Association between first-year virological response to raltegravir and long-term outcomes in treatment-experienced patients with HIV-1 infection.

BACKGROUND: We explored the relationship between virological response in the first year of treatment and long-term outcomes in the BENCHMRK studies. METHODS: Patients failing antiretroviral treatment with 3-class resistant HIV-1 received double-blinded raltegravir (or placebo) with optimized background therapy (OBT) until week 156, followed by open-label raltegravir with OBT up to week 240. In this exploratory analysis of patients randomized to raltegravir, virological response over weeks 16-48 was categorized as continuous suppression (CS; viral RNA [vRNA] always <50 copies/ml), low-level viraemia (LLV; vRNA always <400 copies/ml, >50 copies/ml at least once), or not suppressed (NS; vRNA >400 copies/ml at least once). The association between these first-year vRNA response categories and baseline factors was analysed with univariate and multivariate models. Virological and immunological outcomes for years 2-5 were assessed by first-year vRNA response category (observed failure approach). RESULTS: Baseline vRNA, baseline CD4(+) T-cell count and rapid viral decay (vRNA <50 copies/ml between weeks 2-12) correlated with first-year vRNA response (P<0.001); only rapid viral decay remained significant by multiple regression. Virological response rates were similar in the LLV and CS groups and lowest in the NS group. CD4(+) T-cell count increased through week 240 in the CS and LLV groups. Time to loss of virological response (confirmed vRNA ≥400 copies/ml) through week 240 did not support as strong a difference between the LLV and CS groups (log-rank P=0.11) as previously reported through weeks 156 and 192 (P<0.05). CONCLUSIONS: Treatment-experienced patients on a raltegravir-based regimen with early LLV may have long-term virological and immunological benefit when their therapy is maintained.

Characteristics and comprehensiveness of adult HIV care and treatment programmes in Asia-Pacific, sub-Saharan Africa and the Americas: results of a site assessment conducted by the International epidemiologic Databases to Evaluate AIDS (IeDEA) Collaboration.

INTRODUCTION: HIV care and treatment programmes worldwide are transforming as they push to deliver universal access to essential prevention, care and treatment services to persons living with HIV and their communities. The characteristics and capacity of these HIV programmes affect patient outcomes and quality of care. Despite the importance of ensuring optimal outcomes, few studies have addressed the capacity of HIV programmes to deliver comprehensive care. We sought to describe such capacity in HIV programmes in seven regions worldwide. METHODS: Staff from 128 sites in 41 countries participating in the International epidemiologic Databases to Evaluate AIDS completed a site survey from 2009 to 2010, including sites in the Asia-Pacific region (n=20), Latin America and the Caribbean (n=7), North America (n=7), Central Africa (n=12), East Africa (n=51), Southern Africa (n=16) and West Africa (n=15). We computed a measure of the comprehensiveness of care based on seven World Health Organization-recommended essential HIV services. RESULTS: Most sites reported serving urban (61%; region range (rr): 33-100%) and both adult and paediatric populations (77%; rr: 29-96%). Only 45% of HIV clinics that reported treating children had paediatricians on staff. As for the seven essential services, survey respondents reported that CD4+ cell count testing was available to all but one site, while tuberculosis (TB) screening and community outreach services were available in 80 and 72%, respectively. The remaining four essential services - nutritional support (82%), combination antiretroviral therapy adherence support (88%), prevention of mother-to-child transmission (PMTCT) (94%) and other prevention and clinical management services (97%) - were uniformly available. Approximately half (46%) of sites reported offering all seven services. Newer sites and sites in settings with low rankings on the UN Human Development Index (HDI), especially those in the President's Emergency Plan for AIDS Relief focus countries, tended to offer a more comprehensive array of essential services. HIV care programme characteristics and comprehensiveness varied according to the number of years the site had been in operation and the HDI of the site setting, with more recently established clinics in low-HDI settings reporting a more comprehensive array of available services. Survey respondents frequently identified contact tracing of patients, patient outreach, nutritional counselling, onsite viral load testing, universal TB screening and the provision of isoniazid preventive therapy as unavailable services. CONCLUSIONS: This study serves as a baseline for on-going monitoring of the evolution of care delivery over time and lays the groundwork for evaluating HIV treatment outcomes in relation to site capacity for comprehensive care.

Prevalence of anemia and underlying iron status in naive antiretroviral therapy HIV-infected children with moderate immune suppression.

