HIV management among older people living with HIV (PLWH) may be complicated by the presence of multiple comorbidities and polypharmacy. This study evaluated effectiveness and durability of modern 3-drug antiretroviral regimens among older PLWH.Using data from the Veterans Aging Cohort Study (VACS), PLWH ≥50 years old initiating a dolutegravir (DTG), bictegravir (BIC), elvitegravir (EVG), raltegravir (RAL), or darunavir (DRV)-based 3-drug regimen for the first time between January 1, 2014, and March 31, 2020 were followed from regimen initiation (baseline) until regimen discontinuation (d/c), death, loss to follow-up, or end of study . Suppression [viral load (VL)< 50 copies/mL], change in CD4 cell count, and regimen d/c were compared between regimens 6- and 12-months post-baseline using multivariable logistic or linear regression. Virologic failure  was evaluated over 12 months. For all outcomes, DTG-based regimens were compared to each other regimen. Outcomes were stratified by treatment experience (ART-naïve and ART-experienced).2,489 ART-naive  and 13,810 ART-experienced  individuals were included. Included PLWH were 97% male and 30% were ≥65 years old (Table 1). For both naive and experienced PLWH, those on DTG were more likely suppressed and had greater increases in CD4 counts at 6 and 12 months compared to those on DRV or RAL (Table 2). Odds of VF did not differ by regimen for ART-naive. For ART-experienced, DTG showed reduced likelihood of VF compared to DRV and RAL. Discontinuations within the first year were higher for RAL and DRV compared to DTG. For ART-experienced PLWH, 6-month d/c was greater for DTG vs. EVG. Regardless of treatment status, no other statistical differences in outcomes were observed between DTG-, BIC-, and EVG-based regimens.For both ART-naïve and ART-experienced PLWH >50 years old, treatment responses during the first 12 months of follow-up were similar for those taking DTG-, BIC-, and EVG-based regimens. DTG-based regimens demonstrated greater effectiveness and durability compared to DRV- or RAL-based regimens.Cassidy Henegar, PhD, MSPH, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: full-time employee Charles Hicks, MD, MD, ViiV Healthcare: I am a full time employee of ViiV Healthcare. Vani Vannappagari, MBBS, MPH, PhD, ViiV Healthcare: I am full time employee of ViiV Healthcare and receive GlaxoSmithKline stock as part of my compensation package|ViiV Healthcare: Stocks/Bonds.


P < 0.05 considered significant. Of the 12,093 patients on ART, 53 fully met our inclusion criteria. The median (IQR) age was 51 years (40 to 55 years), and the male/female ratio was 4/5. The median duration on integrase strand-transfer inhibitors (INSTI)-containing regimens was 18 months (12 to 32 months), and 15.09% (8/53) were exposed to RAL. The most administered 3L ART was TDF+3TC+DTG+DRV/r . Only 5.66% (3/53) had unsuppressed viremia (>1000 copies/mL). Resistance testing in proviral DNA was successful for 18/22 participants and revealed 1/18 patients  with archived mutations at major resistance positions (G140R and G163R). Five subtypes were identified, CRF02_AG (12/18), CRF22_01AE (3/18), A1 (1/18), G (1/18), and F2 (1/18). In Cameroon, 3L-experienced patients had a good virological response with a low level of archived mutations in the integrase. This finding underscored the use of DTG-containing ART for heavily treated patients in similar programmatic settings. However, patients with prior exposure to RAL should be closely monitored following a stratified or personalized approach to mitigate risks of INSTI-resistance, alongside pharmacovigilance.To ensure the long-term efficacy of dolutegravir (DTG), we evaluated the genotypic profile in viral reservoirs among patients on third-line (3L) antiretroviral therapy (ART) in Cameroon, according to prior exposure to raltegravir (RAL). A facility-based study was conducted from May through December 2021 among patients on 3L ART from HIV treatment centers in Yaoundé and Douala. Viral load was measured, and genotyping was performed on plasma RNA and proviral DNA. HIV-1 drug resistance mutations were interpreted using HIVdb.v9.1 and phylogeny analysis was performed using MEGA.v7, with IMPORTANCE We described the analysis of the genotypes of the population within third-line antiviral therapy in Cameroon, with a focus on defining the effects of prior raltegravir (RAL) treatment and resistance mutations for current dolutegravir (DTG) treatment. While supporting the current transition to DTG-containing ART in resource-limited settings toward the achievement of the UNAIDS’ goal of HIV elimination by 2030, our findings suggested that RAL-exposed patients may need a specific monitoring approach either in a stratified or personalized model of third-line ART to ensure the long-term success of DTG-containing regimens. Infection with the human immunodeficiency virus (HIV) requires a lifelong antiretroviral therapy (ART) –5, and t–6–10–15–18–With the increasing burden of pretreatment drug resistance above 10% (driven by NNRTI resistance) in several RLS, countries were encouraged to either initiate NNRTI-based ART guided by genotypic resistance testing (wherever applicable) or transition from NNRTI- to dolutegravir (DTG)-based first-line ART –35. More–27–37–39–Out of 12,093 patients receiving ART at the reference treatment centers , 53 (0.44%) patients fully met our inclusion criteria of being on a third-line ART regimen. The study population was composed of 54.71% (29/53) women. The median age was 51 years , and 58.49% (31/53) of the study population resided in the central region of Cameroon.3 (84 to 285 cells/mm3). The overall median duration of ART since treatment initiation was 192 months (162 to 222 months). Specifically, for third-line ART, the most administered regimen was TDF (tenofovir)+3TC (lamivudine)+DTG +DRV/r (ritonavir boosted darunavir) , followed by TDF+3TC+DTG . The median treatment duration under the INSTI-containing regimen was 18 months (12 to 32 months), with 15.09% (8/53) of the participants having a documented exposure to RAL. The median (IQR) viremia before initiation of third-line ART was 3,795 copies/mL  while the median CD4 count was 157 cells/mmAmong these patients on third-line ART, the overall rate of viral suppression (<1000 copies/mL) was 94.34% (50/53). Interestingly, the median (IQR) viremia was <40 copies/mL (00 to <40 copies/mL), indicating an optimal viral control in the study population. Specifically, 75.47% (40/53) of the participants had a controlled viremia (<40 copies/mL), and 24.53% (13/53) had a detectable viremia, further stratified into 18.86% (10/53) with detectable but suppressed viremia (40 to 999 copies/mL) and 5.66% (3/53) with unsuppressed viremia .(i) INSTI resistance in plasma RNA. Of the 13 patients on INSTI with detectable viral load , plasma RNA amplification and sequencing were effective on the three (03) with viremia ≥1000 copies/mL as per standard of care. These samples were from patients exposed to DTG at the moment of the study but without any history of exposure to RAL. Among these patients, no major mutation affecting INSTIs in plasma RNA was found, except an accessory mutation (L74I) detected in 2/3 (66.67%).(ii) INSTI resistance in proviral DNA. Of the 53 patients included in our study, amplification and sequencing of proviral DNA were effective in 18/22 (81.81%), of whom 44.44% (8/18) had documented exposure to RAL. Among unsuccessful amplified samples, three had plasma viremia <40 copies/mL and one had a plasma viremia of 76 copies/mL. Archived mutations were observed in 1/18 (5.56%) patients (in the RAL-exposed arm) at major drug resistance positions for RAL and EVG (G140R and G163R). Other accessory mutations  were found only in patients unexposed to RAL, as natural polymorphisms in the integrase coding region , CRF22_01AE (1/3), and the pure subtype A1 (1/3). In proviral-DNA, five HIV-1 subtypes were detected: the recombinant form CRF02_AG , followed by CRF22_01AE , and the pure subtypes A1 , G  and F2 , as shown in The current transition to a DTG-based ART is predicted to be very effective in rapidly controlling viral replication, which would limit the transmission of resistant viruses and, thus, lead to a control of the epidemic –35. To p–The described demographics feat with the local HIV epidemics, thus supporting the representativeness of our findings to the target population , 43–46. 43–44–3), suggesting an overall poor clinical condition for these patients, and reduced viral replicative fitness , most patients had a moderate viral replication (around 3 log copies/mL) and poor immunity  among RAL-unexposed third-line patients. It is worth noting that G140R – when found in the plasma – is associated with an intermediate-level of resistance to cabotegravir (CAB) and is a revertant mutation from the original G140S/A/C, which are nonpolymorphic mutations that usually occur with Q148 mutations. Alone, G140S/A/C has minimal effects on INSTI susceptibility. However, in combination with Q148 mutations, they are associated with high-level resistance to RAL and EVG and intermediate reductions in DTG and BIC susceptibilities. The appearance of G140R henceforth suggests that Q148 mutation(s) may have been previously selected at the population level under RAL pressure , 56, 57.58–Finally, the most represented viral clade in this study was the recombinant form CRF02_AG, similar to several reports in Cameroon –69. Of n–In conclusion, our evidence suggested a high efficacy of DTG-containing third-line ART in Cameroon, supporting the current WHO’s recommendations and the achievement of the UNAIDS’ goal of HIV elimination by 2030. The low level of archived mutations at integrase-resistance positions in a patient on dolutegravir, previously exposed to raltegravir, underscores the need for a specific monitoring approach for such patients, either in stratified or personalized monitoring model of third-line ART. In perspective, pharmacovigilance components would be complementary for assessing the long-term cost-effectiveness of this highly potent regimen.We conducted a prospective and facility-based study from May through December 2021 among HIV-infected patients followed up at the Douala General Hospital (HGD) and the Yaoundé Central Hospital (HCY). These accredited treatment centers were chosen because they have the largest cohorts of PLHIV in Cameroon. Any patient currently on third-line ART with documented exposure to INSTIs was considered for inclusion. Demographic and clinical information such as sex, age, ART, and duration of treatment was collected from patient records. Laboratory analyses within the frame of the study were performed at the Chantal Biya International Reference Centre for research on HIV/AIDS prevention and management (CIRCB) in Yaoundé, Cameroon.http://www.circb.cm/btc_circb/web/).The CIRCB is a government institution of the Ministry of Public Health dedicated to HIV research and patient monitoring in several aspects, among which HIV early infant diagnosis in the frame of the national PMTCT program; diagnosis of coinfections with HIV; viral load measurement; CD4 and CD8 T lymphocytes counts; biochemical and hematological tests for drug safety; genotypic HIVDR testing (GRT) at subsidized costs with quality control programs conducted in partnership with Quality Assessment and Standardization of Indicators (QASI) and other international agencies  according to the manufacturer's