Current HIV Research - Volume 12, Issue 1, 2014

After more than 30 years of continuous research as well as unselfish efforts, tremendous and exciting developments have been achieved towards the evolution of HIV treatments both in the directions of antiretroviral therapy and effective vaccine for HIV positive patients. Recent research shows that triple-drug antiretroviral therapy can ‘functionally cure’ [1, 2] the HIV positive patients, which is a milestone in the therapeutic treatments of AIDS. Despite the significant progress on the evolution of AIDS/HIV treatments, it is still a curse for the humanity and until today the world’s most serious epidemic as well as leading infectious killer disease. However, Millennium Development Goals (MDGs) Getting to Zero shows a hope to build up a new world without AIDS. In this paper we investigate and focus on those issues of the overall present scenarios of AIDS treatment for the preventive strategies of HIV infections. A mathematical model is analyzed with numerical simulations showing its importance in diseases control and preventions. Optimal control theory is applied to compare the results in the presence of state constraints.

Oxidative stress, defined as the imbalance between the oxidant and antioxidant systems, is thought to be associated with the progression of human immunodeficiency virus (HIV) infection. It has been observed that perturbations in antioxidant defense systems, and consequently redox imbalance, are present in many tissues of HIV-infected patients. Existing evidences suggest that oxidative stress may contribute to different stages of viral life cycle including viral replication and its consequences such as inflammatory response and decreased immune cell proliferation. The level of production of free radical species in HIV-1 infected individuals receiving antiretrovirals (ART) including highly active antiretroviral therapy (HAART) was reported to be higher than those who harbor HIV-1 infection without receiving any treatment or normal and healthy subjects. These observations suggest that the HIV-1 infection alone or in combination with introduction of ARV/HAART may induce oxidative stress and further augment HIV-1 pathogenesis. HIV-1 infection and the treatment with antiretrovirals have been found to cause antioxidant enzyme dysfunction in monocytes and central spinal fluid (CSF) leading to cognitive impairment in women. However, the exogenous application of some natural plant products or recent synthetic antioxidants might be useful in scavenging the free radicals. It is expected that their application as an additional strategy may facilitate ARV therapy or HAART for the effective treatment of HIV-1 infected persons or AIDS patients. This review offers a perspective on the current account of oxidative stress in HIV-1 infected individuals and its possible amelioration using suitable antioxidants, plant products and herbal preparations.

Background: Compensatory mutations have been observed to emerge with drug resistance (DR) mutations, but their effects on virological response to treatment have not been fully examined. In this study, we characterized the emergence and depletion dynamics of a compensatory mutation K43E that correlated with primary nucleoside reverse transcriptase inhibitor (NRTI) drug resistance mutations in Chinese HIV patients on antiretroviral treatment. Method: Single Genome Amplification (SGA) was used to obtain the HIV-1 pol gene quasispecies in three patients over 6 years of Antiretroviral Therapy (ART) treatment. SGA sequences were analyzed by Markov Chain Monte Carlo (MCMC) phylogenetic trees with molecular clock to identify and track compensatory mutation K43E correlated with primary DR mutation M41L. We evaluated the relationship between potential compensatory mutation and DR mutations through Ka/Ks ratio, Jaccard similarity coefficient, and compared these with concurrent viral load data. Conclusion: We determined that a known compensatory mutation, K43E, frequently co-occurs with the drug resistance mutation M41L and may offer a significant advantage in the long-term survival of such drug resistant strains.

