Mpox: Awareness, knowledge and information channels used by individuals accessing a sexually transmitted infections Helpline.

Background: Up until recently, monkeypox (mpox) was considered to be a rare zoonotic infection restricted to Central and West Africa. However, in July 2022, the World Health Organization declared mpox to be a public health emergency of international concern, after there were several outbreaks in non-endemic countries. This study assessed the information channels used by individuals accessing the "Telefono Verde AIDS e Infezioni Sessualmente Trasmesse" of Istituto Superiore di Sanità (National Institute of Health in Italy) with regard to mpox. We also evaluated their awareness, and knowledge about mpox focusing on transmission and prevention. Methods: This is a cross-sectional study conducted on "Telefono Verde AIDS e Infezioni Sessualmente Trasmesse" users, between January and April 2023. The target population was helpline users who were older than 18 years of age, and were phoning the service for the first time (i.e. who have not phoned in the last 12 months). Participants were interviewed using a questionnaire containing 19 questions filled by the interviewer. Collected data were analysed through descriptive statistics, and significance testing. Results: From January to April 2023, "Telefono Verde AIDS e Infezioni Sessualmente Trasmesse" received 2,389 phone calls, 216 of which participated in this study. Most of these were male (85.2%; n=186), single (79.2%; n=171) and in employment (72.2%; n=156). Awareness about mpox was high (71.3%; n=154), with the central and south/islands regional areas having the highest percentage of participants who heard about the virus (84.3%; n=43 vs 72.4%; n=42; p=0.078). Television was the most frequently mentioned source of information about mpox by participants (63%; n=97; p<0.001). This medium was also the most preferred source of information about mpox (39%; n=60; p=0.109). The majority of participants stated that they did not know what mpox is (67.6%; n=146), and less than half knew that it is preventable (42.4%; n=89). Of those who stated that mpox is a preventable illness, less than half knew about the existence of a vaccine (44.9%; n=40; p<0.001). Conclusions: This study provides insights into the awareness, knowledge, prevention tools and information channels of individuals who contacted the "Telefono Verde AIDS e Infezioni Sessualmente Trasmesse". Useful indications for defining future information campaigns were obtained.

Health inequalities: a Research Positioning Exercise at the National Institute of Health, Italy.

BACKGROUND: The Italian National Institute of Health (Istituto Superiore di Sanità, ISS) considers health inequalities (HI) an important area of activity. As the scientific and technical body of the Ministry of Health and the National Health Service, ISS may play a key role to reduce HI. In order to enable ISS in addressing the new and crucial HI challenge, a Research Positioning Exercise was designed and implemented. METHODS: The Exercise included: (i) workshop to strengthen the institutional interest in the field of HI; (ii) review and analysis of ISS publications (years 2000-2017) to identify HI research topics; (iii) survey among ISS researchers regarding main research challenges to address HI in the coming years; and (iv) analysis of input on research challenges from HI international experts. RESULTS: The results of this Exercise suggest that the following points should be included in the future ISS agenda planning: (i) themes which ISS should continue working on (e.g. migrants/vulnerable groups); (ii) themes to be improved: (a) relationship between social determinants and mechanism of HI generation and (b) relationship between risk factors exposure and social determinants; and (iii) new themes to be addressed: (a) mechanisms underlying the resilience observed in Italy; (b) new socioeconomic indicators for HI monitoring; and (c) evidence-based policies aimed at reducing HI. CONCLUSION: Findings of this Exercise show that ISS researchers identified relevant areas, addressing inequalities in addressing the health. Because of ISS structural peculiarity that includes multidisciplinary expertise, the ISS could provide a significant contribution to HI research challenges and knowledge gaps.

A blended training programme for healthcare professionals aimed at strengthening territorial networks for the prevention and contrast of gender-based violence.

