Revista de SIDA e investigación clínica

Objectives: After DNA or RNA virus infection, cytosolic foreign DNA or RNA derived from the infecting viruses is recognized by intracellular pathogen recognition receptors (PRRs) and induces activation of the innate immune system. Transfection of DNA has been used as an experimental model for DNA virus-mediated innate responses. We have previously reported that DNA transfection preferentially induces Type-III IFN (IFN-λ1) rather than Type-I IFN (IFN-β). In this study, we compared the DNA-mediated immune response between healthy controls and HIV-1 infected patients with undetectable viral loads and assessed potential innate immune responses in these patients.

Methods: The study consisted of 50 HIV-1 negative healthy donors, 46 patients on combination antiretroviral therapy with HIV-1 viral loads <50 copies/ml and 7 long term non-progressors (LTNPs). PBMCs were isolated from whole blood using Ficoll-Paque. DNA transfection was performed using Lipofectamine 2000. After 22 hours incubation, total cellular RNA was extracted and real time RT-PCR was performed to determine gene expression level of IFN-λ1, IFN-β and RANTES. Gene induction was compared by fold change.

Results: Baseline levels of endogenous gene expression of IFN-λ1, IFN-β and RANTES in HIV-1 patients were higher than in controls. Following DNA transfection, both HIV infected patients and healthy controls induced gene induction, however, the induction in HIV-1 patients was at a significantly lower level compared to uninfected controls.

Conclusion: HIV-1 treated patients with undetectable viral loads have lower levels of innate immune responses via cytosolic DNA sensing systems. This may be caused by persistent immune activation.

A majority of children with symptoms of Attention Deficit Hyperactivity Disorder (ADHD) from early childhood continue to demonstrate notable ADHD symptoms throughout life. ADHD-associated impulsivity, in adults, has been found to be a predictor of unstable interpersonal relationships and high risk sexual behavior. This study was undertaken to determine the prevalence of adult ADHD in recently diagnosed young male HIV patients. 100 young adult males who were diagnosed with HIV less than a year ago were recruited after an informed consent and were administered the following questionnaires-socio-demographic questionnaire with details of HIV diagnosis, HIV High Risk Behavior Questionnaire (HRBS) to measure High risk sexual behaviors, MINI neuropsychiatric Interview 6.0 to rule out psychiatric co-morbidities, Mini Mental State Examination (MMSE) to rule out major cognitive impairment, Adult ADHD Self Report scale (ASRS) v1.1 to screen for ADHD in adulthood. ADHD-rating scale was administered to parent/ informant to screen for childhood ADHD. Statistical analyses were done using SPSS v 17.0. The prevalence of Adult ADHD in our sample was 20%. 94% of subjects were on Highly Active Anti-Retroviral Therapy (HAART). Adherence to HAART was comparatively lesser in the ADHD group which was statistically significant (p=0.014). Substance use was significantly more in the ADHD group (p=0.03). People with ADHD had significantly higher High Risk sexual behavior than those without ADHD (p<0.001). Hence, these findings suggest that ADHD may contribute to high risk sexual behavior and thereby also the risk of contracting HIV. Future research on a larger population will provide more conclusive evidence. For now, health promotion and specific protection with greater emphasis in this vulnerable population of adult ADHD would be warranted in preventing HIV.

Background: Infection with Human Immunodeficiency Virus is a serious public health problem, costing the lives of many people including health workers. Health care workers practicing in developing countries like Ethiopia are more exposed to HIV following occupational exposure and less likely to use post exposure prophylaxis. Ethiopia has developed guidelines on the prevention of infection in health institutions in July 2004 and also employed the use of post exposure prophylaxis since the implementation of free antiretroviral in January 2005.

Objective: the main aim of this study was to assess prevalence of PEP service use among health professionals in Mekelle town.

Methodology: A health institution based cross sectional study design involving 190 health professionals was employed using a structured self administered questionnaire. Sampling technique was based on the population proportion to size, then to select a study unit systematic random sampling was used. SPSS version 16.00 was used for data entry and analysis. Proportions and percentages were used for descriptions of data.

Result: the study revealed that occupational exposure to blood, non bloody body fluids, needle stick injuries and mucocutaneous were 82.5%, 74.9%, 49.1% and 42.7% respectively. Among the exposed health professionals 19.6% use PEP. The main reasons for not using PEP was source patient HIV test result negative (65.5%), followed by negligence (25%). For those who started PEP all of them get HIV testing before commencing PEP and 80% of them completed in 4 weeks, 20% discontinue the PEP due to adverse effects of the drugs. Training of health professionals on PEP had statistically significant association with PEP utilization (AOR=2. 864, 95% CI=1. 152-7.122)

Conclusion: the finding of this result indicated that occupational exposures were common among health professionals. The use of PEP among exposed health professionals was low. Providing training for all health professionals on infection prevention, including PEP is recommended to lower the occupational exposure and to enhance the use of PEP.

