N = 705) were as follows: a mean age of 42 years, majority female (55%), and 51% married. A majority (78.7%) had a history of opportunistic infections in their ART lifetime. To determine factors associated with VF, 187 records on patients who maintained PLLV and 12 on deceased patients at the time of data review were eliminated from the analysis, leaving 506 patient records. Out of the 506, 89% (451/506) suppressed VL to nondetectable levels while 11% (55/506) had VF, and the difference was significant (P = 0.0001). Virologic failure was significantly associated with ages 10-30 years (P < 0.05). Baseline VL ≥ 1000  and 200-999 copies/ml  were associated with VF. During PLLV, factors associated with VF included the following: PLLV of 200-999 copies/ml (P < 0.05), viral blips , mean maximum VL (P < 0.05), and age (P = 0.043). Married marital status was inversely associated with VF . Regimen change was not significantly associated with virologic outcomes. However, patients who switched regimens to the second line had a high risk of VF . Regimen change was significantly high (P < 0.05) among adolescents and patients with a start regimen of 2NRTI+1NNRTI. Most of the PLLV patients (89%) achieved nondetectable VL after their continued ART monitoring for at least 12 months. Therefore, PLLV was not an indicator of VF. However, a consistent VL of ≥200-999 copies/ml at baseline and more than 12 months of ART care and treatment were significantly associated with VF. Patients with VL 200-999 copies/ml, adolescents, and young adults require intensive ART monitoring and support.Persistent low-level viremia (PLLV) of 200-999 copies/ml has been reported as a risk factor for HIV virologic failure (VF). This retrospective study was aimed at characterizing patients with PLLV, determining factors associated with VF, and determining the effect of regimen change. Data were extracted from electronic medical records for HIV care and treatment. Patients' characteristics ( The aim of combined antiretroviral therapy (cART) is to hinder viral replication and hence suppress HIV-1 RNA viral load (VL) in the blood to below limits of assay detection. Most of the ART care and treatment guidelines globally have indicated VL as a predictor for monitoring virological response to cART. Unfortunately, some patients on cART still experience detectable VL in their blood in the form of viral blips or persistent low-level viremia (PLLV). According to the World Health Organization (WHO), PLLV is defined as viral loads between 50 and 1000 copies/ml on at least two consecutive measures in patients taking ART. PLLV is estimated to be experienced by 0.4-38.7% of HIV-1-infected people on ART . PLLV haSome studies have reported PLLV as an independent indicator of VF while others disagree, especially about the significance of low-level low-range viremia. Notably, clinical implications differ among patients with PLLV ≤ 199 copies/ml and patients with higher viremia 200-<1000 copies/ml, with the latter being associated with VF , 5, 8–11Virologic failure among patients with PLLV can be attributed to the emergence of drug-resistant mutations , 7, 14. There are many studies on PLLV, but most of them have been done in RRS. There is a paucity of information on HIV-1 PLLV in sub-Saharan Africa (SSA), where a high burden of HIV/AIDS is reported. There is therefore a need for studies on PLLV to give information on trends of PLLV, mitigate risks of VF, and help policymakers develop guidelines for managing such patients, especially in SSA. This retrospective study was aimed at characterizing patients with PLLV, determining factors associated with VF among patients with PLLV, and determining the effect of regimen change on virologic outcomes. This study is among the few studies in SSA focusing on PLLV among HIV patients.This was a retrospective study from January 2015 to December 2021. Records of HIV-infected patients enrolled in care at the Comprehensive Care Centre (CCC) at Kenyatta National Hospital (KNH) who experienced PLLV during the period were examined. Kenyatta National Hospital is the largest teaching and referral hospital in Kenya and is located in Kenya's capital city, Nairobi. The CCC at KNH has approximately 10000 HIV patients enrolled for care. Study inclusion criteria are as follows: all age groups, all genders, at least two VL measurements 20-999 copies/ml taken six or more months apart, and patients on cART.Approval to carry out this study was granted by the Kenyatta National Hospital/University of Nairobi Ethical Review Committee (ERC). The study ERC number is P234/04/2021. A waiver was granted for obtaining individual informed consent as the research involved no more than minimal risk.Data were extracted from the electronic medical record (EMR) system for HIV care and treatment using a data extraction built-in tool and exported to Excel. All patient identifiers such as names, home addresses, and telephone number(s) were removed while retaining only the patient serial numbers. Demographic data abstracted included the age of the patients, gender, level of education, and marital status. Medical history data included the age at HIV diagnosis, WHO stage, number of years one had been HIV positive, history of opportunistic infections (OIs) and noncommunicable diseases, Isoniazid Preventive Therapy (IPT) status, duration on ART, and start ART regimen as well as baseline VL measurement. In addition, the regimen switch, minimum and maximum VL measurements at PLLV, duration of PLLV, levels of the first VL measurement at PLLV, and viral load status at PLLV  were abstracted.Data were exported to SPSS v. 21 for analysis. Mean and interquartile ranges for continuous variables  were determined. For categorical variables , frequencies were determined. To evaluate the correlates of the outcomes (VF and nondetectable VL), a chi-squared test of association was used. Risk factors for VF were determined using logistic regression. The significance level for all statistical tests was set at 5% (95% CI).Depending on the region, there are numerous definitions of PLLV, VF, and viral blips, as seen in the published literature. It is therefore necessary to define the terms as used in this study. The terms are defined in A total of 1799 (18%) patients out of approximately 10000 patients in the EMR system at the hospital experienced PLLV between 2015 and 2021. This number was revised to 705 patients based on our inclusion criteria. Patients with baseline VL tests before 2015 were eliminated from the study due to inconsistencies in VL tests done before 2015, when VL was recommended for monitoring disease progression. The inclusion and exclusion criteria have been summarized in The patients' mean age was 42 years ± SD 15.1, the HIV diagnosis mean age was 29 years ± SD 15.9, the mean start VL at PLLV was 154 copies/ml ± 192, the mean duration on ART in months was 96 ± SD 43, the mean minimum VL at PLLV was 68 ± SD 99 and maximum 238 copies/ml ± SD 247, and the mean number of months from initiation of ART to PLLV was 44 ± SD 43. Among those who did not maintain PLLV, the mean duration of PLLV to the outcome was 21.6 months ± 8.6. Overall, 34% (240/705) of patients were aged 41-50 years, 55% (388/705) were female, 50.8% (358/705) were married, and 34.6% (244/705) were on WHO stage 1 at the start of ART. Approximately 40% (281/705) of the participants had baseline viral loads of 20-999 copies/ml. The first VL at PLLV for most patients  was 20-199 copies/ml. It was observed that 19% (133/705) of the patients were diagnosed with HIV at ages 30-39 years and had been positive for more than 10 years . Patients with a history of opportunistic infections were 78.7% (555/705); the specific OIs have been summarized in P = 0.0001). The factors that significantly affected the outcomes included the following: age (P = 0.006), age at HIV diagnosis (P = 0.002), marital status (P = 0.026), first viral load (P = 0.0001), VL status at PLLV  (P = 0.001), and first VL measurement at PLLV (P = 0.0001). None of the selected opportunistic infections and noncommunicable diseases evaluated significantly affected the outcomes  (P = 0.039). In addition, 80% (161/201) of patients switched to a different first-line regimen while 20% (40/201) switched to second-line regimens, and the difference was significant (P = 0.0001). Patients who switched to second-line regimens were more likely to have an outcome of virologic failure (P = 0.028)  than those who switched to a different first-line regimen. Adolescents significantly switched regimens more than the other age groups .In this study, 39.7% (201/506) of patients switched regimens at PLLV. Univariate logistic regression showed that regimen switch was not significantly associated with VF (= 0.157) . RegimenApproximately 18% of patients attending the CCC at KNH between 2015 and 2021 experienced PLLV. This number falls within the estimated prevalence 0.4-38.7%) of patients who experience PLLV while on ART . A large% of patiIn the study population, 89% of the patients ended up suppressing viremia to below levels of quantification, unlike 11% who transitioned to VF. This could be a result of differences in the level of quality of care by different programs or guidelines by NASCOP in Kenya that recommend similar intensive care among PLLV patients like patients experiencing VF . This cord 90 target to achieve suppression.The mean age 29 years) at diagnosis in our study was a risk factor