instructions . Briefly, a protocol using 0.6 mL of plasma was used for RNA extraction, followed by simultaneous amplification and detection on a real-time PCR (RT-PCR). The lower and upper detection limits of the test were <40 and >10,000,000 copies of HIV-1 RNA copies/mL, respectively.HIV-1 RNA quantification was performed on plasma samples using Abbott HIV-1 genotypic resistance testing (GRT) was performed on plasma (HIV-1 RNA) and Buffy coat  aliquots using a highly sensitive integrase genotyping assay . Brieflyhttp://www.hiv.lanl.gov); gaps were then removed from the final alignment. The phylogenetic tree was inferred using the maximum likelihood method on MEGA v7.0.26 software for subtyping and to ensure that there was no cross-contamination of samples. The statistical robustness and reliability of the branching order in the phylogenetic tree were confirmed by a bootstrap analysis using 1,000 replicates on a maximum likelihood tree obtained by molecular phylogeny. Regarding the analysis of drug resistance mutations (DRMs), sequences obtained after capillary electrophoresis on the 3500 Genetic Analyzer  were assembled and manually edited using RECall . DRMs were interpreted using the Stanford HIVdb version 9.0 algorithm (https://hivdb.stanford.edu/hivdb/by-sequences/) and all mutations associated with INSTI resistance were listed. Data were entered, coded, and analyzed using Epi info version 7. The parameters of central tendency (mean and median) and dispersion (standard deviation and interquartile range) were used to describe the continuous variables. The Chi-square test (or Fisher test wherever appropriate) was used to compare frequencies, with a significance level of P < 0.05.All generated sequences  were aligned in BioEdit version 7.2.6  and compared to reference sequences available in the Los Alamos database (OP508478 to OP508495.Integrase sequences generated from proviral DNA in this study are available in GenBank under the accession numbers


VR was similar in I-TLD versus T-TLD at <400 copies/mL (94.15% versus 94.42%) and age, gender, residence, ART-duration, and WHO stages were not associated with VR (p > 0.05). Genotyping was successful for 72.7% (8/11), with no major mutations to integrase inhibitors found. VR is optimal under first-line TLD after 14 months, even among TLE-exposed, thus confirming the effectiveness of transitioning from TLE to TLD in similar settings, supported by strong pharmacological potency and genetic barrier of dolutegravir.To ensure optimal prescribing practices in the dolutegravir-era in Cameroon, we compared first-line virological response (VR) under tenofovir + lamivudine + dolutegravir (TLD) according to prior exposure to tenofovir + lamivudine + efavirenz (TLE). A facility-based survey was conducted among patients initiating antiretroviral therapy (ART) with TLD (I-TLD) versus those transitioning from TLE to TLD (T-TLD). HIV viral load was performed and unsuppressed participants (VL > 1000 copies/mL) had genotyping performed by Sanger sequencing. Of the 12,093 patients followed, 310  complied with study criteria (171 I-TLD vs. 139 T-TLD). The median ART-duration was 14 (12–17) months among I-TLDs versus 28 (24.5–31) months among T-TLDs (15 (11–19) on TLE and 14 (9–15) on TLD), and 83.15% (148/178) were at WHO clinical stages I/II. The viral suppression rate (<1000 copies/mL) was 96.45%, with 97.08% among I-TLDs versus 95.68% among T-TLDs ( In the frame of HIV treatment, the five main goals of antiretroviral therapy (ART) are (i) maximal and durable control of the viral replication, (ii) prevention of HIV transmission, (iii) restoration of immunological function, (iv) reduction of HIV-related mortality, and (v) increased duration and quality of life for people living with HIV . RegardiA facility-based survey was conducted from June through November 2021 among first-line patients living with HIV (PLWH) initiating ART directly with TLD versus those transitioning from TLE to TLD, all followed at the daycare Hospital of the Yaoundé Central Hospital (YCH) and the Douala General Hospital (DGH), the two main hospitals of the capital cities of Cameroon. Laboratory analyses within the frame of the study were performed at the Chantal Biya International Reference Centre for research on HIV/AIDS prevention and management (CIRCB) in Yaoundé, Cameroon. The CIRCB is a government institution of the Ministry of Public Health dedicated to HIV research and patient monitoring in several aspects. Among these aspects are (a) HIV early infant diagnosis in the frame of the national PMTCT program, (b) diagnosis of coinfections with HIV, (c) viral load measurement, (d) CD4 and CD8 T lymphocytes counts, (e) biochemical and hematological tests for drug safety, and (f) genotypic HIVDR testing (GRT) at subsidized costs, with quality-control programs conducted in partnership with the Quality Assessment and Standardization of Indicators (QASI) and other international agencies .Eligible participants were HIV-1 infected patients currently under TLD first-line ART, having been on treatment for at least six months and who consented to participate in the study. Through an exhaustive sampling strategy, two groups of patients were recruited: (i) those initiating ART directly with TLD (I-TLD), and (ii) those transitioning from TLE or TLN to TLD (T-TLD). WHO clinical stages were those reported in patients’ medical reports at treatment initiation. Participants excluded were PLWH with a nondetailed treatment history and those who had received prior ART other than TLE or TDF + 3TC + NVP (TLN). Children and adolescents (≤18 years) were not considered for inclusion in this study as per national guidelines .® m2000rt HIV platform  according to manufacturer’s instructions [Plasma viral load (PVL) at the CIRCB was performed by using the Abbottructions . BrieflyHIV-1 genotypic resistance testing (GRT) was performed on both HIV-1 plasma RNA and proviral DNA following an in-house integrase genotyping assay as described and published elsewhere . BrieflyRegarding the analysis of drug-resistance mutations (DRMs), sequences obtained after capillary electrophoresis on the 3500 Genetic Analyzer  were assembled and manually edited by using RECall . They were then analyzed for interpreting DRMs by using Stanford HIVdb v9. All variants at amino acid positions associated with a decreased INSTI susceptibility  were considered as resistant variants. Samples with resistant mutant or mixture of wild type and mutant at an amino acid position were considered resistant.For subtyping, sequences were aligned in BioEdit version 7.2.6  by using CLUSTAL W, and compared with reference sequences for the major HIV-1 subtypes and circulating recombinant forms (CRFs), available in the Los Alamos database ; gaps wep-values < 0.05 considered statistically significant; logistic regression was used for multivariate multivariable analyses for variables showing a p-values ≤ 0.2 from bivariable analyses.Data were analyzed by using Excel 2016, Epi-info v7. Chi square or Fisher’s exact test was used to describe the associations between variables wherever appropriate, with Out of 12,093 patients receiving ART at the reference treatment centres (YCH and DGH), 310 had been on a DTG-based first-line ART for at least six months. The participants had a median (IQR) age of 41 (34–49) years. The most represented age group included those of 35–44 years of age (34.19%), followed by those 25–34 years of age (21.29%), those 45–54 years of age (20.32%), those 55–64 years of age (10.65%), those 15–24 years of age (4.52%), those 65–74 years of age (2.26%), and finally those 75–85 years of age (0.32%). There was a nearly equal distribution of male and female participants  in the study population and the majority of participants (about 2/3) lived in Yaoundé. Only 178/310 (57.4%) of participants had data on WHO clinical stage at treatment initiation, and the majority of them were in clinical stages I and II , as shown in The overall median ART duration on a first-line regimen was 19 (13–27) months . Regardip = 0.55) between I-TLD vs. T-TLD, as shown in The overall rate of viral suppression (PVL < 1000 copies/mL) after approximately 14 months was 96.45% (299/310), without any significant disparity , HIV-1 integrase genotyping was successful for 72.7% (8/11) of the study participants. Two viral strains were identified, 87.5% CRF02_AG (7/8) and 12.5% F2 (1/8). No major mutations to integrase inhibitors were found.In view of achieving UNAIDS’ target by 2030, 85% of all people living with HIV worldwide knew their status; 88% had access to ART and 92% achieved viral suppression in 2021 ,32. In CParticipants in this study were aged 41 years on average, with nearly equal distribution of male and female participants, which is in line with the national HIV epidemiology , even thRegarding virological response to first-line TLD, very high rates of viral suppression (>95%) were observed in real-life clinical settings after 14 months of TLD uptake, even with prior exposure to TLE. It is important to note that for homogeneity in the trend of data and for an optimal clinical relevance, data on viral load have been harmonized to showcase the rate of detectable VL before transition, which dropped down to 5.04% (at the threshold of >400 copies/mL) after 14 months of transitioning to TLD; this is in line with recent findings on TLD effectiveness worldwide ,45,46,47Moreover, no integrase resistance-associated mutations among virologically unsuppressed patients were reported when using a highly sensitive integrase-genotyping protocol that was validated locally . The absAlthough these findings are overall very encouraging, there is a need to continue monitoring the emergence of DRMs in this population, taking into consideration the suboptimal viral load coverage and risk of drug stock outs in RLS ,49,53,57The limited amount of data on the WHO clinical stages at treatment initiation might have led to some information bias. Nonetheless, the very high rates of clinical stages groups 1 and 2 suggest that this variable might not change even with full data coverage. Furthermore, as per national guidelines, viral load and NRTI resistance were not performed at treatment initiation, which could have helped to mitigate potential effects of baseline viremia and/or preexisting drug resistance mutations on the current TLD efficacy in both groups. This study was conducted during the COVID-19 pandemic, leading to some cases of exclusion due to limited clinic attendance for ART monitoring; however, the sample population was statistically sufficient for assessing the study primary outcomes.In a nutshell, viral suppression is very high under first-line treatment after approximately 14 months following TLD initiation, even among patients with prior exposure to TLE in Cameroon. Our finding suggests that previous exposure to TLE is seemingly not a counterindication for transitioning from TLE to TLD as a public health approach in RLS. Interestingly, no independent factor was found to be associated with these high rates of virological control, suggesting that this observation is exclusively related to the strong pharmacological potency of dolutegravir (DTG). The current transition plan from TLE to TLD in similar African settings should therefore be encouraged, pending long-term ART monitoring for efficacy and drug-resistance surveillance, as well as safety monitoring through pharmacovigilance.