Objectives: Spermidine/spermine-N1-acetytransferase (SSAT) is the key enzyme in the catabolism of polyamines that are involved in regulating NMDA functioning. Over expression of SSAT leads to abnormal metabolic cycling and may disrupt NMDA receptor signaling. In fact, the HIV protein Tat induces neurotoxicity involving polyamine/NMDA receptor interactions. Thus, we investigated abnormal polyamine cycling in HIV+ participants with varying degrees of HIV-associated neurocognitive disorders.

Methods: Acetyl-polyamine (SSAT products) levels were assessed by HPLC in CSF from 99 HIV-infected participants (no cognitive impairment (NCI, n=25), asymptomatic neurocognitive impairment (ANI, n=25), mild cognitive and motor disorders (MCMD, n=24), and HIV-associated dementia (HAD, n=25)). Polyamine levels in brain tissues from a subset of participants (uninfected (n=3), NCI (n=3), and MNCD (n=3)) were also assessed. Human primary astrocytes expressing HIV Tat were assessed for levels of the SSAT activity.

Results: Activation of the polyamine catabolic enzyme, SSAT increases polyamine flux in brain and CSF of HIV infected individuals with HIV-associated neurocognitive disorders. CSF levels of acetylated polyamine increase with the degree of HAND severity as indicated by significantly increased acetylpolyamine levels in HAD participants compared to NCI and ANI (p<0.0001) and between MCMD and NCI and ANI (p<0.0001). In vitro studies suggest that the HIV protein Tat may be responsible in part for astrocyte-derived acetyl polyamine release.

Interpretation: Our data suggest that polyamine metabolism may play a pivotal role in the neurodegeneration process among HAND patients. Changes in polyamine flux may serve as a potential predictive diagnostic biomarker for different severities of HAND.

HIV-1 infection can trigger acute episodes of Idiopathic Thrombocytoponic Purpura (ITP), and Thrombotic Thrombocytopenic Purpura (TTP), particularly in populations with advanced disease and poor adherence to antiretroviral therapy (ART). These diseases should be distinguished because they respond to different treatments. Previous studies done in adults with HIV-TTP have recommended the prompt initiation or re-initiation of ART in parallel with plasma exchange therapy to improve the clinical outcome of these patients. Here, we describe a case of HIVTTP resulting in an acute hemorrhagic stroke in a 16 year old female with perinatally acquired HIV infection and non-adherence to ART, who presented with severe thrombocytopenia, microangiopathic hemolytic anemia, and a past medical history of HIV-ITP. Both differential diagnosis and treatments for HIV-ITP and HIV-TTP were considered simultaneously. A decrease in plasma ADAMTS13 activity (<5%) without detectable inhibitory antibodies confirmed the diagnosis of HIV-TTP. Re-initiation of ART and plasma exchange resulted in a marked decrease in the HIV-RNA viral load, recovery of the platelet count, and complete recovery was achieved with sustained virologic suppression.

This study introduces a new approach for HIV eradication based on a new enzyme combination (reverse transcriptase and DNA polymerase) formula for inhibiting and/or preventing this disease. The pilot study was done on ten patients who were all positive for HIV antibodies, and were never treated with antiretroviral medications. Those patients were registered under surveillance by HIV/AIDS Control Department at the Egyptian Ministry of Health (MOH). All of these patients have the same clinical symptoms of HIV/AIDS and consented to take this combination therapy in the form of subcutaneous injection of 0.1 cc twice daily for 24 weeks. At the end of therapeutic protocol, all of the patients' viral loads were undetectable (less than 16 copies/ml); also there was a significant increase in their CD4 cells counts to over 500 cells/μL. According to these findings, this treatment protocol may be promising therapeutic modality for treating HIV-1 infection causing Acquired Immunodeficiency Syndrome (AIDS).

Objective: Kaposi’s sarcoma (KS) is an angioproliferative disease frequently seen in patients with the acquired immunodeficiency syndrome (AIDS). Previous studies suggest that the HIV-1 protein Tat and Fibroblast Growth Factor 2 (FGF-2) have synergistic angiogenic effects in AIDS-KS tumors. However, the mechanisms by which FGF-2 is released and activated in KS tumors are not clearly defined. We carried out this study to determine whether an FGFbinding protein (FGFBP1 or BP1) that enhances the angiogenic activity of FGF-2 is expressed in AIDS-KS tumors, and to define whether BP1, FGF-2, and HIV-Tat protein-protein interactions could play a potential clinically role in the pathogenesis of AIDS-KS.

