AIDS Research and Therapy - Latest Articles

Predictors of the change in bilirubin levels over twelve weeks of treatment with atazanavir

Aoife Cotter — 2013-05-16T00:00:00Z

ObjectiveTo determine the factors associated with change in bilirubin concentration 12 weeks after the initiation of an atazanavir (ATV)-containing antiretroviral regimen. Methods: We performed a retrospective case note review of all patients prescribed ATV between January 2004 and October 2007 in a cohort of HIV infected subjects. Data collected included baseline demographics, hepatitis B and C serology, current antiretroviral therapy, baseline and week 12 routine bloods. The primary endpoint was the change in bilirubin concentration at 12 weeks after start of ATV. Multvariable linear regression was performed to assess the relationships between the change in bilirubin and variables of interest. Results: Eighty-three ATV-treated patients were included in the analysis of whom 46 (60.5%) were hepatitis C antibody positive. The median (interquartile range) change in bilirubin by week 12 was 16 (4, 22) umol/L; only 1 patient developed grade 4 hyperbilirubinaemia at week 12. After controlling for baseline bilirubin levels, HCV seropositivity and baseline ALP were associated with a smaller change in bilirubin over the 12 weeks with a trend towards lower increases in those receiving tenofovir. Sensitivity analyses reported similar associations with methadone use and injection drug use, when these variables replaced HCV sero-positivity in the model. Conclusion: Patients with hepatitis C co-infection experience smaller changes in bilirubin upon exposure to ATV. Although the underlying mechanism for this association remains unclear, these data support the safe use of this drug in this patient setting. Further research into the clinical predictors of ATV-related hyperbilirubinaemia is warranted.

Self-care practices and experiences of people living with HIV not receiving antiretroviral therapy in an urban community of Lusaka, Zambia: implications for HIV treatment programmes

Maurice Musheke — 2013-05-15T00:00:00Z

Background: Despite the increasingly wider availability of antiretroviral therapy (ART), some people living with HIV (PLHIV) and eligible for treatment have opted to adopt self-care practices thereby risking early AIDS-related mortality. Methods: A qualitative study was conducted in urban Zambia to gain insights into PLHIV self-care practices and experiences and explore the implications for successful delivery of ART care. Between March 2010 and September 2011, in-depth interviews were conducted with PLHIV who had dropped out of treatment (n=25) and those that had opted not to initiate medication (n=37). Data was entered into and managed using Atlas ti, and analysed inductively using latent content analysis. Results: PHIV used therapeutic and physical health maintenance, psychological well-being and healthy lifestyle self-care practices to maintain physical health and mitigate HIV-related symptoms. Herbal remedies, faith healing and self-prescription of antibiotics and other conventional medicines to treat HIV-related ailments were used for therapeutic and physical health maintenance purposes. Psychological well-being self-care practices used were religiosity/spirituality and positive attitudes towards HIV infection. These practices were modulated by close social network relationships with other PLHIV, family members and peers, who acted as sources of emotional, material and financial support. Cessations of sexual relationships, adoption of safe sex to avoid re-infections and uptake of nutritional supplements were the commonly used risk reduction and healthy lifestyle practices respectively. Conclusions: While these self-care practices may promote physical and psychosocial well-being and mitigate AIDS-related symptoms, at least in the short term, they however undermine PLHIV access to ART care thereby putting PLHIV at risk of early AIDS-related mortality. The use of scientifically unproven herbal remedies raises health and safety concerns; faith healing may create fatalism and resignation with death while the reported self-prescription of antibiotics to treat HIV-related infections raises concerns about future development of microbial drug resistance amongst PLHIV. Collectively, these self-care practices undermine efforts to effectively abate the spread and burden of HIV and reduce AIDS-related mortality. Therefore, there is need for sensitization campaigns on the benefits of ART and the risks associated with widespread self-prescription of antibiotics and use of scientifically unproven herbal remedies.