Information on treatment failure (TF) in People living with HIV in a data-poor setting is necessary to counter the epidemic of TF with first-line combined antiretroviral therapies (cART) in sub-Saharan Africa (SSA). In this study, we examined the risk factors associated with TF in Asmara, Eritrea from 2001 to 2020.P-values were 2-sided and the level of significance was set at P < 0.05 for all analyses.A multicenter, retrospective 1:2 matched (by age and gender) case–control study was conducted in four major hospitals in Asmara, Eritrea on adults aged ≥ 18 years who were on treatment for at least 6 months. Cases were patients who fulfills at least one of the WHO therapy failure criterion during the study period. Controls were randomly selected patients on first-line treatment and plasma viral load < 1000 copies/ml in their latest follow-up measurement. Multivariable logistic regression analysis was conducted to identify risk factors for TF. All Of the 1068 participants , 585 (54.7%) were females. The median age at treatment initiation was 46 years [interquartile range (IQR): 39–51]. Median time to combined antiretroviral therapy (cART) failure was 37 months (IQR = 24–47). In the multivariate analysis, factors associated with increased likelihood of TF included initial nucleoside reverse transcriptase inhibitors (NRTI) backbone (Zidovudine + Lamivudine (AZT + 3TC): adjusted odds ratio (aOR) = 2.70, 95% Confidence interval (CI): 1.65–4.41, P-value < 0.001), (Abacavir + lamivudine (ABC + 3TC): aOR = 4.73, 95%CI: 1.18–18.92, P-value = 0.028], and (Stavudine + Lamivudine (D4T + 3TC): aOR = 5.00; 95% CI: 3.03–8.20, P-value < 0.001) in comparison to Emtricitabine and Tenofovir diproxil fumarate (FTC + TDF). Additional associations included prior exposure to cART , record of sub-optimal drug adherence , ambulatory/bedridden at presentation , presence of comorbidities , duration of cART , and use of SMX-TMP prophylaxis .Our findings underscore the importance of optimizing cART adherence, diversification of cART regimens, and interventions directed at enhancing early HIV diagnosis, prompt initiations of treatment, and improved patient-focused monitoring of treatment response. The lack of data regarding the magnitude and possible risk factors for TF in Eritrea makes it difficult to formulate evidence-based improvements in patient management. This study has identified important determinants of therapy failure in Asmara, Eritrea.By undertaking an inquiry into the sociodemographic and clinical risk factors associated with TF, we believe that we have gathered useful information that can be used by clinicians to identify patients who are at a higher risk of TF.Importantly, conflicting findings have also been reported regarding immunologic recovery after cART initiation, particularly the long-term impact of age (note that patients in this setting are relatively old). Therefore, we examined changes in CD4 recovery between cases and controls.Why carry out this study?The study revealed important clinical risk factors for cART therapy failure.The study indicates that treatment response is a multifactorial outcome and control of this epidemic calls for a multifaceted approach involving multiple sectors of the healthcare system in Eritrea. Reduction in late presentation of patients/early diagnosis, prompt treatment initiation, and targeted monitoring and enhancement of adherence.In addition, the need for research on determinants of sub-optimal adherence was implied.What was learned from this study? Howeverth gains .For context, modeling studies predicted that drug resistance mutations (DRMs) to non-nucleoside reverse transcriptase inhibitors (NNRTI) ˃ 10%, could account for 105,000 and 135,000 excess HIV infections and deaths in SSA between 2016 and 2020 , 8.Overall, data regarding the determinants of virologic failure have implicated a combination of factors. These include patient-related factors ; viral factors ; and drug-related factors , inappropriate cART regimen; Drug-drug interactions with non-ARVs, among others) , 10. In Although access to data on virologic failure from SSA has improved in recent years; information from a a large number of countries is missing. More importantly, program-level differences, such as site-level processes or cultural differences and variations in policies and implementation priorities; limits extrapolation of data to other settings. Eritrea, for instance, is regarded as one of the success stories in SSA when it comes to HIV/AIDS prevention—current estimates suggest that the prevalence of HIV is approximately 0.7% . HoweverA retrospective case–control study was carried out to identify the factors associated with virologic failure among adults on first-line antiretroviral therapy. The study was conducted in four major hospitals ; Halibet National Referral hospital (HRH); Sembel hospital (SH); and Haz Haz Zonal Referral Hospital (HzH) located in Asmara, the capital city of Eritrea. A total of 6548 patients  have accessed treatment since 2001. See Fig. Adult patients (≥ 18 years of age) who received first-line cART treatment for a period of more than 6 months at one of the four major hospitals in the study period (2001–2020) were eligible for recruitment. Participants with incomplete records were excluded from the analysis. Cases were patients who fulfills at least one of the WHO therapy failure criterion during the study period. Controls were those who doesn’t fulfill any of the WHO therapy failure criterion during the study period. For each case, two matched randomly selected controls were enrolled based on the plasma viral load.We extracted all records from the registry from the year 2001 to 2020. A total of 356 patients from the four hospitals  with confirmed treatment failure to first-line regimens met the inclusion criteria. Each case was then matched by lottery method with two controls of similar gender and age (± 5-year range) at treatment initiation. Ultimately 248, 192, 144, and 128 HIV-positive patients on first-line treatment with no history of treatment failure were included as controls from each hospital respectively . Double data entry was employed using CSPro 7 for quality control.+ cell count, WHO clinical stage, Initial cART backbone, and baseline functional status. Variables including TB status, cART changes, cotrimoxazole prophylaxis (CPT), comorbid conditions, weight shift (enrollment weight from the current weight), low-level viremia, persistent viremia, previous hospitalizations, and their adherence were also explored as independent predictors of TF.The primary outcome of this study was to determine the factors associated with TF. Moreover, we attempted to describe the patient’s demographic characteristics , and baseline characteristics  after 6 months of effective treatment.+ levels < 200 cells/mm3 despite treatment for 6 months.Immunologic TF: persistent CD4Virologic TF: plasma VL > 1000 copies/ml based on two consecutive VL measurements (after 3 months) with adherence counseling between measurements.3.Adherence was assessed at each follow-up visit as good, fair, and poor if a patient missed < 5%, ≥ 5% and < 10%, and ≥ 10% doses respectively of the expected monthly doses based on pill count.Suboptimal adherence comprises any patient with at least one record of fair or poor adherence.The following definitions were used:+ cell count recovery rate was calculated using the median rate of increase from treatment initiation to 6 months, 6–12 months; 12–24 months, and 24–36 months of treatment. A nonparametric test (Mann–Whitney U test) was used to compare CD4+ cell counts as well as CD4+ recovery rates between cases and controls in the specified periods. Multivariate logistic regression  analysis was subsequently undertaken—only variables with a P-value of ≤ 0.25 in the bivariate analysis were included in the model. The potential for collinearity was minimized by not including pairs of variables with a Spearman r > 0.60 in the same model. Results are presented as crude odds ratios (cOR) and aOR with 95% CIs. A P-value < 0.05 was considered as significant.All analyses were conducted using SPSS version 26 for windows . Where appropriate, demographic and HIV-related characteristics of patients were summarized using percentages, medians [± (IQR)], or mean ± standard deviation (SD). Descriptive analyses were stratified by therapy outcome in all key variables at baseline using Pearson’s Chi-square test or Fisher’s exact test, and the Mann–Whitney U test for continuous data. Normality tests were performed before running any statistical computations. CD4+ cell count of 170 cells/µl (IQR = 84.5–275)  vs females: 187 cells/µl (103–297) and advanced HIV (CD4+ cell count < 200 cells/ul) was present in 621 (58.1%). The frequency of late presentation (LP) was 919 (87.0%). In the period before 2005, 2005–2010, 2010–2014, and 2014–2020, the frequencies were 82 (91.1%), 453 (92.6%), 281 (85.4%), and 103 (69.6%), respectively. Among the LPs, 303 (28.3%) presented very late , and 621 (58.1%) presented extremely late  for HIV care.Among the 1068 participants (356 cases and 712 controls), females account for 45.2% and median age at enrollment was 46 years (IQR: 39–51 years) ranging from 18 to 86 years. Males were older at enrollment than females (39 years [IQR: 33–43] vs 32 years [IQR: 27–37]), P-value < 0.001. VCT was a commoner mode of entry into HIV care for controls than cases  (TableMedian duration on first line regimen was 44 months (IQR: 20–76 months). The most frequently used first-line cART backbones were: d4T + 3TC in 425 (39.8%) followed by; AZT-3TC, 374 (35%) and TDF + FTC, 239 (22.4%). Others were TDF + 3TC, 17 (1.6%) and ABC + 3TC, 13 (1.2%). Majority of the cases were initially placed on