Jornal de AIDS e Pesquisa Clínica

Objectives: Therapeutic vaccination in chronic HIV-infection aims to attenuate disease progression by promoting new HIV-specific T cell-clones. Most clinical trials with therapeutic vaccines are conducted on patients receiving antiretroviral therapy (ART). However, studies of vaccination in untreated individuals are limited. We present the first data from a phase I/II clinical trial with a peptide-based therapeutic vaccine (Vacc-5q) consisting of five short, modified consensus peptides from p17, p24, and Tat. In addition to evaluating safety and immunogenicity of Vacc-5q, we compared responses induced in patients on effective ART with those of ART-naïve patients.

Methods: HIV-infected patients stable on ART (n=10) and treatment naive patients (n=10) received 11 intradermal injections of Vacc-5q over 26 weeks, using GM-CSF as an adjuvant. Immunogenicity was assessed both in vivo by delayed type hypersensitivity (DTH) skin tests, and in vitro by T cell activation assays. Persistence of immune responses was retested after 3.5 years.

Results: Vacc-5q was found to be immunogenic. Specific T cell-responses both in vivo and in vitro increased significantly from baseline to week 4 (p<0.01), and were still present after 3.5 years. No significant differences were observed between ART treated and ART naïve patients at any time point.

Conclusion: Vacc-5q induced potent HIV associated cellular immune responses both in ART treated and in treatment-naïve viremic patients. These responses were comparably strong in both study arms and still present after 3.5 years, indicating that suppression of plasma viral load by ART might not be essential for optimal immunization.

Background: We analyzed the persistence of hepatitis A virus (HAV) antibodies 7 years after primary immunization in pediatric HIV-positive patients and its association with the immunological profile.

Methods: 29 vertically HIV-infected adolescents (median age, 12.9 years) were enrolled. All of them had been HAV-vaccinated with two HAV vaccine doses 7 years before and all had seroconverted. HAV antibodies were measured by electrochemiluminescence. Lymphocyte immunophenotyping was performed by flow cytometry. Adolescents who lost HAV antibodies were revaccinated.

Results: 23/29 patients (79.3%) persisted HAV seropositive (HAV antibodies≥20mlU/mL) 7 years after primary immunization. Age, gender, clinical progression of HIV infection, median viral load, and antiretroviral therapy were similar between those who persisted HAV seropositive and those who lost seropositivity. HIV adolescents who lost HAV antibodies had lower median CD4+ T cells/mm3 (200 vs. 634, p=0.004), lower median B cells/mm3 (103 vs. 335, p<0.001), lower median NK cells/mm3 (67 vs. 209, p=0.002), lower median percentage of naive CD4+ T cells (20% vs. 30%, p=0.026), lower median percentage of naive B cells (52% vs. 68%, p=0.009), higher median percentage of activated memory B cells (19% vs. 7%, p=0.004), higher median percentage of activated CD8+ T cells (51% vs. 22%, p=0.002), and higher median percentage of exhausted memory B cells (23% vs. 8%, p=0.031) than HAV-positive adolescents. 83.3% adolescents responded to revaccination.

Conclusion: Persistence of HAV antibodies occurred in 79.3% of patients. Both antibody maintenance and response to revaccination are closely associated with low immune activation and adequate CD4+ T and B cell levels.

Background: The purpose of this study is to assess the types of sexual behaviors among men who have sex with men (MSM), with and without a condom, and to assess the predictive relationship between sexual pleasure and risky sexual practices among MSM.

Methods: A total 304 MSM (Mean age 32.30, SD=11.28) recruited through informal social networks and the Internet participated in this study. Most participants were single and self-identified as gay (70%). Sexual pleasure was operationalized using one measure with 8 items (reliability analysis was good α=0.76). Participants were asked to recall their sexual experiences and their sexual behaviors over the last two months.

