18 Mar

Antiretroviral Therapy – Introduction – part1

Antiretroviral treatment should be offered to all patients with the acute HIV syndrome, those within six months of seroconversion, and all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy in asymptomatic patients depend on virologic and immunologic factors. In general, treatment should be offered to individuals with fewer than 300 CD4 + T cells/mm3 or plasma HIV RNA levels exceeding 10,000 copies/ml (bDNA assay) or 20,000 copies/ml (RT-PCR assay). Once the decision has been made to initiate antiretroviral therapy, the goal is maximum viral suppression for as long as possible. Results of clinical trials to date indicate that this may currently be best achieved with a potent protease inhibitor (PI) in combination with two nucleoside analogue reverse transcriptase inhibitors (NRTIs). Another option is the combination of saquinavir plus ritonavir combined with one or two NRTIs. Results of therapy are evaluated primarily with plasma HIV RNA levels; these are expected to show a one log (10 fold) decrease at eight weeks and no detectable virus (<500 copies/ml) at 4-6 months after initiation of treatment. Failure of therapy (i.e., plasma HIV RNA levels exceeding 500 copies/ml) at 4-6 months may be ascribed to non-adherence, inadequate potency of drugs or suboptimal levels of antiretroviral agents, or resistance Patients whose therapy fails should change to at least two new agents that are not likely to show cross-resistance with drugs given previously; ideally, the regimen should be changed to a completely new regimen devoid of anticipated cross-resistance and with clinical trial data supporting a high probability of viral response.

Introduction

Use of Testing for Plasma HIV RNA Levels and CD4 + T Cell Count in Guiding Decisions for Therapy

Decisions regarding initiation or changes in antiretroviral therapy should be guided by monitoring the laboratory parameters of plasma HIV RNA (viral load) and CD4 + T cell count, as well as the clinical condition of the patient. Measurement of plasma HIV RNA levels (viral load), using quantitative methods, should be performed at the time of diagnosis and every 3–4 months thereafter. Plasma HIV RNA levels should also be measured immediately prior to and again at 2–8 weeks after initiation of antiretroviral therapy. This second time point allows the clinician to evaluate the initial effectiveness of therapy, since in most patients adherence to a regimen of potent antiretroviral agents should result in a large decrease (~0.5 to 0.75 log10) in viral load by 2–8 weeks.

Once the patient is on therapy, HIV RNA testing should be repeated every 3–4 months to evaluate the continuing effectiveness of therapy. With optimal therapy viral levels in plasma at 6 months should be undetectable, that is, below 500 copies of HIV RNA per ml of plasma. If HIV RNA remains detectable in plasma after 6 months of therapy, the plasma HIV RNA test should be repeated to confirm the result and a change in therapy should be considered. Plasma HIV RNA levels should not be measured during or within four weeks after successful treatment of any intercurrent infection, resolution of symptomatic illness, or immunization. Because there are differences among commercially available tests, confirmatory plasma HIV RNA levels should be measured by the same laboratory using the same technique in order to ensure consistent results. Buy Generic Viagra

A minimally significant change in plasma viremia is considered to be a 3-fold or 0.5 log10 increase or decrease. A significant decrease in CD4 + T lymphocyte count is a decrease of >30% from baseline for absolute cell numbers and a decrease of >3% from baseline in percentages of cells.

Established Infection

Patients with symptomatic disease (wasting, thrush or unexplained fever for > 2 weeks) including AIDS should be offered antiretroviral therapy.

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