OBJECTIVES: a blended training programme combining residential meetings (de visu) and distance training course (DTC) have been developed in order to provide the key elements for prevention, individuation, and care of women victims of violence. DESIGN: the Project involved the identification and testing of a systematic methodology of blended training addressed to social and health operators of 28 Emergency Room (ER) Units in 4 Italian regions (Lombardy - Northern Italy, Lazio - Central Italy, Campania and Sicily - Southern Italy). Tuscany region (Central Italy) collaborated through experts in the field from the Grosseto Task Force. This training approach specifically aimed to increase the professional competences for diagnosis, management and treatment of gender-based violence, as well as to strengthen multidisciplinary territorial networks against violence. SETTING AND PARTICIPANTS: in this Project, 28 ERs in the four Italian regions mentioned above were selected because of their involvement in managing gender-based violence. This selection was performed by a coordinator, one for each region, who also coordinated the recruitment of personnel to be involved in the training programme. The programme has therefore been proposed to social and health operators and police officers in the ERs recruited. In each ER, two referents were identified (a doctor and a nurse) in order to ensure a constant connection between the course participants and the experts involved in the management of the Project and the DTC platform. MAIN OUTCOME MEASURES: evaluation of the increase of knowledge relatively to gender-based violence issue in the ER professionals who have concluded the blended training programme. A systematic analysis and comparison of all accesses concerning women aged ≥14 years in the period 1 July-31 December 2014 (before the blended training programme) and in the period 1 July-31 December 2016 (after the blended training program). RESULTS: among the 866 registered professionals, 636 participants (73.5%) completed the course, 202 (23.3%) professionals did not complete it, 21 (2.4%) did not pass the certification test, and 7 (0.8%) participated as Auditors. Among the participants who completed the course, most of them (70.8%) were females; the average age was 45 for both males and females. The most represented professional role was the nurse (61%), followed by the medical doctor (27.2%). Based on our data, in the post-training period, an increased number of cases of violence were correctly recorded in comparison to the pre-training period. CONCLUSION: the Project allowed to define a training strategy for health professionals of the ERs who respond daily to the health needs of women who are victims of violence. The blended training programme combining residential meetings (de visu) and distance training course has been developed in order to provide the key elements for prevention, individuation, and care of women victims of violence. The observed improvement in the recording and management of cases of gender-based violence is probably due to a greater competence in the awareness and use of specific diagnostic codes by ER professionals.

HIV-1 Tat addresses dendritic cells to induce a predominant Th1-type adaptive immune response that appears prevalent in the asymptomatic stage of infection.

Tat is an early regulatory protein that plays a major role in human HIV-1 replication and AIDS pathogenesis, and therefore, it represents a key target for the host immune response. In natural infection, however, Abs against Tat are produced only by a small fraction (approximately 20%) of asymptomatic individuals and are rarely seen in progressors, suggesting that Tat may possess properties diverting the adaptive immunity from generating humoral responses. Here we show that a Th1-type T cell response against Tat is predominant over a Th2-type B cell response in natural HIV-1 infection. This is likely due to the capability of Tat to selectively target and very efficiently enter CD1a-expressing monocyte-derived dendritic cells (MDDC), which represent a primary target for the recognition and response to virus Ag. Upon cellular uptake, Tat induces MDDC maturation and Th1-associated cytokines and beta-chemokines production and polarizes the immune response in vitro to the Th1 pattern through the transcriptional activation of TNF-alpha gene expression. This requires the full conservation of Tat transactivation activity since neither MDDC maturation nor TNF-alpha production are found with either an oxidized Tat, which does not enter MDDC, or with a Tat protein mutated in the cysteine-rich region (cys22 Tat), which enters MDDC as the wild-type Tat but is transactivation silent. Consistently with these data, inoculation of monkeys with the native wild-type Tat induced a predominant Th1 response, whereas cys22 Tat generated mostly Th2 responses, therefore providing evidence that Tat induces a predominant Th1 polarized adaptive immune response in the host.

Information needs of young Italians accessing the AIDS/STI Helpline at the Italian National Institute of Health.

INTRODUCTION: HIV/AIDS and sexually transmitted infections (STI) have a relevant impact on health and sexual behavior of adolescents and young adults (range of age between 13 and 19 years). The AIDS and sexual transmitted infections (STI) Helpline of the Italian Istituto Superiore di Sanità (National Institute of Health), and also funded by the Italian Ministry of Health, has been active since 1987 providing personalized counselling interventions on HIV/AIDS and STI. AIM AND METHODS: The present study gathered data and questions issues from calls at AIDS/STI Helpline in the period 1987-2014, with the specific aim of assessing the level of awareness and information needs on HIV/AIDS and STI among people aged under 25 years, in relation to potential risky behavior. RESULTS: Data show that young subjects who called the helpline in the period considered are about the 26% of the total users, with a decreasing trend over the years. The 28% of young users reported a "risky behavior" for STI, with a chance statistically higher in the age range 15-19 years and in the MSM (men who have sex with men)/bisexuals users, which tended to decrease in the last years. Of note, a marked increase of the amount of young users not displaying behaviors at risk for HIV or STI has been observed in the years.

