Suboptimal antiretroviral (ART) adherence can lead to virologic failure with consequent HIV-1 resistance. Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a powerful biomarker of cumulative adherence, predictive of future viremia. It has been associated with resistance in Persons With HIV (PWH) in South Africa and the US. We explored the relationship of TFV-DP concentrations with antiretroviral drug resistance at the time of treatment failure in SA.Adult PWH from health clinics in Cape Town, South Africa on efavirenz-based first-line ART containing tenofovir disoproxil fumarate (TDF) with an undetectable (< 50 copies/mL) HIV-1 viral load (VL) were prospectively enrolled in an observational cohort for 12 months. Monthly study visits included blood collection for HIV-1 VL and DBS for TFV-DP. The first confirmed viral breakthrough (VB) > 400 copies/mL triggered HIV-1 genotyping at the subsequent visit. An electronic adherence (EA) device monitored ART adherence in real-time, estimated as a percent for the 30-days prior to VB. Wilcoxon rank sum test was used to compare median [IQR] TFV-DP by genotype outcome.Of 250 individuals, , 21 experienced VB, with a median of 5  months on study, and a median EA of 33.3 %. Demographic characteristics between those with and without VB were similar. Median VL at VB was 4.0  log copies/mL. TFV-DP concentrations trended down towards the VB visit. Median TFV-DP concentrations were significantly higher in those HIV-1 genotype did not amplify due to being virally suppressed at the subsequent visit ; than in those who were successfully genotyped with evidence of drug resistance  and in individuals who did not have resistance . Three genotype collections were not done. Only non-nucleoside reverse transcriptase inhibitor-associated mutations were identified on resistance testing. .TFV-DP in DBS showed a step-wise inverse relationship with VB and drug resistance, with evidence of low cumulative ART adherence in PWH who developed antiretroviral resistance. Monitoring TFV-DP concentrations could be a valuable tool for predicting future VB and future resistance. Maintaining viral suppression in PWH is the objective of ART , 2 and iTraditional adherence tools used in resource limited settings such as pharmacy refill data, pill counts and self-reported adherence vary in diagnostic accuracy . A more The quantification of TFV-DP concentrations in DBS samples as an adherence biomarker is gaining traction , 6, 16. Researchers in the US established that concentrations of TFV-DP in DBS strongly correlate with viral suppression (VL < 20 copies/mL) in PWH on a TDF-based regimen . ExpandiIn individuals with suboptimal cumulative adherence, drug selection pressure drives the mutation of treatment resistant virus, which may be accelerated by the use of non-nucleoside reverse transcriptase inhibitors (NNRTIs) , 20. A sIn South African clinical practice, VL measurement is the standard proxy for acceptable adherence, and this is only measured annually in already suppressed PWH . Since VExtending on findings from ADD-ART , we presThis research examines a subpopulation from the previously published parent study . The ADDBetween November 2016 and November 2018, the study enrolled 250 PWH from 4 public healthcare clinics. Eligible individuals had been receiving a TDF-based regimen for at least 4 months and for less than 24 months. For those who were treatment experienced (on ART for ≥ 12 months), evidence of historic adherence challenge was required . Individuals had to be virally suppressed (VL < 50 copies/mL) a month prior to enrolment. All 250 participants were taking a single tablet regimen containing tenofovir, emtricitabine and efavirenz. (TDF/FTC/EFV). Written informed consent was obtained in the participant’s chosen language, and clinical records reviewed to confirm eligibility. All participants who had a confirmed episode of VB while on the ADD-ART parent study were included in this sub-study.On study, participants were followed up every month for 12 months. Blood samples for VL and TFV-DP concentrations in DBS were obtained monthly. Demographic data were collected and questionnaires on self-reported adherence, HIV stigma , 25 and ® Electronic Monitoring Device was issued to each participant. This provided continuous, EM over the study period. The device holds a 30-day supply of tablets, and a signal is sent to a secure website using cellular networks every time it is opened  were reported for the variables of interest: 30 day EA prior to first VB and TFV-DP drug concentrations at VB. Time in months to first VB and HIV-1 VL at the time of genotyping were also reported.We compared outcomes of HIV-1 genotype resistance testing by amplification and sequencing. Individuals were categorised as: 1. Did not amplify; 2. Amplified with no HIV-1 drug resistance mutations in evidence; 3. Amplified with HIV-1 drug resistance mutations; and 4. Genotype missed.We used the ‘Did not amplify’ category as the reference group to compare median [IQR] TFV-DP by genotype outcome, using the Wilcoxon rank sum test.® adherence plots were computed with R statistical software  using ggplot2, ggallin and dplyr packages. Plots are right justified, with data points beginning from the point of viral breakthrough baseline visits for each participant.For each category, TFV-DP and 30-day WisepillOf the 250 participants  from the original study cohort, 21 (8%) experienced VB at a median of 5  months from study start and were included in this analysis. Most of the participants with VB were female , with a median age of 33  years. Baseline characteristics for the overall cohort are summarized in Table Resistance testing was completed for 18 of the 21 individuals. Data was missing for 3 cases Amplification of virus with HIV-1 drug resistance mutations was identified in five of these individuals. 27.8%) Notably, only NNRTI-associated mutations were identified, namely: K103N, E138K and Y118H.  had no HIV-1 drug resistance mutations. In this category, median VL at genotype was the highest at 4  log copies/mL, and median TFV-DP concentrations at VB were the lowest of all categories, at 40  fmol/punch, Table  with TFVThe remaining 10 individuals (55.6%) did not have viral amplification at the genotyping visit due to re-suppression of the VL, as depicted in Table Median TFV-DP concentrations at breakthrough were the highest: 380 [227–661] fmol/punch  in the re-suppressed group. The corresponding EA median was 45% , also the highest EA across all categories  experienced VB (defined as a confirmed VL > 400 copies/mL) during the 12 month study period. The range for TFV-DP concentrations associated with sustained viral suppression have previously been reported, and a threshold TFV-DP value of 400 fmol/punch was found to be predictive of future viral breakthrough in this cohort . This asAmong the individuals with evidence of NNRTI-associated resistant mutations (n = 5) the TFV-DP concentrations trended downwards towards the visit at which VB occurred which is consistent with a decrease in adherence that precedes the development of resistance. Corresponding EA at breakthrough was also low, but not completely absent in these participants, which was consistent with the TFV-DP concentrations in DBS. In comparison, individuals (n = 3) whose HIV-1 amplified without any resistance mutations (wild type virus) had lower concentrations of TFV-DP than those with mutations, which supports the premise that some degree of drug exposure is required to promote drug resistance.Our findings are similar to those from another South African cohort on a NNRTI based, TDF containing regimen. In that study, Castillo-Mancilla et al. demonstrated that individuals with evidence of HIV-1 drug resistance had higher TFV-DP concentrations compared to those without evidence of resistance on genotyping . HoweverThis mechanism may explain our findings of unsuccessful viral re-suppression, and consequent drug resistance after improved adherence. EM and TFV-DP in DBS may be more useful in individuals on these regimens .A strength of our research is the utilization of two objective metrics of adherence for a more comprehensive illustration of trajectories in those who had viral resistance. Given that adherence was monitored in real-time, we could illustrate longitudinal courses up until the point of breakthrough, despite the missing data on the TFV-DP time course. Building on the findings of a predictive threshold of TFV-DP for detecting VB , this reWe also acknowledge several limitations to our research. First, our study sample was small, and three of the 21 individuals had not undergone resistance testing. Furthermore, multiple missing data points represented in our TFV-DP time course limit the characterization of individual trajectories within each of the genetic testing outcome groups. However, these missing data points on the TFV-DP plots were due to missed study visits when DBS were not obtained. The small cohort with VB may be partly attributed to the Hawthorne effect- modification of adherence behaviour in response to being observed during the study, although this effect is unlikely to have lasted for the duration of the study . ADD-ARTThis study illustrated a step-wise inverse relationship with TFV-DP concentrations and VB with drug resistance in PWH on a NNRTI based regimen in South Africa. Two objective measures of ART adherence, namely, TFV-DP concentrations and EA, showed low (but not completely absent) ART adherence in those who developed drug resistance. Our findings add to the evidence of the utility offered by these measurements in predicting future VB, and drug resistance. In routine clinical care, monitoring TFV-DP trends could give clinicians the opportunity to safety-net individuals meeting the threshold for low TFV-DP concentrations (less than 400 fmol/punch)  for time


