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School of Clinical Medicine

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Browsing School of Clinical Medicine by Author "Archary, Moherndran."

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    Comparison of virological responses of children commenced on an abacavir versus stavudine based antiretroviral regimen at King Edward VIII Hospital : Durban.
    (2016) Montgomery, Stephane.; Archary, Moherndran.
    Background: UNAIDS estimated that in 2014 just over 160 000 children in South Africa were receiving HAART, accounting for 20% of the global HAART cohort. Finding the appropriate HAART regimen that is safe, well tolerated and efficacious is of extreme importance in ensuring continued and ongoing success of the Paediatric HAART program. In 2010 the World Health Organisation, due to concerns of short and long term stavudine toxicity changed the recommendation regarding first-line HAART regimen from a stavudine based regimen. In South Africa, an abacavir based regimen was chosen as the preferred background regimen. However questions have been raised as to whether this change has replaced the safety concerns associated with stavudine with a less efficacious regimen. Method: A Retrospective chart review was conducted to evaluate the virological responses at 6 and 12 months in a cohort of children initiated on an abacavir based regimen at King Edward VIII hospital between January 2012 – December 2012. Data of 94 children under the age of 12 years who were initiated on abacavir and lamivudine with either lopinavir/ritonavir or efavirenz regimen (abacavir cohort) were analysed using Fisher’s exact test and logistical regression to evaluate virological suppression at 12 months. The data was compared to a prior retrospective chart review conducted between 2004 – 2010 at King Edward VIII Hospital during which a stavudine and lamivudine with either Lopinavir/ritonavir or efavirenz (stavudine cohort) was the standard of care. Results: In both the abacavir cohort and stavudine cohort there was no difference in gender distribution and the mean age of initiation was 6years. In the abacavir cohort, 62,8% were initiated on ABC/3TC/EFV and 37,2% on ABC/3TC/KAL. 88,4% were initiated on D4T/3TC/EFV and 11,6% were initiated on D4T/3TC/KAL in the stavudine cohort. The virological suppression rate in the abacavir cohort was 80.7% compared to 85.2% in the stavudine cohort, which was not a significant difference (p= 0,38:). In the abacavir cohort there was no statistical significant difference in virological suppression between patients on efavirenz versus lopinavir/ritonavir (p= 0.427:). Conclusion: This study demonstrates that children treated with an abacavir based regimen have a good probability of virological suppression, and there was no statistical difference between patients initiating an abacavir-based regimen versus a stavudine based regimen. These findings are in keeping with data from several clinical trials and support the WHO recommendation of an abacavir-based regimen for infants and children initiating antiretroviral treatment.
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    Severe acute malnutrition and antiretroviral treatment in children with HIV.
    (2016) Archary, Moherndran.; Bobat, Raziya Ahmed.
    Background: Childhood malnutrition remains a common problem in many parts of the world and is a contributing factor in 45% of the 5.9 million annual deaths in children under 5 years. HIV-infected children have a disproportionately higher prevalence of malnutrition and higher mortality associated with malnutrition as compared to non-infected children. Physiological changes associated with malnutrition and re-nutrition complicate antiretroviral treatment in these children. This thesis explores aspects related to antiretroviral treatment (ART) in severely malnourished HIV-infected children, including the timing of ART initiation, pharmacokinetics of antiretroviral drugs, co-infections with bacterial and mycobacterial infections and the effect of microbial translocation on immune restoration. Methods: Eight-two patients were enrolled in this randomized controlled trial, where HIV-infected children admitted with severe acute malnutrition (SAM) were initiated on ART either early (within 14 days of admission) or delayed (after 14 days with evidence of nutritional recovery). Clinical and laboratory parameters were collected during the admission and patients were followed up at 4, 8, 12, 24 and 48 weeks post admission. A pharmacokinetic evaluation of lopinavir (LPV) was conducted on Day1 and 14 of ART initiation. Samples for evaluation of microbial translocation and immune restoration were collected in 32 study patients and 75 additional patients in 3 control groups. Results/Discussion: There were no significant differences in immunologic, virologic or anthropometric responses at 48 weeks between the early and delayed arms. However, significantly improved rates in the changes in viral load, WAZ (weight-for-age Z score) and HAZ (height-for-age Z score) favoured the delayed arm. Pharmacokinetic (pk) evaluation of the LPV, displayed significant pk variability, reduced bioavailability and consequently greater apparent clearance (CL/F) estimates in comparison to other pk studies of LPV in non-malnourished children. Fat-free Mass (FFM) was shown to affect LPV variability; however delay in ART initiation and “super-boosted” LPV/rtv did not affect LPV variability. Bacterial pathogens were identified in 51% of patients. Of the hospital acquired infections (HAI), 41% were extended spectrum beta-lactamase (ESBL)-producing gram-negative infections. Tuberculosis (TB) co-infection was common (25.6%), with bacteriological confirmation in 38% of treated cases. Malnutrition was associated with increased microbial translocation, immune activation and immune exhaustion, with a negative impact on immune recovery in HIV-infected children on ART. Conclusions: Delaying ART initiation to at least 14 days after starting nutritional support is associated with improved rates of clinical (changes in WAZ and HAZ) and virologic outcomes. However this delay did not improve LPV exposures and dose adjustment of LPV during nutritional recovery needs to be further evaluated. These results can be used to inform changes in clinical practice and national and international guidelines for the management of severely malnourished HIV-infected children.