Current HIV Research - Volume 11, Issue 3, 2013

Despite the relative lack of data, nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)-sparing regimens are increasingly prescribed in clinical practice in treatment-experienced HIV-1 infected patients. We aimed to assess the frequency of NRTI-sparing regimens among these subjects, and to evaluate and compare their safety and tolerability. Patients were included if enrolled in the currently ongoing cohorts (raltegravir and darunavir) of the Surveillance Cohort Long-Term Toxicity Antiretrovirals (SCOLTA) Project. The duration of treatment with antiretroviral therapy was evaluated using the Kaplan-Meier curve and NRTI-sparing and NRTI-based regimens were compared using the log-rank test. From 2006 to 2011, 689 experienced patients were analyzed, of whom 210 (30.5%) were on NRTI-sparing regimens. Patients on NRTI-sparing regimens were older (p=0.004) and had higher median CD4+ cell counts (p=0.002) than patients on NRTI-based regimens. The most frequent combination regimens were raltegravir plus darunavir/ritonavir (n=65; 30.95%) among patients on NRTI-sparing regimen and tenofovir DF/emtricitabine plus darunavir/ritonavir in the NRTI-containing group (n=102; 21.3%). There was no difference between groups in terms of total withdrawal, treatment discontinuation was more likely due to therapeutic failure in NRTI-sparing regimen. NRTI-sparing regimens should be evaluated in a prospective randomized trial.

The effects of antiretroviral (ARV) drugs administered to HIV-infected pregnancy on hematological parameters and hemoglobin (Hb) synthesis in ARV-exposed newborns with and without thalassemia carrier and of ARV drugs in worsening anemia in thalassemia carrier newborns are not well understood. Cord blood samples were collected from newborns of HIV-infected and -uninfected pregnancies. Hematological parameters and hemoglobin typing were analyzed by automated blood counter and capillary electrophoresis (CE), respectively. In the group of thalassemia carrier, the ARV-exposed newborns had significantly lower mean levels of red blood cell counts and hematocrit and had significantly higher mean levels of MCH than the ARV-unexposed newborns. Similar results were found in the group of newborns without thalassemia carrier. There were no statistical differences in mean levels of Hb-A2, Hb-A, Hb-F and Hb-E (when applicable) in ARV-exposed and -unexposed newborns either with or without thalassemia carrier. However, ARVexposed newborns who were thalassemia carriers had the lowest levels of hemoglobin and hematocrit when compared to the other groups. Therefore, ARV drugs used for prevention of HIV-mother-to-child transmission (HIV-MTCT) altered hematological parameters but did not affect hemoglobin synthesis in newborns with and without thalassemia carrier. However, thalassemia and ARV drugs might have synergetic effect in inducing severe anemia.

Hematological effects of antiretroviral (ARV) drugs in HIV-infected patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency are unclear. The aim of this study was to assess effects of highly active antiretroviral therapy (HAART) on hematological and plasma bilirubin changes in these patients. A hundred and nine HIV-infected Thai patients were tested for G-6-PD deficiency and its variant by using fluorescent spot test and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, accordingly. Changes of hematological parameters and plasma bilirubin at baseline and 6 months of HAART were analyzed in G-6-PD deficiency patients. G-6- PD deficiency was found in 10 (9.17%) patients and G-6-PD Canton1376G>T was the most frequent. Of these, 3 patients had coinheritance of G-6-PD deficiency and thalassemia. Increased mean levels of lymphocyte counts, CD4+ T-cells, mean corpuscular hemoglobin (MCH) and hemoglobin from baseline to 6 months of HAART were observed. Whereas, mean levels of total bilirubin and direct bilirubin at baseline were not significantly different from those at 6 months of HAART. Therefore, HAART did not cause hemolytic anemia and hyperbilirubinemia in HIV-infected patients with G-6- PD deficiency. On the other hand, the effective use of HAART is associated with improvements in hemoglobin and MCH levels of these patients.