for VF. In addition, adolescents, youth, and young adults were at a higher risk of VF than the other age groups. Similar findings were reported in an Austrian cohort where patients under 30 years were more likely to experience VF  . A large years atResults from the present study indicate that patients who had baseline viral loads ≥ 200 copies/ml were more likely to experience VF than those with VL ≤ 199 copies/ml. This could indicate the presence of high HIV-1 quasispecies diversity prior to treatment; hence, patients were not able to suppress viremia following six months of ART . In addition, it suggests that patients had very high viral loads prior to treatment. High viral loads  prior to treatment have been reported to delay the efficacy of NNRTI-based ART with incomplete viral suppression . NotablyP = 0.028; OR 3.203) to fail virologically compared to those who changed to another first-line regimen. Similar results were reported in a study including different African countries and also in an independent study in a South African cohort [To give information on the management of PLLV, several studies have evaluated the effect of regimen change during PLLV. Some studies have reported a positive impact, that is, suppression , 16, 17,n cohort , 30. A sn cohort , 30. John cohort  reportedn cohort . Unfortun cohort , 27, 34.In the present study, a switch to another first-line regimen was inversely associated with VF. The patients who had a start regimen of 2NRTI+1NNRTI significantly changed the regimen compared to other start regimen drug combinations. Regimen change to another first-line regimen could have been a result of Kenya adopting dolutegravir (DTG), an Integrase Strand Transfer Inhibitor (INSTI), as a first-line regimen drug in 2017. Patients who were still taking efavirenz and nevirapine (NNRTIs) have been over time switched to DTG except in a few cases . DolutegP = 0.026) . Patients who were married were less likely to transition to VF compared to patients with other marital statuses. This was also observed by Kiweewa et al. [P = 0.08) in relation to VF. Patients with a history of oral candidiasis were 2.4 times more likely to fail virologically than their counterparts. Oral candidiasis among people living with HIV/AIDS is an indicator of immune suppression and severity of the disease. Formal education was not related to virologic outcomes. This is encouraging for ART programs and health practitioners serving populations with low levels of formal education. Gender was also not predictive of virologic outcomes among PLLV patients. This was also reported in a 10-year prospective study in a Ugandan cohort [Married marital status was inversely associated with virologic failure (a et al. , who repa et al. , 38. Of n cohort .This retrospective longitudinal study characterized patients with PLLV and recorded baseline viral loads > 200 copies/ml, consistently high viral loads of 200-999 copies/ml at PLLV, viral blips, and high VL > 200 copies/ml at the beginning of PLLV, including adolescents and young adults, which were all significant risk factors for VF that should be monitored during the management of these patients. In addition, the study shows that regimen switch was not a significant factor for virologic outcomes. However, a switch from a first-line to a second-line regimen was a significant risk factor for VF. Monitoring and support need to be intensified among adolescents, young adults, and patients who have switched to second-line regimens. In addition, the management of adolescents and young adults experiencing PLLV needs to be prioritized, as they may present a barrier to progress toward acquiring the third “90” in the 90-90-90 strategy and HIV cure. One of the limitations of this study was that the baseline viral load tests were measured after six months of treatment except for pregnant and breastfeeding mothers and children who were tested before treatment; this disparity could affect the effect of the variable on outcomes. The thresholds of PLLV and VF differ from study to study, making it difficult to compare previous studies. The findings from the present study and evidence from previous studies show that patients in RLS would benefit immensely if WHO adopted the American DHHS guidelines that define VF as persistent viremia ≥ 200 copies/ml rather than lenient 1000 copies/ml. Therefore, in the interim period, AIDS care programs should target to reduce VL to below 200 copies/ml.


Probiotics are live microorganisms that, when administered in appropriate colonies, can delay the destruction of the immune system and contribute to the maintenance of immunity in HIV patients. Probiotics play an important role in stimulating natural killer T cells, strengthening the functional gut barrier, and reducing systemic inflammation.+ counts by flow cytometry, and after a 1‐month washout period the participants who had received probiotics were switched to placebo, and the participants who had received placebo were given probiotics for 3 months, and they were examined for CD4+ counts 7 months after the start of the study.This study was a randomized double‐blind clinical trial involving 30 patients treated with antiretroviral therapy who had experienced immunological failure despite HIV viral suppression. Patients were divided into two equal groups of 15, group (B) received two probiotic capsules daily with a colony count of 10⁹ CFU per capsule containing seven strains, after 3 months they were examined for CD4p value < .001), which may be due to the natural history of the disease. After probiotics administration, CD4 count increased significantly . Overall, after 7 months of study, there was a significant increase in the mean CD count from 202.21 to 243.86 . In the second group (B), the administration of probiotics in the first 3 months of the study resulted in a significant increase in the mean CD4 count . Termination of treatment with probiotics resulted in a significant decrease  but overall the CD4 count at the end of the study was significantly higher than at baseline .In the first group (A), administration of the placebo resulted in a decrease in CD4 count in the first 3 months (from 202.21 to 181.79,  The study investigates the effect of probiotics in patients who have experienced immunological failure despite virological suppression. If this increase is less than 25–50 in the first year, or if the CD4 count does not increase from baseline despite the decreased viral load, or if CD4 cells are consistently below 100 cells/mm3 or decrease by 50% of the maximum CD4 count during treatment, immunologic failure is present.Immunologic failure: an increase in CD4 cell count of 150/mmGenerally, immunologic failure follows virologic failure, and then clinical exacerbations occur. However, these may occur months to years apart and do not necessarily occur in the order mentioned.In the patients in our study, viral load was minimized and the desired virologic response was achieved, but despite this success, we observed immunologic failure, so according to previous studies we try to increase the gut microflora by probiotics especially with a high count of lactobacilli to reduce intestinal inflammation and achieve an immunologic response.Probiotics are live microorganisms that, when administered in adequate numbers of colonies, can delay immune destruction and help maintain immunity in HIV patients. A study by Ruben Hummeln et al. investigated the effect of probiotics on the immune system of patients with HIV. The results indicate that at the end of Week 25, the group that received a placebo in combination with ART had an increase of mean of 19 CD4 cells/μL and the group that received probiotics in combination with ART had an increase of mean of 46 CD4 cells/μL.Several other studies have shown the effect of probiotics on increasing CD4 cell counts. Based on these results, we designed this study to investigate the effect of probiotics in patients who have immunologic failure despite virologic success.2This study was a randomized double‐blind clinical trial involving 30 patients treated with ART at West Medical Center, Tehran, Iran.3 or those with HIV RNA 10,000 copies/mL or greater qualified for conversion to second‐line therapy ART.According to World Health Organization (WHO) criteria, patients who have received standard first‐line therapy ART for 1 year or more are referred for evaluation of second‐line therapy ART if they have CD4 decline to levels before ART, CD4 decline to less than 50% of peak at baseline, or failure to achieve CD4 levels above 100 c/mmBefore the study began the patients received at least 48 weeks of ART (first line or second line) who had experienced immunological failure despite HIV viral suppression.Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus bulgaricus, Bifidobacterium breve, Bifidobacterium longum, Streptococcus thermophiles with prebiotic fructooligosaccharides.Patients were divided into two groups of 15. Group (B) received two probiotic capsules daily with a colony count of 10⁹ CFU per capsule containing seven strains  or decreased by 50% from the peak during treatment (if known) or CD4 count remained below 100 cells/mm2.2The exclusion criteria included:1.Patients taking antibiotics during the study,2.Patients with concurrent hepatitis B and C,3.Patients not adhering to pill regimen,4.Pregnancy during the study,5.Active infectious diseases,6.Surgical procedures 6 months before or during the study on the gastrointestinal tract,7.Severe liver or kidney failure.2.3+ cells is based on the flow cytometry method. In this method, the blood is first incubated with specific amounts of antibodies conjugated with fluorescent substances such as phycoerythrin, the antimarker to be measured; the cell suspension is then analyzed in a flow cytometer and the values are recorded.The sample needed for this test is whole blood collected with EDTA anticoagulant. The measurement of CD42.4χ2 test was used for the comparison of qualitative variables and the t test or Mann–Whitney U test was used for the analysis of quantitative variables. The effect of probiotics was studied using the logistic regression model.The 3Thirty patients participated in the study, 5 women and 25 men, and were randomly assigned to two groups. During the first 3 months, five patients voluntarily withdrew from the study . We continued the study to the end with 25 patients, 5 women (20%) and 20 men (80%). Our groups included 56 and 44 percent of patients.The average age of the remaining subjects was 41.4 years  and the average duration of treatment with ART was 4.4 years.p value < .001).The mean CD4 count before the administration of probiotics was 168.88 (SD = 71.072) in all patients. After our first intervention, the administration of placebo and probiotics for groups A and B, we observed a significant increase in CD4 count in group A compared with group B  = −69.70, 95% CI: (−97.96 to −41.43), p value < .001).In our second intervention, we exchanged the two groups and administered probiotics for group B and placebo for group A. Again, we observed a significant increase in CD4 counts in the probiotic group compared with the previous phase  = 98.88, 95% CI: (70.66 to 127.11), p value < .001), which could be due to the natural history of the disease. After probiotics administration, CD4 count increased significantly . Overall, after 6 months of study, there was a significant increase in mean CD count from 202.21 to 243.86 .Next, we examined the effect of probiotics on each group separately. We wanted to see how the beginning and the end of taking probiotics affected the CD4 count. In group A, administration of the placebo resulted in a decrease in CD4 count in the first 3 months . Termination of treatment with probiotics resulted in a significant decrease , but overall the CD4 count at the end of the study was significantly higher than at baseline   have lower lactobacilli levels, increased LPS, and sCD14 levels, and increased inflammatory markers such as IL −6 and sCD14.Probiotics also may promote epithelial healing by altering intestinal flora and reduce the risk of viral transmission and hospitalization for coinfection by preventing the decline in CD4So in this study, we administered a kind of probiotics with a high count of lactobacilli then this intervention can lead to reducing inflammation in intestinal mucosa and make a good response for HIV patients with immunologic failure.Our results show that the administration of probiotics increased CD4 cell counts compared with the placebo. After discontinuation of probiotics, CD4 counts approached baseline values again but were still significantly higher.Probiotic administration resulted in an average increase of 62 and 49 CD4 cells/μL in both groups, respectively.+ cells increases by taking probiotics but decreases back to baseline levels after stopping probiotics. The results could also mean that by administering probiotics for a longer time, we could expose more infected cells and achieve a better result.our study showed that the number of CD43 was a main predictor of treatment failure. This finding may be because patients with baseline CD4 counts of ≤100 cells/mm3 have reduced immunity and their response to initial treatment ART may be unsatisfactory.On the other hand, previous studies showed that a CD4 count of <50 cells/mm3.Therefore longer period probiotic intervention in this group of study can help them to overcome immunologic failure in persistent CD4 counts above 100 cells/mmIt is also recommended to consider other Reasons cited for immunologic failure including the role of the thymus gland, which declines with age, and drug toxicity of zidovudine, which clinically causes anemia, neutropenia, pancytopenia, and granulocytopenia in 45% of recipients of this drug.In this type of failure, it is also recommended to first rule out other causes of immunosuppression, such as HIV2, HTLV1, HTLV2, and drug toxicity, and the combination of didanosine and tenofovir is also among the causes that lead to a decrease in CD4 increase and a lack of appropriate immunological response.In our study, we excluded all the mentioned causes of immunologic failure.Bifidobacterium bifidum with Streptococcus thermophilus 2.5 × 10(10) CFU for 2 months, and the other group received a standard diet (control group). CD4 counts were collected at baseline and the end of the study. The mean CD4 count increased in the probiotic group (791 cells/mm3), whereas it decreased slightly in the control group (538 cells/mm3). The change in mean CD4 cell count from baseline was +118 versus −42 cells/mm3 in the children receiving the probiotic diet and the control group, respectively (p = .049).In another study by Livia Trois, conducted on 77 HIV‐infected children aged 2–12 years, they were divided into two groups: one group received probiotics containing p = .003) was observed. After adjustment for the duration of antiretroviral drug use, the additional increase explained by yogurt consumption remained at 0.17 cells/μL/day  which was also significant.In a similar study from Tanzania after the initiation of yogurt‐enriched probiotic consumption, an additional increase of 0.28 cells/μL/day . The patients had consented to participation in this article. The participants had consented to the publication of this article.


Though bictegravir/emtricitabine/tenofovir (BIC/FTC/TAF) have been regulatory approved and included in the National Reimbursement Drug List in China, due to the affordability concern, generic version of efavirenz + lamivudine + tenofovir (EFV + 3TC + TDF) is still recommended as the first-line therapy in the clinical guideline and widely used in clinical practice. The aim of the study is to assess the persistence with first-line BIC/TAF/TAF and EFV + 3TC + TDF in newly treated HIV-1 patients in the real-world setting in Hunan Province in China.A retrospective analysis of the medical records of HIV patients initiating first-line antiretroviral therapy in the First Hospital of Changsha in January 1st, 2021-July 31st, 2022 was conducted. Persistence was assessed as the number of days on the therapy from the index until treatment discontinuation or end of data availability. Kaplan-Meier Curves and Cox Proportional Hazard models were used to evaluate the discontinuation rates. Subgroup analysis was performed excluding BIC/FTC/TAF patients with treatment discontinuation due to economic reason, and EFV + 3TC + TDF patients with a viral load > 500,000 copies/mL.A total of 310 eligible patients were included in the study, with 244 and 66 patients in the BIC/FTC/TAF group and EFV + 3TC + TDF group, respectively. Compared with EFV + 3TC + TDF patients, BIC/FTC/TAF patients were older, more living in the capital city currently, and had significantly higher total cholesterol and low-density level . No significant difference was shown in the time to discontinuation between BIC/FTC/TAF patients and EFV + 3TC + TDF patients. After excluding BIC/FTC/TAF patients with treatment discontinuation due to economic reason, EFV + 3TC + TDF group were shown to have a significantly higher risk of discontinuation than BIC/FTC/TAF group . After further removing the EFV + 3TC + TDF patients with a viral load > 500,000 copies/mL, the analysis showed similar results . 79.4% of the EFV + 3TC + TDF patients discontinued treatment due to clinical reasons, while 83.3% of the BIC/FTC/TAF patients discontinued treatment due to economic reasons.Compared with BIC/FTC/TAF, EFV + TDF + 3TC patients were significantly more likely to discontinue the first-line treatment in Hunan Province in China. In China, HIV imposed a significant disease burden. The China Center for Disease Control and Prevention (CDC) reported 1.05 Million HIV/AIDS cases alive and 351 thousand cumulated death by end of 2020 [Antiretroviral therapy (ART) has been introduced in the HIV treatment and significantly lowered the mortality and morbidity of HIV patients. The Chinese Guidelines for Diagnosis and Treatment of Human Immunodeficiency virus Infection/Acquired Immunodeficiency Syndrome (2021 edition) has recommended initiation ART in treatment-naïve patients with the regimen consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a third drug . The thiPrevious studies have shown that STRs had higher adherence and persistence compared with MTRs –13. NeveThis is a retrospective database analysis using the electronic medical record data in the Department of Infection in First Hospital of Changsha to evaluate the persistence of ART regimens in treatment-naïve HIV-1 patients. The hospital is a tier 3 A hospital in Hunan Province, covering the majority of the treatment of HIV/AIDS patients in the province. The patients’ data collection started on January 1st, 2021 and ended on July 31st, 2022 with the last hospital visit. The study was conducted in accordance with the Chinese Ethical Guidelines for