Clinical Management Of HIV Disease Research Articles

Performance of point-of-care Xpert HIV-1 plasma viral load assay at a tertiary HIV care centre in Southern India.

Sustainable suppression of HIV replication forms the basis of anti-retroviral therapy (ART) medication. Thus, reliable quantification of HIV viral load has become an essential factor to monitor the effectiveness of the ART. Longer turnaround-time (TAT), batch testing and technical skills are major drawbacks of standard real-time PCR assays. The performance of the point-of-care Xpert HIV-1 viral load assay was evaluated against the Abbott RealTime PCR m2000rt system. A total of 96 plasma specimens ranging from 2.5 log10 copies ml-1 to 4.99 log10 copies ml-1 and proficiency testing panel specimens were used. Precision and accuracy were checked using the Pearson correlation co-efficient test and Bland-Altman analysis. Compared to the Abbott RealTime PCR, the Xpert HIV-1 viral load assay showed a good correlation (Pearson r=0.81; P<0.0001) with a mean difference of 0.27 log10 copies ml-1 (95 % CI, -0.41 to 0.96 log10 copies ml-1; sd, 0.35 log10 copies ml-1). Reliable and ease of testing individual specimens could make the Xpert HIV-1 viral load assay an efficient alternative method for ART monitoring in clinical management of HIV disease in resource-limited settings. The rapid test results (less than 2 h) could help in making an immediate clinical decision, which further strengthens patient care.

Rate of decline in CD4 count in HIV patients not on antiretroviral therapy

BackgroundThe progressive decline in the CD4 count in HIV patients leads to a more general decline in immune functioning. The study has been carried out to determine the decline in CD4 count in HIV patients. MethodsThe study was conducted in a medical college hospital at Maharashtra. The information on baseline CD4 count was gathered from positive patient records registered in the central disease registry. The baseline CD4 count was the first count of CD4 obtained when the patient is diagnosed as HIV positive and further two subsequent readings. The time from baseline (t1) till the last CD4 count (t2) was divided into the different quartiles and the median decline in CD4 count in each quartile was determined. As the time between the two CD4 count measurements was not uniform the rate of change in CD4 was measured with respect to time as [X (t2) − X (t1)/(t2 − t1)]. Correlation was assessed using correlation coefficient. ResultsAs the CD4 counts were following skewed distribution, the normality was achieved by cuberoot transformation. The overall rate of decline in CD4 count was estimated to be 35 cells/μL per year with 95% confidence interval (CI) as (17.01, 85.04). The correlation coefficient between decline in CD4 and the initial CD4 count in the four time quartiles was (r = −0.51; p = 0.001, r = −0.79; p = 0.000, r = −0.48; p = 0.015 and r = −0.80; p = 0.000) respectively. The median decline in the CD4 count in 0–6 months was 3 cells/μL, in (6–11) months was approximately 26 cells/μL, in (11–21.5) months was 30 cells/μL and in more than 21.5 months the median decline was 52 cells/μL. ConclusionsThere was a progressive decline in the CD4 count following HIV infection. An understanding of the influence of decline in CD4 count in HIV patients not on ART is important for clinical management of HIV disease.

Perceived stigma reductions following participation in mental health services integrated within community-based HIV primary care

HIV stigma remains a significant challenge for individuals living with HIV disease that can adversely affect overall well-being and patterns of HIV health service engagement. Finding ways to effectively address stigma concerns is, therefore, an important consideration in the clinical management of HIV disease. This study examined changes in perceived stigma in a sample of 48 adults living with HIV disease as an outcome of their participation in a mental health services program integrated with community-based HIV primary care. Participants completed a self-report instrument that provided a multidimensional measure of perceived HIV stigma, including distancing, blaming, and discrimination dimensions. This scale was administered at the baseline mental health service visit and then re-administered at the three-month follow-up point. Study results showed reductions in self-reported perceived HIV stigma over time for the distancing (t = 4.01, p = 0.000, d = 0.43), blaming (t = 2.79, p = 0.008, d = 0.35), and discrimination (t = 2.90, p = 0.006, d = 0.42) dimensions of stigma. These findings suggest that participation in HIV mental health services may have a favorable impact on perceived HIV stigma. Implications of these findings are discussed, including possible mechanisms that might explain the observed results as well as suggested directions for future research in this area. Randomized controlled trials would represent an important next step to investigate the extent to which HIV mental health services can reduce levels of perceived HIV stigma.

