Current HIV Research, Vol. 3, No. 3, 2005
Contents
Review Articles
Chronic
Diarrhea and AIDS: Insights into Studies with Non-Human Primates Pp.199-205
Karol Sestak
Pathophysiology
of HIV-1 in Semen: Current Evidence for Compartmentalisation and Penetration by
Antiretroviral Drugs Pp.207-222
Derek J. Chan
Factors
Affecting Sexual Transmission of HIV-1: Current Evidence and Implications for
Prevention Pp.223-241
Derek J. Chan
HIV
and Inflammation Pp.243-259
Anne Zelie Decrion, Isabelle Dichamp, Audrey Varin and
Georges Herbein
IL-15
and HIV Infection: Lessons for Immunotherapy and Vaccination Pp.261-270
Ali Ahmad, Rasheed Ahmad, Alexandre Iannello, Emil Toma, Richard
Morisset and Sardar T.A.K. Sindhu
Original Research Articles
Effects
on Immunological and Virological Outcome of Patients Using One Protease
Inhibitor or One Non-Nucleoside Reverse Transcriptase Inhibitor in a Triple
Antiretroviral Therapy: Normal Clinical Practice Versus Clinical Trial Findings
Pp.271-276
Tebourski Fethi, Jlizi Asma, Slim Mohamed Amine, El
Gaaied-Ben Ammar Amel, Ben Chaabane Taoufik, Chakroun Mohamed, Letaief-Omezzine
Amel and Garbouj Mounira
Morphine
Exacerbates HIV-1 Viral Protein gp120 Induced Modulation of Chemokine Gene
Expression in U373 Astrocytoma Cells Pp.277-288
Supriya D. Mahajan, Ravikumar Aalinkeel, Jessica L.
Reynolds, Bindukumar B. Nair, Stanley F. Fernandez, Stanley A. Schwartz and
Madhavan P.N. Nair
Abstracts
[Back to top] Chronic
Diarrhea and AIDS: Insights into Studies with Non-Human Primates
Karol Sestak
Diarrhea is the pathophysiological reaction of host’s gastrointestinal tract to a variety of external stimuli. Classified as a clinical syndrome, diarrhea is the leading cause of mortality and morbidity worldwide. Clinical manifestations can occur in two major forms: A) acute, which usually resolves in less than three weeks and B) chronic, which can last for months. Because of its impact on the host immune system, acquired immune deficiency syndrome (AIDS) is currently the major cause of chronic diarrhea in many parts of the world. It is estimated that up to 90% of HIV-infected individuals with symptoms of AIDS exhibit clinical diarrhea [9, 74, 55]. In SIV-infected rhesus macaques, intense infiltration of intestinal lamina propria with virus-containing lymhocytes and macrophages can be found within days after experimental virus inoculation [25, 57]. In addition to acute enteropathy syndrome, viral infection ultimately leads to other alterations of the gastrointestinal tract including persistent and/or chronic diarrhea, a condition similar to untreated AIDS of human patients. In this short review, the chronic diarrhea is presented from the perspective of the non-human primate or simian model of AIDS (SAIDS), and its most common opportunistic and pathogenic co-infections.
[Back to top] Pathophysiology
of HIV-1 in Semen: Current Evidence for Compartmentalisation and Penetration by
Antiretroviral Drugs
Derek J. Chan
Sexual transmission of HIV-1 is dependent on the semen viral load. Seminal viral load may fluctuate and is increased by several HIV-1 related factors and prevailing conditions within the male genital tract. The precise reservoirs of virus production within the male genital tract, whether cell-associated of cell-free, are undefined. The ability of antiretroviral drugs to penetrate the male genital tract and reach therapeutic concentrations is correlated with the degree of viral suppression and therefore relative infectivity. The basic physicochemical properties of the drugs themselves do not predict penetration of semen and other factors, such as active drug transport, may be involved. Measurement of seminal viral load and antiretroviral drug concentration are affected by the physiology of semen and non-standardised methodology (type of test used, specimen collection methods, data presentation issues, and pharmacokinetic assumptions) between studies.
[Back to top] Factors
Affecting Sexual Transmission of HIV-1: Current Evidence and Implications for
Prevention
Derek J. Chan
The predominant mode of HIV-1 transmission globally is from sexual practices. The risk of HIV-1 transmission by sexual means is a function of infectivity, susceptibility and mode of transmission (type of sexual practice). In addition, transmission may be significantly increased or decreased by factors relating to the HIV-1 per se, sexual behaviour, other sexually transmissible infections (STIs), antiretroviral therapy (ART), spermicidal microbicides and HIV-1 vaccines, the host immune system, genital anatomy and nutritional deficiencies. Current research into the factors affecting sexual transmission of HIV-1 appears to benefit developed nations more than developing nations because of structured public health systems and the capacity to translate research findings into prevention strategies. A redistribution of global aid funding would do much to alleviate the pandemic in developed countries.
[Back
to top] HIV and Inflammation
Anne Zelie Decrion, Isabelle Dichamp, Audrey Varin and
Georges Herbein
A main feature of HIV infection is the expression of several proinflammatory cytokines. Proinflammatory cytokines expressed as soluble factors or membrane-bound molecules regulate both HIV replication and T cell apoptosis. Proinflammatory cytokines have key roles in the HIV lifecycle, especially at the level of transcription, favouring the ability of HIV to establish latent reservoirs. In addition, proinflammatory cytokines are involved in both CD4+ T cell and CD8+ T cell apoptosis, resulting in immune suppression. Moreover, several HIV proteins such as Nef, Tat, and Vpr hijack proinflammatory cytokine signaling, further underlining the potential importance of inflammation in HIV pathogenesis. In vivo chronic inflammatory conditions have been correlated to increased levels of viremia and accelerated disease progression. This article raises the possibility that inflammation plays a crucial role in both immune suppression and the formation of viral reservoirs during HIV infection. Understanding the role of inflammation in HIV infection could lead to new therapeutic strategies that could ultimately enhance immune restoration and limit the formation of viral reservoirs in HIV-infected patients.
