Our study reported that HIV patients with a VL greater than 200 copies/ml were at a higher risk of VF and AIDS-related death. Among the ART-treated HIV patients, those who were married or cohabiting (AOR = 0.591; 95% CI: 0.408, 0.856) or divorced or separated (AOR = 0.425; 95% CI: 0.207, 0.873) and acquired HIV homosexually (AOR = 0.572; 95% CI: 0.335, 0.978) were less likely to have high-risk events, while those who had ART modification and used cotrimoxazole during ART were 1.728 times (95% CI: 1.093, 2.732) and 1.843 times (95% CI: 1.271, 2.672) more likely to have high-risk events.
In this study, we reported that patients with VL reaching 200 copies/ml after 6 months of therapy were at a higher risk of VF and AIDS-related death. A retrospective cohort study indicated that among patients with persistent LLV (PLV, defined as persistent plasma viral loads of 51-1000 copies/ml for at least 3 months), a PLV > 400 copies/mL (hazard ratio = 3.3; 95% CI: 1.5–7.1; P = 0.003) predicted VF. Additionally, Quiros-Roldan et al reported that patients with persistent LLV (37–200 copies/ml) did not have an increased risk of death compared with those with sustained VS. Therefore, these two studies may support the association between VL greater than 200 copies/ml and an increased risk of VF and AIDS-related death.
Many studies have reported that respondents who were married and/or ever married were more likely to be associated with VS[20, 21]. Additionally, among individuals with a non-suppressed viral load, marriage was associated with lower odds for VF. In our study, we found that married or cohabiting and divorced patients were negatively associated with high-risk events (VL > 200 copies/ml). Marriage ensures a stable environment and treatment support from a partner and is crucial for HIV patients. Patients who are married or cohabiting show better adherence to ART. However, married patients may be more willing to reduce the chances of HIV transmission to uninfected partners; thus, they would respond to growing public health education on the importance of taking ART[23, 24]. Single patients and widowed patients may have less social support and an unstable living environment, which may affect their adherence to ART. Therefore, single patients and widowed patients may be the key population to target to prevent and control high-risk events for VF and AIDS-related death.
In this study, we reported that patients who acquired HIV homosexually were less likely to have high-risk events. Similar results have been reported previously. Factors associated with a high HIV suppression rate in ART-treated AIDS patients were infection through homosexual transmission (OR = 0.57; 95% CI: 0.35–0.90). A large cohort study in Hunan, China, reported that both cumulative immunological and virological failure rates (10.4% and 26.4% in 48 months, respectively) were the lowest in MSM compared with other population groups. Additionally, Saunder et al. reported that MSM were at a considerably lower risk of VF and less common treatment switches. An explanation for our findings may be that MSM showed better management in HIV/AIDS surveillance and treatment. In China, HIV/AIDS prevention measurements targeting MSM have led to increased earlier HIV testing and improved adherence behaviours. As the acceptance of MSM increases, a supportive healthcare environment was built to ensure the accessibility of medical services to MSM infected with HIV[30, 31]. MSM were diagnosed with HIV infection earlier, started ART with less advanced disease and presented earlier for care. MSM were also more likely to receive regular CD4+ cell count and HIV viral load monitoring, less likely to report missing ART doses, interrupt ART, or be lost to follow-up than women who have sex with men.
Patients who had ART modification were more likely to have high-risk events. Some cohort studies have reported high rates of change in the first ART[32–34]. ART regimens often need to be replaced because of virological failure or toxicity or for simplification[32, 35, 36]. Approximately 29.7% of patients start ART-modified regimens within the first year after ART initiation, with half of these changes being due to drug intolerance and/or toxicity. In resource-limited settings, the rates of ART modification are lower and mainly due to virological failure[32–34, 37]. Therefore, ART modification may be directly due to a higher viral load, including the high-risk event defined in this study. Different ART regimens showed different rates of modification; for example, patients on lopinavir and other protease inhibitors had higher rates of modification than those on efavirenz. After appropriate ART modification, the 6-month and long-term rates of VF and drug resistance are low[39, 40]. However, an unnecessary ART switch increases the risk of developing drug resistance and other poor outcomes, particularly switching to third-line ART regimens, which help to damage this last line of defence against HIV. In this study, the standards for ART modification should be strict, and proper follow-up should be conducted after ART modification to avoid the incidence of high-risk events after switching.
Cotrimoxazole, a fixed-dose combination of trimethoprim and sulfamethoxazole, is widely used against opportunistic infections in patients with advanced HIV disease[41–43]. Increasing availability of cotrimoxazole has resulted in a decline in mortality in individuals living with HIV (PLHIV)[43, 44]. In 2017, WHO published guidelines recommending cotrimoxazole prophylaxis to reduce morbidity and mortality among PLHIV whose CD4 count was ≤ 350 cells/mm3 or at clinical stage 3 or 4 or lifelong cotrimoxazole for any CD4 count in settings with a high prevalence of malaria or bacterial infections. In China, a national free ART programme was officially launched in 2003, and the first guidelines on cotrimoxazole were released in 2005. Currently, the criteria for cotrimoxazole prophylaxis among PLHIV older than 14 years in China are a CD4+ T-cell count less than 200 cells/µL or a total lymphocyte count less than 1200 cells/µL, WHO stage 4 disease or a history of oropharyngeal candidiasis. In this study, the patients who reported cotrimoxazole utilization all had baseline CD4+ T-cell counts less than 200 cells/µL and/or a high VL. Therefore, patients who used cotrimoxazole during ART were more likely to have high-risk events in this study. To the best of our knowledge, continued cotrimoxazole prophylaxis therapy can significantly reduce the risk of severe opportunistic infection in ART patients. However, discontinuing cotrimoxazole use may result in an increased incidence of malaria in a malaria-endemic region. Sisay M et al. reported that the wide utilization of cotrimoxazole to prevent opportunistic infection may contribute to the emergence of antimicrobial resistance. Hence, it is necessary to initiate, fine-tune and stop the utilization of cotrimoxazole.
This study has several limitations. First, because the interval between the viral load tests of all the included patients did not exceed 12 months, some patients who did not undergo viral load testing within 12 months were excluded. Thus, the representativeness of the participants was affected. Second, we did not collect data to evaluate ART adherence, which may be associated with high-risk events, VF and AIDS-related death. Finally, an ART drug resistance test was not performed to determine its impact on high-risk events.