Clinical characteristics of primary HIV infection in injection drug users

Many investigators have identified the potential benefits of early antiretroviral therapy in the treatment of HIV infection, including prolongation of disease-free survival [1,2]. There may be a particular benefit of therapy in the period of acute/early infection, especially if this is initiated before the development of a complete antibody response to the virus [3–5]. The initial objectives of the study were to describe the clinical and virological characteristics of acute/early HIV infection in a prospective, observational cohort in Vancouver, Canada, and to describe the virological and immunological effects of early antiretroviral therapy in such patients. In designing the study, it was apparent that the patient population might include many injection drug users (IDU). This group was included to test the hypothesis that antiretroviral therapy should be discussed with all patients with acute/early HIV infection at the time of initial diagnosis, within the context of structured programmes designed to facilitate access to ongoing care. Patients were referred to the study clinic located in a downtown academic medical centre, within walking distance of areas frequented by IDU. To be considered for inclusion, patients were required to have documented laboratory evidence of HIV seroconversion within the previous 6 months, i.e. positive P24 antigenaemia in the presence of a negative HIV antibody or an indeterminate Western blot confirmatory test. Symptoms of seroconversion were collected by means of a standardized questionnaire. In the first 2 years of this prospective cohort study, 59 patients with acute/early HIV infection were enrolled [48 men (82%) and 11 women (18%)]. Of the male patients, 22 were men who have sex with men, and 25 were IDU. There were six men for whom heterosexual exposure was the most likely risk of infection. Of 11 female patients, eight were IDU and five cited heterosexual exposure as their likely risk of infection (the risk categories were not mutually exclusive). There were similar numbers of IDU and non-IDU reporting symptoms of acute HIV infection in the study. Table 1 describes the symptoms associated with acute/early HIV infection, comparing non-IDU with IDU.Table 1: Clinical characteristics of patients with acute/early HIV infection in the Vancouver cohort comparing non-injection drug users (non-IDU, n = 26) with injection drug users (IDU, n = 33). Antiretroviral therapy was offered to all patients and provided free of charge through the provincial drug treatment programme. Therapy was prescribed according to contemporary clinical standards so that patients received double therapy with two nucleosides before October 1996 and triple therapy with two nucleosides and a protease inhibitor after October 1996. Of the total of 59 patients, 11 refused treatment. These consisted of eight men and three women, six IDU and five non-IDU. Overall, 85% of patients returned for follow-up visits. The median number of follow-up visits was four, with a range of 1–25. The median duration of follow-up was 18 weeks with a range of 2–79. A total of nine patients were lost to follow-up. There were no statistically significant differences in baseline plasma viral load and CD4 cell counts in the 45 patients who accepted treatment compared with the five patients declining therapy. Treatment effects on viral load in IDU compared with non-IDU did not differ (Table 2).Table 2: Comparison of the virological and immunological response to therapy in non-injection drug users (non-IDU, n = 20) and injection drug users (IDU, n = 25) available for follow-up 12 weeks after initiation of antiviral therapy. Symptomatic acute HIV infection was first described as a mononucleosis-like syndrome in 1987 [6]. Since then, we have become aware of the broad range of possible clinical presentations that may occasionally include opportunistic infections [7–9]. In our study group, the most common symptoms were non-specific fever and lethargy, as previously reported (Fig. 1). The incidence of pharyngitis and lymphadenopathy (as in the initial descriptions of acute HIV infection) was reasonably high (approximately 50%), but these signs were not universally present. Their absence thus does not rule out the diagnosis of acute HIV infection. Previous reports have also emphasized the presence of a maculopapular rash. Although a rash was present in nearly half of our cohort, its characteristics were by no means unique, at least in our experience.Fig. 1.: Symptoms (per cent) associated with acute/early HIV infection in the Vancouver cohort (N = 59).Presenting symptoms in IDU were compared with non-IDU. The greater median number of symptoms reported by non-IDU may reflect a higher underlying prevalence of non-specific symptoms in this population. However, pharyngitis and lymphadenopathy were reported with equal frequency in non-IDU and IDU populations, suggesting that these may be cardinal symptoms of seroconversion and may be of great importance in its diagnosis. In conclusion, we have developed a successful network for identifying and treating patients with acute/early HIV infection. Despite the large number of IDU in the cohort, we were able to initiate treatment and maintain regular follow-ups in the majority of patients. Although the benefit of antiretroviral therapy in these patients was evident as early as 12 weeks after the initiation of treatment, it should be noted that in the absence of a control group, not all the changes in viral loads and CD4 cell counts can be attributed to therapy. As therapy was started during seroconversion, the improved virological profile may be partly a reflection of the known natural history of HIV. Long-term follow-up of this cohort is ongoing to examine the durability of the response to antiretroviral therapy as well as tissue HIV viral load and additional immunological parameters. Further data will aid in assessing whether or not these results justify the time and expense required to establish such a programme, given the relatively few patients involved. Valentina Montessori Danielle Rouleau Janet Raboud Sandra Rae Ian Woo Julio S. G. Montaner Brian Conway

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