[Back to top] IL-15 and HIV Infection: Lessons for Immunotherapy and
Vaccination
Ali Ahmad, Rasheed Ahmad, Alexandre Iannello, Emil Toma,
Richard Morisset and Sardar T.A.K. Sindhu
IL-15 is a pleiotropic and multifunctional cytokine that has a diverse array of distinct biological effects in the body. It plays a crucial role in host defense from viral and non-viral intracellular pathogens. The cytokine is essential for the development and differentiation of NK cells and for homeostatic expansion of CD8+ memory T cells, NKT cells and certain subsets of intestinal intra-epithelial lymphocytes (iIEL). It acts as a survival factor and inhibits spontaneous apoptosis in T, B and NK cells by increasing expression of different anti-apoptotic proteins. Several studies have shown that IL-15 production is compromised in HIV-infected AIDS patients and exogenous IL-15 drastically enhances functions of immune cells from these patients. Considering these distinct immune enhancing effects, relative safety in animal models, and minimal effects on HIV replication, IL-15 may represent a better cytokine for immune reconstitution in these patients. Furthermore, IL-15 may also act as a better adjuvant in eliciting antiviral immunity in anti-HIV vaccine strategies.
[Back to top] Effects on Immunological and Virological
Outcome of Patients Using One Protease Inhibitor or One Non-Nucleoside Reverse
Transcriptase Inhibitor in a Triple Antiretroviral Therapy: Normal Clinical
Practice Versus Clinical Trial Findings
Tebourski Fethi, Jlizi Asma, Slim Mohamed Amine, El
Gaaied-Ben Ammar Amel, Ben Chaabane Taoufik, Chakroun Mohamed, Letaief-Omezzine
Amel and Garbouj Mounira
We compared the response of two standard 3-drug regimens containing two-nucleoside reverse transcriptase inhibitor (Zidovudine +Lamivudine) plus either a protease inhibitor (PIs) (Indinavir) or a non-nucleoside reverse transcriptase inhibitor (NNRTIs) (Efavirenz) among treatment-na•ve or treatment-experienced HIV-infected persons. The obtained results will be compared to clinical trial findings. Through a retrospective study, we compared the virological and immunological response of 119 Tunisian HIV-1 infected patients (North Africa) who started for the first time/ in salvage use a triple antiretroviral treatment containing one NNRTI (group A1/group A2) or one PI (group B1/group B2). Viral load (VL) was analysed with Amplicor HIV-1 Monitor test and drug resistance mutations were examined by using two distinct line probe assays (LiPA). The analysis according to the received treatment showed an average of 0.45 log10 drop in the mean VL among groups A2 and B2. For na•ve patients, 62.5% of group A1 reached an undetectable VL versus 53.5% for group B1 (p<0.001). With regard to the CD4 cell count change, we observed a mean increase of more than 65% versus baseline within group A1 in comparison with 42% for group B1 (p<0.001). Genotypic resistance assays showed that patients of group A2 had significantly more resistance mutations than those of group B2 (2.66 vs. 0.75 (p=0.0039)). Finally, 15 patients who were failing were switched to indinavir or efavirenz. When indinavir was replaced by efavirenz, we observed an increase in the plasma VL. With regard to the effects on immunological and virological outcome of patients using PIs or NNRTIs in a triple antiretroviral therapy, our observations in normal clinical practice supported the reported clinical trial findings but are not in favour of replacing indinavir by efavirenz in failing regimen.
[Back to top] Morphine Exacerbates
HIV-1 Viral Protein gp120 Induced Modulation of Chemokine Gene Expression in
U373 Astrocytoma Cells
Supriya D. Mahajan, Ravikumar Aalinkeel, Jessica L. Reynolds, Bindukumar B. Nair, Stanley F. Fernandez, Stanley A. Schwartz and Madhavan P.N. Nair
HIV-1 affects microglia and astroglia, which subsequently contributes to the neurodegenerative changes. Viral proteins cause neurotoxicity by direct action on the CNS cells or by activating glial cells to cause the release of cytokines, chemokines or neurotoxic substances. Opioid abuse has been postulated as a cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) infection and AIDS. HIV-induced pathogenesis is exacerbated by opiate abuse and that the synergistic neurotoxicity is a direct effect of opiates on the CNS. Chemokines and their receptors have been implicated in the pathogenesis of neuroAIDS. Herein we describe the effects of morphine and/or gp120 on the expression of the genes for the b-chemokine MIP-1b and its receptors CCR3 and CCR5 by the U373 cells which are a human brain-derived astrocytoma/glioblastoma cell line. Our results indicate that treatment of U373 cells with morphine significantly downregulated the gene expression of the b chemokine, MIP-1 b, while reciprocally upregulating the expression of its specific receptors, CCR3 and CCR5 suggesting that the capacity of mu-opioids to increase HIV-1 co-receptor expression may promote viral binding, trafficking of HIV-1-infected cells, and enhanced disease progression. Additionally, opiates can enhance the cytotoxicity of HIV-1 viral protein gp120 via mechanisms that involve intracellular calcium modulation resulting in direct actions on astroglia, making them an important cellular target for HIV-opiate interactions.