Medical and Health Research Involving Human Subjects. Ethical approval was required according to the guidelines.Adult patients diagnosed with HIV-1 infection between January 1st, 2021 and July 31st, 2022, with the prescription of BIC/FTC/3TC or generic version of EFV + 3TC + TDF as the first-line treatment, and have at least one hospital visit after prescription, were included in the study. The index date was the first time for patients prescribed with BIC/FTC/3TC or EFV + 3TC + TDF. Persistence was measured by the duration on the regimen, calculated from the index date until the last date when the regimen was prescribed. In clinical practice, BIC/FTC/3TC patients could switch to free ARTs because of the economic burden of BIC/FTC/TAF. Therefore, a subgroup analysis was performed excluding BIC/FTC/3TC patients with treatment switch due to affordability reason. Furthermore, since EFV is not recommended for patients with a viral load > 500,000 copies/mL in the 2021 Edition HIV/AIDS diagnosis and treatment guideline, a subgroup patient population was selected with a viral load ≤ 500,000 copies/mL.Continuous variables were reported with mean and standard deviation (SD). Categorical variables were reported with count (frequency) and percentage. T-test and chi-square test were used in between-cohort comparisons for continuous variables and categorical variables, respectively. The time to discontinuation of index regimen was estimated by Kaplan-Meier curves, with log-rank tests to assess the statistically significant difference between the two regimen groups. Cox proportional hazard models were used to assess the risk of discontinuation. Age group, gender, baseline viral load groups, baseline CD4 cell count groups, baseline total cholesterol, baseline low-density lipoprotein, education level, employment status and current residence were included as the covariates in the model. All statistical analysis were performed with SPSS® version 26.0 . The statistical significance of all tests was assessed with a significance level of 0.05.A total of 310 eligible patients were included in the study, with 244 and 66 patients in the BIC/FTC/TAF group and EFV + 3TC + TDF group, respectively. The demographic and clinical characteristics are described in Table The time to discontinuation for BIC/FTC/TAF vs. EFV + 3TC + TDF in all patients was shown in Fig. The reasons for the treatment discontinuation cases in BIC/FTC/TAF group and EFV + 3TC + TDF group were shown in Table To our knowledge, this is the first study to evaluate the persistence of BIC/FTC/TAF and EFV + 3TC + TDF in real-world setting in China. Our study showed that after excluding the economic burden between ARTs, BIC/FTC/TAF had significant better persistence compared with EFV + 3TC + TDF, which is consistent with previous real-world studies in western countries , 11. TheTDF related side effect is another contributor of treatment discontinuation due to safety concerns in the EFV + 3TC + TDF group. The finding is inconsistent with previous studies. Moreover, though there is a large number of HIV patients with TDF-based regimens in China, the benefits in renal functions of switching from TDF to TAF are supported by previous studies in both Western and Asian HIV patient population –27. In tOur study finding about the treatment discontinuation due to drug resistance in EFV + 3TC + TDF group is consistent with the previous studies about the drug resistance to free NRTI and NNRTI in China –34. DrugThe study shows BIC/FTC/TAF has significantly longer persistence compared with EFV + 3TC + TDF; however, the affordability of BIC/FTC/TAF is still a concern for HIV patients in China. After government reimbursement (≥ 70%), the out-of-pocket expenditure of BIC/FTC/TAF could still be a barrier for HIV patients, especially in HIV patients with low socio-economics status or in rural areas. Previous studies have shown that even in HIV/AIDS patient with the free ART, the out-of-pocket expenditure is still high because of the other costs related with laboratory tests, examinations, medical service and drugs for opportunistic infections, which are not covered by the government , 37. A sThe strength of the study includes the most recent clinical outcomes of treatment options in China. There are several limitations in our study. Firstly, since the study period is from January 1st, 2021 to July 31st, 2022, the follow-up period was relatively short and the sample size was small. The long-term persistence of BIC/FTC/3TC may need to be further assessed with a larger sample size. Secondly, data of the HIV patients in the study were collected from a single hospital in Hunan Province and therefore the study findings might not be generalized to HIV patients in cities/provinces in China. Thirdly, some variables were adjusted in the cox model, confounding effects or selection bias could not be completely ruled out.In summary, our study demonstrated the longer persistence of BIC/FTC/TAF compared with EFV + 3TC + TDF in HIV patients in Hunan Province in China. Given the 95-95-95 goals, the high burden of HIV/AIDS in China highlight the important to select treatment regimens with better safety and efficacy profiles.


We sought to evaluate the variability of HIV-1 and its effect on immuno-virological response among adolescents living with perinatally acquired HIV (APHI).10, adjusted for acquired drug resistance, gender, ART line, adherence, and duration on treatment; p < 0.05 was considered statistically significant.A cohort study was conducted from 2018–2020 among 311 APHI receiving antiretroviral therapy (ART) in Cameroon. Sequencing of protease and reverse transcriptase regions was performed for participants experiencing virological failure, VF, . HIV-1 subtypes were inferred by phylogeny; immuno-virological responses were monitored at 3-time points (T1-T3). Cox regression modeling was used to estimate adjusted hazard ratios (aHRs) of progression to: CD4 < 250, and PVL > 5log3) and decline log10 PVL , similar across subtypes. Among participants with CRF02_AG infection, duration of treatment was significantly associated with both rates of progression to CD4 < 250, and PVL > 5log10, aHR = 0.02 (0.001–0.52), and aHR = 0.05 (0.01–0.47) respectively. Moreover, four potential new HIV-1 recombinants were identified , indicating a wide viral diversity.Of the 141 participants in VF enrolled, the male-female ratio was 1:1; mean age was 15 (±3) years; and median [IQR] duration on ART was 51 [46–60] months. In all phases, 17 viral clades were found with a predominant CRF02_AG . From T1-T3 respectively, there was an increasing CD4 count (213 [154–313], 366 [309–469], and 438 [364–569] cells/mmAmong APHI in settings like Cameroon, there is a wide genetic diversity of HIV-1, driven by CRF02_AG and with potential novel clades due to ongoing recombination events. Duration of treatment significantly reduces the risk of disease progression. HIV molecular surveillance reveals recombinant forms account for almost a quarter of HIV infection worldwide . West-CeThere is increasing evidence that the extreme variability and high evolution rate of HIV-1 favors the emergence of HIV antiretroviral drug resistance (HIVDR). In addition, some recombinant forms, such as the CRF01_AE variant in China, have been shown to have a faster rate of disease progression, and better replicative fitness when compared to pure lineages . In a coThe increase in HIV-1 viral diversity because of the relative adaptation of the virus to a given host environment constitutes a factor that is particularly relevant to the emergence of drug-resistant variants. This provides a unique opportunity to study and monitor the evolution of HIV-1 strains and the clinical implications of these on the treatment, and immune/virological response among adolescents –11.The determination of HIV subtypes is based on comparing a query sequence to a set of reference sequences and obtaining the best match as the putative subtype. A wide array of currently used subtyping tools rely on an initial alignment step to measure similarity with the reference set. The population of APHI is of particular interest because of the long time after infection , and as such viral adaptation to the host is likely to occur.In this study, we evaluated the effect of HIV-1 genetic diversity on immune-virological response and described potential emerging resistant variants among APHI failing first- and second-line antiretroviral treatment. Specifically, we sought to assess HIV-1 genetic variability among these APHI, evaluate the immune-virological response according to HIV-1 subtypes, determine the trends of virological response according to HIV-1 subtypes, and describe the selection of potential resistant variants among these adolescents.