Anemia is common in HIV-infected children and iron deficiency is thought to be a common cause. This study investigates the prevalence of anemia, thalassemia, and underlying iron status in Thai and Cambodian children without advanced HIV disease to determine the necessity of routine iron supplementation. Antiretroviral (ARV)-naive HIV-infected Asian children aged 1-12 years, with CD4 15-24%, CDC A or B, and hemoglobin (Hb) ≥7.5 g/dl were eligible for the study. Iron studies, serum ferritin, Hb typing, and C-reactive protein were assessed. Anemia was defined as Hb <11.0 g/dl in children <5 years of age or <11.5 g/dl in children 5-12 years. We enrolled 299 children; 57.9% were female and the mean (SD) age was 6.3 (2.9) years. The mean (SD) CD4% and HIV-RNA were 20% (4.6) and 4.6 (0.6) log(10) copies/ml, respectively. The mean (SD) Hb and serum ferritin were 11.2 (1.1) g/dl and 78.3 (76.4) µg/liter, respectively. The overall iron deficiency anemia (IDA) prevalence was 2.7%. One hundred and forty-eight (50%) children had anemia, mostly of a mild degree. Of these, 69 (46.6%) had the thalassemia trait, 62 (41.8%) had anemia of chronic disease (ACD), 9 (6.1%) had thalassemia diseases, 3 (2.0%) had iron deficiency anemia, and 5 (3.4%) had IDA and the thalassemia trait. The thalassemia trait was not associated with increased serum ferritin levels. Mild anemia is common in ARV-naïve Thai and Cambodian children without advanced HIV. However, IDA prevalence is low; with the majority of cases caused by ACD. A routine prescription of iron supplement in anemic HIV-infected children without laboratory confirmation of IDA should be discouraged, especially in regions with a high prevalence of thalassemia and low prevalence of IDA.

Intensification of antiretroviral therapy with raltegravir or addition of hyperimmune bovine colostrum in HIV-infected patients with suboptimal CD4+ T-cell response: a randomized controlled trial.

BACKGROUND: Despite virally suppressive combination antiretroviral therapy (cART), some HIV-infected patients exhibit suboptimal CD4(+) T-cell recovery. This study aimed to determine the effect of intensification of cART with raltegravir or addition of hyperimmune bovine colostrum (HIBC) on CD4(+) T-cell count in such patients. METHODS: We randomized 75 patients to 4 treatment groups to receive raltegravir, HIBC, placebo, or both raltegravir and HIBC in a factorial, double-blind study. The primary endpoint was time-weighted mean change in CD4(+) T-cell count from baseline to week 24. T-cell activation (CD38(+) and HLA-DR(+)), plasma markers of microbial translocation (lipopolysaccharide, 16S rDNA), monocyte activation (soluble (s) CD14), and HIV-RNA (lowest level of detection 4 copies/mL) were monitored. Analysis was performed using linear regression methods. RESULTS: Compared with placebo, the addition of neither raltegravir nor HIBC to cART for 24 weeks resulted in a significant change in CD4(+) T-cell count (mean difference, 95% confidence interval [CI]: 3.09 cells/µL, -14.27; 20.45, P = .724 and 9.43 cells/µL, -7.81; 26.68, P = .279, respectively, intention to treat). There was no significant interaction between HIBC and raltegravir (P = .275). No correlation was found between CD4(+) T-cell count and plasma lipopolysaccharide, 16S rDNA, sCD14, or HIV-RNA. CONCLUSION: The determinants of poor CD4(+) T-cell recovery following cART require further investigation. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT00772590, Australia New Zealand Clinical Trials Registry: ACTRN12609000575235.

Latest update of tests and improvements to US Coast Guard viscous oil pumping system.

Over the past nine years, the US Coast Guard has incorporated the prevention through people (PTP) philosophy as a "human factors" approach to learn how maritime operations can be regulated safer and be more efficient by evaluating training, management policies, operational procedures, and establishing partnerships with the maritime industry. One of the key elements of applying a PTP approach is identifying and incorporating lessons learned from major marine casualties and pollution incidents. Since 1997, the US Coast Guard National Strike Force has responded to three major oil spills involving foreign freight vessels grounding, which included the removal of highly viscous oil using various lightering equipment and systems. An informal workgroup consisting of the US Coast Guard, US Navy Supervisor of Salvage (NAVSUPSALV), and various representatives from oil pollution clean-up companies met at the following facilities: the Chevron Asphalt Facility in Edmonds, WA (September 1999), the Oil and Hazardous Materials Simulated Environmental Test Tank (OHMSETT) testing facility in Leonardo, New Jersey (November 1999 and March 2000), the Alaska Clean Seas (ACS) warehouse annex in Prudhoe Bay, AK (October 2000), and Cenac Towing Company facility in Houma, LA (May 2002). The group shared ideas and techniques, and tested different pumps and hose lengths with viscous oil. It was during the early tests that the first quantitative results showed just how efficient lubricated transport of heavy oil product could be, and broadened the knowledge of such methods to the entire industry. Although this technology had existed for many years in the oil production and handling industry, its use had never been investigated in a laboratory setting with regard to salvage response lightering systems.