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Van Zyl G.U.,Stellenbosch University | Rabie H.,Stellenbosch University | Nuttall J.J.,University of Cape Town | Cotton M.F.,Stellenbosch University | Cotton M.F.,Childrens Infectious Diseases Clinical Research Unit
Journal of the International AIDS Society | Year: 2011

Background: The historic use of full-dose ritonavir as part of an unboosted protease inhibitor (PI)-based antiretroviral therapy regimen in some South African children contributes to the frequent accumulation of major PI resistance mutations. Methods. In order to describe the prevalence of major PI resistance in children failing antiretroviral therapy and to investigate the clinical, immunological and virological outcomes in children with PI resistance, we conducted a cross-sectional study, with a nested case series, following up those children with major PI resistance. The setting was public health sector antiretroviral clinics in the Western Cape province of South Africa, and the subjects were children failing antiretroviral therapy. The following outcome measures were investigated: CD4 count, viral load and resistance mutations. Results: Fourteen (17%) of 82 patients, referred from tertiary hospitals, had major PI resistance. All these patients were exposed to regimens that included ritonavir as a single PI. Immune reconstitution and clinical benefit were achieved when using a lopinavir/ritonavir-based treatment regimen in these children with prior PI resistance. At first HIV-1 viral load follow up after initial resistance testing (n = 11), only one patient had a viral load of less than 400 copies/ml; at a subsequent follow up (n = 9), the viral loads of five patients were less than 400 copies/ml. Patients retained on LPV/r had lower viral loads than those switched to a non-nucleoside reverse transcriptase inhibitor (NNRTI). However, two of three patients with follow-up resistance tests accumulated additional PI resistance. Conclusions: In children with pre-existing PI resistance, although initially effective, the long-term durability of a lopinavir/ritonavir-based treatment regimen can be compromised by the accumulation of resistance mutations. Furthermore, a second-line NNRTI regimen is often not durable in these patients. As genotypic resistance testing and third-line treatment regimens are costly and limited in availability, we propose eligibility criteria to identify patients with high risk for resistance and guidance on drug selection for children who would benefit from third-line therapy. © 2011 van Zyl et al; licensee BioMed Central Ltd. Source


Van Zyl G.U.,Stellenbosch University | Bedison M.A.,University of Pittsburgh | Van Rensburg A.J.,Stellenbosch University | Laughton B.,Stellenbosch University | And 4 more authors.
Journal of Infectious Diseases | Year: 2015

We measured cell-associated human immunodeficiency virus (HIV)-1 DNA (CAD) and RNA (CAR) and plasma HIV-1 RNA in blood samples from 20 children in the Children with HIV Early Antiretroviral (CHER) cohort after 7-8 years of suppressive combination antiretroviral therapy (cART). Children who initiated cART early (<2 months; n = 12) had lower HIV-1 CAD (median, 48 vs 216; P <.01) and CAR (median, 5 vs 436; P <.01) per million peripheral blood mononuclear cells than children who started later (≥2 months; n=8). Plasma HIV-1 RNA levels were not significantly lower in early-treated children (0.5 vs 1.2 copies/mL; P =.16). Early treatment at <2 months of age reduces the number of HIVinfected cells and HIV CAR. © 2014 The Author. Source


Madhi S.A.,South African National Institute for Communicable Diseases | Madhi S.A.,University of Witwatersrand | Madhi S.A.,Medical Research Council Respiratory and Meningeal Pathogens Research Unit | Madhi S.A.,Respiratory and Meningeal Pathogens Research Unit | And 51 more authors.
Vaccine | Year: 2015

Background: Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus are all potentially pathogenic, which frequently colonize the nasopharynx (NP) prior to causing disease.We studied bacterial NP-colonization in 321 HIV-infected and 243 HIV-uninfected children vaccinated with 7-valent pneumococcal conjugate vaccine (PCV7) at 6, 10 and 14 weeks of age. Methods: HIV-uninfected infants included those born to HIV-uninfected (HUU) and HIV-infected women (HEU); HIV-infected children with CD4+ lymphocyte ≥25% were randomized to initiate antiretroviral therapy immediately (ART-Immed) or when clinically indicated (ART-Def). Nasopharyngeal swabs for bacterial culture were taken prior to each PCV7 dose (Visits 1-3) and at 20, 39, 47 and 67 weeks of age (Visits 4-7). Swabs were cultured by standard methods and pneumococcal serotyping done by the Quellung method. Results: Colonization patterns for pneumococcus, H. influenzae and S. aureus did not differ between HUU and HEU children; and were also generally similar between ART-Def and ART-Immed children. Prevalence of PCV7-serotype colonization was similar between HIV-infected and HIV-uninfected children, however, overall pneumococcal and specifically non-vaccine serotype colonization tended to be lower in HIV-infected children. HIV-infected children also had a 44% lower prevalence of S. aureus colonization at Visit-1 (p = 0.010); and H. influenzae colonization was also lower among HIV-infected than HIV-uninfected children at Visit-2, Visit-3, Visit-6 and Visit-7. Conclusion: Vaccine-serotype colonization is similar in PCV-immunized HIV-infected and HIV-uninfected children. We, however, identified a lower prevalence of overall-pneumococcal and H. influenzae colonization in HIV-infected children post-PCV vaccination, the clinical-relevance of which warrants further study. © 2015 Elsevier Ltd. Source

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