“Resistance Evolution among Adolescents in Yaoundé and its surroundings” (READY-study) in the Centre region of Cameroon. Participants were recruited following consecutive, and exhaustive sampling. Follow-up was performed at enrollment (T1), at 6 months (T2), and at 12 months (T3). Included in the current analysis were only participants failing first- and second-line ART with plasma viral load (PVL) ≥ 1000 RNA copies/ml  receiving antiretroviral therapy (ART) in one of the selected health facilities within the opies/ml .Included in the study were APHI; aged 10–19 years, receiving a standard reverse transcriptase inhibitor-based first- or ritonavir-boosted protease inhibitor-based second-line ART regimen for at least 6 months, provided written assent, and informed consent from their legal guardian(s), and irrespective of exposure to the prevention of mother to child transmission (PMTCT) antiretrovirals. APHI who were not formally registered in the ART monitoring system of any study site, reported to be ART-naïve, or on a drug regimen not included in the national guidelines, or structured treatment interruption were not enrolled. Moreover, participants who freely withdrew from the study, or were transferred out of a study site before mid- or endpoint were excluded.The minimal sample size was established following statistical calculations . Assumin® DNA Minikit; QIAGEN, Courtaboeuf, France). GRT was done when the viral load was > 1000 copies/mL using an in-house protocol  CD4 count at enrolment was higher among participants harboring non-CRF02_AG viral clades (328 [112–759] cells/mm3), as compared to those with the CRF02_AG variant (207 [33–313]). A similarly variable distribution in median log10 PVL across subtypes was observed with a lower value among participants harboring non-CRF02_AG clades (5.22 [4.57–5.72]), relative to those with the CRF02_AG variant (5.25 [4.52–5.49]). However, this variability across subtypes was not statistically significant, p>0.05 , relative to those with non-CRF02_AG clades (4.48 [3.77–5.06]). Likewise, this difference was not statistically significant with respect to genetic variability , in comparison to the CRF02_AG variant (345 [186–600]). These were accompanied by a declining trend in median logiability . The pro–717), in10 PVL, with a lower value observed in non-CRF02_AG clades (4.28 [3.62–5.23]), as compared to that in the CRF02_AG variant (4.44 [3.81–5.21]). This difference was not statistically significant with respect to HIV-1 subtypes/genetic variants , as opposed to those with the CRF02_AG variant (398 [286–683]). Similarly, there was a declining trend in median logvariants .3), and those with PVL< 5 log10 , and 34.3% (47/137) had PVL > 5 log10 RNA copies/mL  of the participants experienced immunological failure (CD4 < 250 cells/mmopies/mL .3) was 61.00  months. Participants infected with the CRF02_AG variant (57.00: 95% CI: 51.67–62.33 months) had a shorter median time to a poor immunologic outcome as compared to those infected by non-CRF02_AG clades (62.00: 95% CI: 38.88–85.12 months). However, these differences in the survival curves of the different subtypes/variants were not statistically significant, p = 0.538  was 64.00 (95% CI: 41.74–86.26) months. Those with CRF02_AG infection had a shorter median time to this endpoint (60.00: 95% CI: 52.72–67.28 months) as compared to participants infected by non-CRF02_AG clades (91.00: 95% CI: 75.38–106.62 months). The observed differences in survival curves across subtypes were not statistically significant, with p = 0.251  = 0.02, 95% confidence interval (95% CI): 0.001–0.52, and p = 0.017]. Similarly, there was a statistically significant association between the duration of treatment and the probability of a decline in PVL in participants with CRF02_AG infection  .Assessing potentially emerging HIV-1 genetic variants, or unique recombinant forms (URF) associated with reduced viral susceptibility to currently available ARV drugs in the Cameroonian context, using four rapid subtyping tools revealed a high rate of inter-subtype recombination, confirmed by phylogenetic analyses , with thOur study was conducted among adolescents living with perinatally acquired HIV (APHI) in urban and rural settings of the Center region of Cameroon. The predominant genetic variant was CRF02_AG, this is similar to other studies carried out in Cameroon , 19–21. In this study, there was no statistically significant difference across subtypes with respect to CD4 cell count at enrolment. Likewise, there was no significant difference in the proportion of participants who achieved adequate immunological response at 12 months post-enrolment. These results were similar to those obtained in other studies , 25. Moret al [et al in France where infection with CRF02_AG and other non-B viral clades conferred better virological responses than patients harboring B-subtypes [Virological responses at enrolment, 6-, and 12-month follow-ups on treatment were comparable across all subtypes. These were similar to results obtained by Ogbenna et al  but in dsubtypes . These fsubtypes , 28, 30.subtypes , 28, 29.In our study, we identified four sequences with discordant subtypes according to the rapid subtyping tools used, which we classified as potential URFs. In addition, each of these sequences was associated with at least one major drug-resistant mutation. These results are in agreement with those observed in several other studies carried out in Cameroon , 31, 32.As generally observed in longitudinal studies, there were some missing laboratory data over time, as well as loss to follow-up of participants by the end of the study which made it difficult to follow-up the entire sample population. These may have had an impact on data quality and the overall impact of the study findings on the target population. Furthermore, limiting sequencing only to samples that had PVL ≥ 1000 RNA copies/ml and sequencing failure of some samples led to an underestimation of HIV genotypes. Additionally, further analyses like Simplot++ ought to be performed to investigate sequence similarity and confirm the detection of recombination events. However, the multi-time point follow-up period, the personalized monitoring, and repeated genotyping of participants to ensure within-program comparison of subtypes in a bid to limit expected confounders are the strengths of this study.This study revealed a wide variety of HIV-1 genotypes with CRF02_AG predominance. Among participants with CRF02_AG infection, duration on antiretroviral treatment was significantly associated to both rates of progression to poorer immunological outcomes, and higher PVL following treatment failure. Virological outcomes were similar across HIV-1 subtypes/variants. Therefore, provided adequate observance of treatment, and personalized follow-up of this underserved adolescent population with particular importance given to immunological follow-up, current ART regimens have similar efficacy irrespective of subtype.


The purpose of this study is to investigate the incidence of determinants for virologic failure and to identify predisposing factors to enhance treatment efficacy. Tackling this global public health issue is the key to reducing the rate of virological failure and increasing the success of treatment for those living with HIV.This umbrella review delves into various aspects of current anti-retroviral therapy (ART) which is the primary treatment for human immunodeficiency virus (HIV) infection. Comprehensive searches were conducted in online databases including PubMed, Embase, Scopus, and Web of Science, up to May 26, 2023. Following the screening and selection of relevant articles, eligible articles were included in the data extraction. This study adhered to the PRISMA guideline to report the results and employed the NIH quality and bias risk assessment tool to ensure the quality of included studies.In total, 40 review studies published from 2015 to 2023 were included. The bulk of these studies concurred on several major factors contributing to HIV drug resistance and virological failure. Key among these were medication adherence, baseline and therapeutic CD4 levels, the presence of co-infections, and the advanced clinical stage of the infection.The resistance to HIV drugs and instances of determinants for virologic failure have a profound impact on the life quality of those infected with HIV. Primary contributors to this scenario include insufficient adherence to treatment, decreased CD4 T-cell count, elevated viral levels, and certain treatment regimens. Implementing appropriate interventions could address these issues. Sub-Saharan Africa exhibits elevated rates of determinants for virologic failure, attributed to the delay in HIV testing and diagnosis, and late initiation of antiretroviral therapy (ART). It is essential to undertake further research aimed at enhancing the detection of resistance in HIV patients and mitigating viral failure by addressing these underlying causes.The online version contains supplementary material available at 10.1186/s12981-023-00572-6. As of the end of 2021, HIV continues to pose a significant global challenge, affecting approximately 38.4 million individuals worldwide . MoreoveHistorically, the commencement of ART was delayed until CD4 counts dropped below 200, a level at which opportunistic infections may thrive . HoweverAs new genotypes of HIV emerge, the importance of genetic diversity is more clear in the process of treatment, vaccine design  and drugSeveral factors influence adherence to ART and virologic outcomes in HIV-positive individuals. Patient-related factors, such as substance and alcohol abuse, unstable housing, financial difficulties, and psychiatric disorders, can all contribute to non-adherence , 24. AddThis comprehensive review investigates currently prescribed antiretroviral agents in the course of human immunodeficiency virus (HIV) infection. The primary focus is to explore evidence of determinants for virologic failure and its implications for drug resistance to antiretroviral therapy (ART) agents. To ensure transparent reporting, this