Talaromyces marneffei (TM) is a common cause of HIV-associated opportunistic infections in Southeast Asia. Cotrimoxazole (CTX) inhibits folic acid synthesis which is important for the survival of many bacteria, protozoa, and fungi and has been used to prevent several opportunistic infections among HIV/AIDS patients. We question whether CTX is effective in preventing TM infection. To investigate this question, we conducted an 11-year (2005–2016) retrospective observational cohort study of all patients on the Chinese national antiretroviral therapy (ART) programme in Guangxi, a province with high HIV and TM burden in China. Survival analysis was conducted to investigate TM cumulative incidence, and Cox regression and propensity score matching (PSM) were used to evaluate the effect of CTX on TM incidence. Of the 3359 eligible individuals contributing 10,504.66 person-years of follow-up, 81.81% received CTX within 6 months after ART initiation, and 4.73% developed TM infection, contributing 15.14/1,000 person-year TM incidence rate. CTX patients had a significantly lower incidence of TM infection than non-CTX patients  = 0.50, 95% CI 0.35–0.73). CTX reduced TM incidence in all CD4+ cell subgroups , with the highest reduction observed in patients with a baseline CD4+ cell count <50 cells/μL in both Cox regression and the PSM analyses. In conclusion, in addition to preventing other HIV-associated opportunistic infections, CTX prophylaxis has the potential to prevent TM infection in HIV/AIDS patients receiving ART.The dimorphic fungus  Mycobacterium tuberculosis (MTB), Talaromyces marneffei , Human Herpes Virus-8 , and Pneumocystis jiroveci   . As shown in < 0.001] .Table 3+ cell count was independently associated with a higher TM incidence  (Table S1). As shown in + cell count <50 cells/μL, which was significantly higher than those in non-CTX patients with a CD4+ cell count of 50–99 cells/μL or with a CD4+ cell count of 100–199 cells/μL. Similarly, in the CTX group, TM incidence in patients with a CD4+ cell count <50 cells/μL  was significantly higher than patients in the CTX group with a CD4+ cell count of 50–99 cells/μL or with a CD4+ cell count of 100–199 cells/μL  (Table S1).In addition to CTX prophylaxis and baseline CD4χ2 = 0.30, p = 0.96, Table S2). And there was no significant difference in the mortality between the CTX group and the non-CTX group in the first 6 months of follow up .In addition, among 159 patients with TM infection, there was no significant difference in the distribution of seasonality of TM infection between CTX group and non-CTX group  (p < 0.001)  . The eff< 0.001) .Table 5+ cell count of <200 cells/µL, we report for the first time a TM incidence and an incidence rate 4.73% over a median follow up period of 2.47 years and 15.14/1,000 person-year, respectively. These numbers are lower than the reported TM prevalence of 16.1% among hospitalized HIV-infected patients in our recent study from the same hospital (FPHN) [In this 11 year retrospective cohort study of HIV-infected patients starting ART in Guangxi province in China with a CD4l (FPHN) , because+ cell count of <200 cells/µL. This finding is supported by both the whole population multivariable Cox regression analysis of a relatively large study population with fairly good follow up data and by the PSM sub-population analysis that sought to reduce biases in the distribution of potentially confounding variables. Our finding is novel and interesting; however, there are some potential factors that might influence the finding. The first factor is the baseline CD4+ cell count. Lower CD4+ cell counts have been associated with opportunistic infections such as tuberculosis and PJP among HIV/AIDS patients [+ cell count [+ cell count was identified to be a major factor influencing TM infection (Table S1). Was there a significant difference in baseline CD4+ cell count between CTX group and non-CTX group? To address this issue, Kaplan-Meier curves of TM accumulated incidence were drawn for each CD4+ cell subgroup and a PSM analysis matched for baseline CD4+ cell count was performed. In all three CD4+ cell count subgroups and in the PSM analysis with matching baseline CD4+ cell count, the association between CTX use and reduced TM infection was consistently observed, indicating baseline CD4+ cell count does not affect the relationship of CTX use and reduced TM infection. In fact, the benefit of CTX was most significant in the lowest CD4+ cell count subgroup (<50 cells/µL). This provides further support for the finding because if CTX has an inhibitory effect on TM infection, the effect would be expected to be most profound in the patient group who has the highest burden of TM infection, and this was what we found. Another potential confounder is the difference in risk of TM exposure of patients. TM infection is known to occur more frequently during the rainy months in northern Thailand and southern Vietnam [Our study revealed that CTX prophylaxis starting within 6 months