Журнал СПИДа и клинических исследований

Evaluation of implementation activities in real-time allows for both tailoring of the intervention to allow for the best chance at success. Evaluation also acts as an effective audit-feedback mechanism to highlight barriers and facilitators of the implementation to field staff and key stakeholders, as well as a measure of fidelity to the implementation effort itself. The development and use of an implementation fidelity tracker is discussed. This type of implementation tool has widespread implications for evaluation of specific activities pertaining to implementation efforts. Its simplicity and versatility allow for use in a variety of domains.

Background: Recombinant adenovirus serotype 5 (rAd5)-vectored HIV-1 vaccines have not prevented HIV-1 infection or disease and pre-existing Ad5 neutralizing antibodies may limit the clinical utility of Ad5 vectors globally. Using a rare Ad serotype vector, such as Ad35, may circumvent these issues, but there are few data on the safety and immunogenicity of rAd35 directly compared to rAd5 following human vaccination.

Methods: HVTN 077 randomized 192 healthy, HIV-uninfected participants into one of four HIV-1 vaccine/placebo groups: rAd35/rAd5, DNA/rAd5, and DNA/rAd35 in Ad5-seronegative persons; and DNA/rAd35 in Ad5-seropositive persons. All vaccines encoded the HIV-1 EnvA antigen. Antibody and T-cell responses were measured 4 weeks post boost immunization.

Results: All vaccines were generally well tolerated and similarly immunogenic. As compared to rAd5, rAd35 was equally potent in boosting HIV-1-specific humoral and cellular immunity and responses were not significantly attenuated in those with baseline Ad5 seropositivity. Like DNA, rAd35 efficiently primed rAd5 boosting. All vaccine regimens tested elicited cross-clade antibody responses, including Env V1/V2-specific IgG responses.

Conclusions: Vaccine antigen delivery by rAd35 is well-tolerated and immunogenic as a prime to rAd5 immunization and as a boost to prior DNA immunization with the homologous insert. Further development of rAd35- vectored prime-boost vaccine regimens is warranted.

Background: HIV requires lifelong treatment so ARV dose optimization is important for long-term efficacy and safety. Previously, low-dose atazanavir (ATV)/ritonavir(r) plus 2 NRTIs in HIV-infected Thai patients provided adequate plasma ATV concentrations and reduced risk of hyperbilirubinemia. However, long-term efficacy and safety data is limited.

Methods: 127 HIV-infected adults on ATV/r200/100mg plus 2 NRTIs were prospectively followed in Thailand. CD4 cell counts, HIV-RNA, and safety parameters were performed every 6 months. Estimated glomerular filtration rate (eGFR) was calculated by chronic kidney disease epidemiology (CKD-EPI). ATV plasma concentrations (ATV Ctrough) were assessed.

Results: Median body weight was 60 kg and 50% were females. Previous regimens were mainly standard dose ATV/r (54%) and lopinavir/r (29%). 93% of them were on tenofovir and 9.4% had HIV-RNA > 50 copies/mL at the time when lower dose of ATV/r was initiated. The median duration of lower dose ATV/r was 154 (IQR 65-271) weeks and 50.4% had been followed for more than 3 years. HIV-RNA < 50 copies/mL by on-treatment and intention-to-treat analysis were 91.2% and 81.8%, respectively. Bilirubin and eGFR significantly improved [83 to 88 ml/min/1.73m2 (p<0.001)]. Premature discontinuation occurred in 13 (10.2%) patients due to toxicity (CKD, renal stone, hepatitis, pancreatitis) and death (sepsis, cerebral aneurysm, CKD). All 42 cases with available ATV Ctrough had adequate ATV concentrations of >0.15 mg/L.

Conclusions: Long-term use of ATV/r 200 mg/100 mg based-HAART as a maintenance therapy for patients who are sensitive to PI was efficacious and well-tolerated. Use of low-dose ATV/r could benefit resource limited settings because it will reduce toxicity, increase accessibility and save costs.

Background: The proportion of patients on second line in resource limited settings are estimated between 1-5%. The present study describes the profile and outcomes of Indian patients receiving second line ART.

Methods: Information on HIV patients on second line ART was gathered. Socio demographic data, probable transmission route, baseline clinical parameters and comorbidities during therapy are studied along with first-line ART regimen initially introduced, its adherence and the reason for switch and components of the second-line ART regimen.