P < 0.001) and β2-microglobulin-to-creatinine ratio  continued to decrease at week 96. BMD of the spine and hip slightly increased . The median triglycerides, total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol increased from baseline to week 96 , and most of the increases occurred in the first 48 weeks of the switch. Our study showed that switching from TDF-containing ART to elvitegravir/cobicistat/emtricitabine/TAF maintained HBV and HIV viral suppression through 96 weeks among HIV/HBV-coinfected patients. Proteinuria continued to improve, while fasting lipids increased and BMD stabilized at 96 weeks after the switch.Data regarding the durability of tenofovir alafenamide (TAF)-containing antiretroviral therapy (ART) in maintaining hepatitis B virus (HBV) viral suppression among HIV/HBV-coinfected patients are limited. Between February and October 2018, 274 HIV/HBV-coinfected participants who had achieved HIV RNA of <50 copies/mL with tenofovir disoproxil fumarate (TDF)-containing ART and switched to elvitegravir/cobicistat/emtricitabine/TAF were prospectively enrolled. Serial plasma HIV and HBV viral loads, HBV and hepatitis D virus (HDV) serology, renal parameters, metabolic profiles, and bone mineral density (BMD) were assessed through 96 weeks. At baseline and weeks 48, 72, and 96, 5.8%, 5.1%, 5.8%, and 5.1% of the participants had plasma HBV DNA of ≥20 IU/mL, and 0%, 0.7%, 1.5%, and 2.2% had HIV RNA of ≥50 copies/mL, respectively. Hepatitis B surface antigen (HBsAg) loss occurred in 1.5% of 274 participants, and hepatitis B e-antigen (HBeAg) loss or seroconversion occurred in 14.3% of 35 HBeAg-positive participants. Compared with baseline, the median urine protein-to-creatinine ratio (79 versus 63 mg/g, IMPORTANCE Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide as a maintenance therapy showed durable and high rates of viral suppression for HIV/HBV-coinfected patients, with only 5.1% and 2.2% of patients having HBV DNA of ≥20 IU/mL and HIV RNA of ≥50 copies/mL, respectively, at 96 weeks. Our study fills the data gap on the long-term clinical effectiveness of tenofovir alafenamide-containing antiretroviral therapy in people living with HIV who have HBV coinfection. Hepatitis B virus (HBV) infection is highly endemic in Southeast Asia, and about 10% of people living with HIV (PLWH) in Taiwan are affected by chronic hepatitis B , 3, whilTAF and TDF are both prodrugs of tenofovir that can inhibit HIV and HBV replication. Compared to TDF, TAF results in a 90% reduction of tenofovir plasma concentration and has been shown to possess more favorable effects on kidney and bone markers . Switchi8–In HBV-monoinfected patients, treatment with TAF showed noninferior efficacy in achieving viral suppression, similar mean declines in quantitative HBsAg and higher rates of alanine aminotransferase (ALT) normalization at week 48 compared to those who continued TDF , 15. HBsIn this multicenter prospective study, we reported the 96-week results of HIV and HBV viral suppression and evolution of proteinuria, fasting lipids, and BMD after switching from TDF-containing ART to coformulated elvitegravir, cobicistat, emtricitabine, and TAF (E/c/F/TAF) in PLWH coinfected with HBV.A total of 274 HIV/HBV-coinfected participants were included. The clinical characteristics of the participants and the study outcomes at week 48 have been previously presented . In summn = 12), drug-drug interaction with E/c/F/TAF (n = 8), loss to follow-up (n = 8), and adverse effects . Six participants switched to other TAF-containing ART after 48 weeks and continued in the study.In this extension study, 230 (83.9%) of 274 participants completed the 96 weeks of follow-up . A total of 13 (4.7%) and 31 (11.3%) participants dropped out of the study before and after week 48, respectively. After week 48, 31 participants withdrew from the study because of withdrawal of consent  at week 72 also showed an increase of plasma HIV RNA from <50 to 1,231,078 copies/mL, suggesting poor treatment adherence. For this participant, E/c/F/TAF was replaced by coformulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/F/TAF) plus darunavir/cobicistat, and his HBV and HIV loads in subsequent testing were <20 IU/mL and 296 copies/mL, respectively. The other 6 participants continued E/c/F/TAF, and 4 of them reachieved HBV DNA of <20 IU/mL.The proportions of the participants with HBV DNA of ≥20 IU/mL at weeks 72 and 96 were 5.8% and 5.1%, respectively. At each follow-up time point, the proportion of the participants who had plasma HIV RNA of ≥50 copies/mL ranged from 0.7% to 2.2% (P < 0.001). Participants with positive HBeAg had higher median HBsAg levels at enrollment, and they also showed greater declines in HBsAg levels than HBeAg-negative participants from week 48 to week 96 . Loss of HBsAg occurred in 4 (1.5%) participants. Among the 35 HBeAg-positive participants, 2 (5.7%) lost HBeAg without positive anti-HBe antibody and 3 (8.6%) had HBeAg seroconversion. For participants who had ALT levels greater than the upper limit of normal at enrollment, 56.4% achieved ALT normalization by central laboratory criteria and 50% by 2018 AASLD criteria  at week 48 to 566 IU/mL  at week 96 (2 at week 48 to 93.2 mL/min/1.73 m2 at week 96 (P = 0.002) (Table S2). Participants with an eGFR of ≥90 mL/min/1.73 m2, those between 60 and 89 mL/min/1.73 m2, and those between 30 and 59 mL/min/1.73 m2 at baseline experienced mean changes in eGFR of –7.4%, +0.9%, and +9.4%, respectively. In multivariate logistic regression analysis, use of ART without creatinine transport inhibitors, such as rilpivirine, dolutegravir, bictegravir, cobicistat, or ritonavir, before the switch  and higher urine protein-to-creatinine ratio (UPCR)  at baseline were associated with higher risk of an eGFR decline of over 15% at 96 weeks of E/c/F/TAF treatment, while higher CD4 counts at baseline conferred a lower risk  (Table S3).The median estimated glomerular filtration rate (eGFR) decreased from 94.9 mL/min/1.73 mP < 0.001).The UPCR and urine β2-microglobulin-to-creatinine ratio continued to decline from week 48 to week 96, whereas the decrement of urine albumin-to-creatinine ratio (UACR) was similar between week 48 and week 96 (−15.3% versus −12.5%) . The preThe median levels of triglycerides, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol remained steady from week 48 to week 96. The median changes of triglycerides, total cholesterol, LDL-cholesterol, and HDL-cholesterol from baseline to week 96 were 26.5, 24.5, 17.0, and 5.0 mg/dL, respectively, and the median percentage increases were 24%, 15%, 18%, and 12%, respectively . No statBMD assessment was performed in 138 participants at week 96. Among these participants, the mean BMD of the spine and hip increased and peaked at week 48  and slightly declined but were still higher at week 96 than those at baseline  .P < 0.001), positive anti-HCV , and elevated serum rapid plasma reagin (RPR) titers at baseline were more commonly found among anti-HDV-positive than anti-HDV-negative participants  (Table S5). For participants who continued to participate in the follow-up through week 96, HDV seroprevalances at weeks 48, 72, and 96 were 14.2%, 12.4%, and 13.4%, respectively. The proportions of the participants with HDV viremia ranged from 2.3% to 5.4% at each follow-up time point, and their mean HDV RNA levels at baseline and weeks 48 and 96 were 8.6, 8.8, and 7.5 log10 copies/mL, respectively  participants tested positive for anti-HDV IgG. Injecting drug use . With a recent report of TAF-related nephrotoxicity  , and there were no differences between the two groups in terms of shifts in categorical risk of atherosclerotic cardiovascular disease , 30. How= 0.047) . While t= 0.047) . Steatos= 0.047) . Prior s= 0.047) , 33. HowThe HDV seroprevalence was stable through 96, weeks and the incidence rate of HDV seroconvertion in the present study was lower than our earlier estimation between 2007 and 2012  . Neverth2 were not included. Therefore, the benefit of improvement in proteinuria with the switch to TAF-containing ART could not be evaluated in patients with severely impaired renal function. Fourth, more participants discontinued the study between week 48 and week 96, which was influenced by lockdown and border control during the early phase of the COVID-19 pandemic and the introduction of BIC/F/TAF in Taiwan. BIC/F/TAF was associated with fewer drug-drug interactions than E/c/F/TAF, and BIC/F/TAF as a maintenance therapy demonstrated low rates of low-level viremia and virologic failure in virally suppressed PLWH - or TDF plus lamivudine (3TC)-based ART to E/c/F/TAF as a maintenance treatment at 13 hospitals designated for HIV care around Taiwan from February to October 2018. The design, inclusion, and exclusion criteria of the study have been previously described . FollowiThe primary endpoint of this follow-up study was the proportions of participants who maintained undetectable plasma HBV DNA (<20 IU/mL) and plasma HIV RNA (<50 copies/mL) at weeks 72 and 96 after switching from TDF- to TAF-containing ART. Additional endpoints at week 96 included changes in aminotransferases, quantitative HBsAg levels, and rates of HBeAg loss, HBeAg seroconversion, and HDV seroconversion while the participants continued to receive TAF-containing ART. “HBeAg loss” refers to the change from HBeAg positivity and anti-HBe negativity at baseline to HBeAg negativity without the development of anti-HBe after the baseline visit. “HBeAg seroconversion” refers to the change from HBeAg positivity and anti-HBe negativity at baseline to HBeAg negativity and anti-HBe positivity after the baseline visit.Laboratory tests of HBV serologic markers included HBsAg, anti-HBs, HBeAg, and anti-HBe . The eGFR was calculated by the CKD Epidemiology Collaboration (CKD-EPI) equation. The measurement of urine protein included UPCR, UACR, and urine β2-microglobulin-to-creatinine ratio . Anti-HDV IgG was determined by competitive enzyme immunoassay . For participants with a positive anti-HDV IgG, HDV RNA was determined with the use of in-house real-time PCR assay. In brief, the HDV nucleic acid was first extracted from 500-μL plasma using the QIAamp UltraSens virus kit , and cDNA was reverse transcribed from 10 μL eluted RNA using random hexamer primer. The HDV RNA was then determined using a commercialized HDV quantification primer probe set (TIB LightMix kit) , 39 withBMD assessment was performed in participants enrolled at four participating hospitals using dual-energy X-ray absorptiometry . Osteoporosis and osteopenia were defined by BMD T-score according to WHO criteria .P value of <0.1 in univariate analysis, were entered into the model with a backward stepwise regression approach. All P values were two-sided, and a P value of <0.05 was considered statistically significant. Statistical analyses were performed using SPSS software version 25.0 .The continuous variables were presented as medians and interquartile ranges and compared using the Mann-Whitney U test. The categorical variables were compared using the chi-square test or Fisher’s exact test. For paired data, categorical variables were compared using McNemar’s test, and continuous variables were compared using the Wilcoxon signed-rank test. Logistic regression analysis was performed to identify determinants of an eGFR decline of over 15% at week 96. Variables identified as known predictors by previous studies, or those with a The study was approved by the research ethics committee or institutional review board of the 13 participating hospitals -20170065, and VGHKS18-CT1-18). All participants gave written informed consent before enrollment.Deidentified participant-level data will be available on publication of the study. Requests for data should be sent to the corresponding author by e-mail and, on review of the proposed protocol and signing of a data sharing agreement, the data will be made available.


