Current status and future issues in the treatment of HIV-1 infection

Over the past 5 years, advances in human immunodeficiency virus type 1 (HIV-1) clinical research and data on the effectiveness of potent combination therapy have substantially influenced the overall perspective of the long-term management of HIV-1 disease. It is now generally accepted that the benefits of mono- and bio-therapy for HIV-1 infection are only transient owing mainly to antiviral-drug resistance. To obtain continued benefit from antiviral therapy, current guidelines recommend at least triple-drug combinations, or so-called highly active antiretroviral therapy (HAART). In Japan, 13 antiretroviral agents are currently available for combination therapy. Ten of them have been approved for clinical use in the past 3 years. Following the introduction of HAART, marked decreases in AIDS-related morbidity and mortality have been observed. However, in some patients, HAART can be problematic, either because it is difficult for the patient to remain compliant or because previous suboptimum therapies have limited the choice of drugs. For compliant, drug-naive patients, HAART should offer long-term virus suppression, when changing from first- to second- to third-line HAART following drug failure. Long-term treatment might ultimately result in multidrug resistance, leaving few options for salvage therapy. HIV-1 drug resistance testing to enable salvage therapy and the development of new drugs and immunotherapeutic agents to allow new options will therefore remain priorities in HIV-1 research.