HIV-1 Tat-based vaccines: from basic science to clinical trials.

Vaccination against human immunodeficiency virus (HIV)-1 infection requires candidate antigen(s) (Ag) capable of inducing an effective, broad, and long-lasting immune response against HIV-1 despite mutation events leading to differences in virus clades. The HIV-1 Tat protein is more conserved than envelope proteins, is essential in the virus life cycle and is expressed very early upon virus entry. In addition, both humoral and cellular responses to Tat have been reported to correlate with a delayed progression to disease in both humans and monkeys. This suggested that Tat is an optimal target for vaccine development aimed at controlling virus replication and blocking disease onset. Here are reviewed the results of our studies including the effects of the Tat protein on monocyte-derived dendritic cells (MDDCs) that are key antigen-presenting cells (APCs), and the results from vaccination trials with both the Tat protein or tat DNA in monkeys. We provide evidence that the HIV-1 Tat protein is very efficiently taken up by MDDCs and promotes T helper (Th)-1 type immune responses against itself as well as other Ag. In addition, a Tat-based vaccine elicits an immune response capable of controlling primary infection of monkeys with the pathogenic SHIV89.6P at its early stages allowing the containment of virus spread. Based on these results and on data of Tat conservation and immune cross-recognition in field isolates from different clades, phase I clinical trials are being initiated in Italy for both preventive and therapeutic vaccination.

Molecular characterization of HIV-1 subtype C gp-120 regions potentially involved in virus adaptive mechanisms.

The role of variable regions of HIV-1 gp120 in immune escape of HIV has been investigated. However, there is scant information on how conserved gp120 regions contribute to virus escaping. Here we have studied how molecular sequence characteristics of conserved C3, C4 and V3 regions of clade C HIV-1 gp120 that are involved in HIV entry and are target of the immune response, are modulated during the disease course. We found an increase of "shifting" putative N-glycosylation sites (PNGSs) in the α2 helix (in C3) and in C4 and an increase of sites under positive selection pressure in the α2 helix during the chronic stage of disease. These sites are close to CD4 and to co-receptor binding sites. We also found a negative correlation between electric charges of C3 and V4 during the late stage of disease counteracted by a positive correlation of electric charges of α2 helix and V5 during the same stage. These data allow us to hypothesize possible mechanisms of virus escape involving constant and variable regions of gp120. In particular, new mutations, including new PNGSs occurring near the CD4 and CCR5 binding sites could potentially affect receptor binding affinity and shield the virus from the immune response.

Sex workers clients in Italy: results of a phone survey on hiv risk behaviour and perception.

INTRODUCTION: Sex workers (SW) clients represent a bridge population for HIV transmission from high risk to low risk general population. MATERIALS AND METHODS: A cross-sectional anonymous telephone survey was carried out at the AIDS and Sexually Transmitted Infections Helpline of National Institute of Health in Italy. The questionnaire was proposed on a voluntary basis to a sample of 119 subjects from helpline users. RESULTS: The 119 participants were all males, aged between 19 and 59 years and mostly accessed female prostitutes. Vaginal intercourses with SW were more frequently reported, followed by passive oral, active oral sex and active anal intercourses. Cumulatively, 86.6% and 84.6% of vaginal and anal intercourses were respectively reported as regularly protected by condom. DISCUSSION: The telephone interview allowed an eased access, a high response rate and a standardised evaluation of questions. CONCLUSIONS: It is necessary a constant monitoring of the characteristics, behaviour, risk perception and testing of SW clients in Italian and other populations.

Biocompatible anionic polymeric microspheres as priming delivery system for effetive HIV/AIDS Tat-based vaccines.