Resistance to multiple antiretroviral drugs among people living with HIV (PLWH) can result in a high pill burden, causing toxicity and drug interactions. Thus, the goal is to simplify treatment regimens while maintaining effectiveness. However, former resistance analysis data may not be current or complete. The use of proviral DNA genotyping may assist in selecting appropriate treatment options. A retrospective study was carried out on individuals belonging to the Cologne HIV cohort with a resistance history to two or more antiretroviral (ARV) classes and on non-standard antiretroviral therapy (ART). Patients required former viral RNA and a recent proviral DNA resistance test to be available prior to the switch to ART. Potential discrepancies between resistance test results obtained through RNA and proviral DNA methods and the consequent virological and clinical outcomes following ART adjustments were analyzed. Out of 1250 patients, 35 were eligible for inclusion in this study. The median length of known HIV infection was 27 years, and the median duration of ART was 22 years. Of the 35 participants, 16 had received all five ARV classes. Based on proviral DNA genotyping results, ART was simplified in 17 patients. At the last follow-up examination after changing therapy, 15 patients had HIV RNA <50 copies/mL . The mean number of pills per day decreased from eight to three, and the median intake frequency decreased from two to one time/day (ranges 1–2). Our study supports the use of proviral DNA genotyping as a safe strategy for switching to simplified ART regimens. However, the lack of extensive research on the advantages of proviral DNA genotyping makes it challenging to fully assess its benefits in terms of treatment selection. With the progress made in antiretroviral therapy (ART), people living with HIV (PLWH) have been able to achieve life expectancies that are similar to those of non-infected people in Europe and North America . ImproveUnderstanding HIV-1 dynamics in PBMC, particularly in patients with suppressed plasma viremia, is important for the optimal use of proviral DNA resistance analysis in clinical decision-making. In acute infection, proviral DNA levels and diversity increase within the initial years . WithoutThe study was a retrospective longitudinal cohort analysis of individuals living with long-term HIV-1 infection who were on non-standard antiretroviral therapy (ART) due to previous resistance to two or more classes of antiretroviral drugs. Standard ART was defined as therapy utilizing a Nucleoside Reverse Transcriptase Inhibitor (NRTI) backbone as well as either a Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) or an integrase inhibitor (INI) or a (boosted) protease inhibitor (PI), in accordance with 2019 WHO therapy guidelines [Genotypic resistance testing of viral RNA was performed using Sanger sequencing with ViroSeq HIV genotyping kit v2.0  until the end of 2014 or with new-generation sequencing (NGS) with MiSeq  afterwards. Both platforms have the capability to accurately sequence and identify DRMs in peripheral viral loads >1000 cop/mL. The MiSeq platform exhibits excellent levels of sensitivity and specificity in identifying DRMs that are also detectable through Sanger sequencing . For genp-value < 0.05. The statistical analysis was carried out with the statistics program Sigma Plot 2.5 for Windows.Participant characteristics were examined using descriptive statistics, such as mean, median and relative frequency. When comparing the pill burden, decimal places were rounded up to the next integer value. Differences between the results were tested for significance using the paired t-test for means  and using the Wilcoxon signed rank test  for medians. Statistical significance was defined as a two-tailed The study was conducted at the University Hospital of Cologne and approved by the ethics committee of the medical faculty (reference: 20-1484).Between November 2017 and August 2020, 35 out of 1250 (2.8%) patients living with HIV were identified as receiving a non-standard ART regimen due to resistance to two or more ARV classes and in whom resistance tests on proviral HIV DNA templates were present. The recruitment process and study design are presented in Based on the data collected, it was found that a median of six RNA genotypic resistance tests were performed (IQR 2–19). In addition, a median of one proviral DNA genotypic resistance test (IQR 1–3) was conducted. The median time between the last RNA and the current genotypic resistance testing of proviral DNA was 7 years (IQR 0–17). The results revealed that the majority of patients  showed resistance to three or more ARV classes, as shown in All patients developed NRTI-associated resistance mutations over the course of their disease. Only four patients (11%) showed no resistance mutations to NRTIs in proviral DNA resistance testing. The most frequently mutated key positions in plasma were M184  and for thymidine analogue mutations (TAMs) T215  and M41 . In comparison, the TAMs T215  and M41  were detected most frequently in the proviral DNA.In the cumulative history of resistance tests of viral RNA, PI-associated resistance mutations could be detected in 30 out of 35 (86%) patients. In contrast, PI-associated resistance mutations were found in the proviral DNA in only 26 out of 35 (74%) patients. The most frequently detected mutated key positions in plasma were I54 , M46  and V82 . At the proviral level, the order of the most frequently found mutated key positions was the same: I54 , followed by M46  and V82 .In all patients, NNRTI-associated resistance mutations could be found in past resistance tests of viral RNA. In the current resistance testing of proviral DNA, resistance to NNRTIs could be detected in only 26 out of 35 (74%) patients. The most commonly detected key positions for mutations in plasma were K103 , Y181  and G190 . Mutated key position K103  was also detected most frequently in the proviral DNA, followed by Y181  and G190 .Only 54% of the patients had a genotypic resistance test of viral RNA for INIs. Of these nineteen patients, only six showed INI-associated resistance mutations in the cumulative history of resistance testing of viral RNA. The most commonly detected mutated key position in plasma was N155 . One patient each had a mutation at the key position E138, G140 or Q148. In the analysis of proviral DNA testing, it was shown that only one patient exhibited a resistance mutation.Only one patient showed concordant results in the genotypic resistance test of viral RNA and proviral DNA for all three substance classes NRTI, PI and NNRTI. Considering the ARVs individually, the same resistance profiles in RNA and proviral DNA could be demonstrated for the NRTIs in 8 out of 35 (23%) patients and for the PIs and NNRTIs in 10 out of 35 (29%) patients. Of the patients with historical resistance tests for INIs, 12 out of 19 (63%) patients showed concordant resistance profiles in the DNA. Significant differences were seen in the number of resistance mutations found in viral RNA and proviral DNA for the three substance classes of NRTIs, PIs and NNRTIs. The data indicated a higher frequency of resistance mutations in viral RNA compared to proviral DNA . In 10 of these patients, the dosing frequency was also reduced, with the median frequency dropping from twice per day to once per day. . Overall, there was a significant decrease in the number of ARV classes in the patients’ regimens from three to two (p = 0.017). Out of all patients, only two had more ARV classes in their new regimen compared to their old regimen.The number of patients taking NNRTIs fell from six to one, as did it for PIs from 15 to 11. Additionally, the number of patients taking entry inhibitors was reduced from seven to two. Prior to the therapy switch, only eight patients received NRTI-containing regimens. However, following the adjustment, 11 regimens contained the NRTI class. The proportion of patients taking INIs remained relatively stable after switching therapy: prior to simplification, 11 patients were taking INIs, and this number only increased slightly to 12 after simplification. An overview of the existing ART regimens and the underlying resistance-associated mutations based on RNA testing, as well as the mutations detected in proviral DNA testing and the new ART regimens, is provided in Drug resistance incidence in high-income countries has decreased but must still be considered when selecting ART for advanced HIV patients with resistance to multiple drug classes ,3,23. MoThe use of complex ART regimens is often a consequence of resistance that accrues gradually over time, typically during periods in which treatment options were limited . In thisOnly two cases demonstrated therapy failure: one due to a lack of adherence to therapy, leading to an increase in viral load, and another in which the regimen had to be changed due to adverse drug reactions despite continued viral suppression.The efforts to simplify therapy have resulted in a significant reduction in both the number of tablets required and the dosing intervals for 10 patients. This is especially significant as the proportion of non-HIV-associated medication is increasing due to newly emerging comorbidities in old age as a result of a longer life span with HIV infection . In partWhile our work has yielded valuable insights, it is important to acknowledge that there are limitations. The sample size of 35 patients was relatively small, as the inclusion criteria were strict, and the number of patients with an appropriate history is small, even in a university-based specialized outpatient clinic. Of those, only 17 patients were able to undergo therapy adjustment, as others were either unsuitable for therapy adjustment due to current resistance or comorbidities or simply refused. In addition, the retrospective evaluation of real-life data that was not subject to a standardized protocol, resulted in inhomogeneous follow-up data ranging from 3 weeks to 1.75 years. In addition, the therapy changes were elective measures without an urgent medical reason, with the exception of patient 4′s adherence problems. This means that one effective therapy was to be replaced by another. Therefore, due to very low viral loads, a direct comparison of the resistance profiles from RNA and DNA was not possible, and historical findings had to be relied upon. Furthermore, in our analysis, we used a “clinical” cut-off value of 2% to identify minor variants, emphasizing the importance of comprehending both the technical and clinical aspects associated with such detection. Despite the fact that it is technically possible to detect valid variants with frequencies below 2%, there is a possibility of false-positive detections, even in treatment-naïve patients . HoweverThus, it cannot be ruled out that some of the mutations found belong to proviruses without replication capability and without clinical relevance. On the other hand, the PMBCs present in the blood sample only provide an insight into a section of the entire latent infection reservoir ; therefoNevertheless, in cases where changing an ART is being considered, current guidelines suggest taking into account various data of the patient’s history . The use