after ART initiation was associated with a reduced incidence of TM infection in patients with a CD4patients . Severalll count ,29. In o Vietnam ,30. Envi Vietnam ,31. Thes+ cell count <50 cells/μL  as we do not expect the benefit of CTX to persist that long if ART was effective  had a baseline CD4+ cell count ≥200 cells/μL , (iii) had no follow-up records, (iv) had no follow-up records after 10 July 2011 (because the FPHN started to record TM infection as a separate disease after that date). Data from eligible individuals were collected using a standardized case report form. Data collected included baseline CD4+ cell count, WHO HIV clinical stage, time from clinic registration to ART initiation, seasonality at time of TM infection , Hepatitis B surface antigen (HBSAg) positivity, Hepatitis C Virus (HCV) chronic infection (i.e. positive HCV RNA), thrush, hairy cell leukoplakia, PJP, esophageal candidiasis, extrapulmonary tuberculosis, and toxoplasma encephalitis infection [This retrospective cohort study was conducted at the FPHN, which is the largest specialized infectious disease tertiary hospital and HIV/AIDS treatment centre in Guangxi, China. All HIV-positive individuals with standard ART from FPHN were reported to the NFATP, and recommended for hospitalization following diagnosis with TM infection. The Chinese NFATP database does not recognize TM as a distinct disease but groups it in the category of disseminated fungal diseases. However, the NFATP database is linked with the electronic medical records from the FPHN, which allows for a differentiation among the invasive fungal infections including cryptococcal meningitis, talaromycosis, PJP, and esophageal candidiasis. We retrospectively collected data from April 2005 to June 2016 for all HIV/AIDS patients who were older than 16 years who started ART during this study period. Patients were excluded if they met the following criteria: (i) had no baseline CD4nfection ,16,30. TCTX prophylaxis receipt was recorded in the NFATP database at each follow-up visit following ART initiation. Since the exact date on which CTX treatment was started or stopped was not recorded, we regarded patients who received CTX within 6 months after ART initiation as the CTX group and patients who did not received CTX use (i.e. no documentation of CTX use was recorded) within 6 months after ART initiation as the non-CTX group. The observation period was from the date of ART initiation to the date of TM diagnosis. TM diagnosis was confirmed by positive fungal culture from any sterile body site such as blood, bone marrow, lymph nodes, skin lesions, or other body fluids; while non-TM-infected patients included those who were uninfected or asymptomatic. In addition, time to death, time to loss of follow-up, or time to the last follow-up visit before June 2016 were recorded. Baseline was defined as various demographic and clinical indices from the most recent record prior to or following ART initiation.The selection of independent variables was based on the results of previous studies indicating factors that are associated with TM infection, including antiretroviral therapy (ART), CD4 cell counts, WHO HIV clinical stages, HIV transmission routes, tuberculosis, and other opportunistic infections, etc. Categorical variables were expressed as a frequency or proportion, while quantitative variables were expressed as the median ± interquartile range (IQR). Chi-squared  and non-parametric (for quantitative variables) tests were used to compare the characteristics between the two groups. Kaplan-Meier graph was used to show the accumulative TM infection during the follow up period. The statistical testing of difference was performed using the log-rank test. Univariable and multivariable Cox regression analyses were used to evaluate the effect of CTX on TM incidence.For the 1:1 propensity score matching, the characteristics that were statistically different between CTX and non-CTX groups were marched using a calliper beginning with 0.02, and all variables were matched at a difference of the logit of the propensity score of 0.0001 SD. A Chi-squared test was then performed to evaluate the effectiveness of the propensity score matching. Subsequently, a multivariable Cox proportional hazard regression was used to investigate the independent effect of CTX treatment on TM infection.p value of 0.05 or less was considered statistically significant.Data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 23.0  and GraphPad Prism version 6.0 . A two-tailed statistical test with a


