A research report submitted to, the Faculty of Health Sciences,
University of Witwatersrand, in partial fulfilment of the requirements for
the degree
of
Master of Science
in
Population based field epidemiology
March, 2013 / Introduction: Access to highly active antiretroviral therapy has dramatically
increased worldwide since 2004. However, the emergence of HIV drug resistance
presents huge obstacle in ART scale up as it contributes to treatment failure and
poses a greater risk of disease progression and loss of treatment options. The study
therefore investigated the risk factors and the association of HIV drug resistance,
virological failure and CD4 cell count changes in patients on ART at Aurum Institute
for Health Research in South Africa.
Methods: A cohort of HIV infected patients who developed virological failure of their
first HAART regimen was assessed. A genotypic resistance testing was performed
using stored plasma on a subset of patients at first detection of virological failure.
Data were collected prospectively on all registered patients using standardised
forms. Clinical data was obtained from laboratory and pharmacy electronic records.
Logistic regression and Cox proportional hazard models were used to assess factors
associated with HIV drug resistance and virological failure respectively. Linear
mixed-effects regression models were used to assess the changes in the CD4 cell
count among patients who developed HIVDR.
Results: Between January 2003 and December 2010, a total of 146 ART-treated
patients who experienced virological failure were assessed. Of these, 108 (74%)
developed HIVDR, of whom 80 (74%) were males; the median CD4 cell count at
ART initiation was 121 cells/mm3 (interquartile range, 61-210). The most frequent
NNRTI mutations patterns found were mutations leading to resistance to NNRTI
agents with 33% having NNRTI resistance. The second most common resistance
v
pattern was resistance to lamivudine conferred by the M184V mutation (30%). The
multivariable analysis showed that higher CD4 cell count at HIVDR detection was
significantly associated with the reduced odds of developing HIV drug resistant
mutation after adjusting for gender and age(adjusted OR=0.37, 95% CI 0.15–0.94).
Similarly, there was significant association between age at ART initiation (adjusted
HR=0.71, 95% CI 0.52–0.97) and CD4 cell count during follow-up (adjusted HR=
0.54 95% CI 0.36–0.81) with virological failure in those patients who developed
HIVDR. The CD4 cell count slope on average increased by 10 cells per mL per year
for the patients without any resistance (average annual change 9.89 cells per mL,
95% CI -6.90-26.69) and decreased by 10 cells per mL per year for patients who had
any resistance (average annual change -9.61 cells per mL, 95% CI -19.41- 0.17).
Conclusion and recommendation: HIV drug resistant virus was found in 74% of
the South African patients who were accessing HIV care at Aurum Heath Institute
and developed virological failure of first HAART regimen. Higher CD4 count at
detection of HIVDR was significantly associated with lower risk of developing HIV
drug resistant virus. Lower CD4 count and male gender were significantly associated
with the development of virological failure. Patients with virological failure had
significantly great CD4 count declines when any mutation and thymidine analog
mutation (TAM) mutation were present. There is a great need therefore for
multifaceted approach to target interventions that aim to increase patients CD4 cell
counts. Patients should be either screened, possibly with HIVDR testing, prior to reinitiation
of a first-line regimen
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/13683 |
| Date | January 2013 |
| Creators | Gareta, Dickman Pangaume |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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