Impact of low-level viremia with drug resistance on CD4 cell counts among people living with HIV on antiretroviral treatment in China

Abstract

Background Maintaining plasma HIV RNA suppression below the limit of quantification is the goal of antiretroviral therapy (ART). When viral loads (VL) remain in low-level viremia (LLV), or between 201 and 999 copies/mL, the clinical consequences are still not clear. We investigated the occurrence of LLV with drug resistance and its effect on CD4 cell counts in a large Chinese cohort. Methods We analysed data of 6,530 ART-experienced patients (42.1 ± 10.9 years; 37.3% female) from the China’s national HIV drug resistance (HIVDR) surveillance database. Participants were followed up for 32.9 (IQR 16.7–50.5) months. LLV was defined as the occurrence of at least one viral load (VL) measurement of 50–200 copies/mL during ART. Outcomes were drug resistance associated mutations (DRAM) and CD4 cell counts levels. Results Among 6530 patients, 58.0% patients achieved VL less than 50 copies/mL, 27.8% with VL between 50 and 999 copies/mL (8.6% experienced LLV), and 14.2% had a VL ≥ 1000 copies/mL. Of 1818 patients with VL 50–999 copies/mL, 182 (10.0%) experienced HIVDR, the most common DRAM were M184I/V 28.6%, K103N 19.2%, and V181C/I/V 10.4% (multidrug resistance: 27.5%), and patients with HIVDR had a higher risk of CD4 cell counts < 200 cells/μL (AOR 3.8, 95% CI 2.6–5.5, p < 0.01) comparing with those without HIVDR. Of 925 patients with VL ≥ 1000 copies/mL, 495 (53.5%) acquired HIVDR, the most common DRAM were K103N 43.8%, M184I/V 43.2%, M41L 19.0%, D67N/G 16.4%, V181C/I/V 14.5%, G190A/S 13.9% and K101E 13.7% (multidrug resistance: 75.8%), and patients with HIVDR had a higher risk of CD4 cell counts < 200 cells/μL (AOR 5.8, 95% CI 4.6–7.4, p < 0.01) comparing with those without HIVDR. Conclusion Persistent with VL 50–999 copies/mL on ART is associated with emerging DRAM for all drug classes, and patients in this setting were at increased risk of CD4 cell counts < 200 cells/μL, which suggest resistance monitoring and ART optimization be earlier considered.

Carbapenem Resistance among HIV-Infected Patients: A Scoping Review

“…It is worth noting that lower CD4 counts have been linked to increased rates of virological failure and drug resistance in antiretroviral therapy (36). Additionally, a study by Liu et al emphasized the connection between lower CD4 counts and elevated resistance to HIV drugs (37). The absence of this specific data point in our review may be attributed to the limited number of articles that reported CD4 values.…”

Incidence of low-level viremia and its impact on virologic failure among people living with HIV who started an integrase strand transfer inhibitors: a longitudinal cohort study

“…However, the persistence of LLV, although at a lower rate, revealed that integrase inhibitors are not entirely successful in achieving complete viral eradication [ 24 ]. Understanding LLV in this context is pivotal for optimizing therapeutic strategies, as it may serve as a harbinger for treatment failure, drug resistance [ 25 , 26 ], and disease progression. Clinicians should, therefore, remain vigilant in monitoring viral loads for patients exhibiting LLV, even when on integrase inhibitors [ 8 ].…”

Clinical significance and management of low‐level HIV viremia in the era of integrase strand transfer inhibitors

“…In China, the DRMs situation among LLV patients is similarly very high in some areas and varies by marital status and treatment regimen [26]. One study found that DRMs emerged in all ART drug classes when HIV patients had VL values of 50–999 copies/mL [27]. In a study of 2074 LLV participants, 59.21% exhibited DRMs, with 5.01%, 39.68% and 49.13% exhibiting resistance‐associated mutation patterns for PIs, nucleoside reverse‐transcriptase inhibitors (NRTIs) and NNRTIs, respectively [24].…”