Long term outcomes of antiretroviral therapy in a large HIV/AIDS care clinic in urban South Africa: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Clinical, immunologic and virologic outcomes at large HIV/AIDS care clinics in resource poor settings are poorly described beyond the first year of highly active antiretroviral treatment (HAART). We aimed to prospectively evaluate long-term treatment outcomes at a large scale HIV/AIDS care clinic in South Africa.</p> <p>Methods</p> <p>Cohort study of patients initiating HAART between April 1, 2004 and March 13, 2007, and followed up until April 1, 2008 at a public HIV/AIDS care clinic in Johannesburg, South Africa. We performed time to event analysis on key treatment outcomes and program impact parameters including mortality, retention in care, CD4 count gain, virologic success and first line regimen durability.</p> <p>Results</p> <p>7583 HIV-infected patients initiated care and contributed to 161,000 person months follow up. Overall mortality rate was low (2.9 deaths per 100 person years, 95% CI 2.6-3.2), but high in the first three months of HAART (8.4 per 100 person years, 95% CI 7.2-9.9). Long-term on-site retention in care was relatively high (74.4% at 4 years, 95%CI 73.2-75.6). CD4 count was above 200 cells/mm³after 6 months of treatment in almost all patients. By the fourth year of HAART, the majority (59.6%, 95%CI 57.8-61.4) of patients had at least one first line drug (mainly stavudine) substituted. Women were twice as likely to experience drug substitution (OR 1.97, 95% CI 1.80-2.16). By 6 months of HAART, 90.8% suppressed virus below 400 copies. Among those with initial viral suppression, 9.4% (95% CI 8.5-10.3%) had viral rebound within one year of viral suppression, 16.8% (95% CI 15.5-18.1) within 2 years, and 20.6% (95% CI 18.9-22.4) within 3 years of initial suppression. Only 10% of women and 13% of men initiated second line HAART.</p> <p>Conclusion</p> <p>Despite advanced disease presentation and a very large-scale program, high quality care was achieved as indicated by good long-term clinical, immunologic and virologic outcomes and a low rate of second line HAART initiation. High rates of single drug substitution suggest that the public health approach to HAART could be further improved by the use of a more durable first line regimen.</p

SIC-8000 versus hetastarch as a submucosal injection fluid for endoscopic mucosal resection: a randomized controlled trial

Background and Aims Viscous solutions provide a superior submucosal cushion for endoscopic mucosal resection (EMR). SIC-8000 (Eleview, Aries Pharmaceuticals, La Jolla, Calif) is a commercially available FDA approved solution but hetastarch is also advocated. We performed a randomized trial comparing SIC-8000 to hetastarch as submucosal injection agents for colorectal EMR. Methods This was a single-center double-blinded randomized controlled trial performed at a tertiary referral center. Patients were referred to our center with flat or sessile lesions measuring ≥15 mm in size. The primary outcome measures were the Sydney Resection Quotient (SRQ) and the rate of en bloc resections. Secondary outcomes were total volume needed for a sufficient lift, number of resected pieces, and adverse events. Results There were 158 patients with 159 adenomas (84 SIC-8000 and 75 hetastarch) and 57 serrated lesions (30 SIC-8000 and 27 hetastarch). SRQ was significantly better in the SIC-8000 group compared with hetastarch group (9.3 vs 8.1, p=0.001). There was no difference in the proportion of lesions with en bloc resections. The total volume of injectate was significantly lower with SIC-8000 (14.8 mL vs 20.6 mL, p=0.038) Conclusions SIC-8000 is superior to hetastarch for use during EMR in terms of SRQ and total volume needed, although the absolute differences were small

Impact of a ring fitted cap on insertion time and adenoma detection: a randomized controlled trial

Background and Aims: Devices for flattening colon folds can improve polyp detection at colonoscopy. However, there are few data on the endoscopic ring fitted cap (EndoRings, EndoAid, Caesarea, Israel). We sought to compare adenoma detection with EndoRings with that of standard high-definition colonoscopy. Methods: A single-center randomized controlled trial of 562 patients (284 randomized to EndoRings and 278 to standard colonoscopy) at 2 outpatient endoscopy units in the Indiana University Hospital system. Adenoma detection was the primary outcome measured as adenoma detection rate (ADR) and adenomas per colonoscopy (APC). We also compared sessile serrated polyp detection rate (SSPDR), insertion times, withdrawal times, and ease of passage through the sigmoid colon. Results: EndoRings was superior to standard colonoscopy in terms of APC (1.46 vs 1.06, p=0.025) but there were no statistically significant differences in ADR or SSPDR. Mean withdrawal time (in patients with no polyps) was shorter and insertion time (all patients) was longer in the EndoRings arm by 1.8 minutes and 0.75 minutes, respectively. One provider had significantly higher detection with EndoRings and contributed substantially to the overall results. Conclusions: EndoRings can increase adenoma detection without significant increase in procedure time, but the effect varies between operators. EndoRings slows colonoscope insertion

HPTN 068: A Randomized Control Trial of a Conditional Cash Transfer to Reduce HIV Infection in Young Women in South Africa—Study Design and Baseline Results

