The Effect of Commencing Combination Antiretroviral Therapy Soon after Human Immunodeficiency Virus Type 1 Infection on Viral Replication and Antiviral Immune Responses

Abstract

Twelve subjects were treated with zidovudine, lamivudine, and ritonavir within 90 days of onset of symptoms of acute infection to determine whether human immunodeficiency virus type 1 (HIV-1) infection could be eradicated from an infected host. In adherent subjects, with or without modifications due to intolerance, viral replication was suppressed during the 24-month treatment period. Durable suppression reduced levels of HIV-1-specific antibodies and cytotoxic T lymphocyte responses in selected subjects. Proviral DNA in mononuclear cells uniformly persisted. The persistence of HIV-1 RNA expression in lymphoid tissues and peripheral blood mononuclear cells suggests that elimination of this residual pool of virus should be achieved before considering adjustments in antiretroviral therapeutic regimens. In addition, given the reduction in levels of virus-specific immune responses, it would seem prudent to consider enhancing these responses using vaccine strategies prior to the withdrawal of antiviral therapy.

Treatment response in acute/early infection versus advanced AIDS: equivalent first and second phases of HIV RNA decline

“…Time to virologic response was 17.8 weeks [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] for acute/ early versus 14.3 weeks [11][12][13][14][15][16][17][18][19][20][21] for advanced patients (P = 0.22). Mean time to less than 500 (<2.70 log 10 ) and less than 5000 (<3.70 log 10 ) copies per milliliter was 11.2 weeks [5][6][7][8][9][10][11][12][13][14][15][16][17][18] versus 5.7 [3][4][5][6][7][8][9][10]…”

“…In the advanced immunosuppression setting, antiretroviral therapy (ART) results in rapid plasma viremia decline, CD4+ T-cell count improvement, and decreased disease progression and mortality [8]. Treatment during acute seroconversion also hastens the viremia decline beyond the natural equilibration seen in untreated patients [9,10], but there is no consensus regarding the long-term risks and benefits of early treatment [7,8,11].…”

“…In the advanced immunosuppression setting, antiretroviral therapy (ART) results in rapid plasma viremia decline, CD4+ T-cell count improvement, and decreased disease progression and mortality [8]. Treatment during acute seroconversion also hastens the viremia decline beyond the natural equilibration seen in untreated patients [9,10], but there is no consensus regarding the long-term risks and benefits of early treatment [7,8,11].Very limited data directly compare treatment responses among individuals with early and late stage disease. It remains unclear whether comparably high viremia levels observed at the opposite ends of the disease spectrum would decline at the same rate in response to identical treatment interventions.…”

“…Here we found no significant difference in first phase clearance between groups, although there was a trend in advanced patients for higher mean protease inhibitor levels to correlate with more rapid virologic suppression [for indinavir (r = 0.82) and nelfinavir (r = 0.42) but not the nelfinavir metabolite (r = −0.24)]. Overall, patients with cases of undetectable levels of either protease inhibitor had longer mean time to treatment response (19.6 weeks) [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] compared with patients with always-detectable levels (15.6 weeks) [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. …”

Longitudinal Assessment of Changes in HIV-Specific Effector Activity in HIV-Infected Patients Starting Highly Active Antiretroviral Therapy in Primary Infection

“…Highly active antiretroviral therapy (HAART), including at least two reverse transcriptase inhibitors and at least one protease inhibitor or non-nucleoside transcriptase inhibitor, can suppress the replication of HIV in most antiretroviral therapy-naive patients adhering to their drug regimens (13,14). Initiating HAART is recommended for acute HIV-1 infection to reduce viral dissemination and its harmful effects on the immune system (15).…”