Identification of HIV-1 subtype CRF18_cpx in a patient with multidrug resistance in KwaZulu-Natal, South Africa: An epidemiological worry?

The most common HIV-1 subtype in South Africa is subtype C, and detection of other subtypes is rare. We report the first known case of HIV-1 subtype CRF18_cpx identified in KwaZulu-Natal, South Africa, the epicenter of the HIV epidemic, through HIV drug resistance genotyping.

The 31-year-old female patient was initiated on fixed dose combination (tenofovir, emtricitabine, efavirenz) in 2017, with failure to achieve virologic suppression. Change to second-line antiretroviral therapy (tenofovir, emtricitabine and ritonavir-boosted lopinavir) was made in 2018. Adherence was impacted by lopinavir-induced diarrhoea. In 2020, she was switched to zidovudine, lamivudine and ritonavir-boosted atazanavir. Virologic failure persisted, and HIV drug resistance genotyping in April 2021 showed multidrug resistance. Third-line regimen (tenofovir, lamivudine, dolutegravir and ritonavir-boosted darunavir) was commenced in May 2021 and virologic suppression was achieved.

Co-incidentally we discovered from the HIV drug resistance sequence report that the patient was infected with HIV-1 subtype CRF18_cpx. Analysis of the HIV sequence using REGA HIV-1 Subtyping Tool confirmed sequence subtype assignment as HIV-1 CRF 18_cpx (bootstrap confidence = 90%). Subtyping was also confirmed with the COMET HIV-1 tool, HIV BLAST tool and phylogenetic analysis.

Based on our incidental finding, CRF18_cpx may be circulating locally as the patient had no travel history. Introduction of non-subtype C and recombinant viruses are expected to have increased in South Africa due to increased travel. This highlights the need to characterize subtype diversity in South Africa, particularly in KwaZulu-Natal, as HIV subtype can influence pathogenesis, treatment response, drug resistance and efforts towards vaccine development.