Results: Only 7.2% of participants reported being HIV positive and approximately 26% reported not knowing their status. All participants indicated that they would feel higher levels of sexual pleasure if they were not using a condom during their sexual interaction, and all differences were statistically significant. Differences were also found between the following scenarios: a) having sex with or without a condom for receptive anal sex (p=0.036), b) having sex with or without a condom for insertive anal sex (p=0.012), and c) having sex with or without a condom for oral sex (p<0.001). Linear regression indicated that pleasure is a predictor of how many times a man was penetrated without a condom (β=0.255; R2=0.084; p<0.05) and a predictor of how many times a man penetrated another man without a condom (β=0.291; R2=0.066; p<0.05).

Conclusion: Sexual pleasure needs to be prioritized in the development of condoms and other sexual safety measures as well as in the promotion of their use when working with HIV prevention among MSM.

Since the discovery of HIV vaccine three decades back, the quest for HIV vaccines has remained unquenched. There has been a transition of preferred approaches from candidates capable of inducing neutralizing antibody (Nab) or cytolytic T cell (CTL) response to vaccines that can induce broad spectrum responses. Heterologous prime boost strategy is believed to induce broad spectrum immunity of higher magnitude and breadth to effectively counter HIV diversity and hence is being studied extensively in the HIV vaccine field. It is important to understand factors affecting the immune responses generated by the prime-boost regimens to get leads for developing effective regimens. This review focuses on the results of completed clinical trials based on the three most frequently used prime-boost regimens, vector (ALVAC)/protein, DNA/vector (MVA) and DNA/vector (Ad5). It will also discuss probable protective immunological responses responsible for efficacy of the vaccine and role of prime boost strategy in eliciting them.

Purpose: TRANxITION compared efficacy and safety of switching virologically suppressed HIV-1 infected patients from nevirapine (NVP) immediate-release (IR) (200 mg twice-daily) to NVP extended-release (XR) (400 mg oncedaily).

Methods: TRANxITION was an open-label, parallel-group, non-inferiority clinical trial where adult patients with undetectable viral loads, receiving NVP IR plus a fixed-dose NRTI combination, were randomized (2:1) to NVP XR or IR. After week 48, patients initially randomized to IR were allowed to switch to XR.

Summary of results: At week 48, proportions of patients with virologic response (LLOQ=50 copies/mL TaqMan, FAS) were 88.5% (131/148) in the IR arm, and 88.8% (262/295) in the XR arm, observed difference of 0.3% (95% CI -6.1, 6.7). DAIDS grade 3/4 adverse events were similar in the XR and IR arms at week 48: 6.4% (19/295) vs. 6.1% (9/148). After week 48, all but 13 patients in the IR arm switched to XR. At week 144, the proportions of patients with virologic response were 95.0% (115/121) in those switching from IR to XR after week 48 [IR-XR post48], and 95.2% (238/250) in those on XR throughout [XR-XR post48]). DAIDS grade 3 and 4 events at week 144 in IR-XRpost48 (7.7%, [10/130]) differed from the XR-XR post48 group (11.2%, [31/276]).

Conclusions: NVP XR QD resulted in continued virologic suppression at weeks 48 and 144. Up to week 144, rates of serious AEs were modestly higher than at week 24 in both post-week 48 XR arms, most likely due to the openlabel design of the study.

We audited the cause of death and surrogate markers of HIV patients living in a HIV low prevalence area of the UK. Fatality rates from 2001-2010 were compared to two high prevalence areas. 16/104 newly diagnosed patients died. The median time from diagnosis to death was 4.2 years (<1month-18 years): 6 (38%) died <12 months of diagnosis, 3 (19%) within 5 years, seven (44%) >10 years later; twelve (75%) were male, twelve (75%) Caucasian, eight (50%) were infected through heterosexual intercourse; median CD4 count was 44 cells/microL (range 2-475). Twelve (75%) patients died of AIDS, 4 (25%) of Pneumocystis jerovecii pneumonia. The observed case-fatality rate was 2.3 (95% CI 1.4-3.9) fold higher in this low prevalence area compared to high prevalence areas (p<0.001), where universal HIV testing is promoted. It is possible that an early detection of HIV through universal instead of targeted HIV testing in sexually active adults in all areas of the UK could lead to a reduction of premature death due to AIDS.