Impact of HIV-1 CRF55_01B infection on CD4 counts and viral load in men who have sex with men naive to antiretroviral treatment

Abstract

BackgroundCRF55_01B, a newly identified HIV-1 circulating recombinant form (CRF) with a backbone of CRF01_AE, originated from men who have sex with men (MSM) and can be traced back to 2005 in Shenzhen, China. Circulating primarily among MSM, it has now spread throughout most provinces of China with a prevalence ranging from 1·5% to 12·5%. However, its impact on the progression of disease has not been investigated. MethodsMSM with newly diagnosed HIV-1 (n=3418) were screened for HIV-1 genotypes from 2005 to 2015 in Shenzhen, China. Blood samples were collected for measurements of CD4 T-cell counts and viral load at the time of HIV diagnosis and initiation of combination antiretroviral therapy (cART). HIV-1 pol genes were sequenced and the subtype identified, and recent infection was defined as pol with less than 0·5% ambiguous nucleotides. Written informed consent was obtained from all of the participants. The protocol for recruitment was approved by the human subject committee of the Shenzhen Center for Disease Control and Prevention. Generalized linear regression models were applied to examine the relationship between viral subtype and the change rate of CD4 counts and viral load, with adjustments for confounding variables. FindingsOf the 2423 blood samples screened for genotypes, 1031 (42·3%) were CRF07_BC, 841 (34·7%) were CRF01_AE, 323 (13·3%) were CRF55_01B, 166 (6·9%) were subtype B, and 62 (2·6%) were other subtypes (eg, CRF_08BC, CRF59_01B, and C). CRF55_01B has replaced subtype B as the third most predominant strain in Shenzhen since 2012. Among the 1792 recent infections with the three main subtypes, those infected with CRF55_01B showed a significantly higher median viral load (5·4 [IQR 5·0, 5·9]) than CRF01_AE (5·3 [IQR 4·8, 5·7], P<0·01) and CRF07_BC (5·0 [IQR 4·5, 5·5], p<0·05) at the time of cART initiation. In terms of CD4 counts, CRF55_01B-infected (349·5 [IQR 250·2, 474·8]) MSM had a similar median to CRF01_AE-infected MSM (335·0 [IQR 237·0, 464·0], p=0·352), but a significantly lower median than CRF07_BC-infected (370·0, [IQR 278·0, 501·0], p<0·05) MSM at the time of diagnosis. Furthermore, CRF55_01B infection was associated with a significantly faster rate of increase of viral load than CRF07_BC infection (2·1 vs 0·7 log copies per ml per year, p<0·01). Furthermore, it showed a slower rate of decline of CD4 T-cell counts than CRF01_AE (13·6 vs 23·3 [cells per μL]1/2 per year, p<0·05) when the initial CD4 counts were between 200 and 350 cells per μL. InterpretationIt is well known that CRF01_AE leads to higher viral loads than CRF07_BC. However, our study revealed that CRF55_01B induced even higher viral loads than CRF01_AE, and thus the transmission risk of CRF55_01B may be higher than for CRF01_AE and CRF07_BC. Although CRF55_01B showed similar CD4 counts to CRF01_AE, the rate of decline of CD4 T-cell counts was slower, which may translate to a prolonged asymptomatic state. These findings help to explain the rapid increase in prevalence of CRF55_01B in China in recent years. Strengthened surveillance, tailored prevention plans and interventions, and in-depth research focusing on CRF55_01B are needed urgently to forestall a potential epidemic. FundingThis work was supported by the National Natural Science Foundation of China (81573211), the Shenzhen Municipal Technological Project (JCYJ20160331173336891) and the Shenzhen San-Ming Project of Medicine in Shenzhen (SZSM201811071).