Here we describe a prime-boost regimen of vaccination in Macaca fascicularis that combines priming with novel anionic microspheres designed to deliver the biologically active HIV-1 Tat protein and boosting with Tat in Alum. This regimen of immunization modulated the IgG subclass profile and elicited a balanced Th1-Th2 type of humoral and cellular responses. Remarkably, following intravenous challenge with SHIV89.6Pcy243, vaccinees significantly blunted acute viremia, as compared to control monkeys, and this control was associated with significantly lower CD4+ T cell depletion rate during the acute phase of infection and higher ability to resume the CD4+ T cell counts in the post-acute and chronic phases of infection. The long lasting control of viremia was associated with the persistence of high titers anti-Tat antibodies whose profile clearly distinguished vaccinees in controllers and viremics. Controllers, as opposed to vaccinated and viremic cynos, exhibited significantly higher pre-challenge antibody responses to peptides spanning the glutamine-rich and the RGD-integrin-binding regions of Tat. Finally, among vaccinees, titers of anti-Tat IgG1, IgG3 and IgG4 subclasses had a significant association with control of viremia in the acute and post-acute phases of infection. Altogether these findings indicate that the Tat/H1D/Alum regimen of immunization holds promise for next generation vaccines with Tat protein or other proteins for which maintenance of the native conformation and activity are critical for optimal immunogenicity. Our results also provide novel information on the role of anti-Tat responses in the prevention of HIV pathogenesis and for the design of new vaccine candidates.

Communication and cultural interaction in health promotion strategies to migrant populations in Italy: the cross-cultural phone counselling experience.

INTRODUCTION: In the last 10 years migration processes have progressively increased worldwide and in Italy about 5 millions of residing migrants are estimated. To meet health needs of these new residents, effective relational and communication tools, which allow a reciprocal intercultural interaction within health care structures, are therefore necessary. AIM: This article faces the main features of the relational-communication processes associated with health promotion and care in the migrant population in Italy to the aim of identifying the key and critical points within the interaction between different cultures, focusing on the role of specific professional figures, including cultural mediators and health educators. RESULTS: Within the activity of HIV phone counselling operated by Psycho-sociobehavioural, Communication and Training Operating Unit of National Institute of Health in Italy, an intercultural approach was successfully experienced in a project targeted to migrants (2007-2008). Specifically, the presence of cultural mediators answering in the languages of main migrants' groups allowed the increase of calls from migrant people and of the information provided.

Sexual behaviours of clients of sex workers reported within phone calls at HIV/AIDS/STIs Italian Helpline.

BACKGROUND: Clients of sex workers represent a relevant target for interventions aimed at the prevention of HIV and sexually transmitted infections (STIs). Within prevention strategies, the AIDS and sexually transmitted infections helpline (Telefono Verde AIDS/ IST, TVA-IST) of National Institute of Health in Italy has provided, since 1987, specific information and counselling interventions. AIM: The present study reports data on anagraphical characteristics and behaviours of clients of sex workers, anonymously reported at TVA-IST in the period 1987-2010. DISCUSSION: Among 95 149 phone calls (14% of the total) considered 99.5% came from males, over 80% aged under 37 years and prevalently from Northern Italy. Among sexual behaviours, unprotected sexual intercourses were reported in the 26% of the calls. Subjects under 27 years reported a higher frequency of unprotected anal intercourse, while they used protection with oral and vaginal intercourses in a greater extent than older ones. Due to differential behaviours within clients of sex workers, specific informative strategies for this targeted population should adequately consider age-related differences.

A new antigen scanning strategy for monitoring HIV-1 specific T-cell immune responses.

Delineation of the immune correlates of protection in natural infection or after vaccination is a mandatory step for vaccine development. Although the most recent techniques allow a sensitive and specific detection of the cellular immune response, a consensus on the best strategy to assess their magnitude and breadth is yet to be reached. Within the AIDS Vaccine Integrated Project (AVIP http://www.avip-eu.org) we developed an antigen scanning strategy combining the empirical-based approach of overlapping peptides with a vast array of database information. This new system, termed Variable Overlapping Peptide Scanning Design (VOPSD), was used for preparing two peptide sets encompassing the candidate HIV-1 vaccine antigens Tat and Nef. Validation of the VOPSD strategy was obtained by direct comparison with 15mer or 20mer peptide sets in a trial involving six laboratories of the AVIP consortium. Cross-reactive background responses were measured in 80 HIV seronegative donors (HIV-), while sensitivity and magnitude of Tat and Nef-specific T-cell responses were assessed on 90 HIV+ individuals. In HIV-, VOPSD peptides generated background responses comparable with those of the standard sets. In HIV-1+ individuals the VOPSD pools showed a higher sensitivity in detecting individual responses (Tat VOPSD vs. Tat 15mers or 20mers: p≤0.01) as well as in generating stronger responses (Nef VOPSD vs. Nef 20mers: p<0.001) than standard sets, enhancing both CD4 and CD8 T-cell responses. Moreover, this peptide design allowed a marked reduction of the peptides number, representing a powerful tool for investigating novel HIV-1 candidate vaccine antigens in cohorts of HIV-seronegative and seropositive individuals.