A possible role for CCR5 in the progression of atherosclerosis in HIV-infected patients: a cross-sectional study

Laura Fernández-Sender — 2013-05-09T00:00:00Z

Background: Chemokines can block viral entry by interfering with HIV co-receptors and are recognised mediators of atherosclerosis development. A number of experimental drugs that inhibit HIV entry arrest the development of atherosclerosis in animal models. We hypothesised that the expression of chemokine receptors in circulating leukocytes is associated with the rate of atherosclerosis progression in HIV-infected patients. Methods: The increase in intima-media thickness during a 2-year follow-up was used to classify HIV-infected patients (n = 178) as progressors (n = 142) or non-progressors (n = 36) with respect to atherosclerosis. Logistic regression was used to assess variables associated with atherosclerosis progression. Mutations in the CCR5Delta32, CCR2 64I, and CX3CR1 (T280M and V249I) co-receptors as well as the levels of CCR5, CXCR4, CX3CR1, and CCR2 mRNA expression in circulating leukocytes were analysed as independent variables. Results: Among the baseline variables, only genetic variants explained the dichotomous outcome. The expression of CCR2 and CXCR4 did not discriminate between progressors and non-progressors. Conversely, CCR5 and CX3CR1 expression was higher in not only progressors but also patients with detectable viral load. The logistic regression, however, demonstrated a significant role for CCR5 expression as a predictor of atherosclerosis progression (B = 2.1, OR = 8.1, p = 0.04) and a negligible effect for CXC3R1 and CCR2 expression. Conclusions: Available CCR5 antagonists should be investigated for their potential to delay the course of atherosclerosis in HIV-infected patients.

In vivo effect of statins on the expression of the HIV co-receptors CCR5 and CXCR4

Edwin Higuita — 2013-05-01T00:00:00Z

Background: During the HIV-1 replication cycle, several molecules including chemokine receptors and cholesterol are crucial, and are therefore potential targets for therapeutic intervention. Indeed statins, compounds that inhibit cellular synthesis of cholesterol and have anti-inflammatory and immunomodulatory properties were shown to inhibit HIV-1 infection by R5 tropic strains but not by X4 strains in vitro, mainly by altering the chemokine receptor/ligands axes. Therefore, the objective of this study was to characterize in vivo, the capacity of statins to modulate in HIV seronegative and chronically HIV-1-infected adults the expression of CCR5 and CXCR4, of their ligands and the tropism of circulating HIV-1 strains. Methods: Samples from asymptomatic HIV-1-infected adults enrolled in a clinical trial aimed at evaluating the antiretroviral activity of lovastatin were used to evaluate in vivo the modulation by lovastatin of CCR5, CXCR4, their ligands, and the shift in plasma viral tropism over one year of intervention. In addition, ten HIV negative adults received a daily oral dose of 40 mg of lovastatin or 20 mg of atorvastatin; seven other HIV negative individuals who received no treatment were followed as controls. The frequency and phenotype of immune cells were determined by flow-cytometry; mRNA levels of chemokine receptors and their ligands were determined by real-time PCR. Viral tropism was determined by PCR and sequencing, applying the clonal and clinical model of analyses. Results: Our study shows that long-term administration of lovastatin in HIV-infected individuals does not induce a shift in viral tropism, or induce a significant modulation of CCR5 and CXCR4 on immune cells in HIV-infected patients. Similar results were found in HIV seronegative control subjects, treated with lovastatin or atorvastatin, but a significant increase in CCL3 and CCL4 transcription was observed in these individuals. Conclusions: These findings suggest that long-term administration of statins at therapeutic doses, does not significantly affect the expression of HIV-1 co-receptors or of their ligands. In addition it is important to point out that based on the results obtained, therapeutic administration of statins in HIV-infected patients with lipid disorders is safe in terms of selecting X4 strains.

Increasing Hepatitis C treatment uptake among HIV-infected patients using an HIV primary care model

Edward Cachay — 2013-03-28T00:00:00Z

Background: Access to Hepatitis C (HCV) care is low among HIV-infected individuals, highlighting the need for new models to deliver care for this population. Methods: Retrospective cohort analysis that compared the number of HIV patients who initiated HCV therapy: hepatology (2005–2008) vs. HIV primary care model (2008–2011). Logistic-regression modeling was used to ascertain factors associated with HCV therapy initiation and achievement of sustained viral response (SVR). Results: Of 196 and 163 patients that were enrolled in the HIV primary care and hepatology models, 48 and 26 were treated for HCV, respectively (p = 0.043). The HIV/HCV-patient referral rate did not differ during the two study periods (0.10 vs. 0.12/patient-yr, p = 0.18). In unadjusted analysis, predictors (p < 0.05) of HCV treatment initiation included referral to the HIV primary care model (OR: 1.7), a CD4+ count ≥400/mm3 (OR: 1.8) and alanine aminotranferase level ≥63U/L (OR: 1.9). Prior psychiatric medication use correlated negatively with HCV treatment initiation (OR: 0.6, p = 0.045). In adjusted analysis the strongest predictor of HCV treatment initiation was CD4+ count (≥400/mm3, OR: 2.1, p = 0.01). There was no significant difference in either clinic model (primary care vs. hepatology) in the rates of treatment discontinuation due to adverse events (29% vs. 16%), loss to follow-up (8 vs. 8%), or HCV SVR (44 vs. 35%). Conclusions: Using a HIV primary care model increased the number of HIV patients who initiate HCV therapy with comparable outcomes to a hepatology model.