Through the use of highly active antiretroviral therapy a significant reduction occurred in mortality and morbidity caused by Human Immunodeficiency Virus. The use of antiretroviral drugs resulted in the emergence of resistant viral strains due to mutations that cause a selective advantage to the virus. The aim of our study is to monitor the HIV-1 infection in Sicilians patients evaluating the presence of mutations that make the virus resistant to the therapy. The QIAGEN QIAamp Viral RNA Mini Kit was used to extract HIV-1 viral RNA from 300 patients while the TRUGENE HIV-1 Genotyping Kit and the OpenGene DNA Sequencing System determined viral mutations in the RNA samples. The analysis showed that from 300 subjects, 116 developed Antiretroviral Drug Resistance. The percentage of patients with resistance to nucleoside reverse transcriptase inhibitor (NRTI), non nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor was 26%, 23% and 20%, respectively. Comparison between drug resistances and mutations showed that 134 individuals had mutations in genes codifying for reverse transcriptase but a little more than 50% were associated with resistance to reverse transcriptase inhibitors, in particular 78 and 68 subjects developed drug resistances to NRTI and NNRTI classes respectively. Subjects that showed mutations in genes codifying for protease were 216 but only 59 of these were associated with resistance to protease inhibitors. Our findings emphasize the importance of continued resistance surveillance. Monitoring of transmitted resistance continues to be needed among treatment-exposed patients because of the benefit it provides for the development of drugs effective against the most frequently found drug-resistant viruses.

Studies have addressed periodontal disease biomarkers in salivary proteins associated with innate immunity, mostly due to the alteration in the concentration of many of these proteins in the presence of inflammation. On the other hand, some systemic diseases can modify salivary protein concentrations, which may change their importance or role as specific biomarkers. To study the relationship between periodontal disease and concentrations of human beta-defensin 2 (HBD-2) in the saliva of patients infected and not infected with HIV. To evaluate the association between HBD-2 salivary concentration and viral load, the TCD4+ lymphocyte count (LTCD-4+) and the use of antiretroviral therapy (ART) was assessed in HIVinfected patients. Concentrations of HBD-2 were measured in 48 patients not infected with HIV and 53 HIV-infected patients by ELISA, and these data were compared according to periodontal status. Within the group of HIV-infected patients, measures of HBD-2 were assessed according to viral load, LTCD-4+ count and the use of ART. Concentrations of salivary HBD-2 were associated with periodontal disease in non-HIV-infected patients. In HIV-infected patients, salivary HBD-2 was associated with serum status and the use of ART, but it was not related to the periodontal condition. The presence of HBD-2 in the saliva of HIV-infected patients showed no correlations with LTCD-4+ count or viral load. HBD-2 could be a periodontal biomarker in non-HIV-infected patients, but in HIV-infected patients, while salivary HBD- 2 was influenced by the serum status and ART use, it was not correlated with the periodontal condition.

Background: HIV is associated with end-organ diseases of aging via unclear mechanisms. Longitudinally assessing how HIV infection and ART initiation affect biomarkers of end organ function/disease could clarify these mechanisms. We investigated longitudinal changes in clinical biomarkers following 1) HIV infection and 2) ART initiation with evidence of viral suppression. Methods: Cohort: Veterans Aging Cohort Study Virtual Cohort (VACS VC). VACS VC is a longitudinal cohort of HIV infected (HIV+) and race-ethnicity, sex, age, and clinical site-matched uninfected Veterans enrolled in the same calendar year. Inclusion criteria: a negative and successively positive (>six months) HIV antibody test. We used Wilcoxon signedrank tests to analyze 1) the effect of HIV infection on lipids, renal, hepatic and hematologic/cardiovascular biomarkers and 2)whether ART initiation with HIV-1 RNA<500 cpm reverts any changes back to pre-HIV levels. Results: 422 Veterans had at least 1 biomarker measurement available prior to HIV infection and prior to ART initiation. 297 had at least 1 biomarker measurement available prior to HIV infection and after ART initiation with evidence of viral suppression. Mean age prior to HIV infection was 43 years. HIV infection was associated with reduction in total cholesterol, HDL cholesterol, LDL cholesterol, serum albumin, ALT, platelet count, hemoglobin and elevation of FIB-4 score and triglycerides. These changes occurred without significant changes in BMI. ART initiation (with HIV-1 RNA<500cpm) did not reverse alteration in triglycerides, LDL cholesterol, hemoglobin, or FIB-4 to pre-HIV infection levels. Conclusions: HIV infection is associated with longitudinal changes in serum levels of several biomarkers of end-organ function/disease and mortality. Multiple biomarkers (triglycerides, LDL cholesterol, hemoglobin, and FIB-4 ) remain altered from levels prior to HIV infection levels even following inititiation of ART and evidence of viral suppression. These results give insights into underlying mechanisms of increased risk for aging-related chronic diseases in the context of HIV infection.

