Antiretroviral therapy in Papua New Guinea: biological and social factors contributing to HIV treatment failure and drug resistance

Combination antiretroviral therapy (ART) has transformed HIV from a progressive, ultimately fatal illness to a manageable chronic infection. However, the long term benefits of ART are compromised by the development of HIV drug resistance (HIVDR) which is propelled by sub-optimal therapy and non-adherence. The issue of HIVDR is more problematic in low-and –middle income countries where treatment options and laboratory resources to monitor treatment failure and HIVDR are limited. There are >12,000 people living with HIV (PLHIV) accessing ART in Papua New Guinea (PNG). Like many RLS, the delivery of HIV services is often challenged by economic, structural, cultural, and social issues. Monitoring and management of ART in PNG remains a challenge exacerbated by the absence of proper immunological and virological monitoring tools as faced in similar settings globally. Adherence becomes an issue hard to maintain in the face of constant challenges. The aims of the study were to determine the levels of transmitted drug resistance (TDR) in ART naïve patients and acquired drug resistance (ADR) in ART experienced patients in PNG, identify factors that affect adherence, and to characterise HIV subtypes responsible for the PNG HIV epidemic. A cohort of 210 PLHIV consisting of 102 ART experienced and 108 ART naïve were recruited from two major sexual health clinics that administer ART in two Highlands provinces. This study reports low levels of TDR (2.1%, 2/96) whilst ADR was detected in 40.0% (6/15) of ART experienced patients. Over three quarters (77.5%; 79/102) of ART experienced participants had an undetectable viral load, however a significant number of individuals (15.9%, n=13) on treatment were failing therapy according to the WHO definition. Although the majority of participants self-reported excellent ART adherence in the last seven days (78.9%, 75/91), pill count measurements indicated only 40.5% (34/84) with >95% adherence in the last month. Almost half (n=49, 52.0%) of the participants were consistently taking ART outside of recommended time since they started treatment. Taken together, these findings indicate that non-adherence to ART is high in this study cohort. This study confirms that the PNG HIV epidemic is dominated by subtype C strains that are unique to PNG. The HIV epidemic in appears to be the result of a limited number of related strains circulating within the country rather than continuous introduction of unrelated strains from other countries. Further phylogenetic analysis revealed that there is no geographical segregation of subtype C strains in PNG. These findings shows that HIV is spread locally by mobile populations, therefore, targeting these populations will be important for limiting new infections. In conclusion, whilst first line therapy is still largely effective in PNG, there is evidence of virological failure in some ART experienced individuals and drug resistance was detected in both ART naive and experienced participants. Drug resistance monitoring and persistent counselling and education on ART adherence are necessary for the longevity of successful ART program in PNG