A Novel 8-Color Flow Cytometry Panel to Study Activation, Maturation and Senescence of CD4 and CD8 T Lymphocytes in HIV-Infected Individuals at Different Stages of Disease

Multicolor flow cytometry allows to study the markers differentially expressed during maturation, activation, function and senescence on immune cells. Despite the availability of reagents and technology, scarce agreement has been gained regarding phenotypic markers of HIV disease progression other than CD4 T-cell count. In this work, we present a novel high-throughput global analysis of CD4 and CD8 T-lymphocyte profiles by standardized 8-color combinations of antibodies aimed at analyzing HIV disease course progression. For this purpose, two tubes with lyophilized reagent cocktails (CD4- and CD8-specific tubes) were designed to compare the immunological characteristics of HIV-infected persons (37 "high CD4" HAART-treated and 32 "low CD4" naïve or failed-treatment patients) with healthy donors (HD). In particular, T-cell activation (CD25, CD38, CD69), differentiation (CD45RA, CCR7), apoptosis (CD95) and immune suppression profiles (CD25(high)CD127-) in HIV+ patients were compared with HD. Statistical analysis was performed by identifying the parameters associated with disease progression, namely markers that were found to be significantly different between groups with high CD4 counts (including HD) and low CD4 counts (restricted to HIV patients) but not between the HD and the "high CD4" group. This set of markers, including those identifying different maturation and senescence subtypes of CD4 and CD8 T cells, was found to be associated with therapy failure, and it is in fact evaluated in an ongoing study aimed to verify its prognostic value. This robust assay was found feasible on a semi-routine scale for HIV-infected persons, and allows for broader clinical studies aimed at defining markers associated with treatment outcome, possibly having a high impact on the clinical management of HIV disease.

P5-S6.13 Objective assessment of patient satisfaction with their HIV care

BackgroundPatient engagement with HIV services is essential since early diagnosis and care has a direct impact on patient survival and also provides public health benefits associated with reduced infectivity. Positive physician/patient relationships have been linked to higher levels of treatment adherence. Determining and measuring patient priorities in the delivery of HIV services can therefore have a direct impact on perceived satisfaction with services and also improve clinical outcomes.MethodsA systematic review was undertaken to identify existing approaches to identifying patient derived key themes in the delivery of their care. These themes were then examined and expanded using 4 focus groups discussions with HIV services users.ResultsA search of 12 bibliographic databases, a hand search of journal bibliographies and a wider internet search yielded 1474 titles from which 150 study abstracts were appraised. 32 articles were retrieved and reviewed using a quality appraisal checklist. A data extraction form was used by two reviewers to extract relevant information for thematic analysis. The review identified key themes of principal importance to patients attending for HIV care—medical staffs' perceived knowledge about HIV, attitude of clinic staff, maintenance of patient dignity, patient autonomy, confidentiality and an appropriate care environment. Three specific survey tools were identified for measuring satisfaction with HIV services but none had wide geographical validity or else failed to reflected current clinical management of HIV disease. The subsequent focus groups supported the findings of the literature review but following the introduction of HAART issues of staff knowledge about HIV were given less prominence.ConclusionsExisting survey tools to measure patient satisfaction with HIV services lack validity or generalisability. The themes identified from this literature review and patient focus groups should be incorporated in the development of future assessment tools.

Uncontrolled proliferation of the co-authors of clinical and observational studies, and inter-cohort analyses, in the field of clinical management of HIV disease

Uncontrolled proliferation of the co-authors of clinical and observational studies, and inter-cohort analyses, in the field of clinical management of HIV disease

Managing the newly diagnosed HIV‐infected individual

AbstractRecent advances in the treatment of HIV infection have led to prolonged survival and an emphasis on the long‐term clinical management of HIV disease. In this article, the authors discuss the assessment of a patient who is newly diagnosed with HIV infection. The initial assessment provides the opportunity to begin a partnership between the doctor and the patient that may continue for many years. Copyright © 2008 Wiley Interface Ltd.

