Current HIV Research - Volume 8, Issue 2, 2010

A vaccine-induced cellular immune response to simian immunodeficiency virus (SIV) in the gut mucosal tissue may prevent the establishment or severity of new SIV infection. An oral Clostridium perfringens expressing SIV p27 (Cpp27) vaccine that delivers SIV p27 to the gut was evaluated for its ability to prime multifunctional cellular immunity in the gut mucosa. Gut Peyer's patches dendritic cells matured in response to in vitro exposure to Cp-p27 and stimulated production of p27-specific IFN-γ. In mice, the oral vaccination with the Cp-p27 vaccine and systemic immunization with adenovirus expressing SIV p27 (Ad-p27) induced robust systemic and mucosal immune responses. Furthermore, the prime-boost regimen induced p27-specific multifunctional CD8+ T cells in the gut. These results indicate that priming gut tissue with Cp-p27 can enhance the gut mucosal cellular immune response generated via systemic immunization with Adp27.

Chromium is an essential micronutrient; chromium deficiency has been reported to cause insulin resistance, hyperglycemia and hyperlipidemia. The aim was to investigate the effect of chromium supplementation on insulinresistance, other metabolic abnormalities, and body composition in people living with HIV. This was a randomized, double-blind, placebo-controlled trial. Fifty-two HIV-positive subjects with elevated glucose, lipids, or evidence of body fat redistribution, and who had insulin-resistance based on the calculation of homeostasis model of assessment (HOMAIR ≥ 2.5) were assessed. Subjects who were on insulin or hypoglycemic medications were excluded. Subjects were randomized to receive either 400 ug/day chromium-nicotinate or placebo for 16 weeks. Forty-six subjects, 23 in each group, completed the study. Fasting blood insulin, glucose, lipid profile and body composition were measured before and after intervention. Chromium was tolerated without side effects and resulted in a significant decrease in HOMA-IR (median (IQR) (pre:4.09 (3.02-8.79); post: 3.66 (2.40-5.46), p = 0.004), insulin (pre: 102 (85-226); post: 99 (59-131) pmol/L, p = 0.003), triglycerides, total body fat mass (mean ± SEM) (pre: 17.3 ± 1.7; post: 16.3 ± 1.7 kg; p = 0.002) andtrunk fat mass (pre: 23.8 ± 1.9; post: 22.7 ± 2.0%; p = 0.008). Blood glucose, C-peptide, total, HDL and LDL cholesterol, and hemoglobin A1c remained unchanged. Biochemical parameters did not change in the placebo group except for LDL cholesterol which increased significantly. Body weight and medication profile remained stable throughout the study for both groups. In summary, chromium improved insulin resistance, metabolic abnormalities, and body composition in HIV+ patients. This suggests that chromium supplements alleviate some of the antiretroviral-associated metabolic abnormalities.

Objective: We examined the impact of HIV voluntary counseling and testing on self-reported behavioral risks three months after HIV testing. Design: Cohort study comparing self-reported risk behaviors prior to and three months after HIV testing. Setting: Clinica Familiar Luis Angel Garcia, an HIV specialty clinic located in a Guatemalan National Hospital. Subjects, Participants: 144 people undergoing HIV testing were enrolled. 44 were HIV positive. 41 HIV positive and 49 HIV negative subjects returned for follow-up interviews. Intervention: All subjects were tested and received voluntary counseling regarding HIV infection, transmission, prevention, and interpretation of HIV test results. Main Outcome Measure: The primary study outcome measure was changed in self-reported risk behaviors three months after voluntary counseling and testing. Results: Men were more likely than women to report a history of sexually transmitted diseases, more than 2 sexual partners, using alcohol with sex, and receiving money for sex; they were less likely to have a regular partner. 26% of men reported non-heterosexual orientation; no woman did. Alcohol was the primary drug of abuse in both men and women. At three month follow-up HIV positive subjects showed decrease in the average number of sexual partners, use of alcohol with sex, and episodes of unprotected sex. Conclusions: Voluntary counseling and testing resulted in changes in some self-reported risk behaviors, but only among HIV positive subjects. On nearly all measures men reported riskier behavior than women. Alcohol is the most commonly used drug in this population and is often used with sex.