Limited data outside of randomized controlled trials exist reporting the prevalence of integrase inhibitor resistance (INSTI-R) since the approval and recommendation of INSTIs as first-line treatment for HIV. National surveillance data in 2018 estimated INSTI-R to be 6.3% in people with HIV (PWH) who had never achieved viral suppression, with 0.8% attributed to transmitted drug resistance (TDR). The purpose of this study was to describe the prevalence of INSTI-R in patients from a single urban clinic network on INSTI-containing regimens. Prevalence amongst University of Illinois Chicago Community Clinic Network (UCCN) patients on INSTI-containing single-tablet regimens specifically was previously reported.> two recorded HIV-1 RNA viral loads collected > 12 months apart. The primary endpoint was the difference in INSTI-R in UCCN patients compared to national data. Other outcomes included development of virologic failure (VF), defined as > 200 copies/mL in two consecutive HIV-1 RNA viral loads, and patient specific factors associated with VF. The primary endpoint was analyzed using a chi-square test. All other data are presented as descriptive statistics.This was a retrospective study of adult PWH followed at UCCN prescribed an INSTI-containing regimen between September 2017 and September 2020 with Table 1. A total of 5 subjects had INSTI-R prior to switch resulting in a prevalence of 1.6%, which was significantly less than the national prevalence of 6.3% (p< 0.001). Of note, all patients with INSTI-R were previously treated with first generation INSTIs and none were deemed TDR. Study-defined VF occurred in 26 subjects (8.1%). Seven subjects (26.9%) were not taking antiretrovirals for > six weeks at the time of study-defined VF. Outcomes of patients with VF are outlined in Table 2. Subjects with a pre-treatment viral load > 100,000 were more likely to experience VF (p=0.0485).Of 948 patients screened, 321 were included and followed an average of 30 months. Baseline characteristics are presented in Among UCCN patients on INSTI-containing regimens, INSTI-R rates were lower than the estimated national prevalence; however, this comparison is limited due to the large proportion of subjects with viral suppression at baseline.All Authors: No reported disclosures


Tuberculosis (TB) preventive treatment (TPT) is recommended for people living with HIV (PLHIV) in high TB burden settings. While 6 months of daily isoniazid remains widely used, shorter regimens are now available. However, little is known about preferences of PLHIV for key features of TPT regimens.We conducted a discrete choice experiment among adult PLHIV engaged in care at an urban HIV clinic in Kampala, Uganda. In nine random choice tasks, participants chose between two hypothetical TPT regimens with different features . We analyzed preferences using hierarchical Bayesian estimation, latent class analysis, and willingness-to-trade simulations.Of 400 PLHIV, 392  had high quality choice task responses. Pills per dose was the most important attribute , followed by frequency (20.5% [95% CI 19.7 – 21.3]), duration (19.5% [95% CI 18.6 – 20.5]), and need for ART dosage adjustment (18.2% [95% CI 17.2 – 19.2]). Latent class analysis identified three preference groups: one prioritized less frequent, weekly dosing ; another was averse to ART dosage adjustment ; and the last prioritized short and tolerable regimens . All groups highly valued fewer pills per dose. Participants were willing to accept a regimen of 2.8 months’ additional duration [95% CI: 2.4 – 3.2] to reduce pills per dose from five to one, 3.6 [95% CI 2.4 – 4.8] months for weekly rather than daily dosing, and 2.2 [95% CI 1.3 – 3.0] months to avoid ART dosage adjustment.To align with preferences of PLHIV, decision-makers should prioritize the development and implementation of TPT regimens with fewer pills, less frequent dosing, and no need for ART dosage adjustment, rather than focus primarily on duration of treatment. Tuberculosis (TB) preventive treatment (TPT) is strongly recommended to address the high disease burden among people living with HIV (PLHIV) in TB endemic settings . Short-cCurrent WHO guidelines on TB preventive treatment were informed by a single preference study including only 10 participants living with HIV . PrefereChoice-based preference elicitation methods, including discrete choice experiments (DCEs), are increasingly being utilized to more systematically characterize patients’ healthcare preferences and inform policy- and implementation-related decisions –6. CompaWe therefore conducted a DCE among adult PLHIV accessing routine HIV care in Kampala, Uganda. Our objectives were to 1) determine the relative importance of TPT regimen features; 2) simulate how willing participants were to trade one TPT feature for another; and 3) assess the heterogeneity in preferences and identify distinct subgroups of PLHIV with similar preferences.We conducted a cross-sectional survey that included a DCE from July to November 2022. The study took place at the Mulago Immune Suppression Syndrome  clinic, in Kampala, Uganda. The clinic provides comprehensive HIV care to over 16,000 PLHIV and is the largest outpatient HIV clinic in the country.Individuals were eligible for study participation if they were receiving HIV/AIDS care at the clinic, were 18 years or older, had not initiated a TPT regimen in the past year, and were not currently receiving TB treatment. People who were unable or unwilling to provide informed consent or were currently incarcerated were excluded. We defined the inclusion criteria to include individuals eligible for initial TPT or likely to qualify for repeated TPT in the future.The Makerere University School of Public Health Research and Ethics Committee, the University of San Francisco Institutional Review Board and the Uganda National Council for Science and Technology approved the study. All participants provided written informed consent.The DCE was designed using the “balanced overlap” method in Sawtooth Lighthouse Studio version 9.13.2 . An initThe survey was administered one-on-one by a trained interviewer using an electronic tablet. Interviewers first presented general information on TB prevention using a flipbook. Interviewers then explained the DCE attributes and levels using a flipbook with icons from the DCE . In addiWe considered the minimum sample size for the DCE to be 250 PLHIV based on the formula 500c/ta, where ‘c’ is the product of the greatest number of levels for any two attributes, ‘t’ is the number of choice tasks, and ‘a’ is the number of options per choice task . To enabAll analyses were performed in Lighthouse Studio version 9.13.2 (Sawtooth Software) and R version 4.1.2. We excluded participants from analyses if: (1) the dominant fixed choice task was answered incorrectly, (2) the no treatment option was always selected (indicating the participant was not interested in TPT), or (3) participants showed two or more signs of inattention or lack of understanding including ‘straight-lining’ , self-reported difficulty understanding the tasks (“difficult” or “very difficult”) in a question at the end of the survey, and inconsistent choices indicated by a root-likelihood (RLH) fit statistic below 0.651. The RLH threshold was selected based on simulations of random answers as described previously ) . We exclThe majority of participants were female (72%), employed (80%), and ART-experienced, with a median of 10.3 years on ART . Most paOverall, participants assigned the highest relative importance to the number of pills per dose (32.4% [95% CI 31.6 – 33.2]), with one pill per dose being strongly preferred compared to 10 pills per dose . FrequenUsing latent class analysis, we identified three preference groups , all of We explored the association of baseline characteristics with latent class membership and individual preference weights. We found no association between sex, age, poverty, working status, prior history of TB, and years on ART with individual preference weights for duration, number of pills per dose, frequency of dosing and side effects . HoweverWe simulated the tradeoff between treatment duration (in months) and other regimen features . ParticiThis DCE among adult PLHIV in Kampala, Uganda, provides important insights about what features of TPT regimens patients value the most. Although there was substantial heterogeneity of preferences as indicated by three distinct preference groups, all groups showed very strong preference for lower pill burden. While TPT regimens as short as 1 month are now available, participants were willing to accept TPT regimens approximately 3 months longer in order to take 4 fewer pills per dose, 4 months longer to have weekly rather than daily dosing and 2 months longer to avoid ART dosage adjustment. Scale-up of current regimens and future regiment development should consider pill burden, dosing frequency and compatibility with ART rather than focus exclusively on treatment duration.Previous studies have also suggested that pill burden, dosing frequency and compatibility with ART are important considerations for TPT regimens. A study to characterize and understand gaps in the TPT care cascade among PLHIV in Uganda found that pill burden was an important barrier for patients . We prevNotably, more than one-in-four participants (“keep ART as is” group) expressed strong for maintaining their current ART regimen without adjustments. Participants with less ART experience were particularly averse to dosage changes. Additionally, those taking other medications unrelated to HIV were also more resistant changes in their ART dosage, possibly due to concerns about potential drug-drug interactions. Since 2019, the WHO has recommended dolutegravir-based ART regimens as first-line therapy for all PLHIV, and currently over 20 million PLHIV globally are receiving these regimens . While nParticipants in our study generally placed a low value on avoiding mild and moderate or severe side effects compared to other TPT features, a finding that aligns with a best-worst scaling (BWS) choice exercise among PLHIV in South Africa . We alsoOur study had several strengths, including an iterative DCE design process with pilot testing , a largeIn conclusion, our study shows that while there are heterogeneous preferences for TPT-related features among PLHIV in Uganda, there is a strong preference for regimens with lower pill burdens, less-frequent dosing, and no need for ART regimen adjustments. Most participants exhibited a willingness to undergo longer TPT regimens if they could access a TPT regimen with these preferred features. Collectively, our findings suggest that, in order to align with the preferences of PLHIV, policymakers should prioritize the implementation of fixed-dose combinations (FDC) of existing TPT regimens and that future TPT regimens should prioritize reducing pill burden over further reducing treatment duration.Supplement 1Supplement 2Supplement 3