review adheres to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Additionally, the methodological integrity of the included publications is assessed using the National Institutes of Health (NIH) quality and bias risk assessment tool.We conducted a systematic search on four major databases, namely PubMed/MEDLINE, Embase, Scopus, and Web of Science (WoS), up to May 26, 2023. To maximize the identification of relevant publications, we employed Boolean operators between the keywords and performed combined keyword searches. The search inquiry of PubMed/MEDLINE is as follows, with the inquiries for other databases provided as an Additional file ((“HIV”[mesh] OR “Human Immunodeficiency Virus”[Title/Abstract] OR “HIV”[Title/Abstract] OR “AIDS Virus*”[Title/Abstract] OR “Acquired Immune Deficiency Syndrome Virus”[Title/Abstract] OR “Acquired Immunodeficiency Syndrome Virus”[Title/Abstract] OR “aids associated virus”[Title/Abstract] OR “aids related virus”[Title/Abstract] OR “immunodeficiency associated virus”[Title/Abstract]) AND ”[Title/Abstract] OR “antiretroviral therapy”[Title/Abstract] OR “HAART”[Title/Abstract]) AND .As the searching of databases was finished and the relevant articles were obtained, we gathered them in a single file of EndNote to remove duplicates and further to steps of selection and data extraction.A two-prong approach was used for article screening and selection. In the first step, two researchers evaluated the relevance of articles based on their titles and abstracts. In the second step, three other researchers reviewed the full texts of the screened literature. Publications that met the following criteria were included for data extraction:Review articles addressing ART in HIV infection, virologic failure of ART, and resistance to ART in HIV-positive patients.Articles written in English and published in peer-reviewed journals.Inclusion criteriaCase series, and case reports, editorial letters, opinion letters, anecdotal records, and records published in non-academic sources like magazines, websites, and social media.Non-human research studies, ongoing trial studies without published data, and abstracts without full texts.Exclusion criteriaArticles deemed relevant to the study objectives after the second step of selection and met the eligibility criteria were included for data extraction. Details of the extracted data are presented in Table To evaluate the bias risk of the included studies, we utilized the National Institute of Health (NIH) quality assessment (QA) tool. Two independent researchers completed the assessment. Table The initial search strategy yielded a total of 652 papers. Following the first review of papers, 66 duplicates were removed, and two researchers independently assessed the titles and abstracts of the remaining 586 articles. Next, the remaining articles were subjected to a full-text screening where eligibility criteria were applied; 40 articles finally fulfilled the inclusion criteria and were included in this umbrella review Fig. . The quaOf 40 eligible articles, 16 were review articles, 17 were meta-analyses with quantitative synthesis, and the remaining 7 were systematic reviews. More than 1250 studies were enrolled in our review; involving more than 427,058 patients with HIV infection. The number of included studies and the study population in ten and twenty reviews, respectively, were not clearly stated. The included studies were published between 2015 and 2023, covering a broad time frame.Three studies were specifically conducted among adolescents with perinatally acquired HIV infection, while the remaining 37 involved adults. The umbrella review's primary focus was on the current understanding of determinants for virologic failure risks and implications for drug resistance in ongoing antiretroviral therapy (ART) strategies. Thus, the review examined and listed several key items, including the first author (reference), country, year of publication, study population, included articles, type of ART, implications for drug resistance, virological failure risk factors, and main findings of the studies. The comprehensive analysis of these items can be found in Table A wide variety of countries were represented in the studies, with China (n = 5), South Africa (n = 4), UK (n = 4), USA (n = 3), Canada (n = 3), Ethiopia (n = 3), Brazil (n = 3), Switzerland (n = 3), Spain (n = 3), and Italy (n = 2) being the countries with the most involvement. Additionally, India (n = 2), Australia, Denmark, Lebanon, Romania, and Nigeria each contributed one article to the review.Regarding the classes of ART, the non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were the most commonly studied drugs in relation to drug resistance and determinants for virologic failure. Review of included studies demonstrated that poor medication adherence, high HIV viral load, low CD4 level at the baseline and during therapy, co-infection presence, and advanced clinical stage of infection were the most prevalent factors associated with drug resistance and virological failure. Notably, drug resistance related to NNRTIs was more frequently reported than resistance to other types of ART, based on the reviewed studies.The advent of Antiretroviral Therapy (ART) has revolutionized the management of HIV, transforming it from a fatal disease to a chronic condition. The availability and efficacy of ART have played a crucial role in suppressing HIV and improving the quality of life for millions of people living with HIV , 71. HowIn this umbrella review, we sought to address virological failure and its risk factors by evaluating evidence from multiple studies. Our findings have shed light on several important factors that contribute to virological failure in people living with HIV. Poor adherence to treatment emerged as the most commonly reported contributing factor, as evidenced by multiple studies , 63, 67.Poor adherence to treatment can be caused by a variety of factors. Adherence to ART is crucial for its effectiveness, and factors such as difficulty following regimens, side effects of therapy, lack of health knowledge, and limited availability of ART due to formulary restrictions or costs were identified as barriers to adherence . MoreoveIn individuals living with HIV, failure of antiretroviral therapy (ART) can result in increased medication toxicity and the development of drug resistance. Studies have shown that nearly half of those who fail first-line ART are at a higher risk of failing second-line treatment as well , 78. TheAdditionally, the duration of ART use has implications for treatment success and drug resistance. Longer duration of ART use was associated with loss of information, poor adherence, and increased drug interruption, leading to virological failure , 84–86. Drug resistance is an inevitable concern in the treatment of HIV due to the virus's genetic diversity. However, using new strategies to produce medications may reduce the occurrence of drug resistance. Since the discovery of ARTs as a viable therapeutic medication, tremendous progress has been achieved, resulting in the FDA’s approval of five integrase strand transfer inhibitors (INSTIs): Dolutegravir (DTG), Raltegravir (RAL), Elvitegravir (EVG), Bictegravir (BIC), and Cabotegravir (CAB). INSTIs have been demonstrated to successfully block HIV-1 replication and have a more robust genetic threshold to resistance than nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Extensive studies have provided a thorough understanding of the resistance patterns of DTG in recent years. It has been demonstrated that DTG exhibits a prolonged binding half-life to HIV integrase (IN) compared to both RAL and EVG. This characteristic likely contributes to DTG's ability to remain effective against the majority of first-generation INSTI-resistant variants –93. MoreIt is worth noting that regional differences play a role in the occurrence of ART resistance and virological failure. Sub-Saharan Africa, for example, faces a high prevalence of HIV treatment failure, partly due to factors such as inadequate nutritional assistance, delayed HIV testing, and treatment failure , 95–97 –100. In In conclusion, resistance to HIV drugs and virologic failure is a significant issue that affects the quality of life and well-being of HIV-infected individuals. This article has highlighted several primary causes of treatment failure, including poor adherence to medication, low CD4 T-cell counts, high viral levels, and specific types of regimens used. Interventions such as drug use, educational counseling, psychological support, and changes in management can help address these causes. With proper adherence to ART regimens, virologic failure without mutation is rare. However, considerations such as drug interactions must be taken into account and can be managed using online tools. Notably, Sub-Saharan Africa remains a region with high rates of virological failure, mainly due to delayed testing and diagnosis and the delayed initiation of ART. These challenges emphasize the urgent need for improved strategies to detect resistance in HIV patients and reduce the likelihood of viral failure by addressing its underlying causes. Further research is needed to improve the detection of resistance in HIV patients and reduce the likelihood of viral failure by identifying and addressing its underlying causes.Additional file 1. The search results of PubMed, Embase, Scopus, and Web of Science.


