As with the initiation of antiretroviral therapy, the decision to change regimens should be approached with careful consideration of several complex factors. These factors include: recent clinical history and physical examination; plasma HIV RNA levels measured on two separate occasions; absolute CD4T lymphocyte count and changes in these counts.

Other factors that influence decisions include remaining treatment options in terms of potency, potential resistance patterns from prior antiretroviral therapies and potential for compliance/tolerance; assessment of adherence to medications; and preparation of the patient for the implications of the new regimen. Failure of a regimen may occur for many reasons, including initial viral resistance to one or more agents, altered absorption or metabolism of the drug, multi-drug pharmacokinetics that adversely affects therapeutic drug levels, and poor patient adherence to a regimen due to either poor compliance or inadequate patient education about the therapeutic agents. In this regard, it is important to carefully assess patient compliance prior to changing antiretroviral therapy.

It is important to distinguish between the need to change therapy due to drug failure versus drug toxicity. In the latter case, it is appropriate to substitute one or more alternative drugs of the same potency and from the same class of agents as the agent suspected to be causing the toxicity. In the case of drug failure where more than one drug had been used, A detailed history of current and past antiretroviral medications, as well as other HIV related medications, should be obtained. Optimally and when possible, the regimen should be changed entirely to drugs that have not been taken previously. With triple combinations of drugs, at least two and preferably three new drugs should be selected that are not subject to anticipated crossresistance to drugs given previously; this is based on the current understanding of strategies to prevent drug resistance.

Viral resistance to antiretroviral drugs is an important, but not the only, reason for treatment failure. Genetically distinct viral variants emerge in each HIV-related individual over time after initial infection. Viruses with single drug resistance mutations exist even prior to therapy.

VIROLOGIC CONSIDERATION FOR CHANGING THERAPY

Ideally, antiretroviral therapy should maximally suppress viral replication to below levels capable of being detected with HIV RNA assays.

Consensus recommendations have been developed using plasma HIV RNA measurements to guide changes in antiretroviral therapy for HIV infected adults.

Consider changing therapy if:

a) HIV RNA levels drop less than ten-fold (I log) after 8 weeks of therapy.
b) HIV RNA has not decreased to undetectable levels after 4-6 months of therapy.

IMMUNOLOGIC CONSIDERATION FOR CHANGING THERAPY

CD4 + lymphocyte count and percentage are independent predictors of disease progression. Normal CD4 counts in adults in Kenya range from 500-1800 cells per millimeter of volume. Consider changing antiretroviral therapy if there is a rapid and substantial decrease in absolute CD4 + - lymphocyte count (a> 30% decline in < 6 months).