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Volume 5, Emitir 2 (2014)

Artigo de Pesquisa

Survival and Predictors of Mortality among Adult Patients on Highly Active Antiretroviral Therapy at Debre-Markos Referral Hospital, North West Ethiopia; A Retrospective Cohort Study

Ashenafi Shumey, Ashenif Tadele and Neway Hiruy

Background: The number of annual acquired immune deficiency syndrome (AIDS)-related deaths worldwide is steadily decreasing. In resource-poor settings, like Ethiopia the treatment was started recently. The survival and factors contributing to mortality are not yet well established. Objective: To analyze the survival and predictors of mortality among adult patients started highly active antiretroviral treatment from September, 2005 to August, 2010 at Debre Markos Hospital, Ethiopia.

Methods: This was a retrospective cohort study among 930 adults who started HAART between September 2005 and August 2010 at Debre-Markos Hospital. Data was extracted from paper based medical records data base and the survival of patients was estimated by Kaplan-Meier Predictors of mortality were identified by Cox proportional hazards models.

Results: The survival patients were 57.0% (95% CI [53-60] at 72 months. The significant predictors of mortality were advanced WHO stage (AHR=1.6, 95% CI [1.118-2.371]), mild anemia (AHR=2.6, 95% CI [1.886-3.640]), moderate to severe anemia (AHR=4.3, 95% CI [2.998-6.131]), poor adherence (AHR=3.1, 95% CI [2.341-4.129]), CD4 50-99 cells/l (AHR=2.0, 95% CI [1.058-3.889]) , CD4<50 cells/l (AHR=2.2, 95% CI [1.140-4.182]) and not taking cotrimoxazole prophylaxis (AHR=1.7, 95% CI [1.272-2.172]).

Conclusion: The study has shown an overall high mortality. The advanced WHO stage, anemia, not taking cotrimoxazole prophylaxis, poor adherence and low CD4 cell count plays an important role in the mortality of patients. A careful monitoring of patients particularly during the first 3 months of HAART is necessary.

Artigo de Pesquisa

Application of Ambiguous Analysis for Determining Recent Infections of HIV-1 in a China Men Who Had Sex with Men Population

Xiaoyan Bai, Hongwei Zhang, Wei Shao, Lan Li, Zheng Zeng and Hao Wu

Objective: To distinguish HIV-1 recent infection (≤ 300 days) from long-term HIV-1 infection (>300 days) in China men who had sex with men (MSM) population. We analyzed the change over time in the proportion of ambiguous nucleotides in patient plasma sequences. We hypothesized that this method could be used to determine recent infections.

Methods: HIV-1 sequences and clinical data of MSM were collected from June 2007 to September 2010. All the sequences were obtained by single genome amplification and sequencing. HIV-ambi-count was used to calculate the proportion of ambiguous nucleotides, and the optimal cut-off values to identify recent infection were established using receiver operator characteristic analysis (ROC).

Results: A total of 188 sequences from 150 patients were collected (38 patients were sampled twice at different time points), consisting of 118 sequences of subtype CRF01_AE and 70 sequences of subtype B. The optimal cut-off values for determination of early HIV-1 infection in subtypes CRF01_AE and B were 0.31% and 0.347%, respectively. The sensitivity, specificity, positive and negative predictive values were 76.5%, 55%, 89.3% and 32.4% for subtype CRF01-AE (P=0.005), 80.6%, 62.5%, 94.3% and 29.4% for subtype B (P=0.017), respectively. The area under the ROC curve (AUCROC) was 0.652 (95% CI, 0.520-0.783, P=0.03) and 0.75 (95% CI, 0.622-0.878, P=0.022) for subtype CRF01-AE and B, respectively.

Conclusions: The proportion of ambiguous nucleotides may be a good marker to distinguish recent infection from long-term HIV-1 infection with high positive predictive value in the China MSM population.