HIV-load decrease and suppression over time is associated with consistent adherence to antiretroviral therapy (ART). Our study aimed to evaluate the difference in viral load and adherence of patients treated with a combination of either Tenofovir (TDF), Lamivudine (3TC) and Efavirenz (EFV) or TDF / Zidovudine (AZT), 3TC and Nevirapine (NVP) regimens at 24 and 48 weeks.A longitudinal study was conducted from May 2016 to June 2017 among 256 HIV infected adult patients who were enrolled at two approved treatment hospitals in Yaoundé, before the start of first-line ART. Whole blood samples were collected using standard operating procedures. HIV-loads were determined by a quantitative RealTime PCR assay. Adherence was evaluated by pharmacy refill data records. Statistical analyses were performed using the PRISM 5.0 software.Off the 256 HIV infected patients enrolled, 180 (70%) patients completed the study and 76 (30%) patients were lost to follow-up. The success rate in achieving viral load < 40 copies/ml was 1.8 times higher with the EFV regimen at 24 weeks and was 1.2 times higher in the NVP regimen at 48 weeks. At 48 weeks the treatment failure rate was 12.0 and 40.0% in patients on EFV and the NVP regimen, respectively. The rate of adherence varied in both ART based regimens with 84.0 to 74.0% for EFV and 65.5 to 62.5% for NVP, at 24 and 48 weeks respectively.In our study and setting, the rate of viral load decrease was higher in the NVP based regimen than with the EFV regimen. The adherence rate to ART was higher in the EFV regimen, compared to the NVP regimen. This adds to evidence that the EFV regimen is the preferred ART combination for non-nucleoside reverse transcriptase inhibitors (NNRTIs). The introduction of antiretroviral therapy (ART) world wide as treatment for HIV infections has greatly reduced mortality and morbidity among patients living with HIV , 2. The The standard approach for monitoring treatment outcomes in patients on ART depends on the measurement of HIV-load over time. According to the WHO guidelines, virological failure is observed when patients sustain a viral load > 1000 copies/ml after 6 to 12 months of ART. The persistent high viral load in most cases is due to non-adherence .Studies from low- and middle-income countries have shown measuring adherence is more likely to predict virological failure than clinical and immunological criteria. In Cameroon, poor adherence, treatment interruption due to dosage and the loss to follow-up are factors reported most likely to influence virological failure responses. In spite of adherence being found to be an important factor in influencing treatment outcome, there are no standard guidelines for its measurement –10.Cameroon follows and strictly applies the WHO ART guidelines with the EFV regimen  taken as a single dose daily and the NVP regimen  taken twice daily [A longitudinal cohort study was conducted from May 2016 to June 2017 to evaluate ART outcome at two approved treatment and care centers for HIV in Yaoundé . We determined the difference in viral load and assessed adherence in HIV adult patients.The study population consisted of 256 consenting HIV infected adult patients who were all treatment naïve at the beginning of the study. Patients were initiated on either the combination of TDF/3TC/EFV (300 mg/300 mg/600 mg) taken as a single dose daily or AZT/3TC/NVP (300 mg/150 mg/200 mg) taken twice daily. Questionnaires were administered to collect socio-demographic data and treatment information. Whole blood (5 ml) was collected in Ethylenediaminetetraacetic acid (EDTA) collection tubes from each patient for viral load testing at baseline (prior to the start of ART), 24 and 48 weeks, using standard procedures. Laboratory analyses were done at the Center for the Study and Control of Communicable Diseases (CSCCD) of the University of Yaoundé I.RNA viral load testing were performed before the start of ART and at 24 and 48 weeks of treatment using an automated RealTime PCR assay:CobasAmpliprep/CobasTaqman 96 platform . Plasma samples were analyzed based on the manufacturer’s instruction. The detection limit of the assay was < 40 copies per ml.There are no standard guidelines for the measurement of adherence to ART. Drug screening for adherence was evaluated based on pharmacy refill data records reporting the number of patients who came for their drugs on their respectful appointment dates. This enabled us to evaluate the number of patients who continued one of either EFV or NVP containing first-line NNRTI regimens during the study period as being adherent to ART. We classified patients’ rate of adherence as being good, fair, poor or non-adherent based on a rating scale we developed with a define limit of 40% and interval of 20%. The number of patients who continued treatment was converted to percentage in order obtain the rate of adherence. A rate ≤ 40% was considered non-adherent to ART, 40–60% as poor adherence, 60–80% as fair adherence and ≥ 80% as good adherence. At baseline, all patients were considered adherent at 100% to their respective ART regimens.p < 0.05.Data were recorded in a Microsoft Excel sheet and statistical analyses were performed using the Graphpad PRISM 5.0 software package . Descriptive statistics were used to analyze the patient’s demographic information. Repeated measures of the ANOVA test was computed to outline the mean difference in viral load. The Mann-Whitney non-parametric tests