Rates of inappropriate antiretroviral prescription among injection drug users

BackgroundAlthough the survival benefits of antiretroviral therapy (ART) for the treatment of HIV infection are well established, the clinical management of HIV disease continues to present major challenges. There are particular concerns regarding access to appropriate HIV treatment among HIV-infected injection drug users (IDU).MethodsIn a prospective cohort study of HIV-infected IDU in Vancouver, Canada, we examined initial ART regimens vis-à-vis the provincial government's therapeutic guidelines at the time ART was initiated. Briefly, there have been four sets of guidelines: Era 1 (1992 to November 1995; double-drug (dual NRTIs) ART for patients with a CD4 cell count of 350 or less); Era 2 (December 1995 to May 1996; double-drug therapy for patients with a CD4+ cell count of 500 or less); Era 3 (June 1996 to June 1997; triple-drug therapy (dual NRTIs with a PI or NNRTI) for patients who had a plasma viral load of > 100,000 HIV-1 RNA copies/mL; dual therapy with two NRTIs for those with a plasma viral load of 5,000 to 100,000 HIV-1 RNA copies/mL); Era 4 (since July 1997; universal use of triple drug therapy as first-line treatment).ResultsBetween May 1996 and May 2003, 431 HIV-infected individuals were enrolled into the cohort. By May 31, 2003, 291 (67.5%) individuals had initiated ART. We noted instances of inappropriate antiretroviral prescription in each guideline era, with 9 (53%) in Era 1, 3 (12%) in Era 2, 22 (28%) in Era 3, and 23 (15%) in Era 4. Of the 57 subjects who received an inappropriate ART regimen initially, 14 never received the appropriate therapy; among the remaining 43, the median time to the initiation of a guideline-appropriate ART regimen was 12 months (inter-quartile range 5 – 20).ConclusionThe present study identified measurable rates of guideline-inappropriate ART prescription for patients who were injection drug users. Rates were highest in the era of dual therapy, although high rates persisted into the triple-therapy era. As therapeutic guidelines continue to evolve, it is critical that mechanisms be put in place to ensure prescription of ART combinations for IDU that are consistent with current expert recommendations.

Clinical impact of HIV-related lipodystrophy and metabolic abnormalities on cardiovascular disease.

Metabolic complications and altered fat distribution associated with HIV infection and antiretroviral therapy may lead to accelerated coronary artery disease (CAD). The high prevalence of multiple cardiovascular risk factors in a significant number of HIV patients is a cause for concern in both patients and physicians. Non-invasive strategies to measure subclinical CAD have been inconclusive. Long-term studies are underway to determine cardiac event rates, intervention strategies and consequences for the clinical management of HIV disease. In the present paper, we summarize the most prevalent risk factors in individuals with HIV infection receiving highly active antiretroviral therapy by focusing on the clinical implications of metabolic abnormalities and HIV-related lipodystrophy on CAD.

Susceptibility of diverse primary HIV isolates with varying co-receptor specificity's to CXCR4 antagonistic compounds.

The chemokine receptors CCR5 and CXCR4 are an obvious target for HIV therapies. Two compounds, T-22 and AMD-3100, have been shown to inhibit infection of CXCR4-using HIV-1 isolates. The specificity of T-22 and AMD-3100 was further confirmed by their ability to block entry of HIV-1 in GHOST-CXCR4 transfected cells with no effect on viral entry in the GHOST-CCR5 cells. The ability of T-22 to block replication of diverse HIV-1 isolates (group M, subtypes A, B, D, E, and F as well as group O) and HIV-2 primary isolates with varying coreceptor specificities ranging from exclusive CCR5 usage to multiple coreceptor usage was examined in detail. T-22 was found to be highly effective (>90%) at blocking infection of diverse HIV-1 (subtypes A-F, and group O) and HIV-2 isolates that use multiple coreceptors in human PBMCs homozygous for a 32-bp deletion in CCR5 (CCR5-/-), but less effective in CCR5 +/+ PBMCs. Additionally, sequential primary HIV-1 isolates obtained from a longitudinal cohort who had switched from single coreceptor usage to a broad range of multiple receptors could be blocked effectively by both T-22 and AMD-3100 in CCR5-/- PBMCs. Our data suggest that CXCR4 antagonistic compounds are highly effective in blocking the entry of X4-tropic HIV-1, and that these compounds could be a useful additive to current anti-retroviral therapy for clinical management of HIV disease.