Background: Dolutegravir (DTG) is recommended by international guidelines as a main component of an optimal initial regimen of cART  in people living with HIV (PLWH) and in case of switching for failure or optimization strategies. However, studies on the performance of DTG-containing regimens and indications for switching therapies in the long term are sparse. The purpose of this study was to evaluate prospectively the performance of DTG-based regimens, using the metrics of “efficacy”, “safety”, “convenience” and ‘’durability’’, among a nationally representative cohort of PLWH in Italy. Methods: We selected all PLWH in four centers of the MaSTER cohort who initiated a DTG-based regimen either when naïve or following a regimen switch between 11 July 2018 and 2 July 2021. Participants were followed until the outcomes were recorded or until the end of the study on 4 August 2022, whichever occurred first. Interruption was reported even when a participant switched to another DTG-containing regimen. Survival regression models were fitted to evaluate associations between therapy performance and age, sex, nationality, risk of HIV transmission, HIV RNA suppression status, CD4+ T-cell count, year of HIV diagnosis, cART status (naïve or experienced), cART backbone and viral hepatitis coinfection. Results: There were 371 participants in our cohort who initiated a DTG-based cART regimen in the time frame of the study. The population was predominantly male (75.2%), of Italian nationality (83.3%), with a history of cART use (80.9%), and the majority initiated a DTG-based regimen following a switch strategy in 2019 (80.1%). Median age was 53 years (interquartile range (IQR): 45–58). Prior cART regimen was based mostly on a combination of NRTI drugs plus a PI-boosted drug (34.2%), followed by a combination of NRTIs plus an NNRTI (23.5%). Concerning the NRTI backbone, the majority comprised 3TC plus ABC (34.5%), followed by 3TC alone (28.6%). The most reported transmission risk factor was heterosexual intercourse (44.2%). Total interruptions of the first DTG-based regimen were registered in 58 (15.6%) participants. The most frequent reason for interruption was due to cART simplification strategies, which accounted for 52%. Only 1 death was reported during the study period. The median time of total follow-up was 556 days (IQR: 316.5–722.5). Risk factors for poor performance of DTG-containing-regimens were found to be: a backbone regimen containing tenofovir, being cART naïve, having detectable HIV RNA at baseline, FIB-4 score above 3.25 and having a cancer diagnosis. By contrast, protective factors were found to be: higher CD4+ T-cell counts and higher CD4/CD8 ratio at baseline. Conclusion: DTG-based regimens were used mainly as a switching therapy in our cohort of PLWH who had undetectable HIV RNA and a good immune status. In this type of population, the durability of DTG-based regimens was maintained in 84.4% of participants with a modest incidence of interruptions mostly due to cART simplification strategies. The results of this prospective real-life study confirm the apparent low risk of changing DTG-containing regimens due to virological failure. They may also help physicians to identify people with increased risk of interruption for different reasons, suggesting targeted medical interventions. For people living with HIV (PLWH) with detectable viremia (HIV RNA), international guidelines recommend a combination antiretroviral therapy (cART) consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) and one integrase strand transferase inhibitor (INSTI) as an optimal initial regimen unless otherwise indicated ,2,3. An For this reason, a prospective study was designed, aimed at better evaluating in a multidimensional manner the performance of DTG-based regimens over a longer follow-up, controlling for potential confounders.This is a prospective study nested in a multicenter, hospital-based cohort established in the mid-1990s that has currently enrolled over 24,000 people with HIV infection, i.e., the MaSTER cohort . Data waPLWH from four Italian hospital centers of the MaSTER cohort  who initiated a DTG-based regimen, either when cART naïve or following a regimen switch, were included in the study between 11 July 2018 and 2 July 2021.Participants were followed until the study outcomes were recorded or until the end of the study on 4 August 2022, whichever occurred first. Interruption was also reported when a participant switched to another DTG-containing regimen. Performance of DTG-based regimens was evaluated using the metrics of “efficacy”, “safety”, “convenience” and ‘’durability’’. An event due to efficacy concerns was defined as virological failure (HIV RNA > 50 copies/mL at least six months after initiating therapy), whether or not therapy interruption occurred. Events due to safety concerns were defined as a newly occurring laboratory alteration of grades 3–4 and/or clinical progression whether or not there was a therapy interruption. Grade 3+ laboratory alterations were defined using the following measurements: aspartate transaminase (AST) > 260 units/L, alanine transaminase (ALT) > 235 units/L, bilirubin > 2.6 mg/dL, cholesterol ≥ 275 mg/dL, triglycerides > 750 mg/dL, glycemia > 250 mmol/L, creatinine > 1.9 mg/dL, calcium < 7 mg/dL, and iron < 2 g/dL. Conditions considered as clinical progression of HIV disease included a diagnosis of acquired immunodeficiency syndrome (AIDS), cancer, hepatic cirrhosis defined as a FIB-4 ≥ 3.25 [Kaplan–Meier estimators, univariate and multivariable Cox proportional hazards regression models were fitted to associate incidence of efficacy, convenience, safety and durability (interruption) events of DTG therapies with demographics , risk factors for HIV transmission , men who have sex with men (MSM), or other), cART status (naïve or experienced), CD4+ T-cell count, CD8 + T-cell count, CD4/CD8 ratio, HIV RNA at baseline, presence of hepatitis B infection or hepatitis C antibodies (HCVAb), cART backbone, eGFR, FIB-4 score , FramingAll analyses and data visualizations were performed in R statistical programming software using the following packages: survival , dagittyThere were 371 participants who initiated a DTG-based cART regimen in four centers of the MaSTER cohort during the time frame of the study. Median age was 53 years (IQR: 45–58). The majority of the study population were male (75.2%), of Italian nationality (83.3%), with a history of cART use (80.9%) and the majority of them initiated a DTG-based regimen after switching from previous regimens in 2019 (80.1%) .Among experienced people, prior cART regimens were mostly based on a combination of nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in addition to a boosted protease inhibitor (PI) (34.2%) followed by a combination of NRTIs plus a non nucleoside reverse transcriptase inhibitor (NNRTI) (23.5%) . Other pThe reported risk factors for HIV transmission were: heterosexual intercourse (44.2%), MSM intercourse (27.5%), and intravenous drug use (21.6%) .HBsAg chronic carriers and/or positive HCV Ab participants accounted for 4.3% of the population. A previous diagnosis of cancer was present in 33 participants (8.9%) .10 copies/mL (IQR: 1.7–2.09). Median CD4+ T-cell count at baseline was 640 cells/mm3 (IQR: 420–856), CD8 + T-cell count at baseline was 806 cells/mm3 (IQR: 572–1112), and CD4/CD8 ratio at baseline was 0.76 (IQR: 0.48–1.1) (10 copies/mL (IQR: 4.4–5.38) vs. 1.7 Log10 copies/mL (IQR: 1.7–1.7)) and lower values of CD4+ T-cell count (207 cells/mm3 (IQR: 54–463) vs. 700 cells/mm3 (IQR: 536–897)) and CD4/CD8 ratio (0.18 (IQR: 0.09–0.52) vs. 0.83 (IQR: 0.59–1.18)) at baseline (Median HIV RNA at baseline was 1.7 Log.48–1.1) . Naïve pbaseline .At baseline, median FIB-4 score was 1.08 (IQR: 0.74–1.55), median eGFR was 92.34 mL/min (IQR: 79.33–104.02), and median Framingham score was 12 (IQR: 10–15) .Regarding DTG performance in the study cohort, 81 efficacy events (25.2%), 107 convenience events (33.2%), 76 safety events (23.6%) and 58 durability events (18.0%) occurred. These events led to a DTG-containing regimen interruption or change (durability events) in 58 (15.6%) people overall, over a median follow-up of 556 days (IQR: 316.5–722.5). The most frequent reason for interruption was cART simplification, which accounted for 52%, followed by a 29.3% rate of interruption due to toxicity  and a 6.9% interruption due to virological failure. Participants lost to follow-up were only 2 (3.5%), and only 1 patient died during the study period .3; (v) previously cART naïve. In addition to the categories listed above, the Kaplan–Meier survival analysis showed lower performance of DTG-based regimens according to the metric of convenience  were significantly greater in the following participants: those receiving a backbone regimen containing emtricitabine plus tenofovir, cART naïve participants, those with higher HIV RNA, FIB4 at baseline above 3.25, and cancer. Lower hazards of interruption were observed among people with higher CD4+ T-cell count, higher CD4/CD8 ratio at baseline, switching from cART not containing an INSTI compared to naïve people and having an increased Framingham score at baseline .Using the multivariable model, significant higher hazards of interruption were maintained among individuals prescribed a backbone regimen containing emtricitabine plus tenofovir and with higher HIV RNA at baseline. Experienced participants prescribed cART regimens not containing an INSTI had lower hazards of interruption compared with cART naïve people for the metric of durability .The backbone regimen containing emtricitabine plus tenofovir was mainly interrupted due to simplification strategies as we observed in a competing risk analysis .3), reflecting that DTG-containing regimens were mainly prescribed (particularly in the year 2019) in order to optimize cART in those already responding to treatment.In this study, we prospectively evaluated the performance of DTG-based regimens in a multi-dimensional way, using the metrics of “efficacy”, “convenience”, “safety” and ‘’durability’’, in a nested study of