d4T + 3TC (49%) and most of the controls were started on AZT + 3TC (36.7%), P < 0.001. Among the controls, 124 (11.9%) had viremia  and drug stock-outs, 280 (25.6%). The median interval between HIV diagnosis and cART initiation was 3 months IQR: 1–9) before 2005. Between 2005 and 2010 it was 2 months (IQR: 0.00–14), and it was 5 months (IQR: 0.00–45.5) between 2010 and 2016. As of 2016 though, the time to initiation is 1 month (IQR: 0.00–53). Regarding opportunistic infections and events among the study participants the most frequent was weight loss (n = 138), followed by recurrent pneumonia (n = 103), chronic cough (n = 95), oral/vaginal thrush (n = 56), herpes zoster (n = 53), chronic fever (n = 50) and others (n = 94). Among the study participants, 9.3% were treated with anti-TB during their follow-up while 73.2% and 50% of the participants had received Isoniazid and Cotrimoxazole prophylaxis respectively. See Fig. –9 before+ cell having lesser odds of failure than higher CD4+, see Table Multivariable logistic regression analysis was undertaken to identify the predictors of TF. In this analysis, a higher odd of TF was associated with use of specific NRTI as backbones    with TDF + FTC as reference. Other factors included prior exposure to ART ; record of sub-optimal adherence ; ambulatory/bedridden status at presentation ; presence of comorbidities ; duration on cART ; use of SMX/TMP prophylaxis . Last but not least, baseline immune-status (CD4 + cell count) was also a predictor of TF, with those lower CD4The median CD4 + cell count at baseline was significantly lower for cases than controls  vs , P < 0.001 (Mann Whitney–U test). After 6 months of treatment, both cases and controls showed similar median CD4 + cell count, cases showed a marked response to 258 cells/ µl (IQR = 148.0–367.0) almost catching up to that of controls which amounted to 264 cells/µl (IQR = 150.3–375.5), P = 0.787. However, after a year of treatment the median CD4 + cell count among cases declined to 255 cells/ µl (IQR = 148.5–369.5) while it increased to 290.5 cells/µl (IQR = 187.00–406.25) among controls (P = 0.012). Moreover; two years following treatment with cART the difference became even more pronounced, with the median count for cases only increasing to 276.0 cells/µl (IQR = 179.8–445.0). In contrast, median CD4 + cell count for controls showed marked recovery increasing to 337 cells/µl (IQR = 220.0–480.3) (P = 0.001). In the exact same manner, 3 years following treatment a similar pattern in immune response to treatment was observed, cases had a median count of 287.0 cells/µl (IQR = 186.5- 425.0) whereas controls had around 379.0 cells/µL (IQR = 259.0–515.5), with a P value < 0.001. . These findings align with previous studies which suggested that DRMs to TDF are limited  and thatMultiple explanations can be invoked to explain why TDF + EFV-based cART is less associated with TF. First, adverse effects  associated with AZT, ABC, and D4T may potentially compromise treatment or account for differences in adherence rates. Importantly, a study in Kenya demonstrated that TDF had a lower drug change rate (1.9 per 100 person-years) compared to D4T (27 per 100 person-years) —the chanHowever, indirect evidence of the potential role of DRMs was noted in this study. First, large proportions of patients (77.4%) were on 3TC-based regimens and suboptimal response to treatment in patients who were switched to 3TC-based regimens was also noted, this is in line with some literature . More imSimilar to other studies in the region , 27, we By most accounts, the problem of poor adherence to cART in treatment programs in SSA is formidable. However, success has been demonstrated for mitigation efforts that prioritize the integration of adherence interventions as part of routine clinical care. In the United States, cART adherence is discussed at every visit, and patients triaged as poor adherers are promptly referred for counseling or enhanced adherence intervention or support . Alterna+ cell count (baseline CD4+ cell count of < 50 and ≤ 100 cells/ µl) were associated with increased odds of TF. Comparable results have been reported in Ethiopia  is one of the biggest problems facing HIV treatment programs in Asmara, Eritrea. Admittedly, problems related to study design may undermine the accuracy of the late presentation estimates. Either way, we believe that our estimates are largely reliable. Apart from CD4+ cell count, surrogate pointers to the late presentation as a major problem in this setting can be gleaned from several associations in the bivariate analysis. These include the proportion of patients with WHO Stage III and IV disease at baseline, baseline functional status, comorbidities, and the inverse relationship between time of HIV diagnosis and initiation of cART. Predictably, some of these factors emerged as predictors of TF in the multivariable model. Overall, we can conclude that the observed gap between HIV diagnosis and treatment for some patients requires particular scrutiny since it can compound the problem of late presentation.Further, we demonstrated that low CD4Ethiopia , 34–36, Ethiopia , among o+ cell count ≤ 200 cells/μl and/or WHO clinical stage III and IV). There is strong evidence from the region indicating that intervention models mandating weekly or bi-weekly contact with care sites can work. These models are generally credited with early identification and treatment of opportunistic infections (OIs) and reductions in morbidity and mortality.Previous studies have shown that late entry to care is harmful in multiple ways—worse prognosis, shorter survival, and less benefit from cART , 39. Doc+ cell count at specified intervals. In the process, we noted some outstanding points. Immunological recovery (> 500 cells/mm3) was generally poor in a majority of patients (cases: 14% vs Control: 28%), who achieved it after 36 months of treatment. This was contrary to the conclusions in a recent review which noted that achievement of sustained virologic suppression with cART is typically associated with a steady increase in peripheral blood CD4+ cell count recovery (> 500 cells/ µl) [+ cell count (< 200 cells/ µl) will plateau at a CD4+ cell count below the immunological recovery threshold. Our results are generally in line with the latter conclusion. More importantly, we also demonstrated that the rate of CD4+ cells/ µl /month increase differed significantly between cases and controls—a finding that is by no means unique [+ cells/ µl /month was substantially less than what is recommended by some investigators/or guidelines. We can infer based on these results that poor recovery of the immune system remaisn a problem in patients on cART in Asmara. Therefore, to improve outcomes and avoid or delay hard clinical endpoints, these patients should be placed under enhanced monitoring. This conclusion is supported by studies which have suggested that  CD4+ cell count gains < 100 cells/μl/year can be used to identify patients at risk of hard endpoints such as AIDS, serious non-AIDS events, and death [To further understand the relationship between treatment and immunological response. We considered it important to evaluate the kinetics of CD4lls/ µl) . They als unique . In all,nd death .Finally, we have to note that our model suggests that Cotrimoxazole prophylaxis (CPT) was a predictor of virologic failure. Relatable finding was previosly reported in a study conducted in Ethiopia . AccordiTo the best of our knowledge, our study is the first to evaluate the factors associated with virologic failure in Eritrea. Regardless, it has several limitations. First, the study uses secondary data collected retrospectively. This approach has been associated with the incompleteness of clinical data. Moreover, underreporting/missing data elements can lead to biases—particularly if they are systemic. Secondly, the contribution of HIV drug resistance to TF was not assessed. Lastly, adherence information was largely based on self-report. However, recall and social desirability bias may undermine the reliability of this approach. Despite these limitations, we would like to highlight some strengths: first, information on a large number of variables including demographic information; care entry point; prior exposure to cART; date of HIV diagnosis; date of cART initiation and subsequent treatment history; and clinical outcomes were collected. The availability of this information permitted an in-depth analysis of multiple secondary objectives. Second, the sample size was fairly large for multiple variables thereby strengthening the robustness of our results.This multi-center analysis demonstrates that the HIV/AIDS treatment program in Asmara, Eritrea requires optimization in multiple domains. Unlike other countries in the region, patients in this setting are older. At baseline, the majority of the participants presented with advanced HIV, thereby making late presentation a major problem with important individual and public health consequences. Further, it can be asserted that although viral suppression was achieved in a significant number of cases, immunological recovery was poor. Multivariate analysis demonstrated that multiple modifiable risk factors were associated with an increased likelihood of TF. Looking into the future, we believe that there is a need for additional resources and efforts targeted at the optimization of cART adherence, diversification of cART regimens, and interventions directed at enhancing early HIV diagnosis and prompt initiations of treatment. Robust evaluation and monitoring in the first years following treatment initiation will be paramount to detecting poor treatment response and subsequent action, including surveillance of DRMs are needed.