Nucleoside reverse transcriptase inhibitors (NRTIs) are the basis of antiretroviral treatment of HIV-positive patients. Several studies have shown decreased fertility and fecundity among HIV-positive women under antiretroviral treatment. Oocyte impaired competence has been hypothesized to be one of the main mechanisms underlying of this decreased fertility. NRTI side effects are thought to be due to the induced mitochondrial dysfunction. Stavudine, a widely used NRTI, causes persistent mitochondrial damage in various tissues. In order to gain insights into possible mechanisms of HIV-related diminished fertility, we studied the effects of stavudine on mouse oocyte mitochondria. Mitochondrial volume, protein assay and ATP contents were unaltered by stavudine treatment, but we found mitochondrial Cox I depletion in liver and oocytes. Our findings suggest that stavudine induces mtDNA depletion without organelle loss in mouse oocytes. The decrease in Cox I DNA in treated oocytes likely points to mitochondrial dysfunction, which can impair chances of pregnancy and embryo viability. We propose that the competence of oocytes depends primarily on functional capacity of mitochondria and less on their number.

The wide scale application of dried blood spots (DBS) as a collection tool for low-cost HIV drug resistance testing requires a greater understanding of the accuracy of DBS for genotype analysis and the stability of DBS under various environmental conditions. Analysis of a 50μl DBS via a single amplicon, nested PCR-based in-house assay (the Burnet genotyping assay) showed an average nucleotide concordance of 98.9% with plasma samples, although only 65% of nucleotide mixtures detected in plasma were also detected within DBS. The analysis of three DBS resulted in the detection of a greater number of nucleotide mixtures (72 and 109 mixtures detected within one and three DBS, respectively, n = 10). Two DBS extraction protocols (silica particle; NucliSENS, bioMerieux and spin column extraction; High Pure, Roche) were assessed and found to be equivalent (79% and 84% recovery success respectively, n = 19). FTA Elute paper (Whatman) was an inferior DBS collection medium compared to Whatman 903 paper. DBS appeared relatively tolerant to multiple freeze/thaw cycles, with 79% of DBS subjected to ten freeze/thaw cycles successfully amplified compared to 93% of DBS defrosted once (n = 14). High temperature (37°C) and high humidity (>90%) substantially impaired DBS recovery within two weeks of storage (38%, n = 8), whilst storage at -20°C or 4°C adequately preserved DBS for this period (100% recovery, n = 8). Therefore, whilst DBS are suitable for HIV drug resistance surveillance, the use of multiple DBS may be required to ensure accurate detection of minor HIV quasispecies and shortterm storage of samples at either 4°C or -20°C is recommended.

Hodgkin Lymphoma (HL) represents one of the most common types of a non-AIDS-defining tumour that occurs in the HIV population, and its incidence is increasing in the post Highly Active Anti-retroviral Therapy (HAART) era. Despite the aggressiveness of that disease, the outcome of patients with HIV-HL has improved with better, combined antineoplastic and antiretroviral approaches. New and effective antiretroviral drugs, in conjunction with nucleoside analogs, improve the control of the underlying HIV infection when used during treatment of HL with chemotherapy. The inclusion of hematopoietic growth factors in the treatment of patients with HIV-HL may allow for the administration of higher dose-intensity chemotherapy and the prolonged use of antiretroviral drugs, with the aim of improving the survival. In addition, new functional imaging tools, like the Positron Emission Tomography (PET), may help to guide treatment and minimize long term toxicity.

IL-18 is a pleiotropic and multifunctional proinflammatory cytokine that is often produced in response to a viral infection. The biological activities of the cytokine are tightly controlled by its natural antagonist, IL-18 binding protein (IL-18BP), as well as by activation of caspase-1, which cleaves the precursor form of IL-18 into its biologically mature form. The cytokine plays an important role in both innate and adaptive antiviral immune responses. Depending upon the context, it can promote TH1, TH2 and TH17 responses. Increased serum concentrations of IL-18 and concomitantly decreased concentrations of its natural antagonist have been described in HIV-infected persons as compared to HIV-seronegative healthy subjects. We discuss in this review article how increased biological activities of IL-18 contribute towards immunopathogenesis of AIDS, HIV-associated lipodystrophy syndrome and related metabolic disturbances. While the advent of potent anti-HIV drugs has significantly enhanced life span of HIV-infected patients, it has also increased the number of these patients suffering from metabolic disorders. The cytokine may prove to be a useful target for therapeutic intervention in these patients.

