of drug levels, which is increasingly available, is useful in managing patients. David Back and colleagues review the current state of affairs in therapeutic drug monitoring in HIV management. They point out that there appears to be little role currently for monitoring levels of nucleoside reverse transcriptase inhibitors, and contrast that with emerging data on the possible value of using drug concentration measurements of protease inhibitors and non-nucleoside reverse transcriptase inhibitors as a tool in patient care. Their review points out that drug monitoring may be most useful in predicting failure of a regimen, and is more limited in other scenarios (especially limiting toxicity). Back and colleagues also, importantly, discuss many of the challenges that need to be addressed before therapeutic drug monitoring can become a widely used clinical tool. Another strategy to improve on current treatment strategies is to augment the immune response in some way. Maria Allende and Clifford Lane review the use of cytokines (especially interleukin-2) as a means to expand or restore immune function, especially in the context of potent antiretroviral therapy. They discuss cytokine therapy both as a strategy designed to overcome the immune dysregulation that occurs with HIV infection and as a strategy aimed at enhancing HIV-specific immune responses. Although, none of these agents are yet proven to be effective in long-term management of HIV disease, several are in advanced stages of clinical development and are increasingly available. Matthias Egger and colleagues discuss a problem that has emerged as an increasing concern among HIV treaters and patients; that of cardiovascular disease. The development of metabolic problems such as insulin resistance, hyperlipidemia and fat redistribution has led some to predict an epidemic of cardiovascular morbidity in treated HIV-positive individuals. In spite of the absence of data that shows increased myocardial disease among HIV-infected patients, this concern has altered both the approach to treatment as well as the selection of drugs used in treatment. Egger et al. add a useful commentary to this topic. They review cardiovascular epidemiology and estimate the relative and absolute risks of cardiovascular disease that might be associated with the metabolic complications of HIV therapy. They then put these risks into the context of known cardiovascular disease and also compare the risks of treatment-associated cardiovascular disease with the benefits associated with avoiding AIDS-related morbidity. Krystn Wagner and William Bishai review one of the most important HIV-associated diseases, tuberculosis. Co-infection with HIV and Mycobacterium tuberculosis is extremely common, especially in resource-poor environments. Multiple challenges are posed by this situation, including problems with diagnosis and therapy. This review addresses these challenges, outlines current guidelines for the management of active tuberculosis, and concludes with a discussion of emerging therapies for tuberculosis.