Young women in South Africa are at high risk for HIV infection. Cash transfers offer promise to reduce HIV risk. We present the design and baseline results from HPTN 068, a phase III, individually randomized trial to assess the effect of a conditional cash transfer on HIV acquisition among South African young women. A total of 2533 young women were randomized to receive a monthly cash transfer conditional on school attendance or to a control group. A number of individual-, partner-, household- and school-level factors were associated with HIV and HSV-2 infection. After adjusting for age, all levels were associated with an increased odds of HIV infection with partner-level factors conveying the strongest association (aOR 3.05 95 % CI 1.84–5.06). Interventions like cash transfers that address structural factors such as schooling and poverty have the potential to reduce HIV risk in young women in South Africa

Evolutionary diversification of new caledonian Araucaria

New Caledonia is a global biodiversity hotspot. Hypotheses for its biotic richness suggest either that the island is a ‘museum’ for an old Gondwana biota or alternatively it has developed following relatively recent long distance dispersal and in situ radiation. The conifer genus Araucaria (Araucariaceae) comprises 19 species globally with 13 endemic to this island. With a typically Gondwanan distribution, Araucaria is particularly well suited to testing alternative biogeographic hypotheses concerning the origins of New Caledonian biota. We derived phylogenetic estimates using 11 plastid and rDNA ITS2 sequence data for a complete sampling of Araucaria (including multiple accessions of each of the 13 New Caledonian Araucaria species). In addition, we developed a dataset comprising 4 plastid regions for a wider taxon sample to facilitate fossil based molecular dating. Following statistical analyses to identify a credible and internally consistent set of fossil constraints, divergence times estimated using a Bayesian relaxed clock approach were contrasted with geological scenarios to explore the biogeographic history of Araucaria. The phylogenetic data resolve relationships within Araucariaceae and among the main lineages in Araucaria, but provide limited resolution within the monophyletic New Caledonian species group. Divergence time estimates suggest a Late Cretaceous-Cenozoic radiation of extant Araucaria and a Neogene radiation of the New Caledonian lineage. A molecular timescale for the evolution of Araucariaceae supports a relatively recent radiation, and suggests that earlier (pre-Cenozoic) fossil types assigned to Araucaria may have affinities elsewhere in Araucariaceae. While additional data will be required to adequately resolve relationships among the New Caledonian species, their recent origin is consistent with overwater dispersal following Eocene emersion of New Caledonia but is too old to support a single dispersal from Australia to Norfolk Island for the radiation of the Pacific Araucaria sect. Eutacta clade.Mai Lan Kranitz, Edward Biffin, Alexandra Clark, Michelle L. Hollingsworth, Markus Ruhsam, Martin F. Gardner, Philip Thomas, Robert R. Mill, Richard A. Ennos, Myriam Gaudeul, Andrew J. Lowe, Peter M. Hollingswort

Episodic ozone exposure in adult and senescent Brown Norway rats: Acute and delayed effect on heart rate, core temperature and motor activity

Setting exposure standards for environmental pollutants may consider the aged as a susceptible population but the few published studies assessing susceptibility of the aged to air pollutants are inconsistent. Episodic ozone (O-3) is more reflective of potential exposures occurring in human populations and could be more harmful to the aged. This study used radiotelemetry to monitor heart rate (HR), core temperature (T-c) and motor activity (MA) in adult (9-12 months) and senescent (20-24 months) male, Brown Norway rats exposed to episodic O-3 (6 h/day of 1 ppm O-3 for 2 consecutive days/week for 13 weeks). Acute O-3 initially led to marked drops in HR and T-c. As exposures progressed each week, there was diminution in the hypothermic and bradycardic effects of O-3. Senescent rats were less affected than adults. Acute responses were exacerbated on the second day of O-3 exposure with adults exhibiting greater sensitivity. During recovery following 2 d of O-3, adult and senescent rats exhibited an elevated Tc and HR during the day but not at night, an effect that persisted for at least 48 h after O-3 exposure. MA was elevated in adults but not senescent rats during recovery from O-3. Overall, acute effects of O-3, including reductions in HR and T-c, were attenuated in senescent rats. Autonomic responses during recovery, included an elevation in T-c with a pattern akin to that of a fever and rise in HR that were independent of age. An attenuated inflammatory response to O-3 in senescent rats may explain the relatively heightened physiological response to O-3 in younger rats

Cumulative incidence of mortality after ART initiation by KS status.

<p>Cumulative incidence of mortality after ART initiation by KS status.</p

Immunologic and Virologic Outcomes at 6 and 12-months on ART stratified by KS status among 8,676 adult HIV-infected patients initiating ART in Cape Town and Johannesburg, South Africa.

†<p>Models adjusted for sex, baseline CD4 count, age, treatment site, tuberculosis at ART initiation, year of ART initiation.</p>‡<p>VL = viral load, RR = relative risk, CI = confidence interval, relative risk from a log-binomial regression model KS = Kaposi’s sarcoma, ART = antiretroviral therapy,</p>*<p>Failure to achieve a CD4 response defined as an increase of ≥50 cells/mm³ at 6 months and ≥100 cells/mm³ at 12 months.</p>**<p>Failure to suppress VL to <400 copies/ml.</p

Mean predicted* CD4 cell count increase from ART initiation stratified by KS status.

<p>*Trajectories were estimated using two separate mixed linear models, one for the KS+ and one for the KS- to allow the curves to depart from being parallel. Curves were fitted using time as a quadratic function and a random intercept with an unstructured correlation matrix for repeated measures.</p