Tolerability of HAART in patients treated during acute HIV infection.

To the Editor: In a recent issue of Journal of Acquired Immune Deficiency Syndrome, Apuzzo et al analyzed the duration of the highly active antiretroviral therapy (HAART) regimen in patients treated during the early course of infection to identify the reasons for first modifications, or discontinuation, of initial HAART regimens. These included both drug switches and discontinuation in 363 patients who initiated HAART in the Acute Infection and Early Disease Research Project between 2002 and 2005. In this analysis, the initial regimen was modified in 205 subjects (56%); toxicity being the main reason for modification in 105 patients (51%). Between 1997 and 2008, we enrolled 128 subjects in the Acute Infection Database of the National Institute for Infectious Diseases Lazzaro Spallanzani in Rome, Italy. Primary HIV infection was defined by a negative or indeterminate HIV-1 Western blot with simultaneous positive plasma HIV RNA or by a positive HIV-1 antibody test preceded by a documented negative HIV antibody test within the preceding 180 days. Of all subjects, seventeen patients that participated in a structured treatment interruption protocol were excluded and 73 individuals started HAART within 180 days from HIV diagnosis were enrolled. All subjects started HAART with at least 3 antiretroviral drugs according to then existing guidelines. Twenty-eight of 73 patients (38%) were prescribed an unboosted protease inhibitor (PI)-based regimen, 18 of 75 (25%) a ritonavirboosted PI-based regimen, 27 of 73 (37%) a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. The median time from acute infection to initiation of therapy was 27 days (range: 2–174 days); at initiation of therapy, the median CD4 cell count was 504 cells per microliter (range: 200–1319 cells/mL) and the median plasma HIVRNA value was 210,000 copies per milliliter (range: 920–7,300,000 copies/mL). At a 2 years follow-up, the initial regimen was modified in 25 of 73 study subjects (34.2%). Virological failure was not observed in any of these subjects. 2 patients (8%) suspended treatment spontaneously and 1 (4%) for the occurrence of acute hepatitis A. Toxicity was the major reason for treatment modification (22 of 25; 88%) as follows: 8 modifications, all due to gastrointestinal side effects, were observed in the unboosted PI-based regimen group; 7 in the ritonavir-boosted PI group subjects (4 gastrointestinal events, 2 anemia, and 1 rash); and 7 in the NNRTI group (4 for rash and 3 for anemia). None of these toxicities were grade 4, and all anemia cases were due to zidovudine use. The median time from initiation of therapy to the first modification was 35 days (range: 8–688 days). As shown in Table 1, when comparing patients that suspended treatment to those who did not suspend, no significant difference was found in median values at baseline of CD4 and HIVRNA, in median time (days) from infection and HAART initiation, in median time to first modification between PIbased and NNRTI-based regimen, and in overall duration of the 2 class regimens. Moreover, no difference was found in age, gender, HIV exposure category, and frequency of retroviral acute symptoms. More strict criteria for acute HIV infection were used in our study in comparison to study by Apuzzo et al (180 vs. 365 days), and our patients were treated during an earlier stage of infection (27 vs. 89 days), when acute antiretroviral symptoms occur more frequently. Although the overall rate of treatment modification/ discontinuation in our study (22 of 73; 34.2%) was significantly less frequent than that reported by Apuzzo et al (108 of 363; 56%), the rate of toxicityrelated modification did not seem different (30.1 vs 28.9). In summary, a significant difference in the number of modifications of HAART was found in our study compared with that of Apuzzo et al; this difference is not correlated to toxicity but to individual motivation. In our population for instance 2 patients (8%) suspended treatment spontaneously, and 1 (4%) for the occurrence of acute hepatitis A. We could speculate that in some cases, it is better to wait before initiation of HAART during acute HIV infection, especially in patients who exhibit marked difficulty to accept their positivity for HIV infection. As a result of this, such subjects may reject treatment more easily or may be more inclined to modify and to suspend treatment. This possibility underlines the need for a strong relationship