Longitudinal analysis of clinical markers following antiretroviral therapy initiated during acute or early HIV type 1 infection.
BACKGROUND
Treatment of acute human immunodeficiency virus type 1 (HIV-1) infection may have unique immunologic, virological, and clinical benefits. However, the timing of treatment, optimal starting regimens, and expected response to therapy have not been defined.Methods. One hundred two subjects treated during acute and early HIV-1 infection were observed prospectively to determine the effect of time elapsed before initiation of therapy on time to virological suppression and absolute CD4+ cell count. Subjects were divided into pre- and postseroconversion groups on the basis of HIV-1 antibody status at the time of initiation of treatment. Absolute CD4+ cell counts were compared between these groups and with those of historical untreated persons who had experienced seroconversion. Potential predictors of time to virological suppression and CD4+ cell count at > or =12 months were assessed.


RESULTS
Ninety-nine (97%) of 102 subjects achieved virological suppression. The median time to suppression was 11.1 weeks (95% confidence interval, 9.4-14.9) and was independent of initial regimen. The mean CD4+ cell count at 12 months was 702 cells/mm3 (95% confidence interval, 654-750 cells/mm3) and showed an increasing trend over 60 months. Treated subjects demonstrated a statistically significant gain in the CD4+ cell count, compared with untreated historical control subjects, at > or =12 months. Comparable virological and immunologic outcomes were seen in the pre- and postseroconversion groups. Baseline virus load and nadir CD4+ cell count predicted time to virological suppression and CD4+ cell count at > or =12 months, respectively.


CONCLUSIONS
Early treatment of HIV-1 infection is well tolerated and results in rapid and sustained virological suppression. Preservation of CD4+ cell counts may be achieved with early therapy, independent of seroconversion status. Protease inhibitor-based and nonnucleoside reverse-transcriptase inhibitor-based regimens show comparable performance in tolerability, time to virological suppression, and CD4+ cell count when used as a first regimen.
Kassutto
Sigall
S
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Maghsoudi
Kaveh
K
Johnston
Mary N
MN
Robbins
Gregory K
GK
Burgett
Nicole C
NC
Sax
Paul E
PE
Cohen
Daniel
D
Pae
Eunice
E
Davis
Ben
B
Zachary
Kimon
K
Basgoz
Nesli
N
D'agata
Erika M C
EM
DeGruttola
Victor
V
Walker
Bruce D
BD
Rosenberg
Eric S
ES
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D000208:Acute Disease; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D005260:Female; D015497:HIV-1; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D016016:Proportional Hazards Models; D011446:Prospective Studies; D019562:Viral Load
D019380:Anti-HIV Agents