Highly active antiretroviral therapy (HAART) is currently a combination of three (less frequently four) antiretroviral drugs; these target pathways involved in various stages of HIV replication in the body. Treatment failure is a problem facing doctors and patients using HAART. The most common cause of therapeutic failure is the development of HIV drug resistance. The emergence of resistance is associated with processes involving mutation occurring in the viral genome under the influence of evolutionary factors. Sequencing reactions were performed using the AmpliSens HIV Resist-Seq. Assembly of consensus sequences from fragments obtained during sequencing was carried out using Unipro UGENE softwar. Isolate genotyping was performed using the MEGA-X software with the Neighbor-joining algorithm. According to the analysis, 72.05% of patients had at least one significant mutation associated with drug resistance for the corresponding viral subtype. HIV-1 A6 remains the predominant HIV-1 genetic variant in Russia’s Northwestern Federal District. Among samples with drug resistance mutations, in all cases, mutations associated with pharmacological resistance to two or three drug groups were found. Given the high incidence of resistance mutations in patients on ineffective ART, surveillance of HIV-1 drug resistance, in both ART-receiving and ART-naive individuals, appears necessary. A lack of vigilance and control measures may lead to the spread of primary ART-resistant HIV strains. The human immunodeficiency virus (HIV) is a retrovirus of the genus lentivirus that causes a slowly progressive disease upon infection . Poorly 9 to 1010 new viral particles are formed daily, while the mutation rate is from 10−5 to 10−3 errors/bp/cycle [The genetic diversity of HIV is a direct consequence of features of its rapid replication cycle. In the body of an infected individual, from 10bp/cycle .Together, the processes of mutation and recombination in HIV evolution have led to the diversity currently seen. HIV-1 features three groups, designated as M, N, and O. Group M includes most of the common variants of the virus; the other two contain only a small number of strains ,4. BasedIn terms of global HIV infections, subtype C (predominant in Asia and southern Africa) is the leader 47.2%), while in developed countries, subtype B is the most common (12.3%). The regional HIV epidemic  was caused by a subtype A variant, which continues to dominate in those territories ,6. With .2%, whilHighly active antiretroviral therapy (HAART) is currently a combination of three (less frequently four) antiretroviral drugs; these target pathways involved in various stages of HIV replication in the body . TreatmeHAART has been in use for many years, and an ever-increasing number of patients are receiving it. As such, the emergence of transmissible drug resistance (DR) among HIV-infected individuals was a known, even expected, threat. Indeed, this outcome has already been seen in some countries . To asseTo date, 25 antiretroviral drugs have been registered in Russia, which makes it possible to draw up more than 100 HAART regimens. These include two fusion inhibitors, eight nucleoside reverse transcriptase inhibitors, four non-nucleoside reverse transcriptase inhibitors, nine protease inhibitors, and two integrase inhibitors. According to the latest guidelines, TDF + 3TC + DTG and TDF + FTC + DTG are the preferred ART regimens, but EFV and two NRTI regimens remain the most common.The local HIV epidemic began in the Soviet Union in the 1980s and is now rapidly developing in Russia. In the first half of 2020, 38,126 individuals with antibodies to HIV-1 were newly identified in Russia. By the end of the first half of 2020, 1,094,050 Russians with laboratory-diagnosed HIV infection were known to be living in the country [In Russia, the dominant viral subtype is A6. In some publications, this subtype is referred to as: ‘IDU-A’, from the words ‘injecting drug users’, or ‘A-FSU’, from the words ‘former Soviet Union’ countries. Previously, this sub-subtype was classified as A1. However, due to significant differences between it and other HIV-1 subtype A1 variants in terms of structure and distribution, it was recategorized into a separate, relatively homogeneous group ,13. The The study was approved by the Ethics Committee of the Saint Petersburg Pasteur Institute. It included analysis of HIV isolates obtained from 643 patients who contacted the Northwestern Federal District AIDS Center for diagnostic clarification of drug resistance status in the period 2014–2018. The inclusion criteria were as follows: those over 18 years of age, viral load above 1000 copies/mL, and no interruption in ART. The exclusion criteria were as follows: age less than 18 years, viral load below 1000 copies/mL, and interruption in ART (or no ART).® HIV-Monitor-FRT commercial kit , with a sensitivity threshold of 500 copies/mL. Samples with a detectable viral load (VL) were analyzed using RT-PCR and Sanger sequencing. For reverse transcription and amplification of HIV RNA, the RT-PCR-kit-Pro/Rev and PCR-kit-Pro/Rev commercial kits  were used. Sequencing reactions were performed using the AmpliSens® HIVResist-Seq kit  according to manufacturer instructions, as described earlier [Quantitative analysis of HIV RNA was carried out with the AmpliSens earlier . SequencAssembly of consensus sequences from fragments obtained during sequencing was carried out using Unipro UGENE software ,16,17. TOf the 638 patients, more than half (62.54%) were male. The study group was dominated by the age category 18–34 years old (55.64%); the median age was 36 years. The ART regimen typically included two nucleoside reverse transcriptase inhibitors (NRTIs) plus one non-nucleoside reverse transcriptase inhibitor (NNRTI) (84.22%). Schemes with PI in the composition were much less common (15.78%). The most common schemes were TDF + 3TC + EFV and ABC + 3TC + EFV.In 533 patients, an HIV-1 viral load greater than 1000 copies/mL was detected, which made it possible to obtain viral genome sequences encoding protease and reverse transcriptase. Some of the obtained and analyzed nucleotide sequences of the HIV-1 pol gene region were deposited in the international GenBank database under the numbers: MK510016-MK510079, MN317576-MN317587, OL505461-OL505538, ON367567-ON367728, and ON653444-ON653592.Two typing methods, phylogenetic analysis  and sequAccording to the analysis, 72.05% of patients had at least one significant mutation associated with drug resistance for the corresponding viral subtype. In total, we encountered 140 different drug resistance mutations . The most common mutations in patients are presented in In the vast majority of studied isolates (60.98%), DR mutations (DRM) for NRTI + NNRTI drugs were encountered. In 3.94% of cases, multiple drug resistance (MDR) to three classes of drugs were found together .Analysis of stable mutation combinations in the studied isolates showed thymidine analogue resistance mutation (TAM) patterns: TAM-1 (3.94% CI 2.46–5.96%) and TAM-2 (2.44% CI 1.30–4.13%). A stable non-TAM mutation combination was also seen: L74V + Y115F (8.82% CI 6.55–11.55%). In addition, stable combinations of mutations associated with DR to NNRTIs were identified: K101E + G190S (17.82% CI 14.67–21.34%), K103N (18.20% CI 15.01–21.74%), and K103N + V108I (8.26% CI 6.06–10.92%).The HIV-1 genetic diversity in the examined group matches known features of the situation in the Russian Federation: an absolute predominance of sub-subtype A6 (72%) . It is iGenotyping is extremely important for testing of a sample for the presence of ARV-resistant HIV variants since viral genetic variants can differ in their biological properties, in the rate of viral evolution, and in disease progression, as well as in the contributions of various mutations to the formation of ART resistance. In this regard, additional studies are needed to assess the contribution of recombinant forms to the viral genetic diversity in the region. Insufficient attention to the high diversity of HIV recombinants, and a lack of complete data on common recombination points, can lead to an erroneous determination of the presence or absence of DR in the virus .In addition, in a single case, a complex recombinant between CRF_03AB and the A1 subtype was encountered; our recombination analysis for it was carried out using the pol gene. The incidence of DR mutations in patients with virological failure of ART was extremely high. At the same time, mutations to reverse transcriptase inhibitors were most often found. Mutations associated with resistance to protease inhibitors were found in only eight cases (6%). This may be due to a higher genetic barrier to resistance with PIs, or their less frequent use in treatment regimens of the patients examined ,22.In comparison with 2012 data for St. Petersburg, the frequency of HIV DR mutations more than doubled from 30% to 72.05% . At the Despite the increase in DRM prevalence, the ranking structure of mutations remained similar. The first place, in terms of occurrence, is still occupied by M184V (66.98%). In the second and third places were the G190S (30.96%) and K103N 23.08%) mutations. They are associated with simultaneous DR to several non-nucleoside reverse transcriptase inhibitors. A similar situation was observed in a 2012 study .08% muta,25,26.A dependence of substitution at position 190, featuring alanine (A) or serine (S), on the viral subtype was also revealed. The 190A substitution occurred only in strains of non-A subtypes, while the 190S mutation occurred mainly in strains of the A6 subtype. The literature also describes the prevalence of substitution at position 190 of reverse transcriptase with serine for subtype A  and alanMutations that are present in the viral genome at the moment of infection persist longer than those that arise during treatment. The duration of mutation persistence, to a certain extent, depends on its degree of influence on the replicative ability of the virus. For example, the M184V mutation reduces viral replication and is usually undetectable 5–20 weeks after HAART is discontinued. The K103N mutation can be detected 9–12 months after discontinuation of therapy or even later .Combinations of mutations associated with resistance to thymidine analogs (TAM) described in detail in the literature were found in the obtained profiles in isolated cases, while patterns along the TAM-1 and TAM-2 trajectories were encountered with the same frequency. It is interesting to note that both patterns are associated with the T215Y mutation, yet it is known that patterns following the TAM-2 trajectory (with T215F) have an advantage . SubstitAmong PI drug resistance mutations, the major mutation M46I/L was seen in all cases, and the minor mutation L89T was seen in three cases. In addition, two mutations were identified in the tenth position of the protease region. One of them, L10LF, was identified in a single case; it is a minor PI resistance mutation. The other, L10I, was found in 40 cases (7.5%); it increases replication in viruses with other PI resistance mutations .When analyzing the results of the study, it is also necessary to take into account the fact that standard genotyping assays require high minimum viral loads (1000 copies/mL) and detect only resistant variants making up more than 20% of the sample’s viral population. Perhaps the use of next-generation sequencing would allow for better identification of resistant HIV variants .HIV-1 A6 (IDU-A) remains the predominant HIV-1 genetic variant in Russia’s Northwestern Federal District among patients with ineffective ART. A significant increase in the frequency of occurrence of HIV-1 drug resistance mutations in the region, compared to 2012, was shown. Among samples with drug resistance mutations, in all cases, mutations associated with pharmacological resistance to two or three drug groups were found. Given the high incidence of resistance mutations in patients on ineffective ART, surveillance of HIV-1 drug resistance, in both ART-receiving and ART-naive individuals, appears necessary. A lack of vigilance and control measures may lead to the spread of primary ART-resistant HIV strains.


