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BACKGROUND: The persistence of latently infected T cells remains the principal barrier to HIV cure. Understanding how the early immune responses shape persistence of HIV on antiretroviral therapy (ART) will be fundamental for potential eradication. Here, we aimed to determine the relationship between CD8 T-cell function and phenotype before therapy and HIV persistence on ART. METHODS: Blood samples from 29 individuals enrolled during primary HIV infection (at baseline and every 3 months up to 2 years post-ART initiation) were obtained. HIV-specific T-cell function and expression of the activation markers were evaluated before ART by flow cytometry. Cell-associated HIV DNA and unspliced (US)-RNA were quantified in purified CD4 T cells by real-time polymerase chain reaction. Data were analyzed using nonparametric statistics. RESULTS: Elevated immune activation, dominance of monofunctional CD8 T cells, and skewed distribution of memory profile were observed before ART. After ART initiation, HIV DNA and US-RNA levels rapidly diminished, reaching a plateau by 30 weeks after ART. The proportion of baseline HIV-specific effector memory and terminal effector CD8 T cells directly correlated with HIV DNA levels at 1 year after ART. A strong positive correlation was observed between the proportion of bulk and HIV-specific PD-1 CD8 T cells measured before ART and HIV DNA at 1 year after ART. CONCLUSIONS: A higher proportion of terminally differentiated CD8 T cells and increased PD1 expression were associated with HIV persistence on ART after treatment of primary infection. Thus, the quality of the early CD8 T-cell immune response may serve as a predictor of HIV persistence on ART.

The HIV epidemic in Argentina has changed since the first case was reported in 1982. Since the beginning of the 1990s, a decrease in the number parenterally acquired infections has been observed, with a marked increase in transmission through unprotected sexual contact (heterosexual and homosexual), and in the number of women living with HIV/AIDS [1]. Few prevalence studies have addressed the hepatitis B and C virus coinfection in Argentina. We performed this study in a large single clinic in Buenos Aires, taking care of more than 3,000 HIV patients. During a seven-month period (9/2004 to 3/2005), all HIV-positive patients ≥ 18 years old, who were followed up at our unit and who had their scheduled controls for HIV viral load (VL) at the Argentinean National Reference Centre for AIDS (CNRS), were invited to participate in the study. The study was approved by the Fernandez Hospital Ethics Committee. Patients gave their informed consent to be included in the study. Six hundred subjects were asked to enter the study, and 593 accepted. Studied population: 65.6% males, 64% young adults between 20 and 40 years old. The main route of HIV infection was through sexual contact (70%). Of the 593 samples, 52% (n=308) showed positive results for serological markers (HBcAb/HBsAg/anti-HCV) for hepatitis B or C coinfection. Coinfection rates and subjects characteristics are described in Table 1. Table 1 Demographics, rates of HCV/HBV coinfection, main routes of infection, median levels of CD4 cell count, HIV viral load, HAART, frequency of ALT level among HIV-positive patients studied HBV genotype A was identified in 85% of the samples with detectable HBV DNA, instead of genotype F, the most prevalent in our country among blood donors [2]. Among the 22 HBsAg-positive samples, four showed mutations in the rt domain of the pol gene. These samples belonged to patients who had a prolonged history of exposure to lamivudine (median: 25 months) and none of them had received tenofovir. This data reinforces the importance of adequate management of drugs with HBV/HIV dual activity when selecting antiretroviral therapies in coinfected patients, as stated in the last update of the European and North American guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents [3,4]. The main isolated HCV genotype was 1 (65%), followed by genotype 3 (16.5%). Our study shows a change in the prevalence of HCV and HBV coinfection comparing with a previous report of the same geographical area [5], among people living with HIV/AIDS in Buenos Aires, the city with the highest prevalence of HIV in Argentina. A reduction in prevalence rates of dual HIV/HCV (from 58.5% in 1999 to 21%, p 0.000) and HIV/HBV coinfection (from 14.5% in 1999 to 3.7%, p 0.000) was observed. This could be related to the decreasing number of injecting drug users in our country because of the introduction of non-injecting recreational drugs and the increasing transmission through unprotected sex [1]. Despite the decrease in the rates of HCV/HIV and HBV/HIV coinfections the prevalence of those coinfections continues to be high and it could lead to the increase in the morbidity and mortality associated with liver disease, especially in the context of expanded antirretroviral therapy in Argentina. The epidemiological data presented in this study provides information for the development of prevention campaigns for hepatitis C through harm reduction policies and for hepatitis B vaccination programs among people living with HIV/AIDS.