Results: Out of the total 2174 HIV patients 53% were on first line ART and of these 51 patients on second line ART were studied. The average time of initiation of first line ART was 17.67 months with median of 2 months whereas switch to second line ART was in 53.75 months with median of 60 months. Almost 71% of the patients on second line ART had been diagnosed with HIV infection with low CD4 count of <200. However 54%, 67% and 58% patients show more than 50% rise in their CD4 count post switch to second line after 3, 6 and 12 months of treatment which is a substantial improvement. Twenty-five per cent of patients showed non adherence. Tenofovir based regimens had a slight advantage with lesser number of side effects being reported.

Conclusion: Early diagnoses of infection, early initiation of ART and drug adherence are the cornerstones for success in managing HIV patients. Understanding the profile and drug resistance pattern is necessary for ensuring effective and long term survival.

One of the less acknowledged tools in the international guidelines of combination antiretroviral therapy (cART) for HIV-1 infection is therapeutic drug monitoring (TDM). Yet anywhere there is a Clinical Pharmacology Unit or other facility for measuring plasma drug concentrations, physicians often measure the plasma levels of antiretrovirals as well as of comedications and find it useful. The aim of this article is to provide an overview of how relevant it is for a clinician to assess individual drug levels. Moreover we wanted to investigate to what extent the field is already assisted by web-based tools (i.e.: drug interaction charts). Finally we tried to look how pharmacogenetics may reduce the need for TDM, and whether this diagnostics is cost-effective.

We searched PubMed by “drug interactions and HIV”, “drug level and HIV”, “therapeutic drug monitoring”, and we investigated the Liverpool Drug Interaction website, the DHHS Guidelines website, the UCSF website, and the AETC online Guide for HIV/AIDS Clinical care. Furthermore, we assessed the role that the main national and international guidelines for antiretroviral treatment attributed to TDM and searched for the various clinical subsets in which drug monitoring is particularly relevant.

Finally, we suggest that cross-sectional studies of subjects failing therapy or experiencing drug-related adverse events, as well as longitudinal studies of particular conditions, may show the importance of problem-targeted rather than routine TDM.

Background: The long-term efficacy of NVP+ABC+3TC as a simplification strategy for the treatment of HIV-1 infected patients with undetectable viral load has not been properly assessed in randomized trials. This low-cost treatment with limited renal and bone side effects must be of particular interest in this era of cost-containment urgency and also in limited resource settings.

Methods: Observational study of 232 HIV1-infected patients with undetectable viral load who initiated nevirapine (NVP) + abacavir (ABC) + lamivudine (3TC). Reasons for the switching were treatment simplification (56%), renal problems (6%), osteopenia/osteoporosis (7%), hyperlipidemia (11%) and others (20%). HIV-1 viral load, CD4 cell count and fasting biochemistry profiles were determined on a routine clinical practice. The aim of the study was to evaluate long-term efficacy of this combination and its effect on renal function and lipid metabolism.

Results: 232 patients had a mean follow-up of 4 years (712 patients-year). The mean increment of CD4 after 4 years was 83 cells/μL (13% from baseline). Viral load remained undetectable in all but 14 patients (6%). Triglycerides levels decreased by 10% overtime (p < 0,05). 25 patients (10,7%) stopped therapy due to NVP associated side effects; no ABC associated side-effects were observed. No changes were found in renal function or bone mineral density.

Conclusions: The combination of NVP+ABC+3TC is a safe option for maintaining longterm viral suppression and immunological control, preserving renal function and improving hypertriglyceridemia.

Stethoscopes are essential tools of the medical profession and because of their universal use, might be a source of microorganisms that cause nosocomial infections. Stethoscopes come in direct contact with numerous patients daily and their disinfection after each use is not an established practice. Several studies in medical literature have demonstrated that many physicians’ stethoscopes are contaminated with pathogenic bacteria and could serve as a mode for transmission of infection. In view of contamination and spread of infection by the stethoscope, we have devised a handmade disposable stethoscope which is safe, easy and economical and can be specially used in HIV positive patients.

