HIV Transmitted Drug Resistance in the Philippines: The Case for Baseline Genotyping and Drug Resistance Testing

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	AE	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.