Cost-effectiveness of point-of-care viral load monitoring of antiretroviral therapy in resource-limited settings: mathematical modelling study

BACKGROUND Monitoring of HIV viral load in patients on combination antiretroviral therapy (ART) is not generally available in resource-limited settings. We examined the cost-effectiveness of qualitative point-of-care viral load tests (POC-VL) in sub-Saharan Africa. DESIGN Mathematical model based on longitudinal data from the Gugulethu and Khayelitsha township ART programmes in Cape Town, South Africa. METHODS Cohorts of patients on ART monitored by POC-VL, CD4 cell count or clinically were simulated. Scenario A considered the more accurate detection of treatment failure with POC-VL only, and scenario B also considered the effect on HIV transmission. Scenario C further assumed that the risk of virologic failure is halved with POC-VL due to improved adherence. We estimated the change in costs per quality-adjusted life-year gained (incremental cost-effectiveness ratios, ICERs) of POC-VL compared with CD4 and clinical monitoring. RESULTS POC-VL tests with detection limits less than 1000 copies/ml increased costs due to unnecessary switches to second-line ART, without improving survival. Assuming POC-VL unit costs between US$5 and US$20 and detection limits between 1000 and 10,000 copies/ml, the ICER of POC-VL was US$4010-US$9230 compared with clinical and US$5960-US$25540 compared with CD4 cell count monitoring. In Scenario B, the corresponding ICERs were US$2450-US$5830 and US$2230-US$10380. In Scenario C, the ICER ranged between US$960 and US$2500 compared with clinical monitoring and between cost-saving and US$2460 compared with CD4 monitoring. CONCLUSION The cost-effectiveness of POC-VL for monitoring ART is improved by a higher detection limit, by taking the reduction in new HIV infections into account and assuming that failure of first-line ART is reduced due to targeted adherence counselling.

Measurement and stability of the pointing of the BepiColombo Laser Altimeter under thermal load

The BepiColombo Laser Altimeter (BELA) has been selected to fly on ESA׳s BepiColombo mission to Mercury. The instrument will be the first European laser altimeter designed for interplanetary flight. This paper describes the setup used to characterize the angular movements of BELA under the simulated environmental conditions that the instrument will encounter when orbiting Mercury. The system comprises a laser transmitter and a receiving telescope, which can move with respect to each other under thermal load. Tests performed using the Engineering Qualification Model show that the setup is accurate enough to characterize angular movements of the instrument components to an accuracy of ≈10 μrad. The qualification instrument is thermally stable to operate during all mission phases around Mercury proving that the transmitter and receiver sections will remain within the alignment requirements during its mission.

Teeth restored using fiber-reinforced posts: in vitro fracture tests and finite element analysis

In dentistry the restoration of decayed teeth is challenging and makes great demands on both the dentist and the materials. Hence, fiber-reinforced posts have been introduced. The effects of different variables on the ultimate load on teeth restored using fiber-reinforced posts is controversial, maybe because the results are mostly based on non-standardized in vitro tests and, therefore, give inhomogeneous results. This study combines the advantages of in vitro tests and finite element analysis (FEA) to clarify the effects of ferrule height, post length and cementation technique used for restoration. Sixty-four single rooted premolars were decoronated (ferrule height 1 or 2 mm), endodontically treated and restored using fiber posts (length 2 or 7 mm), composite fillings and metal crowns (resin bonded or cemented). After thermocycling and chewing simulation the samples were loaded until fracture, recording first damage events. Using UNIANOVA to analyze recorded fracture loads, ferrule height and cementation technique were found to be significant, i.e. increased ferrule height and resin bonding of the crown resulted in higher fracture loads. Post length had no significant effect. All conventionally cemented crowns with a 1-mm ferrule height failed during artificial ageing, in contrast to resin-bonded crowns (75% survival rate). FEA confirmed these results and provided information about stress and force distribution within the restoration. Based on the findings of in vitro tests and computations we concluded that crowns, especially those with a small ferrule height, should be resin bonded. Finally, centrally positioned fiber-reinforced posts did not contribute to load transfer as long as the bond between the tooth and composite core was intact.

Are implants more reliable than severely compromised endodontically treated teeth as abutments for zirconia-based FPDs? : In vitro results of long-term preclinical load simulation

OBJECTIVES The aim was to study the impact of the defect size of endodontically treated incisors compared to dental implants as abutments on the survival of zirconia two-unit anterior cantilever-fixed partial dentures (2U-FPDs) during 10-year simulation. MATERIALS AND METHODS Human maxillary central incisors were endodontically treated and divided into three groups (n = 24): I, access cavities rebuilt with composite core; II, teeth decoronated and restored with composite; and III as II supported by fiber posts. In group IV, implants with individual zirconia abutments were used. Specimens were restored with zirconia 2U-FPDs and exposed to two sequences of thermal cycling and mechanical loading. Statistics: Kaplan-Meier; log-rank tests. RESULTS During TCML in group I two tooth fractures and two debondings with chipping were found. Solely chippings occurred in groups II (2×), IV (2×), and III (1×). No significant different survival was found for the different abutments (p = 0.085) or FPDs (p = 0.526). Load capability differed significantly between groups I (176 N) and III (670 N), and III and IV (324 N) (p < 0.024). CONCLUSION Within the limitations of an in vitro study, it can be concluded that zirconia-framework 2U-FPDs on decoronated teeth with/without post showed comparable in vitro reliability as restorations on implants. The results indicated that restorations on teeth with only access cavity perform worse in survival and linear loading. CLINICAL RELEVANCE Even severe defects do not justify per se a replacement of this particular tooth by a dental implant from load capability point of view.

Hepatitis B Infection, Viral Load and Resistance in HIV-Infected Patients in Mozambique and Zambia.

BACKGROUND Few data on the virological determinants of hepatitis B virus (HBV) infection are available from southern Africa. METHODS We enrolled consecutive HIV-infected adult patients initiating antiretroviral therapy (ART) at two urban clinics in Zambia and four rural clinics in Northern Mozambique between May 2013 and August 2014. HBsAg screening was performed using the Determine® rapid test. Quantitative real-time PCR and HBV sequencing were performed in HBsAg-positive patients. Risk factors for HBV infection were evaluated using Chi-square and Mann-Whitney tests and associations between baseline characteristics and high level HBV replication explored in multivariable logistic regression. RESULTS Seventy-eight of 1,032 participants in Mozambique (7.6%, 95% confidence interval [CI]: 6.1-9.3) and 90 of 797 in Zambia (11.3%, 95% CI: 9.3-13.4) were HBsAg-positive. HBsAg-positive individuals were less likely to be female compared to HBsAg-negative ones (52.3% vs. 66.1%, p<0.001). Among 156 (92.9%) HBsAg-positive patients with an available measurement, median HBV viral load was 13,645 IU/mL (interquartile range: 192-8,617,488 IU/mL) and 77 (49.4%) had high values (>20,000 UI/mL). HBsAg-positive individuals had higher levels of ALT and AST compared to HBsAg-negative ones (both p<0.001). In multivariable analyses, male sex (adjusted odds ratio: 2.59, 95% CI: 1.22-5.53) and CD4 cell count below 200/μl (2.58, 1.20-5.54) were associated with high HBV DNA. HBV genotypes A1 (58.8%) and E (38.2%) were most prevalent. Four patients had probable resistance to lamivudine and/or entecavir. CONCLUSION One half of HBsAg-positive patients demonstrated high HBV viremia, supporting the early initiation of tenofovir-containing ART in HIV/HBV-coinfected adults.