Update on highly active antiretroviral therapy: progress and strategies

HIV patients who have detectable viral loads (1,000-5,000 copies/mL) and/or evidence of immunologic dysfunction (CD4+ T-lymphocyte count < 500/mm3) should be treated with a potent combination antiretroviral regimen. Currently, this is to consist of two nucleoside reverse transcriptase inhibitors (NRTIs) with at least one protease inhibitor (PI), or a non-nucleoside reverse transcriptase inhibitor (NNRTI), or another combination with adequate potency. The specific regimen should be designed to achieve an undetectable viral load by an ultrasensitive method (< 50 copies/mL). It should be chosen with a view towards maximizing adherence and minimizing significant drug-drug interactions and side effects. Long-term adherence with the initial highly-active regimen will minimize development of resistant viral mutants and preclude the use of higher complexity regimens. If a regimen is failing in the setting of adequate patient adherence, a new regimen should be chosen using at least two new medications to which viral strains are likely to be sensitive (by genotyping determination). If this is not possible, one may consider treatment interruption or, depending on the clinical status of the patient, continue the current suboptimal regimen until new drugs become available. The predictive value of resistance testing is currently being examined in patients who have failed their first therapy. Further developments include vaccine, cytokine-, and gene therapy-based treatment strategies.