were used to calculate the mean difference in the level of detectable viral load. Relative risk ratio and percentage relative effect were used to predict the likelihood of achieving virological suppression. Different level approach namely: good, fair, poor and non-adherence was used to evaluate adherence according to pharmacy records and the proportion of patients who remained on treatment using cross contingence tables. The level of significance of all analyses was set at Of the 256 infected patients enrolled in the study, 180 (70%) patients completed the study with 76 (30%) patients lost to follow-up. Of the 180 patients, 72 (40%) were male and 108 (56%) were female, with 100 patients on the EFV regimen and 80 patients on the NVP regimen. The age of the participants ranged from 24 to 57 years, with the most representative age group ranging from 38 to 43 years old. The characteristics of the study population are shown in Table p < 0.0001. The median baseline HIV-loads were 4440, 2270 and 40 copies/ml at time points 0, 24 and 48 weeks, with semi interquartile ranges of 1976–8100, 204.8–7029 and 40–995, respective copies  of patients on the EFV regimen as compared to 14.2% (n = 12/84) patients on the NVP regimen. Patients taking EFV had a 75.0% increased rate in obtaining a viral load < 40 copies/ml. Patients on the NVP regimen at 48 weeks were 1.2 times more likely to achieve a viral load of < 40 copies/ml with an increased possibility of 23.0%, compared to patients on the EFV regimen (0.5). The proportion of patients with viral load < 40 copies/ml at 48 weeks was observed in 60.0% (n = 48/80) of patients on the NVP regimen and in 52.0% (n = 52/100) of patients on the EFV regimen . Viral load < 40 copies/ml was observed in 26.0%  was attained from 24 weeks to 48 weeks in both regimens, with a greater increase level observed in the NVP group (from 14.2 to 60.0%) than with the EFV group (29.9 to 52.0%)  from 24 weeks to 48 weeks, with Sequential viral load monitoring is the recommended approach in defining treatment failure, despite its costly nature. We compared patients’ viral load at 24 and 48 weeks in each treatment regimen to evaluate treatment failure. Treatment failure was calculated based on two successive measurements of viral load with results > 1000 copies/ml, according to the WHO criteria. Data collected at 24 weeks were used as the baseline and that at 48 weeks was considered as the first time point to evaluate the virological failure rate. In patients on the NVP regimen, the rate of virological failure was higher, with 40.0%, than that of patients on the EFV regimen, with a rate of 12.0%. Twelve patients on the EFV regimen experienced treatment failure compared to thirty-two patients on the NVP regimen. Thus, patients on the EFV regimen were less likely to encounter treatment failure compared to those on the NVP regimen Table .Table 3TWe evaluated the rate of adherence to ART regimens from pharmacy refill data, taking into consideration the number of patients still on treatment in both regimens. From 24 weeks to 48 weeks there was a decrease in the adherence rate and increase in non-adherent rate in both regimens. The proportion decreased from 84.0% to 78.0,% in patients taking the once-daily tablet EFV regimen and from 65.5 to 62.5% in patients taking the twice-daily tablet NVP regimen. The adherence rate was higher in the EFV group compared to the NVP group at 24 and 48 weeks, despite the decreased difference observed. The proportion of patients considered non-adherent increased from 16.0 to 22.0% in the EFV regimen and from 34.5 to 37.6% in the NVP regimen  and Alula et al., (2017) and raises concerns over poor maintenance of cohorts in longitudinal studies in Africa  and Alul. Neverthp < 0.0001) in the mean value of HIV-load over time in both the EFV and NVP regimens (p = 0.0011 and p = 0.0055). This decrease in viral load was a result of the effectiveness of ART in preventing the replication of HIV. Our results are in accordance with the findings of Edward et al., (2015) who in their study in HIV-infected adults reported the effectiveness of ART in bringing about a dramatic decrease in viral load [We observed an overall significant decrease  in the level of viral load < 40 copies/ml throughout the study, implying a progressive reduction in viral load at each time point. Patients on the EFV regimen at 24 weeks of treatment were better at achieving viral load < 40 copies/ml. At 48 weeks, patients on NVP had a better outcome in achieving the same viral load level. These results could be attributed to a difference in baseline HIV-load level in each regimen before ART initiation and treatment interruption during ART influencing the viral load. Hence, no constant decrease in HIV-load level. This finding is in accordance with the findings of Wu et al., (2015), in a five year longitudinal study evaluating the effectiveness of first-line ART in HIV/AIDS patients and with the findings of Meresse et al., (2013), reporting the