HIV-1 Subtype Shift in the Philippines is Associated With High Transmitted Drug Resistance, High Viral Loads, and Fast Immunologic Decline

Abstract

Objectives: The Philippines has one of the fastest growing HIV epidemics in the world. A subtype shift from B to CRF01_AE may have contributed to the increase in cases. We undertook a genotyping and transmitted drug resistance (TDR) study to determine if the dominant subtype has any advantages in resistance and transmission.

Methods: Filipinos who were treatment-naive who were living with HIV were recruited from two large government treatment hubs from March 2016 to August 2018. HIV-1 viral load, CD4 count, genotyping, and TDR testing were performed. Demographic and clinical data were collected and compared across subtypes.

Results: A total of 298 Filipinos living with HIV were recruited. Median CD4 count was 143 cells/µl and HIV viral load was 2,345,431 copies/ml. Sanger-based sequencing showed 230/298 (77.2%) had subtype CRF01_AE, 41 (13.8%) subtype B, and the rest had other subtypes or recombinants. Overall TDR was 11.7%. TDR was associated with lower viral loads and no previous HIV testing. CRF01_AE had a higher likelihood of a viral load >100,000 copies/ml and having a baseline CD4 count <50 cells/mm³.

Conclusion: TDR in the Philippines is high at 11.7%. CRF01_AE was observed to have a higher baseline viral load and lower CD4 counts compared with other cocirculating subtypes. Further research needs to confirm this observation because it suggests that CRF01_AE may have a survival advantage that led to replacement of subtype B as the dominant subtype. Drug resistance testing is recommended in the Philippines when initiating NNRTI-based antiretroviral therapy but may not be necessary for INSTI-based regimens.

Keywords: CRF01_AE; Drug resistance; Epidemiology; HIV; Philippines.