Long-Term Outcome of an HIV-Treatment Programme in Rural Africa: Viral Suppression despite Early Mortality

Objective. To define the long-term (2–4 years) clinical and virological outcome of an antiretroviral treatment (ART) programme in rural South Africa. Methods. We performed a retrospective observational cohort study, including 735 patients who initiated ART. Biannual monitoring, including HIV-RNA testing, was performed. Primary endpoint was patient retention; virological suppression (HIV-RNA < 50 copies/mL) and failure (HIV-RNA > 1000 copies/mL) were secondary endpoints. Moreover, possible predictors of treatment failure were analyzed. Results. 63% of patients (466/735) have a fully suppressed HIV-RNA, a median of three years after treatment initiation. Early mortality was high: 14% died within 3 months after treatment start. 16% of patients experienced virological failure, but only 4% was switched to second-line ART. Male gender and a low performance score were associated with treatment failure; immunological failure was a poor predictor of virological failure. Conclusions. An “all or nothing” phenomenon was observed in this rural South African ART programme: high early attrition, but good virological control in those remaining in care. Continued efforts are needed to enrol patients earlier. Furthermore, the observed viro-immunological dissociation emphasises the need to make HIV-RNA testing more widely available

Diagnosing pregnancy status using infrared spectra and milk composition in dairy cows

Data on Holstein (16,890), Brown Swiss (31,441), Simmental (25,845), and Alpine Grey (12,535) cows reared in northeastern Italy were used to assess the ability of milk components (fat, protein, casein, and lactose) and Fourier transform infrared (FTIR) spectral data to diagnose pregnancy. Pregnancy status was defined as whether a pregnancy was confirmed by a subsequent calving and no other subsequent inseminations within 90 d of the breeding of specific interest. Milk samples were analyzed for components and FTIR full-spectrum data using a MilkoScan FT+ 6000 (Foss Electric, Hiller\uf8d, Denmark). The spectrum covered 1,060 wavenumbers (wn) from 5,010 to 925 cm 121. Pregnancy status was predicted using generalized linear models with fat, protein, lactose, casein, and individual FTIR spectral bands or wavelengths as predictors. We also fitted a generalized linear model as a simultaneous function of all wavelengths (1,060 wn) with a Bayesian variable selection model using the BGLR R-package (https://r-forge.r-project.org/projects/bglr/). Prediction accuracy was determined using the area under a receiver operating characteristic curve based on a 10-fold cross-validation (CV-AUC) assessment based on sensitivities and specificities of phenotypic predictions. Overall, the best prediction accuracies were obtained for the model that included the complete FTIR spectral data. We observed similar patterns across breeds with small differences in prediction accuracy. The highest CV-AUC value was obtained for Alpine Grey cows (CV-AUC = 0.645), whereas Brown Swiss and Simmental cows had similar performance (CV-AUC = 0.630 and 0.628, respectively), followed by Holsteins (CV-AUC = 0.607). For single-wavelength analyses, important peaks were detected at wn 2,973 to 2,872 cm 121 where Fat-B (C-H stretch) is usually filtered, wn 1,773 cm 121 where Fat-A (C=O stretch) is filtered, wn 1,546 cm 121 where protein is filtered, wn 1,468 cm 121 associated with urea and fat, wn 1,399 and 1,245 cm 121 associated with acetone, and wn 1,025 to 1,013 cm 121 where lactose is filtered. In conclusion, this research provides new insight into alternative strategies for pregnancy screening of dairy cows

Теоретичні та практичні аспекти приватизації в Україні

Цели статьи заключаются в изучении спроса покупателей на объекты приватизации и анализе финансового состояния предприятий к принятию решения об их приватизации (на основе данных за I квартал 2006 года), раскрытии основных критериев целесообразности принятия решения о приватизации объектов ведения хозяйства.Цілі статті полягають у вивченні попиту покупців на об'єкти приватизації та аналізі фінансового стану підприємств до прийняття рішення про їх приватизацію (на основі даних за I квартал 2006 року), розкритті основних критеріїв доцільності прийняття рішення про приватизацію об'єктів господарювання

Changes in milk characteristics and fatty acid profile during the estrous cycle in dairy cows

