Between August 1992 and January 2009, 328 individuals enrolled into the cohort. Subjects without follow-up beyond study enrollment (n=5) and those who received hydroxyurea (n=9) or other non-HAART regimens (n=35) were excluded from analysis. The remaining 279 subjects included 274 men and 5 women contributing 1191 person-years for analysis. At study referral, 96 (34%) subjects were HIV antibody-negative/RNA-positive, and 28 (10%) were HIV antibody-positive with a negative or indeterminate Western Blot assay. Subjects were first evaluated at the Primary Infection Clinic a median of 43 [interquartile range (IQR) 21-83] days following HIV infection (); at study screening, 26 (9%) were HIV-antibody negative, and 19 (7%) were HIV antibody-positive with a negative or indeterminate Western Blot assay.
Demographic and other characteristics of subjects, by study group
Forty-seven subjects initiated HAART within 30 days of infection (group 1: acute treatment); dates of HIV infection of all of the acutely treated subjects were estimated as the date of symptom onset. Eight of these subjects were HIV antibody-negative when starting HAART. Eighty-nine subjects initiated HAART between 31 and 180 days following infection (group 2: early treatment), and 47 subjects initiated HAART more than 181 days after HIV infection (group 3: delayed treatment). There were 27 historical and 69 contemporary control subjects who never initiated HAART.
Most subjects in the cohort were young, Caucasian men who have sex with men (). Most (84%) subjects experienced symptoms consistent with the acute retroviral syndrome. There were significant baseline differences between groups in age, seroconversion symptom severity, time from HIV infection to study screening, baseline CD4+ T-cell counts and HIV RNA levels, initial HAART regimens, and duration of study follow-up.
In the first year following infection, after adjusting for baseline CD4+ T-cell count, age, and severity of seroconversion symptoms, the mean CD4+ T-cell count declined 177 (95% CI 88-266) cells/mm3 for historical controls in the year following HIV infection and 128 (95% CI 82-174) cells/mm3 for contemporary controls. At treatment initiation, the mean CD4+ T-cell count was lower among subjects in the delayed treatment group (group 3, 319 cells/mm3, n=22) compared to subjects who received acute treatment (group 1, 469 cells/mm3, n=43) or early treatment (group 2, 531 cells/mm3, n=87). At HAART start, the mean HIV RNA level was higher among acutely treated subjects (5.6 log10 copies/mL, n=43) compared to subjects who received early treatment in group 2 (4.7 log10 copies/mL, n=88) and those who delayed treatment in group 3 (4.7 log10 copies/mL, n=23).
Only 23 subjects were observed to have CD4+ T-cell counts below 200 cells/mm3 at any time during the study. Of the fourteen subjects who had CD4+ T-cell counts below 200 cells/mm3 at least 90 days after infection, three did not receive OI prophylaxis, five received OI prophylaxis at least part of the time, and the remaining six had only single measurements below 200 and did not receive prophylaxis. Five subjects were diagnosed with candidal esophagitis immediately after HIV infection. There were an additional ten OIs in two treated and eight untreated subjects that occurred at least four weeks after infection, and five subjects died (including one who had experienced an OI). Only one death, in a subject who had discontinued HAART, was thought to be related to HIV infection. Among the 14 subjects, the first OI or death occurred a median of 404 (IQR 154-1207) days after infection. Further analysis of these endpoints was not performed due to small numbers.
There were 178 subjects who experienced at least one HIV-related diagnosis greater than four weeks after infection (). Among 47 subjects who delayed the start of HAART greater than 180 days (group 3), 36 (77%) had an HIV-related diagnosis before initiating therapy and contributed to time-to-event analyses only as part of control groups. Due to small sample size, the remaining group of eleven subjects was not analyzed further. Median time to diagnosis of an HIV-related condition based on Kaplan-Meier time-to-event analysis was 443 (IQR 154-1003) days for group 1, 474 (IQR 142-1774) days for group 2, 616 (IQR 206- not available) days for contemporary controls, and 113 (IQR 83-237) days for historical controls (). Compared to contemporary controls, time to diagnosis of an HIV-related condition did not differ for group 1 [adjusted hazard ratio (aHR) 1.60, 95% CI 0.95-2.69, p=.08] or group 2 (aHR 1.18, 95% CI 0.78-1.79, p=.4) but was shorter for historical controls (aHR 3.74, 95% CI 2.35-5.95, p<0.0001). However, compared to historical controls, time to diagnosis of an HIV-related condition was significantly delayed for both the acute and early treatment groups (aHR 0.43, 95% CI 0.24-0.76, p=.004 for group 1; aHR 0.32, 95% CI 0.19-0.53, p<.0001 for group 2). There was no difference in time from HAART start to the diagnosis of an HIV-related condition between group 1 subjects who started HAART within 30 days and group 2 subjects who started HAART between 31 and 180 days after infection (aHR comparing group 2 to group 1: 0.66, 95% CI 0.38-1.14, p=.14) ().
List of the initial1 HIV-related diagnoses in 178 subjects
Survival from HIV-related diagnoses over time since infection (Fig 1A) and since start of HAART (Fig 1B)