Abstract:
Global access to antiretroviral therapy (ART) is continuously increasing hence it is
estimated that in four years of therapy 5-10% of patients will have their first line of
therapy failing, due to development of resistance. Predictors of treatment failure
include: plasma viral load above 1000 copies/mL, fall of cluster of differentiation 4 (CD4)
count below 350 cells/mm3 in spite of therapy. This study was carried out to evaluate the
reliability of these predictors in the detection of treatment failure. Eighty one (81)
subjects were recruited from the comprehensive care clinic (CCC), Nairobi, based on
the inclusion criteria. The reverse transcriptase region (RT) of the HIV-1 genome was
amplified using nested polymerase chain reaction (PCR) and a total of 80 samples
were directly sequenced. The sequences were individually blasted into the Stanford
HIV Drug Resistance data base insitu tools, where genotypic drug resistance was
defined by one or more resistant-related mutations. Isolates showed that the majority
of patients who showed extreme treatment failure (CD4 count <100cells/μl and high
viral load >100,000 copies/ml) were directly related to mutations such as T215Y,
MI84V, M41L, K65KN, K103N, V90I, G190A, Y181C, and H221Y. The positive
predictive value (PPV) of viral load was 100% reliable in the prediction of treatment
failure however CD4+ count was 89% reliable. The Pearson correlation coefficient of
CD4 count and viral load, was observed to be significant at the 0.01 level, r = -0.762
hence R2
= 0.58. The correlation coefficient is indicative of a weak correlation
between viral load and CD4+ count. The HIV-1 subtypes in this study were as
follows: subtype A1 was the highest 47(58%) subjects, subtype D 22(27%), subtype C
5(6.25%) subjects and subtype G present in one subject respectively. There were two
circulating recombinant factor (CRF01_AE and CRF02_AG). The data obtained
suggests that viral load is reliable in the detection of treatment failure, however HIV-1
genotypic drug resistance test should be highly considered for patients suspected to be
failing therapy before they are switched