Methods: BP1 was localized in AIDS-KS lesions by immunohistochemistry and in situ hybridization studies. The binding of radiolabeled FGF-2 to His-tagged BP1 or the FGF-receptor 1 was assessed in the presence and absence of HIV-Tat and other viral proteins. Mice carrying tetracycline-regulated BP1 transgene mice were used to determine whether activation of BP1 during wound healing induces KS-like lesions.

Results: BP1 expression was detected in AIDS-KS tumor keratinocytes, spindle cells, and infiltrating mononuclear cells. In addition, HIV-Tat competed for the binding of FGF-2 to immobilized BP1, but does not affect the interactions of FGF-2 with its high affinity receptor (FGFR-1). In contrast, two other HIV-proteins, Nef and gp120, did not affect the binding of FGF-2 to BP1 or to FGFR-1. Finally, up-regulation of BP1 expression in tetracycline-regulated –conditional BP1 transgenic mice subjected to skin wounds, induced KS-like skin lesions.

Conclusion: Taking into consideration the results of previous studies showing that both HIV-Tat and BP1 enhance the mitogenic and angiogenic activity of locally-stored FGF-2, both in vitro and in vivo, our findings suggest a novel mechanism by which the release and activity of FGFs can be modulated in AIDS-KS tumors by HIV-Tat as well as BP1.

Background: Studies on HIV/HBV co-infection in Nigeria yielded prevalence ranging between 10% and 70%, giving the widest variation in prevalence of HIV/HBV co-infection from studies emanating from any country all over the world. However, estimation of clinical and public health impacts of HIV/HBV co-infection requires a robust and reliable epidemiological data for an appropriate estimation of the logistical, economic, and humanitarian impact of the two viruses in Nigeria.

Objective: The aim of this review was to estimate the prevalence and burden of HBV infections in HIV-infected patients in Nigeria. Methods: Estimates were derived from a random effects meta-analysis of observational studies reporting the prevalence of HBV/HIV in Nigeria. The derived estimate for the prevalence of HBV/HIV co-infection was applied to the total HIV-infected populations in Nigeria to give an estimated burden of HBV/HIV co-infection in Nigeria.

Result: Thirty three studies with quality data from seventeen states in Nigeria, up to December 16, 2013, were included. I-squared heterogeneity was 98%. Random effect model (REM) estimate of prevalence among HIV-infected patients from the 33 studies was 15% (95% CI 13-17). The prevalence of HIV/HB co-infection among attendees of HIV clinics was 17% [95% CI 13-20], among pregnant HIV-infected patients were 10% [95% CI 6-15], 12% [95% CI 6-17] among HIV-infected children and among newly discovered HIV-infected voluntary blood donor (VBD) patients 10% [95% CI 6-15]. Meta- regression showed no significant associations between the mean age of the patients, the proportion of female patients, year of the study and prevalence of co-infection. The burden of HBV/HIV co-infection in Nigeria, based on the estimate, was 984 000 C.I. [852 800-1115 200].

Conclusion: In Nigeria, the estimated prevalence of HBV/HIV infection is 15% resulting in a substantial burden for the country.

Background: Recent research suggests that pregnancy is a potentially safe option for couples with at least one HIV-infected adult. Data regarding provider discussion of fertility intentions with women living with HIV (WLWH) or in serodiscordant relationships is limited.

Methods: We conducted a cross-sectional self-administered survey of health professionals who provide HIV services to women in order to assess knowledge and behaviors regarding family planning options for HIV-infected women and serodiscordant couples.

Results: Of 77 respondents, 47(61%) met the inclusion criteria (health care provider who cares for WLWH). Approximately half (57%) of the participants indicated that they always or usually discuss contraception or fertility intentions with their HIV+ female patients of reproductive age. When asked to indicate their awareness of techniques to decrease HIV transmission risk among serodiscordant couples attempting pregnancy, most participants reported awareness of multiple options. Discussion of contraception or fertility intentions was not associated with provider gender, age, and experience in caring for HIV-infected patients, previous training in women’s health or provider’s awareness of options to decrease transmission risk.

Conclusions: HIV providers in this study were knowledgeable of practices that can lead to safer conception and prevent HIV transmission among individuals in serodiscordant relationships but did not always discuss this information with their patients. Further research is needed to explore optimal methods for encouraging such conversations.