We report a case of incomplete HIV-1 suppression on a dolutegravir, lamivudine, and abacavir single-tablet regimen with the emergence of the H51Y and G118R integrase resistance mutations.Integrase sequencing was performed retrospectively by Sanger and next-generation sequencing. Rates of emergence and decline of resistance mutations were calculated using next-generation sequencing data. Dolutegravir plasma concentrations were measured by ultra-performance liquid chromatography-tandem mass spectrometry. The effects of H51Y and G118R on infectivity, fitness, and susceptibility to dolutegravir were quantified using cell-based assays.During periods of non-adherence to treatment, mutations were retrospectively documented only by next-generation sequencing. Misdiagnosis by Sanger sequencing was caused by the rapid decline of mutant strains within the retroviral population. This observation was also true for a M184V lamivudine-resistant reverse transcriptase mutation found in association with integrase mutations on single HIV genomes. Resistance rebound upon treatment re-initiation was swift (>8000 copies per day). Next-generation sequencing indicated cumulative adherence to treatment. Compared to WT HIV-1, relative infectivity was 73%, 38%, and 43%; relative fitness was 100%, 35%, and 10% for H51Y, G118R, and H51Y+G118R viruses, respectively. H51Y did not change the susceptibility to dolutegravir, but G188R and H51Y+G118R conferred 7- and 28-fold resistance, respectively.This case illustrates how poorly-fit drug-resistant viruses wax and wane alongside erratic treatment adherence and are easily misdiagnosed by Sanger sequencing. We recommend next-generation sequencing to improve the clinical management of incomplete virological suppression with dolutegravir. A world2.2.1.The patient provided written informed consent for the anonymous publication of their clinical data. People living with HIV who are treated at Erasmus Medical Center are enrolled to the National Database HIV Monitoring Foundation , a situation that waives the need for institutional ethics approval.2.2.min = 0.8 – 1.2 mg/L and t1/2 = 14 hours, DTG concentrations below 0.01 mg/L indicated that DTG had not been taken for four days or longer.Viral RNA purification, Sanger sequencing, and next-generation sequencing (NGS) were performed as previously described . We set 2.3.To test the linkage between reverse transcriptase (RT) and integrase mutations, month 36 HIV-1 RNA was reverse transcribed on limit-dilutions and in duplicates (to exclude random recombination) and then cloned and sequenced as described previously , except 3.3.1.The patient was diagnosed with a subtype B HIV-1 infection in 1993. Treatment was initiated in August 1996 with indinavir, 3TC, and stavudine, and periods of irregular retention in care followed related to issues of illicit substance addiction. In 1999, the patient stopped treatment and resumed in 2002 with ritonavir-boosted lopinavir (r/LPV) plus nevirapine. In 2003, treatment was changed to r/LPV plus 3TC and didanosine (ddI). The patient interrupted treatment from January to May 2004, when the r/LPV+3TC+ddI combination was reinitiated. Treatment was again interrupted at the patient’s initiative from April 2004 to June 2006, and r/LPV+3TC+ddI was restarted. After another patient-initiated interruption from September 2006 to June 2007, the same treatment was again prescribed. In December 2009, treatment was switched to r/LPV plus tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). From 1999 to 2008, resistance mutations were documented against nucleoside  and non-nucleoside  reverse transcriptase (RT) inhibitors by routine Sanger sequencing. No resistance was observed against protease or INSTIs. In August 2013, the CD4+ T-lymphocyte count was 10. In 2015, the patient was switched to a single-tablet regimen of DTG plus lamivudine (3TC) and abacavir (ABC) to facilitate treatment adherence and achieve viral suppression with a CD4+ T-cell count of 10 and a viral load of 6.13E+05 RNA copies/mL of plasma. The patient had not been previously treated with another INSTI. Following this treatment switch, the patient attended blood draws but not appointments with the treating physician. This situation hindered treatment assessment and adjustment. Thirty-six months after switching to DTG/3TC/ABC, the patient was hospitalized with pneumococcal pneumonia, where they were offered various interventions to improve treatment adherence. The CD4+ T-cell count was 100, and the plasma viral load was 1.42E+05 copies/mL. A genotypic resistance test using Sanger sequencing revealed the H51Y integrase mutation. Since H51Y by itself has a minimal effect on susceptibility to DTG  RNA copies/day) over two periods of non-adherence to treatment (months 11–15 and 16–24) was comparable or lower to those reported for R263K in two separate clinical cases with BIC and DTG  [The characterization of the effects of H51Y and G118R on infectivity, fitness, and susceptibility to DTG allowed us to interpret our clinical observations as follows: impaired replicative capacity contributed to the waning of drug-resistance mutations during episodes of non-adherence to treatment, whereas resistance levels helped mutations to rematerialize quickly after drug resumption. Our case report exemplifies how the decline of integrase resistance mutations during a period of non-adherence to treatment can prevent their diagnosis by Sanger sequencing. Using linear regression, we calculated that G118R fell under the Sanger sequencing limit of detection  in 42 days despite a concomitant increase in viral loads. This rapid decline happened despite the severe immunodeficiency of the patient who consistently had CD4+ T-lymphocyte counts <110. We speculate that immune competence (i.e. higher CD4+ T-cell counts) can accelerate the disappearance of integrase resistance mutations. The average rate of decline of integrase mutations , and drug resistance, all contribute to the pace of changes in the retroviral population. Drug adherence can be particularly challenging to evaluate, as adequate drug plasma levels at scheduled visits can result from ‘white coat adherence’ before blood collection. Methods to evaluate cumulative treatment adherence, such as unscheduled drug level dosing or antiretroviral drug quantification in hair, can be intrusive, negatively affect linkage to care, necessitate additional consent, or be methodologically challenging to implement . We founThere is a general understanding that DTG- and BIC-based treatment regimens are highly robust against virological failure and the development of resistance mutations. This notion is supported by several studies, including the NADIA clinical trial that compared DTG with the protease inhibitor darunavir and demonstrated high levels of suppression regardless of nucleotide/nucleoside reverse transcriptase inhibitor resistance –14. HoweWe expect most patients to achieve viral suppression with the global expansion of DTG-based antiretroviral therapy. This improvement will shift the clinical focus towards individual cases of incomplete virological suppression, like the one reported here, as well as similar cases in resource-limited countries. When this technology is available, we expect that NGS will also benefit patients from rural settings, who can only manage infrequent visits, by unraveling resistance mutations that may be missed by Sanger sequencing and evaluating cumulative drug adherence, as illustrated here. Thus, more work is warranted to characterize the emergence and maintenance vs. reversion dynamics of integrase resistance mutations against second-generation INSTIs and how NGS can be used as a diagnostic tool in clinical practice for optimal patient care.3.5.We report a case of rapid fading of resistance mutations after patient-initiated treatment interruption that prevented their detection by Sanger sequencing despite high viral loads. Next-generation sequencing was superior and served as an indicator of cumulative drug adherence. We conclude that this method should be favored when managing patients with incomplete viral suppression.


To optimize oral healthcare among people living with HIV (PLHIV) in sub-Saharan Africa (SSA), we sought to evaluate the type and distribution of oral candidiasis with respect to ART-profile and immuno-virological parameters among PLHIV in the Cameroonian context.a cross-sectional study was conducted among 163 patients (51 ART-naïve and 112 ART-experienced) residing in Yaoundé, Cameroon, from February through May 2019. Oral candidiasis was assessed, while viral load (VL) and CD4-count were measured on Abbott m2000rt and Cy-flow counter platforms, respectively. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) v.21 with p<0.05 considered statistically significant.3 and CD4>200 cells/mm3, respectively (p<0.0001). In the light of viral load, the occurrence of oral candidiasis was largely observed among subjects with VL≥1000 copies/ml, 83.3% (15/18), against 16.7% (3/18), with VL<1000 copies/ml, irrespective of the candidiasis form (p<0.0001).in all, 18 cases of two forms of oral candidiasis were identified (13 erythematous and 5 pseudomembranous), with the majority, 27.7% (11/51), observed among ART-naïve patients against 6.3% (7/112) in ART-experienced (p=0.006). With respect to immuno-virological profile, 77.8% (14/18) and 22.2% (4/18) of cases were identified among participants with CD4<200 cells/mmamong PLHIV, erythematous and pseudomembranous candidiasis are commonly found in the absence of ART, driven by immunodeficiency and active viral replication. In spite of the protective role of ART, PLHIV experiencing immuno-virological failure should be referred for management of oral candidiasis. Candida albicans. It represents more than 60% of yeasts isolated in humans [3 [Candidiasis is an opportunistic muco-cutaneous fungal infection caused by saprophytic fungi mainly n humans ,2. Candin humans . Biologin humans . Thus, tn humans -7. Of non humans . Accordin humans , with ann humans . Oral man humans ; thus, on humans . The occumans [3 . Apart fumans [3 . Meanwhiumans [3 . In ordeStudy design and setting: a cross-sectional and analytical study was conducted from February through May 2019 among PLHIV attending the Chantal BIYA International Reference Centre for Research on HIV/AIDS prevention and management (CIRCB), and the Jamot Hospital of Yaoundé. These two health facilities were chosen because of their strong involvement in the monitoring of people living with HIV in Cameroon and in the city of Yaoundé in particular.Sampling and enrollment criteria: a statistical formula frequently used to determine sample size in medical studies [ studies ; togethe studies  were useα= standard normal variate ; p= prevalence of HIV in Cameroon (2.7); d= precision of the estimate (0.05). Substituting the figures in the above formula yields 40 (nearest whole number). Thus, a minimum of 40 participants was required. Participants enrolled were those who fulfilled the following criteria; a) be a person living with HIV/AIDS; b) understood the purpose of our finding and gave his/her consent to take part in the study; c) be at least 18 years old. We excluded patients who fell short of the aforementioned criteria. Also, those with other co-morbidities , as well as those on prolong use of antibiotics (other than HIV- ART) and pregnant women were not included in this study.where: ZClinical data collection and examination: a structured-questionnaire was used to obtain sociodemographic characteristics of each participant. Treatment history (for those exposed to ART) and oral hygiene competence (brushing frequency) were equally assessed. We performed oral examination using a dental consultation tray, a tongue depressor, and a mouth mirror. Based on oral clinical presentation, location of lesions, presence or absence of bleeding, and whether the whitish coating had peeled off, the presence and type of oral candidiasis was determined. We assessed oral hygiene using Silness and Loe classification model [on model : where; Assessment of immunological and virological parameters: blood samples collected from HIV-infected patients were analyzed at the clinical diagnostic laboratory of CIRCB for CD4 cell count and plasma viral load. Briefly, CD4 count was performed using the Cyflow Counter-Sysmex Partec as per the manufacturer´s instructions [ructions ; viral lructions , with a Variables: variables included gender, age, oral hygiene, treatment , and oral candidiasis. The rate and type of oral candidiasis was distributed according to gender, age, CD4 count, viral load, and treatment.Data processing and statistical analysis: data were entered into Microsoft Excel 2013 and analyzed using the statistical software SPSS version 21 with results presented as mean, standard deviation, median, quartiles, frequencies and percentages. Bivariate analysis was done using Fischer´s exact and Chi-square test to determine oral candidiasis associated factors. Multivariate analysis was done using the logistic regression model. All p-values <0.05 were considered statistically significant.Characteristics of the study population: a total of 163 participants were enrolled including 63 (38.7%) males and 100 (61.3%) females. Considering treatment-exposure, 51 (31.3%) were ART-naïve while 112 (68.7%) were ART-experienced patients. In the ART-naïve population, we had 20 (39.2%) males and 31 (60.8%) females, while in the ART-experienced population, 43 (38.4%) were males while 69 (61.6%) were females . Majority, 21.6% (11/51) was found among ART-naive PLHIV compared to the ART-experienced group that recorded merely 6.3% (7/112); p=0.006 (OR: 4.125: 95%CI: 1.49-11.39) (9-11.39) . Two for9-11.39) .Distribution of oral candidiasis according to CD4 count: based on CD4 cell count, all oral candidiasis cases observed among naïve patients had CD4<200 cells/mm3, with 30.4% (7/23) and 17.4% (4/23) having the erythematous and pseudomembranous forms, respectively (3 and CD4>200 cells/mm3 (p=0.65). Those with the pseudomembranous form (CD4 counts 200 cells/mm3) represented 2.7% (1/37) and 0.0% for CD4>200 cells/mm3  were found to have erythematous candidiasis, whereas 24% (6/25) had VL≥1000 copies/mL  (87-7.21) . Pseudom87-7.21) . Among A87-7.21) .Distribution of oral candidiasis with respect to oral dental hygiene practice: it was observed that all the diagnosed cases (18) of oral candidiasis were among individuals who practiced average, 10.4% (15/144) and poor, 23.1% (3/13), oral care, (p=0.24) ((p=0.24) .Distribution of oral Candidiasis according to ART regimen: according to ART regimen, patients on TDF+3TC+EFV had the highest number of oral candidiasis cases, 6.3% (5/79) followed by patients on AZT+3TC+NVP, 20.0% (2/10), p=0.11 , oral hygiene, CD4 count (<200 cells/mm3 and ≥200 cells/mm3), and viral load (<1000 copies/ml and ≥1000 copies/ml), we found that compliance  and viral load  were significantly associated with the occurrence of oral candidiasis.This study was aimed at evaluating the relationship between oral candidiasis and HIV coinfection, taking into account ART-exposure, immunological and virological status of HIV-infected individuals. Women by virtue of biological difference (anatomy) and sociocultural reasons, are naturally more prone to STIs acquisition than their male counterpart ,18. Of t3 with OR= 6 and OR=3 respectively [et al., who found that patients with high viremia had an eleven-fold increased risk of developing oral candidiasis compared to those virologically suppressed [3) should be managed and monitored for oral candidiasis.Actually, the relationship between candidiasis and CD4 cells is not direct. The major role in the resolution of oral candidiasis is mediated by a synergistic action between innate and acquired cell-mediated immunity . Macrophectively ,34. Thesectively ; which pppressed . ConsideLimitations: results obtained were based on two study sites and may not be applicable to the entire population/country. Also, no psychometric testing was used while collecting data and the ART-naïve population was small. There was lack of follow-up for these patients and the characterization of the oral microbiome in HIV-infected and HIV-uninfected subjects with their ART status was not done and could have been worth evaluating. Hence, studies covering these aspects should be carried out especially for the ART-naïve populations.In resource limited settings like Cameroon, oral candidiasis is still of concern among PLHIV with about 1/10 people affected. Erythematous and pseudomembranous candidiasis are commonly found in the absence of ART, driven by immunodeficiency and active viral replication as well as inadequate and poor oral hygiene. In spite of the protective role of ART, PLHIV experiencing immuno-virological failure should be referred for management of oral candidiasis.Oral candidiasis is an important indicator of suppressed immunity among people living with HIV;Antiretroviral treatment preserves the immune system and limit opportunistic oral candidiasis.With the dispensation of the Cameroon´s “test and treat” strategy for HIV, oral candidiasis is now more associated with virological failure and not immunological failure;The occurrence of oral candidiasis among people living with HIV in the city of Yaoundé Cameroon is largely associated with poor and inadequate oral hygiene practice.


There have been limited studies linking baseline factors, including the viral load (VL) test, with virological non-suppression since the introduction of dolutegravir (DTG)-based regimens as first-line antiretroviral treatment (ART) in Ethiopia. This study aimed to identify baseline factors associated with virological non-suppression between October 2020 and July 2022. A follow-up study was conducted in eastern Ethiopia among newly diagnosed people living with HIV (PLHIV). A questionnaire and a checklist were used to collect the data. Five milliliters of venous blood were obtained at baseline and six months to determine the VL. A VL test was performed using the Abbott RealTime HIV-1 assay. To determine predictors of virological non-suppression, bivariate and multivariate logistic regression analyses were used. There were 235 PLHIV enrolled, 70.6% of whom were female, with a mean age of 33.9 years. Of the 161 retained on ART, virological non-suppression was 8.7% at six months. Baseline predictors of virological non-suppression were age ≤ 30 years, a history of substance use, and a VL greater than 4-log10 copies/mL. In this cohort, virological non-suppression was found to be optimal but still lagged slightly behind the third 95%–target. Thus, targeted interventions, the introduction of baseline VL testing to improve treatment outcomes, and fostering the attainment of UNAIDS 95–95–95 targets are recommended. Furthermore, broader research is recommended to explore the reasons for virological non-suppression in the study area. The human immunodeficiency virus (HIV) is a significant threat to public health. Africa is the most severely affected continent, accounting for more than two-thirds of all PLHIV . In EthiIt is well known that virological non-suppression has become a common public health challenge in several African countries due to various multidimensional factors . The estThe ultimate goal of combination ART (cART) for PLHIV is to achieve long-term virological suppression. However, various factors influence virological suppression, including baseline socio-demographic factors, behavioral, clinical, ART, and immunological profiles, and laboratory characteristics. The male gender, being younger in age, and having poor ART adherence, low CD4 count, opportunistic infections, WHO clinical stage III/IV, a history of substance use, ART regimen type, active co-infection with tuberculosis (TB), not using cotrimoxazole prevention, a lack of awareness of the benefits of viral suppression, ART-induced side effects, pretreatment drug resistance, and a high baseline VL are some of the risk factors reported so far ,18,19,20The WHO recommended that low-and-middle-income countries (LMIC) carry out VL monitoring at six months, at twelve months, and then annually for people who are stable on ART . EthiopiDTG is an integrase inhibitor that was recently approved. It is available as a once-daily dosing for HIV patients, has a high genetic barrier to resistance, and is safer than non-DTG-based cART . HoweverThis cohort follow-up study was conducted in 15 selected public health facilities  in eastern Ethiopia . The enrA multi-center, health facility-based cohort of PLHIV follow-up study was