The HIV-1 Nef protein brings about increased T cell activity and viral titers through mechanisms that are poorly understood. Nef activity has been described as an enhancer, but not an inducer, of certain signaling pathways that lead to T cell activation and viral production, particularly from resting T cells. The protein has also been found to associate with and promote autophosphorylation of a serine kinase, Pak2, but the Nef-associated kinase level is very low and difficult to study. Here we demonstrate that Nef expression mediates phosphorylation of Mek1 serine298 in T cell lines as well as primary human T cells, thus directly affecting the Erk cascade. This phosphorylation is through a Pak and Rac activity. We also find that Pak2 in Nef expressing cells is phosphorylated on serine192/197, the first biochemical description of the Nef-mediated activation state for this kinase.

Human herpes viruses cause significant morbidity in patients with the acquired immunodeficiency syndrome. Even after the introduction of highly active anti-retroviral therapy (HAART), herpes viruses remain the leading causes of blindness in AIDS patients. Cytomegalovirus (CMV) retinitis and the closely-related immune reconstitution uveitis syndrome are the most common causes of blindness, but progressive outer retinal necrosis and acute retinal necrosis due to varicella zoster and herpes simplex are also important causes of vision loss. Successful treatment of these conditions requires an aggressive approach with multi-drug intravenous therapy or repeated intravitreal antiviral injections. Since the rate of retinal detachment is alarmingly high despite successful antiviral therapy, internists and ophthalmologists must work closely together to recognize and treat complications as they arise. Fortunately, Epstein-Barr virus is a rare cause of retinal infection and human herpes virus (HHV)-6, HHV-7, and HHV-8 do not appear to be primary pathogens. However, increasing evidence suggests that HHV-6 and HHV-7 play important roles in modulating the immune system and potentiating infection by CMV.

This study evaluated the salivary concentrations of lactoferrin (Lf) in HIV-seropositive and -seronegative subjects correlating these levels with the incidence of periodontal disease, quantity of Candida spp and systemic condition of the HIV-seropositives (viral load and T lymphocytes CD-4+ count and antiretroviral therapy). Whole saliva samples were obtained from 109 subjects who were divided into four groups according to the extent of their HIV infection and their periodontal condition. The salivary Lf concentrations were determined by a standard enzymelinked immunosorbent assay and the quantification of Candida spp. was obtained from all subjects. Among the HIV- participants, higher concentrations of Lf were found in individuals with periodontal diseases (p<0.0001). A similar result was found for HIV+ participants (p<0.0001). No correlation was found between the concentration of salivary Lf and the quantification of Candida spp or between the Lf concentration and the systemic condition of the HIV+ subjects. The existence of periodontal diseases can modulate an early inflammatory process in the oral mucosa by increasing the expression of Lf, where Lf can act as an antibacterial peptide in HIV- and HIV+ patients. These results suggest that Lf is a possible marker for periodontal diseases in immunocompetent and immunocompromised subjects.

There are some evidences regarding beneficial effects of carnitine in improvement of depression symptoms. Incidence of depression is significantly higher among HIV positive individuals compared to HIV negative populations. Also carnitine deficiency is prevalent in HIV positive individuals. In a cross-sectional study correlation between serum carnitine level and depression severity based on the Beck Depression Inventory questionnaire was assessed in 100 HIV/AIDS (42 males and 58 females) patients. According to the Beck Depression Inventory definitions, 31%, 16%, and 21% of the patients experienced mild, moderate, and severe depression, respectively. The mean ± SD serum concentration of total carnitine in the patients was 37.96 ± 26.08 (µmol/L). Fifty-four (54%) patients were categorized as carnitine deficient. A non-statistically significant negative correlation between patients’ depression scores and total levels of serum carnitine was found. Considering the prevalence of depression among HIV/AIDS patients and probable role of carnitine in the pathogenesis of depressive disorders, more studies are needed to reveal correlation between depression and the body storage of carnitine.