HIV-1 tat promotes integrin-mediated HIV transmission to dendritic cells by binding Env spikes and competes neutralization by anti-HIV antibodies.

Use of Env in HIV vaccine development has been disappointing. Here we show that, in the presence of a biologically active Tat subunit vaccine, a trimeric Env protein prevents in monkeys virus spread from the portal of entry to regional lymph nodes. This appears to be due to specific interactions between Tat and Env spikes that form a novel virus entry complex favoring R5 or X4 virus entry and productive infection of dendritic cells (DCs) via an integrin-mediated pathway. These Tat effects do not require Tat-transactivation activity and are blocked by anti-integrin antibodies (Abs). Productive DC infection promoted by Tat is associated with a highly efficient virus transmission to T cells. In the Tat/Env complex the cysteine-rich region of Tat engages the Env V3 loop, whereas the Tat RGD sequence remains free and directs the virus to integrins present on DCs. V2 loop deletion, which unshields the CCR5 binding region of Env, increases Tat/Env complex stability. Of note, binding of Tat to Env abolishes neutralization of Env entry or infection of DCs by anti-HIV sera lacking anti-Tat Abs, which are seldom present in natural infection. This is reversed, and neutralization further enhanced, by HIV sera containing anti-Tat Abs such as those from asymptomatic or Tat-vaccinated patients, or by sera from the Tat/Env vaccinated monkeys. Thus, both anti-Tat and anti-Env Abs are required for efficient HIV neutralization. These data suggest that the Tat/Env interaction increases HIV acquisition and spreading, as a mechanism evolved by the virus to escape anti-Env neutralizing Abs. This may explain the low effectiveness of Env-based vaccines, which are also unlikely to elicit Abs against new Env epitopes exposed by the Tat/Env interaction. As Tat also binds Envs from different clades, new vaccine strategies should exploit the Tat/Env interaction for both preventative and therapeutic interventions.

HIV virology and pathogenetic mechanisms of infection: a brief overview.

Studies on HIV virology and pathogenesis address the complex mechanisms that result in the HIV infection of the cell and destruction of the immune system. These studies are focused on both the structure and the replication characteristics of HIV and on the interaction of the virus with the host. Continuous updating of knowledge on structure, variability and replication of HIV, as well as the characteristics of the host immune response, are essential to refine virological and immunological mechanisms associated with the viral infection and allow us to identify key molecules in the virus life cycle that can be important for the design of new diagnostic assays and specific antiviral drugs and vaccines. In this article we review the characteristics of molecular structure, replication and pathogenesis of HIV, with a particular focus on those aspects that are important for the design of diagnostic assays.

The epidemic of HIV infection and AIDS, promotion of testing, and innovative strategies.

In Europe, the incidence of new diagnoses of HIV infection in 2008 was 86.7 cases per one million population, and most cases were attributable to sexual transmission. In Italy, in 2007, the incidence was 60.0 cases per one million population (in the areas in which surveillance exists), and 73.7% of the cases were attributable to sexual transmission. At present, there are an estimated 170,000-180,000 persons living with HIV/AIDS in Italy, some of whom are unaware of being infected. Based on available epidemiological data and taking into consideration the level of risk of exposure to HIV, we describe several proposals for promoting access to HIV testing in diverse population groups and contexts, including some innovative approaches. The promotion of HIV testing is fundamental for public health and human rights and must be associated with treatment, care and prevention activities, which must be guaranteed for the entire population.

Laboratory diagnostics for HIV infection.

Laboratory diagnosis of human immunodeficiency virus (HIV) infection is fundamental for detecting and monitoring infection. Many diagnostic tools are available that are based on both detection of HIV-specific antibodies and virus antigen, or nucleic acid. As technology evolves, HIV testing assays are being improved providing better sensitivity and specificity. In this short review, we summarize the common and new methodologies that are being used in laboratories, from the HIV antibody-based assays to the new tests for the detection of HIV nucleic acids.

Suggested strategies for the laboratory diagnosis of HIV infection in Italy.