Use of doravirine (DOR), a new nonnucleoside reverse-transcriptase inhibitors recently approved for HIV treatment, is still unclear in clinical practice and real-life data are scarce.We retrospectively investigated the rationale for switching people with HIV to DOR-containing/-based regimens in a real-life cohort. Among 132 patients , the main reasons to start DOR were prevention of toxicities (39.4%) and dyslipidemia (18.2%). DOR was combined with integrase inhibitors in 40.9% cases, and in 25.7% of patients, DOR was prescribed without availability of a genotypic resistance test.P = .008 and .01, respectively).Twenty-four weeks after the switch to DOR-containing/-based regimens, no significant changes in CD4+ T-cell count, CD4/CD8 ratio, detectable HIV-RNA, serum creatinine levels, and body weight were detected. By contrast, a significant reduction in lipids (both cholesterol and triglycerides) was observed in 52 patients for whom a follow-up assessment was available (Our data confirmed that switching to DOR-containing/-based regimens may have a favorable impact on lipid profile and a neutral impact on weight gain. However, more data are needed to support its use in patients who do not have a genotypic test available or have an extensive nonnucleoside reverse-transcriptase inhibitors-associated resistance, as well as its use in a dual regimen, especially in combination with second-generation integrase inhibitors. DOR, which is available both as a single-tablet (combined with tenofovir disoproxil fumarate and lamivudine) or as a single agent, is recommended in combination with other antiretroviral agents both in treatment-experienced and in naive people living with HIV (PLWH). Despite the availability of several highly effective and well-tolerated antiretroviral regimens, DOR may still be a valuable additional option in the treatment armamentarium, due to its safety profile, tolerability, minimal drug–drug interaction, and its activity against viruses harboring the major resistance mutations selected by the other available NNRTIs.,4 Moreover, DOR provided good pharmacokinetics forgiveness over 72 hours after drug interruption in healthy volunteers. Data from the clinical trials showed also that DOR has little or no impact on lipids, and it could be of help for subjects with metabolic issues.–8 In addition, in aging people comorbidities  and polypharmacy (possibly perpetrating drug interactions) represent 2 important challenges when selecting HIV treatment, which could benefit from the availability of drug such as DOR.,10 Several antretroviral regimen options are possible, both in a naive setting and in switching strategies since many agents are available to clinicians (particularly when there are no resistance mutations in the background).,11Doravirine (DOR) is a new-generation nonnucleoside reverse-transcriptase inhibitor (NNRTI) recently approved for the treatment of human immunodeficiency virus 1 (HIV 1).,7,12 and have also explored its role in switching strategies.,13However, when the genotype confirms the presence of resistance mutations, the choices get narrower and more complex regimens are needed. DOR has not been studied in the setting of resistance mutations; clinical trials have compared this new NNRTI with boosted darunavir (bDRV) and efavirenz (EFV) in naive setting, Nonetheless, clinical practice might diverge from this recommendation.Although DOR efficacy on viruses harboring major NNRTI resistance mutations, such as K103N, Y181C, and G190A, has been shown in vitro, no clinical data are currently available regarding the use of DOR in patients infected with drug-resistant HIV. Thus, current guidelines do not recommend DOR use in this context.–16 and it is important to define how clinicians have interpreted the role of DOR in the current HIV armamentarium. Therefore, this study aimed to describe the reasons leading clinicians to switch patients to a DOR-containing regimen and its role in clinical practice. Second, we aimed at assessing the changes in virological, immunological, and metabolic parameters from baseline to week 24 after the switch.Data regarding the use of this new NNRTI in a real-life setting are still scarce,This is a retrospective multicentre cohort study, including 6 Italian HIV centers . Moreover, for this study, we used the general authorization of the Italian Guarantor for the use of anonymized demographical and clinical data. For each patient, we collected demographics , clinical , and laboratory data . Furthermore, we gathered all data available regarding HIV major resistance mutations for each antiretroviral class as per Stanford University HIV Drug Resistance Database. Resistance test available before patients started any antiviral agent was performed by using the Sanger sequencing methods for sequencing of plasma HIV-RNA. As per EACS guidelines 2021, “confirmed virological suppression” was defined as a double consecutive detection of HIV viral load <50 copies/mL within the previous 6 months. Reasons for DOR introduction were obtained from patient health records and categorized as follows: proactive switch , dyslipidemia, weight gain, other ongoing toxicity or undesired side effects with current antiretrovirals, virological failure, and management of drug-to-drug interactions. Among patients with at least 6 months of follow-up after DOR introduction, we compared lipids, body weight, creatinine, and viroimmunological parameters , before switch and 24 weeks after.In Italy, the use of DOR was approved in January 2020. All PLWH (older than 18 years), who switched to DOR-containing regimens from February 1, 2020, to December 31, 2021, were included. The study was conducted accordingly to Declaration of Helsinki and to principles of good clinical practice. It included retrospectively collected and anonymized data. Retrospective studies including such kind of data, as per Italian law , are waived both from patient’s consenting and Ethical Approval.P value of <.05 was set as the level of significance. Statistical analysis was performed using STATA software, version 11 .Continuous variables were compared by Student t test for normally distributed variables and the Mann–Whitney U test for nonnormally distributed variables. Categorical variables were evaluated using the Chi-squared or 2-tailed Fisher exact test. Values for continuous variables were expressed as median [interquartile range IQR)] or as percentages for categorical variables. Two-tailed tests were used to determine statistical significance; a 3. At the time of switch, 107 patients (81.1%) had an undetectable HIV viral load, while 18.9% of subjects had plasma HIV-RNA >200 copies/mL (IQR: 664–7280). At baseline, according to historical cumulative genotypes, nucleoside reverse-transcriptase inhibitor (NRTI) and NNRTI resistance mutation rates were 21.9% and 21.2%, respectively, while resistance rates for integrase inhibitor (INI) and protease inhibitor (PI) were, respectively, 3.8% and 4.5%. Among 28 subjects who had NNRTI resistance mutations, 17 (60.7%) had K103N and 3 (10.7%) had Y181C. Six patients (21.4%) had the E138A accessory mutation, selected in patients who received rilpivirine or etravirine.Over the study period, 132 PLWH were switched to DOR-containing regimens , showed the V108X mutation which causes a low-level reduction in susceptibility to DOR.Overall, the prevalence of subjects with resistance at 2 or more classes (described as “heavily treatment-experienced patients” according to recent definitions) was 31%.The main reasons for switching to DOR-containing regimens were proactive switch (39.4%), dyslipidemia (18.2%), virological failure (17.4%), and managing drug-to-drug interactions (12.9%). Seven patients (5.2%) were switched to DOR-containing regimens for significant weight gain . Among patients switched from a PI-based regimen to a DOR-containing regimens, 14 of 24 (58.3%) and 13 of 17 (76.5%) were switched off from bDRV for dyslipidemia and ongoing drug-to-drug interactions perpetrated by the presence of the boosting agents, respectively.Nine patients (6.8%) were switched for ongoing toxicity. In particular, in 7 of 9 cases toxicity was associated with an INI-based regimen .DOR was often administered with 2NRTIs (43.2% cases) or as a dual therapy along with INIs (in 40.9% cases), mostly dolutegravir (45/54 cases). In 6.1% cases, it was associated with both a PI and an INI, while in 6.8% it was combined with multiple different drugs.Treatment with DOR was discontinued during the first month in 5.3% (7/132) patients for the following reasons: 2 virological rebounds due to scarce adherence, 2 due to gastrointestinal intolerance, 1 due to central nervous system side effects , 1 because of difficulties in swallowing tablets, and 1 due to headache.Fifty-two patients were followed for at least 24 weeks after DOR introduction. Differences in parameters after baseline are summarized in Table P values = .008 and .01, respectively). A nonsignificant body weight reduction was observed in the subgroup of 38 patients who measured weight before and 24 weeks after the switch .No differences were observed regarding the proportion of subjects with virological suppression, CD4+ T-cell count or CD4/CD8 ratio, detectable HIV-RNA, and serum creatinine levels. A significant decrease was found in both cholesterol and triglycerides levels  and dyslipidemia, followed by virological issues. This approach is consistent with other studies, in whom the main reasons for the switch were high cardiovascular/metabolic risk, treatment simplification, drug-to-drug interaction and toxicity.,21In our study, the prevalence of patients with multiple historical genotypic resistances was high, but DOR was selected only when no major mutations compromising its efficacy were present.,11 with a baseline resistance testing, in our experience DOR was used only for switching strategies. In 25.7% of patients, DOR was prescribed without a genotypic resistance test, but with a long history of persistently undetectable HIV-RNA.While the most recent international guidelines suggest using DOR in combination with 2 NNRTIs as a first line antiretroviral regimenMoreover, in our study a large proportion of patients (40.9%) was switched to DOR+INI, despite the absence of data exploring this 2-drug combination in clinical trials. Indeed, data from ARCA cohort showed how on samples coming from 6893 patients who were NNRTI experienced prevalence of high or intermediate level of resistance to NNRTIs was of 6.1% and 12.7%, respectively. However, these authors showed how the previous exposure to efavirenz and etravirine was significantly associated with a high probability of detecting a DOR high-level resistance, while rilpivirine was associated with a very low probability. Due to the very low prevalence of DOR resistance, results from this study support the use of DOR even in NNRTI experienced patients, but a note of caution should be paid in patients who were previously exposed to etravirine or efavirenz.This may suggest that clinicians have a certain level of confidence in exploiting the high genetic barrier of DOR (which is higher than other NNRTIs) and its innovative resistance profile when there is no available cumulative genotype or as a rescue therapy in patients with limited options and complex clinical history, although clinical trials provided data limited only to naive patients or switched patients with previously undetectable HIV-RNA. Moreover, according to previously published data, we know that DOR resistance is uncommon in PLWH who have been treated with NNRTI.