Variability of critical epitopes within HIV-1 heptad repeat domains for selected entry inhibitors in HIV-infected populations worldwide [corrected

Two of the fusion inhibitors T-20 and 5-helix polypeptide have been shown to be potent inhibitors of cell-to-cell fusion and are currently under investigation as therapy for HIV-1. To examine variability of HIV-1 gp41 heptads repeat regions (HR1 and HR2), with special emphasis on the presence of T-20 resistance mutations and 5-helix variability at critical epitopes, in treatment-naive patients infected with diverse HIV-1 subtypes from different geographic regions. A total of 150 specimens representing HIV-1 group M subtypes (A-G) from persons naive to HIV-1 viral entry inhibitor therapy were used to amplify and sequence a 506 bp segment of transmembrane protein. In general, both HR1 (a.a. 540-593) and HR2 (a.a. 628-673) domains were highly conserved. Sequence analysis of the T-20 resistant domain (a.a. 547-549, GIV) revealed that 99% of the specimens (149 of 150) carried a T-20 sensitive genotype. The critical epitopes involved in the 5-helix interaction include residues at positions 628W, 631W, 635I, 638Y, 642I, 645L, 649S, 652Q, 656N, and 659E. Analysis of the 150 specimens revealed that all had identical residues at six of these positions, whereas two positions had minor variations (635 and 649) and two (645 and 659) appeared to have subtype-specific substitutions. This data indicates that there is limited resistance to T-20 in these worldwide populations and that the critical epitopes for effective 5-helix binding are highly conserved across all subtypes. Taken together, these data suggest that T-20 and 5-helix should provide useful additives to current antiretroviral therapy for clinical management of HIV disease.

The Clinical Management of HIV Disease

Summary HIV disease has had a significant impact on society and, perhaps more than any other illness, has profoundly affected the way in which medical, legal, public health, and information services are provided. Fortunately, the epidemic arrived at a time of unprecedented strides in biotechnology and information access. This article describes selected World-Wide Web resources about the clinical management of HIV disease.

Heterogeneity of care for HIV-infected individuals decreases with the physician knowledge.

In order to gain an understanding of the determinants of clinical management of HIV disease in adults just prior to the introduction of comprehensive guidelines, we undertook the present study among members of the British Columbia Persons with AIDS Society (BCPWA). The aim of this study was to examine whether the heterogeneity of care for HIV-infected individuals decreases with physician knowledge of HIV/AIDS and the stability of the physician-patient relationship. Eligible participants had to be full members (i.e. HIV positive) of the society, residents of British Columbia, and had to have previously agreed for the BCPWA society to include unsolicited material with their monthly newsletter. Our analysis demonstrates that compliance with appropriate care was associated with a more stable physician-patient relationship and with the perception on the patient's part of a greater level of knowledge on the part of their physician.

HIV infection in women.

HIV - virology HIV - immunology epidemiology and natural history of HIV AIDS in women drug use in HIV-infected women counselling around HIV testing in women of reproductive age counselling around infected women and families testing and screening basic principles of medical supervision antiviral drugs and prophylaxis clinical management of HIV disease - developed countries, developing countries terminal care community care and community support does pregnancy accelerate progression of HIV disease? termination of pregnancy ther effect of HIV on pregnancy outcome vertical transmission particular issues in prophylaxis and treatment during pregnancy clinical manifestations, management and therapy of HIV in childbirth contraception and safer sex other sexually transmitted disease - cervical intraepithelial neoplasia other gynaecological problems - menstrual, pelvic pain, infertility, herpes, candida particular issues for African women nosocomial infection and infection control procedures HIV-infected health care workers supportive organization for women women and families - future trends, hopes and requirements.