ABSTRACT
We sought to determine the utility of repeat genotypic resistance testing (GRT) and the clinical response in HIV-1-infected patients with known resistance to three of the major classes of antiretroviral drugs. The HIV-1 genetic sequences for 20 patients who had high-level 3 class resistance demonstrated on a prior GRT (3C-GRT 1) measured during the period from November 1, 2000 through July 1, 2004 were retrospectively evaluated. At the time of 3C-GRT 1, the median CD4 count and HIV-1 RNA viral load were 168 cells/mm(3) and 4.5 log copies per milliliter, respectively. The median time to the second GRT (3C-GRT 2) was 17 months. At that time, the median CD4 count and VL were 140 cells/mm(3) and 4.9 log copies per milliliter (p = 0.8 and p = 0.12, respectively). On 3C-GRT 2, all patients retained essentially identical mutations, with the exception of the loss of the M184V mutation in 6 patients. After 3C-GRT 2, all patients continued on protease inhibitor-containing highly active antiretroviral therapy (HAART) regimens. At 24 weeks after 3C-GRT 2, there was no significant change in CD4 count or HIV-1 RNA viral load (p = 0.68 and p = 0.30, respectively). Repeat GRT in patients with documented high-level 3 class resistance does not provide new or clinically useful information. Under continued antiretroviral selective pressure, the viral genetic sequences in this patient population remained stable. In addition, continuing HAART regimens containing protease inhibitors appeared to forestall further immunological and virologic deterioration in patients with multiple resistance mutations. Providers should focus on obtaining access to combinations of novel agents for patients with 3 class resistance rather than repeated GRT.
Subject(s)
Anti-HIV Agents/pharmacology , Drug Resistance, Viral/genetics , HIV Infections/drug therapy , HIV-1/drug effects , HIV-1/genetics , Reverse Transcriptase Inhibitors/pharmacology , Adult , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , Drug Therapy, Combination , Female , Genotype , HIV Infections/immunology , HIV Infections/virology , HIV Protease/genetics , HIV Reverse Transcriptase/genetics , HIV-1/enzymology , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Mutation , RNA, Viral/blood , Reverse Transcriptase Inhibitors/therapeutic use , Treatment Failure , Treatment OutcomeABSTRACT
The Havana trial, a randomized, prospective study, demonstrated that expert interpretation of genotypic resistance test (GRT) results improved virological outcomes in human immunodeficiency virus type 1 (HIV-1)-infected patients for whom highly active antiretroviral therapy (HAART) was failing. The impact of expert advice in routine clinical practice is unknown. We retrospectively evaluated the virological outcomes of 74 patients for whom HAART was failing and whose clinical providers accepted or rejected HAART regimens recommended by an expert panel who routinely reviewed GRT results. Fifty (68%) of 74 patients received regimens recommended by the expert panel ("advice accepted" [AA]), and 24 patients (32%) received regimens per the clinician's preference ("advice rejected" [AR]). After 24 weeks, AA and AR groups had median decreases in the plasma HIV-1 RNA viral load of 2.6 and 1.3 log(10) copies/mL, respectively (P=.0001). Twenty-six (52%) of 50 patients in the AA group and 5 (21%) of 24 patients in the AR group had a plasma HIV-1 RNA viral load of <50 copies/mL (P=.01). Consideration should be given to enlisting expert assistance in the interpretation of GRT results in routine clinical practice.