the Italian MaSTER cohort. The population examined had a median age of 53 years and was mainly composed by PLWH experienced for cART, since naïve participants were only 19% of the overall population. The majority of participants had undetectable HIV RNA and a high CD4+ T-cell count (median of 640 cells/mmThe results of the study in terms of independent predictors of the outcomes for each of the study metrics are summarized in (a) the backbone regimen containing emtricitabine plus tenofovir. Regarding this finding, however, we did not directly compare the efficacy of the backbone regimens with each other and we are not able to fully explain our results. They most likely reflect the extensive use of tenofovir in cART combinations, expecially in naïve patients, therefore increasing the possibility of its statistical association with detectable viraemia; (b) the condition of being cART naïve, probably because of a “selection of the fittest” effect, because treatment experienced participants (mostly with undetectable HIV RNA) were those on stable treatment and therefore with consolidated adherence to cART. In addition, naïve participants with higher baseline HIV RNA ((c) having higher HIV RNA at baseline, as already found in a previous work of the MaSTER cohort [(d) FIB4 score > 3.25. Regarding this finding, the correlation between poor cART adherence and increased values of FIB4 score is known to grow in the eventuality of there being detectable viremia in people with liver fibrosis [(a) previous cART not containing an INSTI. This finding seems to confirm the appropriateness of switching to an INSTI-based regimen to simplify regimens containing alternative drugs without compromising the virological control in line with the conclusions by Raffi F. et al. [(b) higher CD4+ T-cell count and higher CD4/CD8 ratio at baseline, in line with the findings of a study nested in a cohort of South African PLWH in which lower baseline CD4+ T-cell count was associated with a greater propensity toward virological failure, underlining the importance of preserving the immune system even in people prescribed well tolerated and effective drugs [Concerning the metric of efficacy, our results suggest that potential risk factors for the occurrence of an efficacy event were:  HIV RNA  may needR cohort , pointinR cohort ; (d) FIBfibrosis . These f. et al. , who repve drugs .(a) the backbone regimen containing emtricitabine plus tenofovir, suggesting the importance of taking into consideration the potential toxicity of NRTIs in composing the backbone of the cART regimens. For example, the risk of renal and bone toxicity associated with the use of TDF is well known [(b) the condition of being cART naïve, probably, for the same reasons already mentioned for the metric of efficacy; (c) having higher HIV RNA at baseline, confirming the importance of maintaining HIV RNA control for prevention of the clinical events, even independently from the immunological status of the patient. For example, a previous study performed in the MaSTER cohort demonstrated how a longer delay from HIV diagnosis to HAART was an independent predictor of new AIDS-defining events and deaths. Thus, a longer time spent with lower HIV RNA plasma levels was found to be protective from clinical progression [(d) eGFR at baseline below 60 mL/min and FIB4 score > 3.25, reflecting the importance of care for PLWH with kidney failure and advanced liver disease, ensuring regular checkups and medical interventions to avoid an unfavorable outcome. In contrast, protective factors for occurrence of safety events were: (a) previous cART not containing an INSTI, in line with what already discussed for the metric of efficacy and the findings of a review by Raffi F. et al., in which switching to INSTI regimens, in virologically suppressed PLWH, was associated with improved tolerability and greater reported patient satisfaction and outcomes compared to other ARV drug classes [(b) higher CD4+ T-cell count and higher CD4/CD8 ratio at baseline, according to previous study showing the importance of having higher basal CD4+ T-cell count and a good CD4/CD8 ratio to avoid AIDS-defining events and deaths [(c) an increased Framingham score at baseline, probably supporting the overall safety profile of using INSTI in PLWH with high risk of cardiovascular adverse events. A decreased risk of cardiovascular disease with the use of INSTI containing regimens compared to other ARV drug classes is described in a retrospective study of a large cohort of PLWH [Concerning the metric of safety, we found as potential risk factors: ll known ,18; (b) gression ; (d) eGFd deaths ,20; (c)  of PLWH . By cont of PLWH . These pthe status of chronic HBsAg carrier at baseline was also found to be a risk factor for occurrence of a convenience event. It is well known that people with HIV and HBV co-infection with controlled plasma viral load still have an increased risk of liver disease progression, liver-related mortality, and overall mortality compared to people with either HIV or HBV alone [Since the metric of convenience constitutes a composite outcome of efficacy and safety, in general it shares the same risk and protective factors. However, BV alone ,24,25. MBV alone . In addiBV alone . Thus, cIn the present cohort, durability appeared to work in favor of DTG based regimens with 58/371 (15.6%) participants stopping the initial regimen, especially if one considers that changing any drugs in the regimen was considered as an outcome. Moreover, durability events were mostly due to cART simplification which explained half of the interruptions, followed by treatment modification or interruption due to drug regimen toxicity, occurring in 29.3% of interruptions; this is in line with the results of previous studies  and sugg(a) the backbone regimen containing tenofovir, mainly due to simplification strategies as shown in the KM estimates resulting from competitive risk analysis ((b) the condition of being cART naïve, in apparent accordance to the findings of a multicenter Italian cohort in which treatment in naïve people showed a lower probability of maintaining DTG containing regimens at three and five years compared to treatment-experienced PLWH [(c) having higher HIV RNA at baseline, confirming and supporting the findings already discussed about the metrics of efficacy, safety and convenience; (d) a FIB-4 at baseline above 3.25 compared to those whose FIB-4 was in the range from 1.45 to 3.25, confirming results of previous studies in which a positive association between liver fibrosis and suboptimal cART was observed [(e) a baseline cancer diagnosis was associated with higher hazards of interruptions of DTG-containing therapies. It may be that antiretroviral therapy was optimized to minimize drug interactions and chemotherapy-related toxicities. It is known that PLWH are at increased risk of cancer when compared to the general population, particularly for malignancies driven by viral and bacterial co-infections, although they also have excess risk of infection-unrelated malignancies [(a) previous cART not containing an INSTI and previous cART containing other prior cART regimens that were composed of single class, triple class, non-boosted PI regimens and combinations including both INSTI and PI in which previous INSTI exposure accounted for only 8.1% ((b) higher CD4+ T-cell count and CD4/CD8 ratio at baseline, confirming results observed for the metrics of efficacy, convenience and safety, and reflecting the importance of earlier diagnosis and cART introduction to restore or maintain a better immune status; (c) an increased Framingham score at baseline, probably indicating a good durability of DTG based regimens in participants with high cardiovascular risk, as we have already discussed for the metric of safety.When exploring potential risk factors associated with the metric of durability, we found that the following factors were associated with an increased risk of treatment interruption: analysis . We can ced PLWH . Since, observed  and encoobserved ,30; (e) gnancies ,32. Recegnancies . Despitegnancies , with INgnancies . In contnly 8.1% ; (b) higLastly, in this cohort, no statistically significant associations were observed between the outcomes analyzed and the demographic  or epidemiological  patient characteristics.This study is affected by several limitations. Firstly, for some parameters analyzed, there was a large confidence interval, due to fragmented data in the follow-up period; this was probably due to the COVID-19 pandemic which occurred concomitantly with enrollment and follow-up of participants, reducing the precision of our estimates. Secondly, since the study is not randomized, it is affected by the intrinsic limitations in any observational datasets, including possible confounding by indication biases. Third, although INSTI drugs, particularly DTG, showed better efficacy, safety and durability compared to PI drugs in improving lipid profiles ,36,37, wThis prospective “real-life” study showed that DTG-based regimens were started particularly in the year 2019 mainly as a switching therapy, and in experienced PLWH already responding to cART in terms of viral suppression. In this type of population, durability appeared to work in favor of DTG-based regimens that were maintained without any changes in 84.4% of participants, with only a low frequency of interruptions, mostly for reasons of cART simplification. Risk factors for interruption were: a backbone regimen containing tenofovir (driven mostly by simplification strategies), being cART naïve, a higher viral load at baseline, a high FIB4 score and having cancer. By contrast, greater CD4+ T-cell count and CD4/CD8 ratio at baseline appeared to be protective factors. Therefore, although uncontrolled, the present results confirm the apparent low risk of changing DTG-containing regimens due to virological failure and help physicians to identify people with an increased risk of interruption. Targeted medical interventions are important to further maximize performance of the regimens in terms of efficacy, convenience, safety and durability.