HERMES is a prospective study, including all treatment-naive patients attending scheduled visits at hospitals in the CISAI group in 2007. The present cross-sectional analysis aims to assess the baseline prevalence and characteristics of Metabolic Syndrome (MS) in a population of HIV-positive treatment-naive patients. MS was diagnosed using the National Cholesterol Education Program (NCEP) definitions. A total of 292 subjects were enrolled, median age was 37 years, 75% of them were males. The prevalence of MS was 12.3%. The most frequent trio of abnormalities that led to the diagnosis of MS was high blood pressure, triglycerides and HDL. Univariate analysis showed that MS was associated with the following variables: age, education, physical activity, advanced HIV disease (CDC stage C or HIV-RNA >100,000 copies + CD4 <100 cells/mm3). Higher educational levels remained protectively associated with MS in multivariate analysis. A higher risk of MS was also associated with advanced HIV disease. Actually, treatment-naïve HIV-positive patients in an advanced stage of the disease have a higher prevalence of abnormal levels of triglycerides, HDL cholesterol and blood glucose than those at a less advanced stage. These findings of the HERMES study suggest, therefore, that HIV infection per se is associated to MS.

The goal of this work is to determine whether relationship power in couples and sexual double standard can predict the risk of sexually transmitted infections/human immunodeficiency virus (STI/HIV) as a function of cultural and gender differences. The sample was made up of 689 adolescents living in Spain, of both sexes, aged between 14 and 19 years, who were sexually active in the past six months and who had a stable partner. Of them, 58.9% were native Spaniards and 41.1% were immigrants of Latin American origin. The results show that origin, age, double standard and the control over decision-making in the couple can predict the risk of STI/HIV; thus, the immigrants, the older participants, those who scored higher in double standard, and those with less control over decision-making were at higher risk of STI/HIV. With regard to gender, the males displayed more double standard and more control over decisionmaking, and the females displayed higher control over the relationship. The need to adapt STI/HIV prevention programs to the cultural and gender inequality differences in the couple is commented on in the discussion.

Objective: To compare the treatment outcomes and mortality in a rural community-based ART (CBART) program with a hospital-based ART program in the same district. Methods: The study design was a non-randomized cohort study consisting of 185 persons living with HIV (PLWHIV) in the CBART cohort and 200 PLWHIV in the hospital cohort. Eligibility for both cohorts was: being HIV-infected and eligible for ART, being treatment naive, age 18 years or older, and being a resident of Rwimi sub-county. The intervention consisted of a community-based program which included weekly home visits to patients by trained volunteers who delivered antiretroviral drugs (ARVs), monitored and supported adherence to treatment, and identified and reported adverse reactions and other clinical symptoms. Outcome variables were compared to patients in a hospital-based cohort who received the standard care delivered to all other HIV patients in the hospital. The main outcome measures were HIV- 1 RNA viral load (VL), CD4 cell count and mortality after six months of treatment. Results: Successful ART treatment outcome as measured by virological suppression (VL<400 copies/ml) in the CBART cohort was similar to those in the hospital-based cohort (90.1% vs 89.3%, p=0.47). The median CD4 cell count increased significantly in both cohorts (community-based cohort 159 cells/μl vs 145 cells/μl in the hospital-based cohort). Mortality was not significantly different in both cohorts (community-based cohort 11.9%, hospital-based cohort 9.0%). Conclusion: The findings show that outcomes of a CBART intervention in a rural area compare favorably to outcomes of hospital-based care. If the study results are sustainable over a longer time period, this model could be considered for ART roll-out to impoverished rural/remote populations in Uganda and elsewhere.