Artigo de Pesquisa

Switching from Abacavir/Lamivudine to Tenofovir DF/Emtricitabine Reduces Biomarkers of Inflammation: A Randomized Proof of Concept Study

Alozie O, Prosser R, Huppler Hullsiek K, Duprez D, Rhame F, Henry WK and Baker JV

Background: Abacavir use has been associated with cardiovascular disease (CVD) risk, but this effect has not been consistent across studies.

Methods: To explore abacavir-related CVD risk we studied 27 HIV-positive participants taking fixed-dose abacavir/ lamivudine-based antiretroviral therapy (ART) with viral suppression and randomized them to remain on their current regimen (n=13) or switch the nucleoside component to tenofovir disoproxil fumarate (DF)/emtricitabine (n=14). Plasma biomarkers were measured at baseline and at 1 and 6 months.

Results: At baseline, median (IQR) age was 46 years (41-53) and CD4+ count 620 cells/mm3 (477-836). There were no baseline differences in individual CVD risk factors between groups, however, 10-year Framingham Risk Score (FRS) trended higher for those taking abacavir (8.5%) versus tenofovir DF (4.7%). Switching to a tenofovir DF-based ART regimen, compared with staying on abacavir-based ART, was associated with a 79% lower level of high sensitivity C-reactive protein (hsCRP; p=0.04) and a 52% lower inflammatory/coagulation rank composite (consisting of hsCRP, interleukin-6 and D-dimer levels). These findings were not attenuated after adjusting for 10-year FRS (-79% for hsCRP, p=0.06; -50% for inflammatory composite, p=0.003).

Conclusion: Larger, prospective, randomized studies are needed to verify whether switching from abacavir/ lamivudine- to tenofovir DF/emtricitabine-based ART, in the context of viral suppression, reduces inflammation and corresponding CVD risk.

Artigo de Pesquisa

Are Serotonin Alterations the Link between Thrombocytopenia and Poor Immune Status among HIV Infected Individuals?

María José Míguez-Burbano, Allan Rodriguez, Mayra Vargas, Gabriella Tantalean, RanjiniValiathan and Wenyaw Chan

Objective: Thrombocytopenia (TCP<150 × 103 cells/mm3) has emerged as a relevant factor in the clinical course of HIV. However, the mechanisms mediating such observations have not been well characterized, limiting the possibility of creating targeted interventions. Notably, platelets are the storage and transporter system for serotonin and Brain derived neurotrophic factor (BDNF), which recent laboratory studies associated with viral replication and lymphocyte survival. Thus, we posit that (1) TCP will be associated with reduced levels of BDNF and serotonin (2) That these alterations will lead to poor viro-immune responses to antiretroviral therapy.

Methods: To achieve this goal, a total of 400 people living with HIV were consecutively enrolled to characterize the frequency of thrombocytopenia in hazardous and non-hazardous alcohol user populations in the HAART era. Then, participants underwent immune and laboratory assessments, to determine if TCP was associated with alterations in serotonin (5-HT) and brain derived neurotrophic factor (BDNF).

Results: The prevalence of thrombocytopenia in this antiretroviral treated cohort was 14%. Rates were significantly higher in the heavy alcohol users, HAU versus the non HAU group (Heavy: 25% versus HAU: 15% versusnon-HAU: 10%). Multivariate model analyses indicated that having TCP, low BDNF levels (<5000 pg/ml), and number of drinks per day were predictors of serotonin levels. PLWH with TCP had about 2-fold lower PPP-BDNFlevels (5037.4 ± 381 vs. 9137.5 ± 7062 pg/ml p=0.0001). Other significant predictors of BDNF levels at the last visit included receiving selective serotonin reuptake inhibitors and PPP serotonin levels. Multivariate analyses also confirmed that altered serotonin levels were associated withhigh viral loadsboth low CD4 cell counts.

Conclusions: Thrombocytopenia is a relatively frequent complication of HIV, andis particularly prevalent among hazardous alcohol users (HAU). These findings suggest that TCP is associated with altered levels of BDNF and serotonin, suggesting that they may be the bridge linking TCP and poor viro-immune responses observed in this group. These results could have important clinical and therapeutic implications.

