
Background: The Philippines has one of the fastest growing HIV epidemics in the world. Parallel to the increase is a shift in HIV subtype from B to CRF01_AE. No transmitted drug resistance (TDR) surveillance has ever been conducted. With the widespread rollout of antiretrovirals and the limited repertoire of 6 drugs (tenofovir, lamivudine, zidovudine, nevirapine, efavirenz, lopinavir/ritonavir) makes TDR monitoring imperative. In addition, a high rate of hepatitis B (HBV) co-infection (17%) in the general population raises the risk of TDR with prior NRTI monotherapy.
Methods: Following IRB approval, we performed TDR surveillance at the Philippine General Hospital, one of the largest tertiary referral centers in the country. Treatment-naïve patients had their HIV RT and PR genes sequenced using WHO approved-protocols for HIV genotyping. Generated sequences were analyzed using the Stanford Drug Resistance Database. Pertinent demographic and clinical data were collected. The current results represent year 1 of the study.
Results: 95 treatment naïve patients were analyzed. Median age was 30 years (range 20-68). There were 88 males and 7 females. Median CD4 count was 90 cells/mL (range 0-936) and median viral load was 1792000 copies/mL. 18 patients were co-infected with HBV, but all denied previous HBV treatment.
Six samples were found to have drug resistance mutations:
Sample | Age | Sex | CD4 (cells/mL) | Genotype | Mutation |
02-010 | 25
| M | 556
| AE | Y181C |
02-020
| 28
| M | 442
| E138G | |
02-030
| 31
| M | 197
| AE | E138G |
02-033
| 40
| M | 81
| AE | T215A |
02-044
| 22
| M | 526
| AE | M184V, G190A |
02-082
| 68
| M | 40
| AE | Q58E |
Distribution of subtypes and recombinants are as follows: CRF01_AE=78, B=9, CRF01_AE/B=4, CRF01_AE/F1/B=2, CRF02_AG= 1, CRF01_AE/CRF15_01B=1 (Figure 1).
Multivariate analysis with various factors did not show any significant associations predicting TDR, likely because of the low number of patients with resistance mutations.
Conclusion: The TDR rate for HIV in the Philippines is 6.3%. This is above the threshold for recommending baseline TDR genotyping for all local HIV patients. All HIV with TDR were subtype CRF01_AE, and this may signal a higher risk of TDR as the epidemic shifts further to a non-B subtype.
Figure 1. Phylogenetic tree showing CRF01_AE with little clustering whereas B is highly clustered.

E. M. Salvana,
Merck:
Scientific Advisor
and
Speaker's Bureau
,
Consulting fee
and
Speaker honorarium
C. Penalosa, None
G. Arevalo, None
N. Dungca, None
J. Lim, None
K. Leyritana, None
R. Destura, None