The International AIDS Society–USA Panel updated recommendations for antiretroviral therapy (ART) for adult HIV-1 infection in 1999, based on new clinical and scientific data. The panel, composed of 17 physicians with expertise in HIV research and care, emphasized the importance of individualized treatment, adherence, and monitoring. Key recommendations include starting ART for patients with plasma HIV RNA levels above 30,000 copies/mL or CD4+ cell counts below 350 × 10^6/L, regardless of the other parameter. Patients with CD4+ cell counts above 500 × 10^6/L and HIV RNA levels between 5,000 and 30,000 copies/mL may also be candidates for treatment, depending on the risk of progression. Treatment is generally not recommended for patients with CD4+ cell counts above 500 × 10^6/L and HIV RNA levels below 5,000 copies/mL, as they are at low risk of near-term clinical progression. Initial therapy should be individualized based on regimen potency, tolerability, and patient preferences. Recommended regimens include combinations of two nucleoside reverse transcriptase inhibitors (nRTIs) and a protease inhibitor, or two nRTIs and a nonnucleoside reverse transcriptase inhibitor (NNRTI). Three-nRTI regimens are being evaluated but may be less effective in patients with high baseline HIV RNA levels. NNRTIs should be used in regimens designed to maximize HIV suppression, as resistance can develop if previous NNRTI use has occurred. Monitoring includes assessing adherence, CD4+ cell counts, and HIV RNA levels. Adherence is crucial for optimal treatment outcomes, and strategies such as clear instructions, pill organizers, and regular follow-ups are recommended. HIV RNA levels should decrease rapidly after therapy initiation, with a minimum 1.5- to 2.0-log decline by week 4. CD4+ cell counts may increase over time, reflecting immune reconstitution. Drug resistance testing is important for guiding treatment changes, but its limitations include the inability to detect resistance in latent or minority populations. Changing therapy is recommended if virologic failure occurs, defined as inadequate viral suppression, unsatisfactory CD4+ cell count increase, or clinical progression. Factors such as drug failure, adverse effects, or regimen inconvenience may necessitate changing therapy. When changing therapy, a new regimen should be selected based on the underlying reason for the change and available options. The panel also addressed the importance of long-term management of HIV as a chronic infection, emphasizing the need for ongoing clinical and scientific attention. The recommendations aim to optimize treatment outcomes, minimize complications, and improve quality of life for HIV-infected individuals.The International AIDS Society–USA Panel updated recommendations for antiretroviral therapy (ART) for adult HIV-1 infection in 1999, based on new clinical and scientific data. The panel, composed of 17 physicians with expertise in HIV research and care, emphasized the importance of individualized treatment, adherence, and monitoring. Key recommendations include starting ART for patients with plasma HIV RNA levels above 30,000 copies/mL or CD4+ cell counts below 350 × 10^6/L, regardless of the other parameter. Patients with CD4+ cell counts above 500 × 10^6/L and HIV RNA levels between 5,000 and 30,000 copies/mL may also be candidates for treatment, depending on the risk of progression. Treatment is generally not recommended for patients with CD4+ cell counts above 500 × 10^6/L and HIV RNA levels below 5,000 copies/mL, as they are at low risk of near-term clinical progression. Initial therapy should be individualized based on regimen potency, tolerability, and patient preferences. Recommended regimens include combinations of two nucleoside reverse transcriptase inhibitors (nRTIs) and a protease inhibitor, or two nRTIs and a nonnucleoside reverse transcriptase inhibitor (NNRTI). Three-nRTI regimens are being evaluated but may be less effective in patients with high baseline HIV RNA levels. NNRTIs should be used in regimens designed to maximize HIV suppression, as resistance can develop if previous NNRTI use has occurred. Monitoring includes assessing adherence, CD4+ cell counts, and HIV RNA levels. Adherence is crucial for optimal treatment outcomes, and strategies such as clear instructions, pill organizers, and regular follow-ups are recommended. HIV RNA levels should decrease rapidly after therapy initiation, with a minimum 1.5- to 2.0-log decline by week 4. CD4+ cell counts may increase over time, reflecting immune reconstitution. Drug resistance testing is important for guiding treatment changes, but its limitations include the inability to detect resistance in latent or minority populations. Changing therapy is recommended if virologic failure occurs, defined as inadequate viral suppression, unsatisfactory CD4+ cell count increase, or clinical progression. Factors such as drug failure, adverse effects, or regimen inconvenience may necessitate changing therapy. When changing therapy, a new regimen should be selected based on the underlying reason for the change and available options. The panel also addressed the importance of long-term management of HIV as a chronic infection, emphasizing the need for ongoing clinical and scientific attention. The recommendations aim to optimize treatment outcomes, minimize complications, and improve quality of life for HIV-infected individuals.