Background: This study evaluated treatment satisfaction, gastrointestinal tolerability, depressive symptoms and alterations in laboratory parameters before and after switching from ritonavir capsule to tablet formulation. Methods: HIV+ adults switching from ritonavir capsules to tablets were eligible for the study. The HIV Treatment Satisfaction Questionnaire (HIVTSQ), Gastrointestinal Symptom Rating Scale (GSRS) and CES-D Depression inventory were self-administered before, and 3-4 months after switching. Results of laboratory tests within three months of each questionnaire were collected. A subset underwent plasma drug level sampling. Wilcoxon signed rank sum test was used for comparison of continuous variables and McNemar’s test for dichotomised data. Results: Most of the 71 participants were Caucasian men, median age 51 years. Participants were taking ritonavir in combination with either atazanavir (n=48 [67.6%]), darunavir (n=18 [25.4%]), fosamprenavir (n=3 [4.2%]) or saquinavir (n=2 [2.8%]). In general after the switch to tablets, participants reported improved treatment satisfaction (median [interquartile range] HIVTSQ score 53/60 [48, 58] after vs 49/60 [45, 54] before, p <0.001), fewer gastrointestinal symptoms (GSRS score 4/45 [1, 9] vs 5/45 [3,13], p < 0.001) and had higher HDL cholesterol (1.22 mmol/L [1.07, 1.45] vs 1.09 mmol/L [0.90,1.32], p = 0.003) and lower total cholesterol/HDL ratio (3.82 [3.05, 4.40] vs 4.23 [3.45, 4.84], p<0.001). There were no significant changes in plasma viral load, CD4 counts, depression scores, or atazanavir or ritonavir trough levels. Conclusion: Results of this study suggest that the newer tablet formulation of ritonavir is better tolerated and has fewer gastrointestinal side effects than the older capsule formulation.

Cognitive barriers to participation in actual HIV vaccine trials have not been previously comprehensively reviewed. In this review article, barriers in actual early phase, phase 2B, and phase 3 HIV vaccine trials are quantified and categorized, and compared between the Organization for Economic Co-operation and Development (OECD) countries and the non-OECD countries. Participation rates were standardized to allow for comparisons. In both the OECD and the non- OECD countries, barriers included subjective norms and discrimination, vaccine safety concerns, and logistical concerns. More actual HIV vaccine trials can incorporate questions about and quantify barriers to participation, and this may aid future recruitment strategies.

Objective: To explore the relationship between religious affiliation and HIV infection in a war-ravaged community in sub-Saharan Africa. Design: Mixed quantitative and qualitative methods. Methods: Individuals attending HIV voluntary counseling and testing clinics in Butembo in Eastern Democratic Republic of the Congo (DRC) completed a questionnaire and were tested for HIV infection. Risk factors for HIV seropositivity were explored, with attention to religious affiliation as a potential risk factor. Structured interviews of key informants were used to complement quantitative data. Results: Three hundred and eighty individuals attending six clinics were enrolled. Nearly all participants (97%) selfidentified as Christian (44% Catholic; 53% non-Catholic Christian). Twenty-eight patients (7.4%) tested positive for HIV. Age>30 years (adjusted OR 47 [95%CI 2.9-770, p=0.007]), married status (adjusted OR 3.7 [95%CI 1.1-13, p=0.037]), and Catholic religion (adjusted OR 2.7 [95%CI 1.1-6.8, p=0.030]) were independent risk factors for HIV seropositivity in a multivariable logistic regression model. Rates of HIV were higher among Catholic than non-Catholic Christian participants in both single and married participants. The proportion of participants reporting condom use as a primary prevention modality did not differ significantly between religious groups; however, within both Catholic and non-Catholic Christian groups, increasing church attendance was associated with decreased use of condoms. Qualitative data highlighted divergent views toward condom use among Catholic health workers. Conclusions: In this cross-sectional survey in Eastern DRC, Catholic (relative to non-Catholic Christian) religious affiliation was associated with an increased risk of HIV. Increasing dialogue between biomedical practitioners and religious leaders may strengthen HIV prevention efforts in SSA.