The relationship of the estrous cycle to milk composition and milk physical properties was assessed on Holstein (n = 10,696), Brown Swiss (n = 20,501), Simmental (n = 17,837), and Alpine Grey (n = 8,595) cows reared in northeastern Italy. The first insemination after calving for each cow was chosen to be the day of estrus and insemination. Test days surrounding the insemination date (from 10 d before to 10 d after the day of the estrus) were selected and categorized in phases relative to estrus as diestrus high-progesterone, proestrus, estrus, metestrus, and diestrus increasing-progesterone phases. Milk components and physical properties were predicted on the basis of Fourier-transform infrared spectra of milk samples and were analyzed using a linear mixed model, which included the random effects of herd, the fixed classification effects of year-month, parity number, breed, estrous cycle phase, day nested within the estrous cycle phase, conception, partial regressions on linear and quadratic effects of days in milk nested within parity number, as well as the interactions between conception outcome with estrous cycle phase and breed with estrous cycle phase. Milk composition, particularly fat, protein, and lactose, showed clear differences among the estrous cycle phases. Fat increased by 0.14% from diestrus high-progesterone to estrous phase, whereas protein concomitantly decreased by 0.03%. Lactose appeared to remain relatively constant over diestrus high-progesterone, rising 1 d before the day of estrus followed by a gradual reduction over the subsequent phases. Specific fatty acids were also affected across the estrous cycle phases: C14:0 and C16:0 decreased ( 120.34 and 120.48%) from proestrus to estrus with a concomitant increase in C18:0 and C18:1 cis-9 (0.40 and 0.73%). More general categories of fatty acids showed a similar behavior; that is, unsaturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, trans fatty acids, and long-chain fatty acids increased, whereas the saturated fatty acids, mediumchain fatty acids, and short-chain fatty acids decreased during the estrous phase. Finally, urea, somatic cell score, freezing point, pH, and homogenization index were also affected indicating variation associated with the hormonal and behavioral changes of cows in standing estrus. Hence, the variation in milk profiles of cows showing estrus should potentially be taken into account for precision dairy farming management

Computational models as predictors of HIV treatment outcomes for the Phidisa cohort in South Africa

Background: Selecting the optimal combination of HIV drugs for an individual in resourcelimited settings is challenging because of the limited availability of drugs and genotyping.Objective: The evaluation as a potential treatment support tool of computational models that predict response to therapy without a genotype, using cases from the Phidisa cohort in South Africa.Methods: Cases from Phidisa of treatment change following failure were identified that had the following data available: baseline CD4 count and viral load, details of failing and previous antiretroviral drugs, drugs in new regimen and time to follow-up. The HIV Resistance Response Database Initiative’s (RDI’s) models used these data to predict the probability of a viral load &lt; 50 copies/mL at follow-up. The models were also used to identify effective alternative combinations of three locally available drugs.Results: The models achieved accuracy (area under the receiver–operator  characteristic curve) of 0.72 when predicting response to therapy, which is less accurate than for an independent global test set (0.80) but at least comparable to that of genotyping with rules-based interpretation. The models were able to identify alternative locally available three-drug regimens that were predicted to be effective in 69% of all cases and 62% of those whose new treatment failed in the clinic.Conclusion: The predictive accuracy of the models for these South African patients together with the results of previous studies suggest that the RDI’s models have the potential to optimise treatment selection and reduce virological failure in different patient populations, without the use of a genotype

Safety and Efficacy of a Dapivirine Vaginal Ring for HIV Prevention in Women.

BACKGROUND: The incidence of human immunodeficiency virus (HIV) infection remains high among women in sub-Saharan Africa. We evaluated the safety and efficacy of extended use of a vaginal ring containing dapivirine for the prevention of HIV infection in 1959 healthy, sexually active women, 18 to 45 years of age, from seven communities in South Africa and Uganda. METHODS: In this randomized, double-blind, placebo-controlled, phase 3 trial, we randomly assigned participants in a 2:1 ratio to receive vaginal rings containing either 25 mg of dapivirine or placebo. Participants inserted the rings themselves every 4 weeks for up to 24 months. The primary efficacy end point was the rate of HIV type 1 (HIV-1) seroconversion. RESULTS: A total of 77 participants in the dapivirine group underwent HIV-1 seroconversion during 1888 person-years of follow-up (4.1 seroconversions per 100 person-years), as compared with 56 in the placebo group who underwent HIV-1 seroconversion during 917 person-years of follow-up (6.1 seroconversions per 100 person-years). The incidence of HIV-1 infection was 31% lower in the dapivirine group than in the placebo group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.99; P=0.04). There was no significant difference in efficacy of the dapivirine ring among women older than 21 years of age (hazard ratio for infection, 0.63; 95% CI, 0.41 to 0.97) and those 21 years of age or younger (hazard ratio, 0.85; 95% CI, 0.45 to 1.60; P=0.43 for treatment-by-age interaction). Among participants with HIV-1 infection, nonnucleoside reverse-transcriptase inhibitor resistance mutations were detected in 14 of 77 participants in the dapivirine group (18.2%) and in 9 of 56 (16.1%) in the placebo group. Serious adverse events occurred more often in the dapivirine group (in 38 participants [2.9%]) than in the placebo group (in 6 [0.9%]). However, no clear pattern was identified. CONCLUSIONS: Among women in sub-Saharan Africa, the dapivirine ring was not associated with any safety concerns and was associated with a rate of acquisition of HIV-1 infection that was lower than the rate with placebo. (Funded by the International Partnership for Microbicides; ClinicalTrials.gov number, NCT01539226 .)