–8 Of course, when the treatment switch is toward a boosted PI-including regimen plus DOR, this possible benefit may be lost.Although follow-up is available only in a subgroup of patients and limited to 24 weeks, our data suggest a significant favorable impact on the lipid profile, confirming the results from both clinical trials and real-life settings, which compared DOR-based regimens versus boosted protease inhibitor-based regimens.No statistically significant impact on body weight was detected after 24-week follow-up. In naive patients, clinical trials with DOR showed that weight changes were similar across all treatment groups  at week 96 . Whether switching to a DOR-based regimen in real-life may affect body weight or body composition, particularly among those who experience weight gain during treatment with other regimens, deserves to be further investigated.Also in switch strategies, weight gain was not significant at 144-week follow-up.Last, since PLWH are aging with an increasing number of comorbidities and polypharmacy, it remains to be established which is the best companion for DOR among the elderly, given that tenofovir disoproxil fumarate may affect renal function and bone metabolism.In conclusion, DOR-based regimens may become more appealing because this strategy may be a good alternative for patients suffering from hypertriglyceridemia, hypercholesterolemia, and weight gain. Of note, more data are needed on the use of DOR in patients that do not have a genotypic test available  or have an extensive NNRTI-associated resistance.As intriguing as the option of DOR combined with second-generation INI may be, no trials have yet explored this regimen. Therefore, as robust data are scanty, caution is advised.E.Q.-R. was involved in conceptualization. M.M. and M.D.A. were involved in original draft preparation and methodology data curation. MM was involved in formal Analysis. D.R., G.Z., G.L., A.F., C.P., F.C., M.F., A.M.C., and E.Q.-R. were involved in writing—review and editing. All authors have read and agreed to the published version of the manuscript.


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.We analysed data of 6,530 ART-experienced patients  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.μL  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  comparing with those without HIVDR.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, which suggest resistance monitoring and ART optimization be earlier considered.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/ The use of antiretroviral therapy (ART) has resulted in substantial reductions in HIV/AIDS-related morbidity and mortality worldwide –4. MaintDuring ART, PLWH may experience small increases in VL (50–200 copies/mL) that do not reach the threshold for virological failure (VF), known as LLV , 10, 11.μL, while patients who initiate ART with a CD4 > 200 cells/μL are at reduced risk of death and serious opportunistic infections [To date, the implications and clinical significance of LLV with drug resistance are still not clear in China. Additionally, few or no studies have analyzed the possible role of LLV with drug resistance as a tool to predict CD4 cell count < 200 cells/fections –32. Whethttps://hivdb.stanford.edu/hivdb/by-mutations/, accessed Oct 16, 2018). NFATP guideline defines virological failure (VF) as a confirmed HIV RNA ≥ 1000 copies/mL. LLV was defined as the occurrence of at least one viral load (VL) measurement of 50–200 copies/mL during ART. The evaluation of CD4 cell count was performed after the event of LLV. The adherence questionnaire form included: (a) have you ever missed ARV drugs? (b) Have you ever missed ARV drugs because of side effects? (c) Have you ever missed ART because of excessive drugs? (d) Have you ever had difficulties taking ARV drugs at the exact time? For each question, a Likert scale: (a) never, (b) rarely, (c) sometimes, and (d) often is adopted in response. Never missing ARV drugs (or > 95% in multiple follow-up) is considered to be good adherence. Ethical approval for the study was obtained from the National Center for AIDS/STD Control and Prevention, China CDC Institutional Review Board. All individuals in this study provided written consent at the time of participation, and written informed consent was obtained from all study participants. All methods were performed in accordance with the relevant guidelines and regulations.We assessed all the data from China’s national HIVDR surveillance database from Jan 1, 2008, to Dec 31, 2015 . In this study, eligibility criteria were: 18 years or older; having received ART for more than 12 months; attending a participating clinic for routine HIVDR survey; having detailed viral load measurement data and CD4 cell count. In samples with VL ≥ 50 copies/mL, HIVDR genotyping was performed by in-house PCR as previously described , 23, 33.2 test or Fisher’s exact tests. Logistic regression was used to examine the associations between LLV, DR and CD4 cell counts. Weighted analyses were used to derive representative estimates of the detection rates of patients harboring HIV with mutations conferring resistance to ARV drugs belonging to the non-nucleoside reverse transcriptase inhibitor (NNRTI), transcriptase inhibitor (NRTI) and protease inhibitor (PI) classes. Weight was calculated based on the number of patients followed in each local center. All tests of significance were two-sided, with p < 0.05 indicating that an association was statistically significant. All the statistical analyses were performed with SAS 9.4 software .The significant differences in categorical variables were analyzed using χμL, 14.2% with a VL ≥ 1000 copies/mL. All patients received free ART treatment through the NFATP, and most patients used lamivudine (3TC) based regimens . The percentage of patients who missed dose in the past month was 26.1%. For more detailed information, see Table 11,976 PLWH were eligible in this study; 5446 did not meet eligibility criteria, and finally 6530 PLWH were included for analysis  had resistance to any type of HIV drugs. The detection rate of resistance to NNRTI drugs was higher than that to NRTI drugs and PI drugs. Of 925 patients with VF (VL ≥ 1000 copies/mL), 495 (53.5%) had resistance to any types of HIV drugs. The detection rate of resistance to NNRTI drugs was higher than that to NRTI drugs and PI drugs. Compared with patients with VL 50–999 copies/mL, the detection rate of NRTIs and PIs increased significantly in patients with VF (p < 0.01); however, the detection rate of NNRTIs did not have the same result in patients with VF (p = 0.97) . Model 2: After adjusting sex, age, occupation, marital status, route of HIV infection, duration of ART, initial ART regimens, ART regimens at survey, and missed doses, patients with VL 201–999 copies/mL and DR, VF and no DR, VF and DR had higher detection rates of CD4 cell counts < 200 cells/μL, compared with VL 50–200 copies/mL and no DR  and increased the risk of CD4 cell counts < 200 cells/μL. Additionally, patients were more likely to experience subsequent CD4 cell counts < 200 cells/μL if they had emergent drug resistance at the time of VL 50–999 copies/mL. To be noted, accumulation of DRAM increases when maintaining a failing ARV drug regimen with VL ≥ 50 copies/mL, leading to a loss of future therapeutic options together with a large cross-resistance between ARV drug within each ARV class.The definitions of VF and LLV vary in different periods of each country. Substantial differences exist between guidelines in developed countries, which use VL thresholds of 50–200 copies/mL to define VF, and WHO guidelines for developing countries, which apply a more lenient threshold of 1000 copies/mL –8. CliniOur results indicate that resistance testing of samples with VL < 1000 copies/mL provides clinically relevant information. It is worth noting that the prevalence of resistance to two and three ARV drugs were 26.4% and 1.1% respectively among patients with LLV. However, this prevalence increased to 72.9% and 3.6% respectively among patients with VL ≥ 1000 copies/mL. The results support guidelines recommending resistance monitoring for all patients with VL ≥ 50 copies/mL, even if genotypic resistance tests are less efficient at low viral loads . Among pμL had better recovery of immune function after ART [In this study, patients with HIVDR had lower CD4 counts than those without even if they had a relatively low VL. The results also showed that poor adherence (e.g. missed doses in the past month) are influenced by CD4 cell count. Poor adherence may be the reason for the low level of CD4 counts in patients with LLV Table . Earlierfter ART , 35, 44.fter ART . The levfter ART , and theThe results of this study showed that although patients take more time to achieve a normal CD4 cell count and less time to achieve an undetectable VL, once the CD4 cell count is normal, DRAM are reduced. The patterns of DRAM observed in this survey Fig.  are consOur study has several limitations. First, amplification of both RT and protease genes was successful in 79.8% and 97.5% of samples with VL of 50–999 and ≥ 1000 copies/mL. This difference might lead to bias. However, multivariable analysis showed that only VL independently predicted amplification failure (p < 0.01). Exposure to the different ARV drugs was well balanced between two groups in which reverse transcriptase and protease gene amplification was successful and unsuccessful (p = 0.41). Second, only patients alive at the time of the surveys were included in this study, so the statistical relationships among LLV, CD4 cell counts < 200 cells/μL and HIVDR might be reduced. Third, the lower frequency of VL monitoring used in NFATP might in part underlie the detection rates of LLV and HIVDR.This study was intended to better understand the consequences of LLV on patients from NFATP. Our analyses showed that the risk of CD4 cell counts < 200 cells/μL was higher after LLV, especially when drug resistance occurred, and DRAM appeared as soon as LLV persistence. It included the largest patient data on this topic so far, covering 6,530 patients from various regions of China. Compared with previous studies from developed countries, the detected rates of LLV in China were higher and the risk of CD4 cell counts < 200 cells/μL and HIVDR after LLV was more pronounced, indicating that LLV is a serious threat to NFATP programmes in China.