conducted in eastern Ethiopia. The cohort comprised all newly diagnosed HIV-positive clients who were on DTG-based first-line ART as per the current national guidelines. During the baseline data collection period, study participants were enrolled consecutively and followed up on the ART for the next six months. All the study participants received standard HIV care at participating facilities, including initial ART adherence and routine laboratory monitoring. In addition, available clinical and immunological data at ART initiation were collected. Participants provided blood samples for the baseline VL test at the time of ART initiation and then at six months, as indicated in the national guidelines. Eligible individuals who had already started ART prior to providing a blood sample and those who were critically ill at the enrollment period were excluded from the study.The sample size was calculated using the WHO sample size determination criterion for HIV pretreatment drug resistance (PDR) . This stAt baseline, a structured interviewer-administered questionnaire and checklists were used to collect socio-demographic factors, clinical data, laboratory parameters, and information regarding the initiated first-line ART regimen. Study participants or caregivers/guardians of children/adolescents aged less than 18 years were interviewed by trained nurses using a face-to-face interview technique. Moreover, following standard operational procedures, approximately 5 mL venous whole blood samples were collected from all newly diagnosed HIV-positive individuals using tubes containing the anticoagulant ethylene diamine tetra-acetic acid. Plasma samples were harvested by centrifugation of whole blood at 3500 rpm for 5 min and aliquoted into Cryo tubes of 1.8 mL volume. Plasma samples were labelled with the medical registration number (MRN), before the format with some basic information to identify samples was sent to Harari Health Research and Regional Laboratory, Harar, Ethiopia, for HIV-1 RNA VL testing. The samples were then stored at −80 °C for long-term analysis. A similar approach to the baseline data collection method was used at the six-month follow-up. The interviews were conducted, data were collected, and relevant parameters were recorded using checklists. The VL was determined at six months as part of the routine follow-up.https://www.abbottmolecular.com accessed on 8 March 2023). The presence of the HIV-1 target sequence is indicated by the fluorescent signal generated using fluorescently labeled oligonucleotide probes on the Abbott m2000rt machine. The test was performed in the presence of positive, negative, and internal controls. The detection limit of the assay for the plasma sample was over the range of 40–10,000,000 copies/mL.The collected plasma samples were processed and the VL tests were performed at the Harari Health Research and Regional Laboratory in Harar, Ethiopia. The samples were thawed at room temperature before the VL was run. The Abbott m2000sp automated sample preparation system and the Abbott m2000rt with quantitative Abbott RealTime HIV-1 assay (RT-PCR)  were used for the extraction of HIV-1 RNA and the determination of plasma VL, respectively. The sample preparation (m2000sp) instrument was used for automated extraction, purification, and preparation of HIV-1 RNA. The m2000rt amplifies, detects, and measures the HIV-1 RNA load. A volume of 0.2 mL of the plasma samples was used for RNA extraction according to the manufacturer’s instructions. The extracted HIV-1 RNA (eluent) was amplified and detected on the m2000rt Abbott platform, both at baseline and at six months of follow-up following the manufacturer’s instructions  of 95% and a p-value of <0.05 were considered statistically significant.EpiData Manager version 4.6.0.4 was used to code and enter the data. STATA/SE version 14.0 was used for the statistical analysis. For analysis, the log10 transformation of the HIV-RNA VL was used. Demographic and clinical characteristics were summarized using a descriptive analysis. Bivariate and multivariate logistic regression models were used to determine baseline factors associated with virological non-suppression at six months. All variables with In this study, 235 newly diagnosed PLHIV who initiated first-line ART were enrolled, with 70.6% of them female. The mean age of the participants was 33.9 years (SD: ±12.1), with a range of 2–70 years. The overall history of substance use at baseline was 35.3%, and the khat chewing habitual was 34% (80/235) .Three-quarters of the study participants were from hospitals (74.9%). More than half of the newly diagnosed participants (60.4%) were linked to ART care through outpatient department (OPD) services. The current TB co-infection was 17%, whereas the overall comorbidity rate at the start of ART was 39.2% .Approximately 72.8% started ART treatment on the same day as diagnosis. At enrollment, 55.7%, 79.6%, 76.2%, 96.2%, and 94.9% of the participants were at WHO clinical stage I, working in functionality status, had a detectable VL (>150 copies/mL), had initiated TDF + 3TC + DTG (1J) first-line ART, and 2NRTI + INSTI classes, respectively. The proportion of participants with baseline HIV RNA VL results greater than 100,000 copies/mL was 23.4%, with results ranging from the target not detected to 4,102,070 copies/mL .The overall ART treatment outcomes at six months were 68.5% retention in ART, 16.6% loss to follow-up (LTFU), 8.9% transferred out, and 5.9% deceased . Of the p = 0.0032). To control for confounding factors, variables with p-values of 0.25 in bivariate analysis were imported into a multivariate logistic regression model , a history of substance use at baseline , and a baseline HIV RNA VL greater than 4log10 copies/mL  were independently associated with virological non-suppression at six months. The odds of virological non-suppression at six months were approximately nine times (AOR = 8.90) higher in those younger than 30 years old compared to those older than 30 years old. Moreover, among PLHIV with a history of substance use and a VL greater than 4-log10 copies/mL at baseline, the likelihood of viral non-suppression at six months was 7.5 (AOR = 7.50) and 12.6 (AOR = 12.64) folds higher, respectively .The magnitude of virological non-suppression in this study was 8.7%, and the predictors of virological non-suppression at six months were age less than 30 years, a history of substance use, and a baseline VL > 4-log10 copies/mL. Virological suppression is an important factor in PLHIV health maintenance and plays a great role in the prevention of new HIV cases. In contrast, non-suppression of virological treatment is a key challenge for HIV programs, particularly in LMICs, because the likelihood of drug resistance and subsequent viral transmission, especially that of drug-resistant strains, increases when virological suppression is not achieved.The rate of virological non-suppression was comparable with studies conducted in various places in Ethiopia: 8.3% at TASH , 10.24% In the current cohort, viral non-suppression was unlikely among PLHIV aged less than 30 years compared to their counterparts. The result was similar with other studies from SSA African countries such as Uganda, Tanzania, and South Africa ,37,38. TThis study showed that the likelihood of virological non-suppression was 7.5 folds higher among PLHIV who reported substance use  during ART initiation. Studies conducted in South Africa revealed that substance use had higher odds of unsuppressed viral load than those who reported no substance use ,45. MoreThe current study also found that PLHIV with a baseline VL > 4-log10 copies/mL had higher odds of virological non-suppression six months after first-line ART. Previous studies found that a low baseline VL was a predictor of viral suppression (AHR = 1.56) , whereasIn summary, baseline VL testing is not performed in the majority of LMICs, including Ethiopia, and people who test positive for HIV begin ART without a VL test. In light of this, in addition to the efforts to achieve the targets of the 95s, it is preferable to reconsider the current guidelines for the routine and the first VL test at six months for PLHIV. Not only can baseline VL testing benefit HIV-positive individuals, but it can also assist healthcare professionals in implementing VL-triggered adherence support strategies that may improve patient treatment results . As a reThis study has several strengths, including being conducted at multiple sites over a period of six months in eastern Ethiopia. The cohort comprised newly diagnosed PLHIV who started ART in routine HIV care. Baseline factors that can predict virological non-suppression were assessed, including baseline VL testing and the untapped area in Ethiopia. This study provides insight by generating baseline regional epidemiological and clinical data for the health sectors, which will be used for program-wide trend monitoring.However, this study has some limitations. The result of HIV drug resistance was not included, which could lead to virological non-suppression. The rate of virological non-suppression may be underestimated owing to the relatively small sample size because of the loss to follow-up, transfer out, and deceased participants. Furthermore, those with low baseline viremia at enrollment could deceitfully lower the virological non-suppression at six months. In this study, COVID-19 may have also affected the adherence of the patients. Moreover, immuno-hematological parameters were not adequately captured, as they were not implemented routinely because of their minimal importance and shortage of supplies. Therefore, it is important to consider these limitations when interpreting the conclusions of this study.Virological non-suppression after six months of receiving DTG-based first-line ART is found to be optimal in newly diagnosed HIV-positive people. A younger age, a history of substance use, and a VL more than 4-log10 copies/mL at ART inception were baseline predictors of virological non-suppression at six months. Therefore, HIV treatment and care programs, as well as stakeholders, should pay due attention to PLHIV with the identified determinants—potentially through targeted interventions such as optimizing differentiated service delivery for those who did not achieve viral suppression. This finding emphasizes the significance of baseline VL monitoring. To improve treatment outcomes and reduce the incidence of HIV transmission, efforts are needed to introduce cost-effective, rapid, and decentralized baseline VL testing. Furthermore, conducting more comprehensive and broader research is recommended to explore reasons for virological non-suppression in the study area.