HIV Testing practices among New England college health centers

Nilay Patel — 2013-03-18T00:00:00Z

Background: The prevalence of human immunodeficiency virus (HIV) continues to increase among certain populations including young men who have sex with men (MSM). College campuses represent a potential setting to engage young adults and institute prevention interventions including HIV testing. The purpose of this study was to evaluate testing practices for HIV and other sexually transmitted infections (STIs) on college campuses. Methods: Medical directors at four-year residential baccalaureate college health centers in New England were surveyed from June, 2011 to September, 2011. Thirty-one interviews were completed regarding experiences with HIV testing, acute HIV infection, other STI testing, and outreach efforts targeting specific at-risk groups such as MSM. Results: Among schools that responded to the survey, less than five percent of students were tested for HIV at their local college health center in the past academic year (2010–2011). Significant barriers to HIV testing included cost and availability of rapid antibody testing. One-third of college health medical directors reported that their practitioners may not feel comfortable recognizing acute HIV infection. Conclusions: Improved HIV testing practices are needed on college campuses. Programs should focus on outreach efforts targeting MSM and other at-risk populations.

Reviewer Acknowledgement 2012

Kailash Gupta — 2013-03-13T00:00:00Z

Contributing reviewersA peer-reviewed journal would not survive without the generous time and insightful comments of the reviewers whose efforts often go unrecognized. AIDS Research and Therapy has been blessed by the support of highly qualified peer reviewers and would like to show its appreciation by thanking the following for their assistance with review of manuscripts for the journal in 2012.

Prevalence of intestinal parasite and associated risk factors among HIV/AIDS patients with pre-ART and on-ART attending dessie hospital ART clinic, Northeast Ethiopia

Assefa Missaye — 2013-02-25T00:00:00Z

Background: Intestinal parasites are a major concern in most developing countries where HIV/AIDS case are concentrate and almost 80% of AIDS patients die of AIDS-related infections. In the absence of ART, HIV/AIDS patients in developing countries unfortunately continue to suffer from the consequences of opportunistic parasites. But this prevalence has dramatically decreased in countries where antiretroviral agents are widely available. Therefore, the aim of this study was to assess the prevalence of intestinal parasite and risk factor among pre- ART and on ART adult HIV/ AIDS patients attending ART clinic in Dessie hospital. Methods: A comparative cross-sectional study was conducted among pre-ART and on ART adult HIV/AIDS patients of Dessie Hospital. A total of 272 (136 from each group) study subjects were selected by using systematic random sampling. Stool sample was collected and processed using direct wet mount, formol-ether concentration technique and modified Ziehl-Neelson staining techniques. A structured questionnaire was used to collect data on Sociodemographic & associated risk factors. Data was entered and analyzed by using SPSS 16 software and logistic regressions were applied to assess any association between explanatory factors and outcome variables. Results: The overall prevalence of IP in pre-ART and on-ART was 39% and 17.6%, respectively with significant decrease of intestinal parasite in the ART era (p < 0.001). All Cryptosporidium spps infections were found in the pre-ART patients and significantly associated for lower CD4 <200cells/mm3. Absence of toilet (AOR = 7.57; 95% CI = 1.3,44.22), source of water (AOR = 6.03; 95% CI = 1.14,31.98), living condition (AOR = 13.29, 95% CI = 5.14, 34.35); WHO stage (AOR = 6.06; 95% CI = 2.49,14.74) and ART status (AOR = 7.55; 95% CI = 3.24,17.59) have significant association with prevalence of intestinal parasite. Conclusion: The overall prevalence of IP was differ by ART status and opportunistic parasite like cryptosporidium spps were found in low CD4 counts in ART naive patients. This study identified some environmental and some clinical finding as determinant factor for IP infections. Therefore, public health measures and adherence to ART should be strengthened to improve the quality of life of these patients.