Most studies on the real-world effectiveness and safety of dolutegravir/lamivudine (DTG/3TC) have been conducted in Western countries, and Asian reports are lacking. We evaluated the effectiveness and safety of DTG/3TC in Korean adult people living with HIV (PLWH). This retrospective study was conducted from July 2020 to July 2022 at a tertiary hospital in Korea. Those who were followed up for more than 12 months were included. We analyzed the baseline characteristics, effectiveness, resistant profiles, body weights, metabolic parameters, and safety of DTG/3TC treatment in 151 PLWH, dividing them into the treatment-naïve group and the switching group. The median DTG/3TC treatment durations in the treatment-naïve and switching groups were 507.5 and 525.0 days. In the treatment-naïve group, the viral RNA titer was undetectable at 6 and 12 months in 95% of patients. In the switching group, virologic suppression was well-maintained. Meanwhile, the creatinine levels were slightly elevated in both groups compared to baseline. Five participants complained of mild side effects, such as indigestion, constipation, diarrhea, and fatigue. However, no patient stopped treatment during the follow-up period. Since there was no virological failure or serious complications observed in this study, DTG/3TC may be a good treatment option for PLWH in Korea. Since the discovery of the human immunodeficiency virus (HIV) in 1983, highly active antiretroviral therapy (HAART) has been developed . As ART Dolutegravir (DTG)-based 2DRs are attractive because of the following advantages: a high barrier to resistance, low risk of drug–drug interactions, and daily dosing schedule ,4. For tIn the Republic of Korea, DTG/3TC was approved by the Ministry of Food and Drug Safety in early 2020. It is considered a good treatment option for treatment-naïve PLWH or virologically suppressed PLWH with other ARTs. According to the HIV clinical practice guideline recommendation in Korea (revised in 2021), it corresponds to recommendation level 1A for treatment-naïve PLWH with HIV RNA titers less than 500,000 copies/mL . HoweverWe performed a single-center retrospective observational study at a tertiary hospital with 2400 beds in South Korea. We analyzed all PLWH aged > 19 years who were treated with DTG/3TC, including the treatment-naïve and those who switched from other ARTs to DTG/3TC, from July 2020 to July 2022. Those who were followed up for more than 12 months were included, and the window period for laboratory tests was 1 month. We investigated the baseline characteristics, clinical outcomes, adverse events, and antiretroviral resistance test results for the previously treated and treatment-naïve groups. This study was approved by the institutional review board (IRB) of Severance Hospital. The IRB waived the requirement for written consent from patients, as this study followed a retrospective design (IRB authorization number: 4-2021-1311).We measured the initial viral load, CD4+ T cell count, and CD8+ T cell count at baseline, 6 and 12 months after treatment with DTG/3TC was started to evaluate the treatment effects, and we reviewed the side effects in each patient. Other important blood tests, such as lipid profile, renal function, liver function, and blood glucose level assessments, as well as body weight determination, were performed at baseline before treatment and after 6 and 12 months of treatment. The HIV diagnosis and AIDS definitions followed the definition of the World Health Organization (WHO). Viral suppression was defined as an undetectable viral load, equal to or less than 50 copies/mL. Low-level viremia was defined as one or more viral load results that are detectable (more than 50 copies/mL) but equal to or less than 1000 copies/mL. Virological failure was defined as a persistently detectable viral load exceeding 1000 copies/mL after at least 6 months of undergoing ART [https://hivdb.stanford.edu/page/algorithm-updates/ (accessed on 1 March 2021)”.All virological analyses were performed at the Virology Unit laboratory and Department of Diagnostic Laboratory Medicine at Severance Hospital. HIV RNA was quantified by PCR using a VIDAS , which gives three possible outputs: (i) a quantitative result for HIV RNA values of ≥20 copies/mL; (ii) a semi-quantitative result (detectable below 20 copies/mL) when HIV RNA is detectable but not precisely quantifiable; and (iii) a qualitative result (‘undetectable’) when no signal can be detected. HIV RNA was defined as being undetectable when no signal could be detected (‘target not detected’). Genotyping drug resistance tests were performed using the ViroSeq HIV-1 Genotyping System 2.0 , and antiretroviral resistance mutations were identified using the Stanford HIV Drug Resistance Database 9.0 “2 test or Fisher’s exact test. Continuous variables were compared between the treatment-naïve and switching groups using the unpaired t-test for normally distributed data or the Mann–Whitney U test for non-normally distributed data. The paired T-test, Wilcoxon signed-rank test and repeated measure ANOVA was used to determine the effects and side effects before and after the treatment. Statistical significance in the multivariate logistic regression analysis was defined as p < 0.05.All statistical analyses were performed using SPSS Statistics for Windows version 26.0 . Descriptive statistics were used to summarize the patient demographics. When the values were normally distributed, the mean and standard deviation(SD) were used, and when the values were not normally distributed, the median and interquartile range(IQR) were used for comparison. Categorical variables were compared between the treatment-naïve and switching groups using the χAmong the 165 PLWH administered DTG/3TC, 151 patients were enrolled in the study . As showOf the 131 people in the switching group, 110 (84.0%) were changed to DTG/3TC for drug simplification, and 3 (2.3%) people changed due to gastrointestinal problems, such as diarrhea or indigestion. The remaining 8 (6.1%) patients changed because of the side effects of the existing medicine, and 10 (7.6%) changed due to unknown reasons. The ART types previously used by those in the switching group are listed in We also performed an antiretroviral resistance test in each group which is shown in p < 0.001). In the switching group, there was no significant difference in the CD4 + T cell count changes (p = 0.080) (As shown in = 0.080) .p = 0.026). Cholesterol level also changed from 184.62 ± 38.64 mg/dL to 177.70 ± 37.47 mg/dL at 12 months (p = 0.004). There were no significant changes in blood urea nitrogen (BUN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), glucose control, or body weight before and after DTG/3TC administration in either group. But in both group, increase in creatinine observed from 0.9 mg/dL  to 1.0 mg/dL  and 1.1 mg/dL  (p < 0.001) in treatment naïve and 0.99 ± 0.17 mg/dL to 1.04 ± 0.16 mg/dL and 1.02 ± 0.16 mg/dL (p < 0.001) respectively.As shown in After starting DTG/3TC, five people  complained of side effects. One treatment-naïve patient had an increase in AST up to three times the normal level for unknown reasons but continued to take the drug, and the AST level eventually returned to normal again. The remaining four patients complained of indigestion, diarrhea, constipation, and fatigue, but their symptoms were mild, and they were still taking the drug without changing the ART. None of the 151 patients who took DTG/3TC complained of serious side effects and were taking the drug without stopping.2DR based on DTG is recommended as a first-line therapy because of its high resistance barrier, low drug–drug interaction, and ease of administration ,12. In tPrevious clinical studies have not sufficiently included the Asian population. In the TANGO study, Asians accounted for only 3.5% of the total study population, and in the GEMINI study, Asians accounted for only 10% of the total study population ,7. In AsNevertheless, it should be noted that mild deterioration of renal function was observed, although there was no case of worsening renal function defined as acute kidney injury (AKI) in the Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines . The sliThis drug also showed positive results in patients with resistance mutations. For example, even in patients with M184I, a mutation with low-level resistance to 3TC, no viral blip or virological failure was observed. There have been no large-scale studies yet to prove the effect of 2DR including DTG/3TC in M184I, but several studies have shown the potential effect of 2DR based on DTG as a nucleoside-sparing regimen . FurtherThis study has several limitations. We reviewed this as an observational study with fewer participants for limited days around 12 months and not a long-term follow-up, so virologic failure or some side effects may have been missing. In particular, several experts are concerned about complications associated with chronic exposure to ART drugs. Long-term exposure to integrase inhibitors, particularly DTG, persists significantly in neurocognitive impairment among some persons . HoweverIn conclusion, this study showed that DTG/3TC could be effectively used in patients without resulting in the occurrence of major adverse side effects. Therefore, DTG/3TC might be a good treatment option for PLWH in Korea.