In Cambodia, the current national guidelines recommend ART for all patients regardless of CD4 cell count with a test and treat approach. The recommended first-line regimen in Cambodia includes tenofovir (TDF)/lamivudine (3TC)/dolutegravir (DTG), whereas the second-line regimen in case of failure of DTG-based first-line regimen includes zidovudine (AZT)/3TC/atazanavir (ATV)/r. For patients already treated with NNRTI-based first-line regimen, the current guidelines recommend AZT/3TC/DTG for those failing NNRTI-based regimen. The last treatment cascade estimates by UNAIDS revealed that among the 74,000-estimated number of PLHIV in Cambodia in 2021, 62,636 (84%) were aware of their status, 62,561 (84%) were on ART, and 60,976 (82%) were virologically suppressed. During the course of ART, HIV VL monitoring is recommended at 6 and 12 months after the initiation of treatment, and then yearly. For patients with virological failure (VF), an adherence boosting of 3 months is required before repeating HIV VL testing. If HIV VL remains detectable, switching to ARV second-line regimen is recommended. There is still limited access to genotypic drug resistance testing. Currently, genotypic resistance testing is performed at Pasteur Institute of Cambodia (IPC), mainly for patients who have failed PI-based second-line treatment, which represents a very limited number of patients.

HIV Pre-treatment Drug Resistance (PDR) surveillance was not implemented since decade and pre-therapy genotypic resistance testing is not recommended. However, increasing trend of PDR have been reported in neighbouring countries. As Cambodia scale up the use of DTG-based first-line ART, it remains important to conduct periodic PDR surveys to document any signals of increases in pre-treatment resistance to integrase strand-transfer inhibitors that may affect population-level treatment outcomes. In the same time, routine surveillance of PDR to tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or lamivudine (3TC) must be implemented as PrEP programmes scale up. DTG-based first-line and second-line regimen has been widely implemented since 2019. By Q3 2022, there were 39,242 PLHIV had started DTG first-line regimen and 25 patients were on the second-line regimen. However, data of acquired drug resistance (ADR) in patients failing DTG-based regimen are unavailable. Surveillance for NRTI and DTG-resistant virus among people for whom DTG-containing regimens are failing will be required.

In addition to the individual need for access to resistance genotyping for PLHIV who have failed treatment, WHO recommends regular monitoring of the prevalence of resistance in order to better adapt management programmes to the population. This WHO strategy on HIV drug resistance was updated in 2021 and specifically recommends: 1) a national action plan on HIV drug resistance; 2) monitoring of early warning indicators of HIV drug resistance; and 3) surveillance of HIV drug resistance.

In response to these recommendations, the implementation of an HIV ARV resistance survey was planned in the last Global Fund grant. However, in the absence of specific recommendations for ARV resistance surveillance in the national strategic plan, as well as limited access to resistance genotyping testing, this activity has not been carried out.

It is essential to build national ownership of ARV resistance prevention, surveillance and management. It is necessary to develop operational recommendations for biological and clinical management that are feasible and adapted to the context, combined with a training programme for actors on the challenges of ARV resistance.

Finally, the lack of local capacity to screen for HIV drug resistance is a challenge. Genotypic resistance testing is currently carried out in the IPC biology laboratory, but alternative options need to be explored. The WHO HIVResNet network, which includes two laboratories in Bangkok and one in Ho Chi Minh City, is developing a training programme and may be an option to increase laboratory set-up within NCHADS. The use of DBS (blotting paper) could also be an interesting alternative to perform ARV resistance testing in decentralised areas where access to viral load is already a problem.

This technical assistance request aims at filling this gap by defining and developing a national action plan for HIV drug resistance surveillance.