HIV/AIDS surveillance data indicate that, in 2008, approximately one-fourth of all HIV infections in adults remain undiagnosed in Italy and that close to 60% of AIDS diagnosed individuals discovered their seropositivity at the diagnosis of AIDS. Late diagnosis of HIV infection is associated with increased mortality and morbidity and increased cost to healthcare services. From a public health perspective, knowledge of HIV status is associated with a reduction in risk behaviour. Thus, a routine screening for HIV infection is important for both a better prognostic outcome, and control of HIV spreading in the population. In Italy there are not shared guidelines for the laboratory diagnosis. In this paper, we suggest two algorithms that can be adopted for the diagnosis of HIV infection in individuals undergoing HIV testing.

Containment of infection in tat vaccinated monkeys after rechallenge with a higher dose of SHIV89.6P(cy243).

We previously reported that cynomolgus monkeys vaccinated with the human immunodeficiency virus (HIV)-1 Tat protein controlled infection after challenge with the simian human immunodeficiency virus (SHIV) 89.6P(cy243) for up to 2 y of follow-up. To evaluate the breadth of the protective immunity elicited by the Tat protein, the vaccines along with the naïve monkeys were intravenously rechallenged with a fivefold higher dose (50 MID(50)) of the same SHIV-89.6P(cy243). The vaccinated monkeys exhibited a statistically significant and long-lasting reduction of viral replication compared to control monkeys. This effect was associated with a strong anamnestic response to Tat, while responses to Gag and Env were nearly undetectable. Taken together, these data provide further evidence for the usefulness of Tat-based vaccines.

Anti-tumor CD8+ T cell immunity elicited by HIV-1-based virus-like particles incorporating HPV-16 E7 protein.

Here we report a novel strategy for the induction of CD8(+) T cell adaptive immune response against viral and tumor antigens. This approach relies on high levels of incorporation in HIV-1 VLPs of a mutant of HIV-1 Nef (Nef(mut)) which can act as anchoring element for foreign proteins. By in vitro assay, we found that VLP-associated Nef(mut) is efficiently cross-presented by antigen presenting cells. Inoculation in mice of VLPs incorporating the HPV-16 E7 protein fused to Nef(mut) led to an anti-E7 CD8(+) T cell response much stronger than that elicited by E7 recombinant protein inoculated with incomplete Freund's adjuvant and correlating with well-detectable anti-E7 CTL activity. Most relevantly, mice immunized with Nef(mut)-E7 VLPs developed a protective immune response against tumors induced by E7 expressing tumor cells. These results make Nef(mut) VLPs a promising candidate for new vaccine strategies focused on the induction of CD8(+) T cell immunity.

Native HIV-1 Tat protein targets monocyte-derived dendritic cells and enhances their maturation, function, and antigen-specific T cell responses.

Vaccination of cynomolgus monkeys with the biologically active HIV-1 Tat protein induces specific Th1 responses, including CTLs. Similar responses are also induced by vaccination with tat DNA, but not by vaccination with inactivated Tat or Tat peptides. This suggested that the native Tat protein may act differently on APC as compared with inactivated Tat or peptide Ag. In this study, we show that biologically active Tat is very efficiently taken up by monocyte-derived dendritic cells (MDDC) in a time (within minutes)- and dose-dependent (starting from 0.1 ng/ml) fashion, whereas uptake is very poor or absent with other APC, including T cell blasts and B lymphoblastoid cell lines. Although maturation of MDDC reduces their pino/phagocytic activity, mature MDDC take up Tat much more efficiently than immature cells. In addition, Tat uptake is abolished or greatly hampered by oxidation/inactivation of the protein or by performing the experiments at 4 degrees C, suggesting that MDDC take up native Tat by a receptor-mediated endocytosis. After uptake, active Tat protein induces up-regulation of MHC and costimulatory molecules and production of IL-12, TNF-alpha, and beta chemokines, which drive Th1-type immune response. In contrast, these effects are lost by oxidation and inactivation of the protein. Finally, native Tat enhances Ag presentation by MDDC, increasing Ag-specific T cell responses. These data indicate that native Tat selectively targets MDDC, is taken up by these cells via specialized pathways, and promotes their maturation and Ag-presenting functions, driving Th1-type immune responses. Thus, Tat can act as both Ag and adjuvant, capable of driving T cell-mediated immune responses.