Feasibility and robustness of an oral HIV self-test in a rural community in South-Africa: An observational diagnostic study

BackgroundHIV-self-testing (HIVST) could be a strategy to get more people tested for HIV in resource limited settings. One of the prerequisites of a successful HIVST programme is the availability of an easy to use, valid HIV-test which is robust against field conditions and procedural errors by untrained lay users.Methods and findingsThe primary objective of this study was to evaluate the ability of untrained persons to correctly interpret the OraQuick HIV Self-Test results with oral fluid compared with results obtained by trained users using the matched lot OraQuick Rapid HIV-1/2 Antibody Test and blinded to the results of the Self-Test. Sensitivity of the OraQuick HIV Self-Test in untrained users was 101 in 102 (99.02%; 95%CI = 93.88–99.95%)—and specificity– 1,241 in 1,241 (100.0%; 95%CI = 99.62–100.0%). Forty-eight Self-Tests were excluded in the accuracy analysis (due to a result read as invalid, not sure or ambiguous) resulting in a test system failure rate of 3.45% (95% CI 2.56%-4.55%). At least one observation of difficulty or error with one or more of the test steps were seen in 1,193 (84.6%) participants. Age, education and health literacy were independently associated with the sum score of procedural errors and difficulties. Four tests did not provide a valid result as determined by the trained user’s interpretation of the Self-Test.ConclusionsThe OraQuick HIV Self-Test provides reliable and repeatable results in a rural field environment in spite of procedural errors.</div

AIDS awareness and VCT behaviour: An application of the integrated model of behaviour prediction

In order to limit the expansion of the HIV and AIDS epidemic in South Africa, it is important to develop targeted prevention strategies. The voluntary HIV counselling and testing (VCT) programme appears to be effective for preventing the spread of the HI virus. This study adapted guidelines of the integrated model of behaviour prediction (IMBP) into a questionnaire and examined the extent to which it predicts behaviour. A sample of 92 sports team members from Limpopo ranging from 14 to 30 years of age completed the questionnaire. Results suggested that beliefs about the outcomes of behaviour and beliefs about the expectations of others had a direct influence on the intention to undergo HIV counselling and testing. Efficacy beliefs, namely beliefs that there are factors that can facilitate behaviour, can lead to actual testing behaviour if accompanied by self-efficacy. Knowledge, intention and stigma are not related to VCT behaviour. Findings show that some constructs influence intention and test behaviour, but in ways not predicted by the model. Thus, the adequacy of the IMBP to determine HIV and AIDS-preventative behavioural intentions is questioned. Dit is belangrik om doelgerigte voorkomende strategieë te ontwikkel om die verspreiding van MIV en VIGS in Suid Afrika te bekamp. Die vrywillige MIV-voorligtings- en toetsingsprogram (VVT) blyk effektief te wees om die verspreiding van die MI virus te stuit. In hierdie studie is ʼn vraelys ontwikkel wat op die geïntegreerde model van gedragsvoorspelling (GMG) gebaseer is. Die studie ondersoek die mate waarin die GMG gedrag kan voorspel. ʼn Steekproef van 92 sport spanlede van Limpopo tussen die ouderdomme van 14 tot 30 jaar, het die vraelys voltooi. Resultate toon dat oortuigings oor die uitkoms van gedrag en oortuigings oor die verwagtings van ander ‘n direkte invloed uitoefen op die intensie om VVT te ondergaan. Oortuigings dat daar faktore is wat gedrag kan fasiliteer het ‘n invloed op die intensie slegs as ʼn mens ook die gemak waarmee gedrag uitgevoer kan word insien. Kennis, intensie en stigma is nie verwant aan toetsgedrag nie. Die bevindinge toon dat sommige konstrukte wel intensie en toetsgedrag beïnvloed, maar nie op die manier wat die model voorstel nie. Resultate bevraagteken die vermoë van die GMG om MIV en VIGS- voorkomende gedragsintensies te bepaal