NGX-4010, a capsaicin 8% patch, for the treatment of painful HIV-associated distal sensory polyneuropathy: integrated analysis of two phase III, randomized, controlled trials

Stephen Brown — 2013-01-28T00:00:00Z

Background: HIV-associated distal sensory polyneuropathy (HIV-DSP) is the most frequently reported neurologic complication associated with HIV infection. NGX-4010 is a capsaicin 8% dermal patch with demonstrated efficacy in the treatment of HIV-DSP. Data from two phase III, double-blind studies were integrated to further analyze the efficacy and safety of NGX-4010 and explore the effect of demographic and baseline factors on NGX-4010 treatment in HIV-DSP. Methods: Data from two similarly designed studies in which patients with HIV-DSP received NGX-4010 or a low-concentration control patch (capsaicin 0.04% w/w) for 30 or 60 minutes were integrated. Efficacy assessments included the mean percent change from baseline in Numeric Pain Rating Scale (NPRS) scores to Weeks 2–12. Safety and tolerability assessments included adverse events (AEs) and pain during and after treatment. Results: Patients (n = 239) treated with NGX-4010 for 30 minutes demonstrated significantly (p = 0.0026) greater pain relief compared with controls (n = 100); the mean percent change in NPRS scores from baseline to Weeks 2–12 was −27.0% versus −15.7%, respectively. Patients who received a 60-minute application of NGX-4010 (n = 243) showed comparable pain reductions (−27.5%) to patients treated for 30 minutes, but this was not statistically superior to controls (n = 115). NGX-4010 was effective regardless of gender, baseline pain score, duration of HIV-DSP, or use of concomitant neuropathic pain medication, although NGX-4010 efficacy was greater in patients not receiving concomitant neuropathic pain medications. NGX-4010 was well tolerated; the most common AEs were application-site pain and erythema, and most AEs were mild to moderate. The transient increase in pain associated with NGX-4010 treatment decreased the day after treatment and returned to baseline by Day 2. Conclusions: A single 30-minute application of NGX-4010 provides significant pain relief for at least 12 weeks in patients with HIV-DSP and is well tolerated.Trial registrationC107 = NCT00064623; C119 = NCT00321672

Virological failure of staggered and simultaneous treatment interruption in HIV patients who began Efavirenz-based regimens after allergic reactions to nevirapine

Krittaecho Siripassorn — 2013-01-25T00:00:00Z

ObjectiveThe objective of this work was to study the virological outcomes associated with two different types of treatment interruption strategies in patients with allergic reactions to nevirapine (NVP). We compared the virological outcomes of (1) HIV-1-infected patients who discontinued an initial NVP-based regimen because of cutaneous allergic reactions to NVP; different types of interruption strategies were used, and second-line regimen was based on efavirenz (EFV); and (2) HIV-1-infected patients who began an EFV-based regimen as a first-line therapy (controls). Methods: This retrospective cohort included patients who began an EFV-based regimen, between January 2002 and December 2008, as either an initial regimen or as a subsequent regimen after resolving a cutaneous allergic reaction against an initial NVP-based regimen. The study ended in March 2010. The primary outcome was virological failure, which was defined as either (a) two consecutive plasma HIV-1 RNA levels >400 copies/mL or (b) a plasma HIV-1 RNA level >1,000 copies/mL plus any genotypic resistance mutation. Results: A total of 559 patients were stratified into three groups: (a) Simultaneous Interruption, in which the subjects simultaneously discontinued all the drugs in an NVP-based regimen following an allergic reaction (n=161); (b) Staggered Interruption, in which the subjects discontinued NVP treatment while continuing nucleoside reverse transcriptase inhibitor (NRTI) backbone therapy for a median of 7 days (n=82); and (c) Control, in which the subjects were naïve to antiretroviral therapy (n=316). The overall median follow-up time was 43 months. Incidence of virological failure in Simultaneous Interruption was 12.9 cases per 1,000 person-years, which trended toward being higher than the incidences in Staggered Interruption (5.4) and Control (6.6). However, differences were not statistically significant. Conclusions: Among the patients who had an acute allergic reaction to first-line NVP-based therapy and later began an EFV-based regimen, virological outcomes resulting from a staggered interruption of treatment (with a continuation of NRTI backbone therapy for 7 days after discontinuing NVP) did not differ from those of the patients who began an EFV-based regimen as their initial therapy (Control). However, the virological failure of Simultaneous Interruption was possibly higher than those of Control and Staggered Interruption.