We report here a new diagnostic approach to the direct detection of HIV in blood or other body fluids that is rapid, sensitive and potentially applicable in a point-of-care setting. The approach follows on the development of a novel BioNanoSensor (BNS) device that utilizes piezoelectric technology to detect the presence of the HIV surface glycoprotein gp120 in a nanoscale format. The detection range of the BNS device for the biomarker gp120 displayed a low-end sensitivity of 6.5×104 HIV viral particles/ml, while using a small fluid sample (5 μl) and with a reaction time of less then 30 seconds. Performance of this device indicated that the BNS has utility for direct detection of HIV particles prior to, and independent from, antibody formation. Accordingly, this device holds utility to monitor the status of HIV infection both early after exposure to virus as well as during chronic HIV infection. The BNS parameters of small sample volume, compact device size, and detection sensitivity indicate that the BNS is potentially useful in the pointof- care and/or home setting for monitoring decisions regarding HIV treatment on a real-time basis.

Objective: To determine the prevalence and risk factors for chronic obstructive pulmonary disease (COPD) among HIV-infected adults in Nigeria.

Design: Cross-sectional study.

Methods: HIV-infected adults aged ≥ 30 years with no acute ailments accessing care at the antiretroviral therapy clinic of Jos University Teaching Hospital were enrolled consecutively. Participants were interviewed to obtain pertinent demographic and clinical information, including exposure to risk factors for COPD. Post-bronchodilator spirometry was carried out. HIV related information was retrieved from the clinic medical records. COPD case-definition was based on the Global Initiative for Obstructive Lung Disease (GOLD) criteria using post-bronchodilator FEV1/FVC <0.7. COPD prevalence was also calculated using the lower limit of normal for FEV1/FVC criteria (LLN) from the European Respiratory Society normative equation. Factors associated with COPD were determined using logistic regression models.

Results: Study population comprised 356 HIV infected adults with mean age of 44.5 (standard deviation, 7.1) years and 59% were female. The mean time elapsed since HIV diagnosis was 7.0 (SD, 2.6) years and 97.5% of the respondents were on stable ART with virologic suppression present in 67.2%. Prevalence of COPD were 15.4% (95% confidence interval [CI] 11.7-19.2), 12.07% (95% CI 8.67-15.48), 22.19% (95% CI 18.16-26.83) using GOLD, ERS LLN and GLI LLN diagnostic criteria respectively. In multivariate analyses adjusting for gender, exposure to cigarette smoke or biomass, history of pulmonary tuberculosis, use of antiretroviral therapy, current CD4 T-cell count and HIV RNA, only age > 50 years was independently associated with COPD with OR 3.4; 95% CI 1.42-8.17 when compared to ages 30-40 years.

Conclusion: HIV-associated COPD is common in our population of HIV patients.

Background: A detailed analysis of the spatio-temporal correlation of the yearly geo-referenced data indicated that the information obtained through such analysis can contribute to more effective in budget allocation, drug distribution and recruitment of human skilled resources, as well as guiding the design of vaccination programs. Hence, the current literature review was conducted to show the global spatial and temporal distribution of TB and importance of research regarding worldwide spatial and temporal distribution of tuberculosis in TB control programs.

Objective: The purpose of the literature review was to assess the worldwide spatial and temporal distribution of tuberculosis.

Methods: The literature review was done through identification and evaluation of a range of different types of sources including academic and professional journal articles, books, and web-based resources. Search engines were used to search web resources and bibliographic databases following aspects of the process associated with the production of a literature review such as evaluating information sources, searching and locating information resources, developing conceptual framework and mind mapping, and writing the literature review. In addition, references which had themes in common were grouped together. Finally, reflections on the findings of the literature review were made.

Results and Conclusions: There is sufficient evidence about the existence of significant high-rate space and time TB clustering and spatial variability across study regions. Significant clustering of TB was seen in “TB Epidemic” and hyperendemic “hotspots” often characterized by crowding, HIV infection, unemployment, and other social determinants. General development measures which were correlated with TB incidence trends varied geographically. People movement also found to be another risk factor indicating difference in TB occurrence among countries. The information obtained could contribute to more effective budget allocation, drug distribution and recruitment of human skilled resources, as well as guiding the design of vaccination programs.

Patients with HIV benefit from early diagnosis, however, the approach and cost of HIV testing is often unknown. Thus, this study explored the implementation of a universal (non-risk-based) nurse-initiated HIV rapid testing program in the Primary Care Clinic at the Veterans Health Administration, Los Angeles Ambulatory Care Clinic near Downtown Los Angeles. Over the course of the first five years of this program, nurses administered a total of 2,117 tests. The mean programmatic cost of the first five years is estimated at about $4,868 (SD $1,344) per year ($11.50 per test). The overall cost of the implementation may have slightly increased cost but within a reasonable range.