HIV-1-specific immune responses in subjects who temporarily contain virus replication after discontinuation of highly active antiretroviral therapy

Abstract

Therapeutic intervention with highly active antiretroviral therapy (HAART) can lead to suppression of HIV-1 plasma viremia to undetectable levels for 3 or more years. However, adherence to complex drug regimens can prove problematic, and subjects may temporarily discontinue HAART for variable periods. We studied 6 HIV-1-infected individuals who stopped therapy. Off HAART, levels of viremia were suppressed to fewer than 500 copies/mL in 2 subjects for more than 12 and more than 24 months, respectively, and in 1 subject for 4 months on 1 occasion. Three subjects failed to contain plasma viremia. Broad and strong HIV-1-specific immune responses were detected in subjects with prolonged suppression of viral replication. This longitudinal study suggests that containment of HIV-1 replication to low or undetectable levels after discontinuation of HAART is associated with strong virus-specific immune responses. Boosting of HIV-1-specific immune responses should be considered as an adjunctive treatment strategy for HIV-1-infected individuals on HAART.

Figure 1

Longitudinal study of virological and immunological parameters in subjects nos. 6 and 8. Plasma viremia is shown in a and e. The horizontal bars at the top of a and e represent the estimation of adherence to HAART. Filled bars reflect full adherence; gray bars intermittent adherence; and open bars no drug therapy. The frequency of HIV-1–specific CTLp/10⁶ PBMCs is shown in b and f. Binding antibody titers to gp120 and p24 are shown in c and g. Neutralizing antibody titers to previral isolates (pre-ID₉₀) and postviral isolates (post-ID₉₀) are shown in d and h.

Figure 2

Longitudinal study of virological and immunological parameters in subjects nos. 11 and 12. Plasma viremia, measured by RT-PCR, is shown in a and e. The horizontal bars at the top of a and e represent the estimation of adherence to HAART. Filled bars reflect full adherence; gray bars intermittent adherence; and open bars no drug therapy. The frequency of HIV-1–specific CTLp/10⁶ PBMCs is shown in b and f. Binding antibody titers to gp120 and p24 are shown in c and g. Neutralizing antibody titers to previral isolates (pre-ID₉₀) and postviral isolates (post-ID₉₀) are shown in d and h.

Figure 3

Longitudinal study of virological and immunological parameters in subjects nos. 11, 3005, and 31. Plasma viremia was measured by RT-PCR (a and c) or bDNA (e). The horizontal bars at the top of a, c, and e represent the estimation of adherence to HAART. Filled bars reflect full adherence; gray bars intermittent adherence; and open bars no drug therapy. The frequency of HIV-1–specific SFC/10⁶ PBMCs is shown in b, d, and f.