HAART treatment

Viral replication is often quite efficiently reduced by HAART to undetectable levels [124—132], and can greatly prolong the time to progression to AIDS [133]. However, viral sanctuaries of replication-competent HIV-1 persist in the patient, preventing eradication of the virus [124, 128, 129]. Latently infected resting CD4 T cells represent the most important sanctuary because they can persist for the whole life of the patient [127, 130, 134, 135]. In fact, in most treated patients - and despite several years of efficient HAART treatment - the... 

Kaposi sarcoma (KS) - an angiogenic-inflammatory neoplasm - is the most prevalent cancer in HIV-infected patients and its appearance is preceded by infection with human Heipesvitus-8 (HHV-8). Although chemotherapy has become the treatment of choice approved by the FDA, there are also good response rates in patients treated with IFN-a. Fortunately, today highly active antiretroviral therapy (HAART) has dramatically decreased the incidence of KS in AIDS patients. 

So far, five different protease inhibitors have been approved by the FDA for the treatment of HIV infection [3, 4]. Clinical trials in which protease inhibitors were evaluated in monotherapy demonstrated the potency of this class of inhibitors (decrease in HIV RNA levels, increase in CD4 cell counts). Treatment regimens were subsequently broadened to include reverse transcriptase inhibitors in combination with protease inhibitors. The result of these clinical trials has led to a list of guidelines with recommendations for the optimal treatment options. Prolonged control of the infection with combination therapy (highly active antiretroviral therapy, HAART ) could be shown. 

Gable CB, Tierce JC, Simison D et al (1996) Costs of HIV-f/AIDS at CD4+ counts disease stages based on treatment protocols, J Acquir Immune Defic Syndr Hum Retrovirol 12 413 20 Gebo K, Fleishman J, Conviser R et al (2(X)6) Contemporary costs of HIV health care in the HAART era. In Presentation at the 13th conference of retroviruses and opportunistic infections,... 

Currently, treatment of DSP and ATN is similar to many other neuropathies that have predominantly painful sensory involvement (Mendell and Sahenk 2003 Gonzalez-Duarte et al. 2007). It is purely symptomatic as there are no proven regenerative therapies to reverse the underlying process. An 8-month prospective pilot study reported an improvement in subjective quantitative sensory testing (QST) in HIV-infected patients who responded to HAART (Martin et al. 2000). The patients who did not respond to HAART did not show any improvements in QST. It is possible that suppression of viral load will slow the progression of DSP. Some studies have found a correlation between viral load and incidence (Childs et al. 1999), or severity (Simpson et al. 2002) of sensory neuropathy. Others, however, did not find any correlation between plasma viral loads and incidence of DSP or ATN (Brew et al. 2003). 

Studies of chemokine processing linked to HIV infection have provided several potential therapeutic targets. Treatment of HIV/AIDS patients with HAART includes... 

In the peripheral nervous system (PNS), HIV-1 infection and its treatment using HAART are associated with the development of neuropathic pain syndromes characterized by severe lancinating pain as well as parathesias and burning pain in the extremities. Damage to peripheral nerves has been associated with these syndromes. HIV-1-associated polyneuropathy has become the most common neurological complication of HIV-1 infection (Pardo et al. 2001). More than half of individuals with... 

New York State Department of Health AIDS Institute. Drug-Drug Interactions Between HAART, Medications Used in Substance Use Treatment, and Recreational Drugs. 2005. Available at www.hivguidelines.org... 

Sutinen J, Hakkinen A-M, Westerbacka J, Seppala-Iindroos A, Vehkavaara S, Halavaara J, Jarvinen A, Ristola M, Yki-Jarvinen H. Rosiglitazone in the treatment of HAART-asso-ciated lipodystrophy—a randomized double-blind placebo-controlled study. Antiviral Ther 2003 8 199-207. 

Support for the hypothesis of a casual relation between stavudine and lipodystrophy comes from another randomized study in which stavudine-containing HAART regimens were switched to a combination of zidovudine, lamivudine, and abacavir (157). Eight patients were randomized to continue stavudine and 14 patients switched to the triple combination. Imbalance in the treatment arms resulted from exclusion of patients who maintained treatment for a minimum of 6 months of follow up. Over 48 weeks after randomization, the average leg and arm fat mass fell in the continuation arm but increased in the switch arm. One patient in the switch arm, who had previously taken zidovudine and lamivudine, had a therapeutic failure. 

Soon after the introduction of highly active antiretroviral combination treatments (HAART), lipodystrophy was associated with the use of protease inhibitors, and several reports have confirmed that a syndrome of peripheral lipodystrophy, central adiposity, breast hypertrophy in women, hyperlipidemia, and insulin resistance with hyperglycemia is an adverse event associated with the use of potent combination antiretroviral therapy, particularly including HIV-1 protease inhibitors (982-987). 

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