Study of Tests to Evaluate Effectiveness of Anti-HIV Drugs

• INCLUSION CRITERIA:

In order to enroll, subjects must:

Be HIV infected.

Be currently receiving highly active anti-retroviral therapy. Drugs available through expanded access or compassionate use protocols are permitted.

Have received at least 6 months of HAART therapy.

Currently be receiving and be willing to temporarily discontinue the selected antiretroviral for the indicated duration.

Have a viral load between 1,000 and 100,000 copies/ml within 6 weeks prior to screen or at screening.

If one value is greater than 100,000 copies and one value less, the average of the two viral loads will be used to determine eligibility. Similarly, if one value is less than 1,000 and one value greater than 1,000, the average viral load will be used to determine eligibility.

Have two viral load tests by bDNA method in the NIH laboratory that differ by less than 20% (log10bDNA) in the three weeks prior to enrollment. Viral loads performed through participation in another NIAID study are acceptable. Alternatively, new patients coming to the clinic are permitted to have two screening visits.

Have a CD4 T cell number greater than 100 cells within 4 weeks of enrollment or greater than 100 cells within 8 weeks of enrollment if no more recent CD4 cell count is available.

Be adults age 18 or older.

Self-report adequate adherence to antiviral medications (missing at most one dose of drug weekly) and commit to work towards adherence during study participation.

EXCLUSION CRITERIA:

In order to enroll, subjects must not:

Have a positive pregnancy test.

Have evidence of recent HIV infection, defined as a history of a negative HIV ELISA within 12 months of screening.

Have any acute infection that might alter viral load with the previous 4 weeks.

Have received a vaccine in the previous 4 weeks.

Have symptomatic HIV disease for which rapid institution of a salvage regimen would be advisable.

Be receiving concomitant medications or have a concomitant illness with malabsorption or emesis that could be expected to result in inadequate concentrations of antiretroviral drugs.

Be receiving an anti-retroviral regimen that includes drugs that should not be used concomitantly (e.g., stavudine and zidovudine) or inadvisable dosages of antiretroviral agents.

Have any laboratory abnormality for which withdrawal of a drug or drug regimen might be considered. For the purposes of general guidance, Grade III toxicities would result in exclusion from study with the exception of stable thrombocytopenia or proteinuria or elevated bilirubin resulting from Gilbert's syndrome or indinavir treatment. Grade II SGOT or SGPT might be a reason for study exclusion if not explained by underlying hepatitis or if in a pattern of recent increase over a stable baseline.

Have genotypic evidence at screening that would suggest that discontinuing the selected antiretroviral would result in suboptimal therapy that would clearly place the remainder of the regimen at risk for the development of new resistance mutations during the discontinuation period. Two prominent possibilities would be patients taking NNRTI regimens and discontinuing NRTIs or PI component in patients who have genotypes with no NNRTI mutations. During the discontinuation period, it would be possible that the patient may acquire new resistance mutations to NNRTIs. Genotype may be performed as part of the screen or be performed through PMD.

Have had a change in antiretroviral regimen in the past 6 weeks.

Have received cytotoxic chemotherapy including hydroxyurea in the last 6 weeks, or have anticipated need for chemotherapy during study.

Have evidence of active hepatitis B infection and wish to interrupt either tenofovir or 3TC.

Have any suggestion of a trend to increase or decrease in viral load in the past 6 weeks.

Have significant active substance abuse or psychiatric illness that might interfere with study assessments or with your ability to return for study visits.