There is little evidence comparing treatment outcomes between adolescents and other age groups, particularly in resource-limited settings. A retrospective analysis of data from seven HIV clinics across urban Gauteng (n=5) and rural Mpumalanga (n=2), South Africa was conducted. The analysis compared HIV-positive antiretroviral treatment (ART)-naive young adolescents (10-14 years), older adolescents (15-19), and young adults (20-24 years) to adults (≥25 years) initiated onto standard first-line ART between April 2004 and August 2010. Log-binomial regression was used to estimate relative risk (RR) of failure to suppress viral load (≥400 copies/ml) or failure to achieve an adequate CD4 response at 6 or 12 months. The effect of age group on virological failure, mortality, and loss to follow-up (LTFU; ≥90 days since scheduled visit date) was estimated using Cox proportional hazards models. Of 42,427 patients initiating ART, 310 (0.7%) were young adolescents, 342 (0.8%) were older adolescents, and 1599 (3.8%) were young adults. Adolescents were similar to adults in terms of proportion male, baseline CD4 count, hemoglobin, and TB. Compared to adults, both older adolescents (6 months RR 1.75 95% CI 1.25-2.47) and young adults (6 months RR 1.33 95% CI 1.10-1.60 and 12 months RR 1.64 95% CI 1.23-2.19) were more likely to have an unsuppressed viral load and were more likely to fail virologically (HR 2.90 95% CI 1.74-4.86; HR 2.94 95% CI 1.63-5.31). Among those that died or were LTFU, the median time from ART initiation until death or LTFU was 4.7 months (IQR 1.5-13.2) and 10.9 months (IQR 5.0-22.7), respectively. There was no difference in risk of mortality by age category, compared to adults. Young adolescents were less likely to be LTFU at any time period after ART initiation (HR 0.43 95% CI 0.26-0.69) whereas older adolescents and young adults were more likely to be LTFU after ART initiation (HR 1.78 95% CI 1.34-2.36; HR 1.63 95% CI 1.41-1.89) compared to adults. HIV-infected adolescents and young adults between 15 and 24 years have poorer ART treatment outcomes in terms of virological response, LTFU, and virological failure than adults receiving ART. Interventions are needed to help improve outcomes and retention in care in this unique population.
Purpose Despite the extensive breadth of research into the critical challenge of succession in family business, generational succession in family business has been investigated from predominately one-dimensional perspective. The purpose of this paper is to respond to call for a multi-perspectives examination of leadership succession in order to embrace the dynamic and complex nature of succession in a family business. Accordingly, the authors investigated the key personal and professional factors associated with effective family-business succession across four key stakeholders: incumbent, successor, family, and nonfamily members. Design/methodology/approach The explanatory research design included 16 interviews in Phase 1 and 41 prospective case study interviews in Phase 2, both with Australian family businesses that had or were about to experience generational transition. Findings Incumbents and successor interview findings support the benefits of maintaining a cohesive family business, adaptable family culture, and familiness for effective succession. The authors also identified several personal components (e.g. family-business socialization and external experiences) that can help determine the commitment of successors and how this commitment can change once they assume a leadership position. Business size was the professional component supported by incumbent, successor, and nonfamily members as having a significant impact on succession process. As family business grows and becomes more highly complex, a clearly defined set of procedures become imperative. Practical implications Family-business practitioners can apply the findings to manage the processes and expectations of family and the business to achieve effective generational succession and thereby increase the sustainability of the business. Originality/value This research provides a coherent and comprehensive understanding of the interdependencies of competing priorities in the complex succession process that is essential for family-business sustainability and performance.
The emergence of HIV drug resistance is a major obstacle to effective antiretroviral (ARV) treatments. This study examined the drug resistance profiles among South African patients virologically failing ARV therapies between 2000 and 2003, prior to the introduction of a national treatment program. Samples were obtained from 65 HIV-1 subtype C-infected patients (39 children and 26 adults) who had received at least two nucleoside reverse transcriptase inhibitors (NRTIs) and either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI). Resistance assays were performed using the HIV-1 ViroSeq Genotyping System and mutations were defined according to the Stanford Sequence Resistance Database. Ninety-one percent of patients harbored resistance mutations; the most frequent NRTI mutations were M184V/I (37%), D67N (32%), T215Y/F (25%), K70R (21%), M41L (20%), K219Q/E (14%), and K65R (14%), reflecting the frequent use of lamuvidine and zidovudine. K103N (25%), V106M (20%), and G190A (17%) were found among patients failing nevirapine- or efavirenz-containing regimens. Of the patients who received PIs, the most common mutations were V82A/T (12%), M46I (11%), and L90M (8%). Mutations were similar among adults and children. These data indicate that HIV-1 drug resistance develops in South African subtype C-infected patients failing ARV therapy with mutations comparable to those found among patients infected with subtype B viruses.
Lipodystrophy Syndrome (LD) is common in HIV-infected children, particularly in those taking Didanosine, Stavudine, or Zidovudine. Lipoatrophy in particular causes major stigmatization and interferes with adherence. In addition, LD may have significant long-term health consequences, particularly cardiovascular. Since the stigmatizing fat distribution changes of LD are largely permanent, the focus of management remains on early detection and arresting progression. Practical guidelines for surveillance and avoidance of LD in routine clinical practice are presented. Diagnosis of LD is described and therapeutic options are reviewed. The most important therapeutic intervention is to switch the most likely offending antiretroviral to a non-LD-inducing agent as soon as LD is recognised. Typically, where lipoatrophy or lipohypertrophy is diagnosed, the thymidine nucleoside reverse transcriptase inhibitor (NRTI) is switched to a non-thymidine agent such as Abacavir (or Tenofovir in adults). Where dyslipidaemia is predominant, a dietician review is helpful, and the clinician may consider switching to a protease inhibitor (PI)-sparing regimen or to Atazanavir.
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