The aim of the study was to report the epidemiological profile of HIV-1 positive patients from, Istanbul, Turkey, which has one of the lowest HIV-1/AIDS prevalences in Europe. The patients were followed by ACTHIV-IST group which was established by the Infectious Diseases Departments of five teaching hospitals (three university hospitals and two public hospitals) in Istanbul, Turkey. The HIV-1positive patients were added to the standard patient files in all of the centers; these files were then transferred to the ACTHIV-IST database in the Internet. A total of 829 naiv-untreated HIV-1 positive patients were chosen from the database. The number of male patients was 700 (84.4%) and the mean age of the patients was 37 years (range, 17-79). In our study group 348 (42%) of the patients were married and 318 (38.7%) of the patients were single. The probable route of transmission was heterosexual intercourse in 437 (52.7%) patients and homosexual intercourse in 256 (30.9%) patients. In 519 (62.6%) patients the diagnose was made due to a screening test and in 241 (29.1%) patients, the diagnose was made due to an HIV-related/non-related disease. The mean CD4+ T cell number in 788 of the patients was 357.8/mm3 (±271.1), and the median viral load in 698 of the patients was 100,000 copies/mL (20-9,790,000). In Turkey, the number of HIV-1 positive patients is still low and to diagnose with a screening test is the most common way of diagnostic route.

Introduction: Studies show that HIV counseling and testing (HCT) can improve linkage to HIV prevention, care and treatment services. However, uptake of HCT among couples remains low in most settings. We investigated the determinants of HCT uptake among individuals in long-term relationships in two districts in Uganda. Methods: This case-control study was conducted among 787 (400 in Kampala and 387 in Soroti) individuals in long-term sexual relationships, aged 18-54 years, using interviewer-administered questionnaires. Cases were individuals who had ever tested for HIV (selected from health facility records and traced in the community for interview) while controls were individuals who had never tested for HIV, identified from the same community as the cases. Data were collected on sociodemographic and behavioral characteristics; entered into FoxPro and analyzed using STATA version 12.1. We performed multivariable logistic regression to estimate the odds ratio (OR) and 95% Confidence Intervals (95%CI) associated with prior HCT and couples’ HCT uptake, controlling for suspected confounders. Results: Of the 787 participants, 522 had ever tested for HIV (cases) while 265 had never tested for HIV (controls). Compared to those that had never tested for HIV, those that had ever tested for HIV were significantly more likely to be females (Adj. OR=3.23, 95%CI: 2.27, 4.60), to be 25-29 years old (Adj. OR=2.15, 95%CI: 1.32, 3.50), to report exposure to a couples’ HCT promotional campaign (Adj. OR=2.01, 95%CI: 1.30, 3.10) and to believe that HIV discordance is possible among married couples (Adj. OR=1.77, 95%CI: 1.20, 2.63). Compared to individuals that had ever received individual HCT, those that had ever received couples’ HCT were significantly more likely to report prior discussion of HIV testing with partner (Adj. OR=4.35, 95%CI: 2.61, 7.28) and to be residents of Soroti district (Adj. OR=6.01, 95%CI: 3.74, 9.65). Conclusion: Prior HCT was significantly associated with female gender and exposure to a couples’ HCT promotional campaign while prior couples’ HCT was significantly associated with prior discussion of HIV testing with partner. To increase HIV testing among couples, these findings suggest a need for HCT promotional campaigns that promote communication about HCT between partners.