Artigo de Pesquisa

Masculinity and Barebacker Identification in Men who have Sex with Men

Christopher W. Wheldon, David L. Tilley and Hugh Klein

Purpose: Barebacking is a term that is used to refer to intentional involvement in unprotected anal sex. This paper examines the relationship between masculinity and self-identification as a barebacker, and how these factors related to HIV risk practices in a sample of men who have sex with other men (MSM).

Method: As part of the Men4Men Study, a brief Internet-based survey was completed in 2007 with English-speaking MSM aged 18+ who were not involved in a marital/romantic relationship at the time of interview. 886 participants were recruited by placing electronic postings and banner advertisements on Weblogs, social and sexual networking sites, and listservs frequented by MSM.

Results: A number of factors differentiated men who self-identified as barebackers from those who did not, and barebacking identity was linked with greater involvement in HIV risk practices. Multivariate analysis revealed that having a high level of masculinity was associated with a greater likelihood of self-identifying as a barebacker.

Conclusions: HIV prevention and intervention efforts targeting MSM ought to address issues of self-identification as a barebacker as well as the extent to which men adhere to a masculine ideology.

Artigo de Pesquisa

Long-Term Persistence of Vaccine-Induced HIV Seropositivity in Healthy Volunteers

Corinne Desaint, Christine Durier, Armel Poda, Anne Krivine, François Simon, Hélène Bodilis, Gilles Pialoux, Lise Cuzin, Isabelle Poizot-Martin, Pascale Morineau, Jean-Daniel Lelievre, Benjamin Silbermann, Jean-Pierre Aboulker and Odile Launay

Objectives: To assess the long-term serological impact of HIV preventive vaccine trial participation, vaccineinduced HIV seropositivity (VISP) was evaluated and related factors were investigated. The anti-HIV antibody reactivity ratio distribution was estimated.

Methods: ANRS COHVAC is an open national prospective multicentre cohort study including healthy volunteers who received at least one dose of vaccine candidate of ANRS HIV preventive vaccine trials since 1992. VISP was studied in a cross-sectional study at the time of the cohort’s initial visit, starting in 2008. Anti-HIV antibody detection was performed using the ABBOTT ARCHITECT® HIV Ag/Ac Combo Enzyme Immunoassay (EIA) in a centralized laboratory. A ratio greater than or equal to 1 was considered to define HIV seropositivity.

Results: 293 participants were evaluated for a median period of 6 years (range: 2-18 years) after their inclusion in vaccine preventive trials. The frequency of VISP was estimated at 7.2% (21 out of 293) for all volunteers, and 69.0% (20 out of 29) for volunteers who received recombinant HIV-1 envelope protein, after a median period of 16.6 years after immunization (range: 16.3-18.4). The ARCHITECT test ratio among positive volunteers was low, with a median of 3.02 (range: 1.02 -14.04).

Conclusion: Healthy volunteers should be informed of possible VISP persistence for nearly 17 years, following HIV envelope vaccination inducing antibody responses. A single, routine serology test is unable to differentiate between VISP and a recent HIV infection. The combination of different technologies, applicable to resource-limited settings, is needed to distinguish vaccine-induced seropositivity from an HIV infection.

Artigo de Pesquisa

Perspectives of Clinicians and Social Services Personnel on Needs of Older Adults with HIV Who Access Healthcare at a Major Metropolitan

Kimberly Petrovic and Christine Waszynski

We explored the perspectives of clinicians (nurses, nurse practitioners, and physicians) and social services personnel (i.e., case coordinators, social workers) on the needs of older adults living with HIV and who receive healthcare at a major metropolitan hospital. We utilized a small qualitative study (n=10) as a means of developing an understanding of the perspectives shared within the framework of inter-professional collaboration for purposes of quality care for older adult patients with HIV. Five themes emerged from our qualitative research study. The first theme involves the idea of access to healthcare while the second theme suggests that older adults with HIV experience psychological issues. Third, older adults with HIV demonstrate high levels of adherence to medication regimens. Next, HIV is no longer viewed as a ‘death sentence’. Finally, education across disciplines and professions is necessary.

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