People with HIV (PWH) face many challenges in obtaining HIV care. Long-acting (LA)-injectable antiretroviral therapies (ART) can address some of these barriers. This project aimed to determine the percentage of patients who could receive the LA-injectable ART cabotegravir/rilpivirine (CAB/RPV) as an alternative to an oral daily pill regimen based on clinical indications.We retrospectively reviewed medical records of adult PWH seen at the University of Missouri Health Care (MUHC) HIV outpatient clinic in Columbia, MO. We collected demographics, CD4 counts, hepatitis B status, HIV viral load, and HIV genotype resistance data. The primary endpoint was the percentage of PWH who would qualify to receive the LA-injectable ART CAB/RPV based on an undetectable HIV viral load, no documented chronic hepatitis B status, and no resistance to either CAB or RPV based on the Stanford University HIV Drug Resistance Database.Six hundred and twenty-five unique PWH were receiving care at MUHC with a median age of 49 years old, 20% female, 27.5% Black/African American, 4.8% Hispanic and/or Latino, and 9.1% with AIDS (CD4 count < 200 cells/uL). 17.9% of PWH were not eligible for the LA-injectable ART CAB/RPV due to a detectable HIV viral load . An additional 7.2% did not qualify due to having a genotype resistance to CAB or RPV and 1.8% did not qualify due to having chronic hepatitis B. Altogether, 151 PWH (24.2%) had one or more clinical contraindications for the LA-injectable ART CAB/RPV based on current guidelines. Genotype resistance testing was not available for 59.6% of PWH. However, out of the 474 PWH who are eligible to receive the LA-injectable ART CAB/RPV, only 76 (16.1%) are currently in care and on this regimen.In this study, we identified a high percentage of patients with no available genotype and a low uptake of the new LA-injectable ART CAB/RPV. To optimize the use of the the LA-injectable ART CAB/RPV and to make it accessible to PWH who could benefit from it, further research needs to be done using both quantitative and qualitative measures to identify barriers and facilitators at the patient, provider, and system level and to develop effective implementation strategies.Dima Dandachi, MD, MPH, ContraFect Corporation: Grant/Research Support|Missouri Foundation for Health: Grant/Research Support|ViiV healthcare: Grant/Research Support|ViiV healthcare: Honoraria


This study aimed to assess the prevalence of oral lesions in patients living with HIV infection and their association with CD4 count, viral load, and antiretroviral therapy in patients with HIV.A cross-sectional study was conducted on a sample of 161 patients attending the… All the patients were examined for their oral lesions, current CD4 counts, type, and duration of the therapy. Data analyses were carried out using Chi-Square, Student T/Mann-Whitney, and logistic regression tests.p = 0.04), as well duration of treatment (p = 1.53e-3) and age (p = 0.02). Hyperpigmentation was related to race (p = 0.01) and smoking (p = 1.30e-6). CD4 count, CD4:CD8 ratio, viral load, or type of treatment were not associated with oral lesions. Logistic regression showed that the duration of treatment has a protective effect on the periodontal disease with dental mobility , independent of age or smoking. To hyperpigmentation, the best model included smoking , without race or type and duration of treatment.Oral lesions were observed in 58.39% of patients with HIV. Periodontal disease with 78 (48.45%) or without mobility 79 (49.07%) was observed more frequently, followed by hyperpigmentation of oral mucosa 23 (14.29%), Linear Gingival Erythema (LGE) 15 (9.32%), candidiasis pseudomembranous 14 (8.70%). Oral Hairy Leukoplakia (OHL) was observed only in 3 (1.86%). A relationship between periodontal disease with dental mobility and smoking was found . Despite all advances in the prevention and treatment, the pandemic of Human Immunodeficiency Virus (HIV) is still a worldwide health problem. Approximately 38 million people globally are living with HIV, being that 1.7 million people acquired HIV and 690.000 lives were lost to AIDS (acquired immunodeficiency syndrome) related illnesses in 2019. Despite the availability of effective treatments, only 67% of people living with HIV have access to Antiretroviral Therapy (ART)Oral lesions are one of the most important indicators of HIV infectionOral lesions associated with HIV infection have a negative impact on the quality of life of infected patients and make it difficult to treat various systemic diseasesThe treatment of HIV infection with HAART increased survival and reduced mortality for AIDS-related diseasesThe ‘Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)’ guidelinesThis cross-sectional study was conducted on a sample of 161 patients attending the Centro de Referência em Atenção Especial à Saúde (CRASE) in Governador Valadares, Brazil. Sample size calculation was realized using the effect size of 0.30, α error of 0.05, power of the sample of 0.80, and significance level <0.05 in. G power software version 3.1.9.6. The patients were registered to the CRASE for their primary health care and regular checkup from July 26 to December of 2019. The study protocol was approved by the research committee at the Federal University of Juiz de Fora, Brazil, under the number (#1.821.072). All information about the patients and their identity was anonymous. Subjects were given both verbal and written information about the nature of the study and written consent was obtained.The inclusion criteria were patients who were diagnosed as HIV positive and were on ART therapy independent of age and sex and patients diagnosed as HIV positive with viral load indetectable who were not using ART therapy. All adult patients living with HIV/AIDS (PLWHA) who attended the clinic and satisfied the inclusion criteria were recruited. The exclusion criteria were patients who did not follow up the treatment and patients who did not accept to participate in the study.A well-structured questionnaire to collect relevant social and demographic details from the study patients was applied. The initial or baseline CD4 count, and other data were retrieved from medical records and other relevant documentation. Patient records were evaluated, and oral examination was conducted by a single examiner trained in oral diagnosis (SNA) and performed on all PLWHA at the time of routine medical consultation. A thorough clinical examination of the oral cavity was performed with sterile gauze and spatula under artificial light. Oral lesions were diagnosed according to the criteria of EEC Clearinghouse ClassificationAll the patients were examined for their oral manifestations, current CD4 counts, and the type and duration of the therapy. PLWHA who were found to have dental lesions, such as caries, periodontal disease, or missing teeth, were referred to dental clinics for management.3) and viral load were considered only when evaluated at most two weeks before data collection. The duration of the HAART therapy was also divided into two ranges: 1) ART therapy ≤2 years and 2) ART therapy >2 years. Type of therapy was classified into monotherapy, dual therapy, and HAART. The star of treatment after diagnosis was divided into ≤1 and >1 year.The subjects were grouped according to the status of CD4 count, viral load type, and duration of treatment received as follows: The CD4 counts which were recorded were divided into under three ranges:1) CD4 count <200; 2) CD4 count between 200 and 500 and 3) CD4 count >500. The viral load (cp/mL of blood) was divided between >1000, 40 to 1000, and undetectable. The CD4+ T cell count  were applied to assess comparisons between groups. Logistic regression analysis was also realized to evaluate the periodontal disease, smoking, age, and duration of and antiretroviral therapy. As well, hyperpigmentation and duration of treatment and race. The significance level was set at 95% (p <  0.05).All the ranges were expressed in percentages. All the findings were tabulated, and the results were analyzed using measures of central tendency. The data collected were analyzed using JASP Team (2020) software version 0.14.1 (University of Amsterdam). Differences in the prevalence of oral manifestations associated with HIV-infected patients were compared between age, gender, ethnicity, the habits of smoking, alcohol drugs habits, possible transmission, duration of treatment, the start of treatment, antiretroviral therapy, TCD4 cell count, and viral load. Chi-Square, Student A total of 161 patients with HIV were enrolled in the study. 15 of 176 patients were excluded due to undetectable viral load and absence of treatment at the time of the data collection.The mean age of HIV patients was 43.63 ± 12.66 years (range: 18–75 years), with a predominance of male 83 (51.55%) than female 78 (48.45%) patients. The mean age at the time of diagnosis was 35.83 ± 11.77 years. Low education (<8 years) was observed in most participants (64%). Regarding the habits of patients, most of the patients reported the non-use of cigarette smoking 121 (75.16%), non-alcohol consumption 106 (65.84%), and illicit drugs 153 (95%) . Most ofp =  0.76). No statistical difference was observed between sex, race, habits, duration of infection, duration of HIV treatment, and time between diagnosis and start of treatment , being 53 (56.38%) and 41 (43.62%) of male and female patients, respectively. Regarding the habits of patients, most of the patients with oral lesions reported the non-use of cigarette smoking 67 (71.28%), non-alcohol consumption 60 (63.83%), and non-use of illicit drugs 89 (94%). A higher prevalence of associated oral manifestations was observed for non-Caucasian patients 60 (64.52%). Among patients with associated oral manifestations, the HAART therapy was considered by most patients 60 (63.83%), followed by dual therapy 31 (32.98%) and monotherapy 3 (3.19%). No differences were observed for the different ART therapies (reatment .p =  0.61) and age at diagnosis (p =  0.40).No statistical difference was observed between the presence of associated oral manifestations and age (3) data was available only from 73 patients. The minority of patients 13 (17.81%) had a CD4+ T cell lower than 200. Thirty-six patients had a CD4+ T cell count between 200–500 (49.32%), and 24 (32.88%) had a CD4+ T cell count above 500. Regarding the ratio between CD4+ T and CD8+ T the high prevalence of patients and associated oral manifestations was observed for ratio <1 (87.5%). The viral load (cp/mL of blood) was available from 126 individuals. Associated oral manifestations were observed more frequently on patients with undetectable viral load, however without statistical significance (p =  0.28) (The CD4+ T cell count (cells/mm=  0.28) .p =  0.04), duration of treatment (p =  1.53e-3), and with age (p =  0.02) but not type of treatment, viral load, or CD4+ T cell count. Hyperpigmentation was related to race (p =  0.01) and smoking (p =  1.30e-6) but not with type or duration of treatment as well viral load or CD4+ T cell count.This study found the prevalence of 6 associated oral manifestations . Betweenr² = 0.15, p =  1.03e-3). The results showed that duration of treatment has a protective effect on periodontal disease with dental mobility  and smoking has a risk effect . To hyperpigmentation, the best model  included only smoking .According to periodontal disease with mobility, the best model in the logistic regression included duration of treatment, age, and smoking  showed TCD4+ below 200 cells/mm3 and most patients showed undetectable viral loads. Therefore, these results should be interpreted with caution due to this limitation.HIV-associated oral manifestations have been reported to appear more frequently when there is a decreased TCD4+ cell count and increased viral load,Oral lesions in HIV-infected patients did not follow a common pattern and differs according to regions of the world. Periodontal health should be considered an important factor for a better quality of life in patients living with HIV27Candida species in the subgingival tissueUnlike conventional gingivitis, LGE usually does not respond to routine oral hygiene measuresCandida is a common opportunistic pathogen and Oral Candidiasis (OC) in the variant of pseudomembranous candidiasis was seen in 14 patients using ART. These values are corroborated with the data found in the literatureIt is important to highlight that although there was a decrease in associated oral manifestations with HIV patients after ART therapy, the prolonged use of some therapies can increase some types of oral lesions, such as hyperpigmentation, xerostomia, and hypertrophy of salivary glandsThis study had some limitations such as only patients over 18 years of age participated in the study and the study group was restricted to the Governador Valadares region, not the entire state, or country. Not all patients had CD4 + T cell counts and viral loads data at the time of oral examination. Also, in this study, only dental mobility and gingivitis were evaluated due to structural limitations.These results demonstrated a presence of associated oral manifestations in patients on ART therapy, although this incidence is high only for periodontal disease with or without mobility. However, it must be important to emphasize that the presence or absence of oral lesions can serve as an indicator of HIV and indexes of treatment successOur results showed that among patients living with HIV undergoing antiretroviral treatment oral lesions can be observed, predominantly periodontal disease with or without dental mobility. Pseudomembranous candidiasis and oral hairy leukoplakia were also observed, however less commonly. No relationship was found between associated oral manifestations in HIV patients and the start of the treatment, TCD4+ and TCD8+ cell count, TCD4:TCD8 ratio, or viral load. The data indicate that there is a protective effect of duration of treatment with relation to periodontal disease with mobility and that hyperpigmentation seems to be more related to smoking than type and duration of treatment.The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.The study protocol was approved by the research committee at the Federal University of Juiz de Fora, Brazil (#1.821.072).Subjects were given both verbal and written information about the nature of the study and written consent was obtained.The authors declare no conflicts of interest.