impact of treatment interruption on virological response [We observed a significant increase p = 0.00 in the lresponse .Patients taking the EFV combination were less likely to experience virological failure (48.0 and 12.0%), compared to the NVP regimen group (76.0 and 40.0%) at 24 and 48 weeks, respectively. The overall failure rate (24.0%) at 48 weeks of ART could be due to non-adherence in both treatment regimens. Similar results obtained in a cohort study in Uganda, South Africa and in a meta-analysis study reporting patients on EFV based regimens were less likely to experience virological failure than patients based on NVP regimens -21. Our In Cameroon till date, there are no clear-cut guidelines for the use of administrating one of either EFV or NVP containing first-line NNRTI regimens, despite the proven efficacy of the EFV regimen compared to the NVP-based regimen. While several studies in resource-rich settings have provided evidence of increased risk of virological failure associated with the NVP based regimen, only a few studies have been done to verify this hypothesis in resource poor settings , 21.In this study, we observed good and fair adherence to ART at 24 and 48 weeks. Good adherence (81.0%) was observed in patients on the EFV regimen and probably resulted in the reduction in viral load. Fair adherence 64.0%) was detected among patients on the NVP regimen and might be associated with the high treatment failure. The high adherence rate in patients on the EFV regimen compared to the NVP regimen could be attributed to the dosing frequency difference in the regimens. Patients on the EFV regimen are administered a single dose, easy to administer, compared to patients on the NVP regimen taking a twice-daily dose. The good adherence rate to EFV regimen is in accordance with the findings of a cross-sectional survey that reported adherence variations of between 71.0 and 93.0% 4.0% was . Our resIn this study, the proportion of patients with reduced viral loads were found to be more adherent to ART and consisted of patients in the age group ranging from 32 to 43 years. This could be because this population represents a more responsible set of individuals who may be more organized and motivated in improving their health and lifestyle. This result is in contrary to the findings from a study performed to analyze adherence among older HIV infected patients and in a prospective cohort study in Cameroon. They reported that older patients (> 50 years) showed higher tolerance to ART and young patients (< 36 years) showed poorer adherence , 26. FurLimitations of the study include the loss to follow-up of patients, as that might have influenced the efficacy of our findings. In addition, we evaluated adherence based on pharmacy records, on the number of patients who continued treatment, and did not investigate the correlation or association between number of doses, adherence and viral outcome. Our findings add evidence to the need of improving strategies to evaluate adherence in HIV patients on ART. Large cohort studies are needed to validate these findings and evaluate the different methods used for assessing adherence to ART. It is important to investigate the various factors influencing adherence. The results from these studies can be incorporated to enhance the management of HIV infected individuals on ART.Adherence and patient counselling play an important role in maintaining successful ART outcomes. Ineffective ART induces virological failure. There was a significant decrease in the viral load suppression in both regimens. The EFV regimen was more effective in suppressing viral load and is less likely to induce a virological failure response, compared to the NVP regimen.


This study was aimed to assess immunological recovery, failure, and factors associated with CD-4 T-cells progression over time, among adolescents and adults living with HIV on Antiretroviral Therapy in Northern Ethiopia.A retrospective cross sectional study was done on 19,525 HIV patients on ART. Data were collected using a data retrieval checklist from a database. All eligible data in the database were exported to Microsoft excel 2010 and then data verification and filtration were done before exporting to STATA 14.0 for analysis. Factors associated with recent CD-4 count were modeled by using Generalized Linear Model poison family.3) at baseline, only 28.35%, 95% CI (27.45–29.26) of them had immunological recovery (≥ 500 T-cells/mm3). Only 2.14%, 95%CI (1.94%- 2.35%) of the patients had immunological failure. Baseline CD-4 count (Incidence Rate Ratio (IRR) = 1.0007, 95%CI = 1.00069–1.00078), patients from military health care facility , good adherence  and viral load suppression  were positively associated with recent CD-4 count in the full model. Whereas, being male , patients with on Anti-Retroviral Therapy (ART) regimen of 1e (TDF-3TC-EFV), 2f (AZT-3TC-ATV/r), and 2h (TDF-3TC-ATV/r) ,  and  respectively were negatively associated with the recent CD-4 count in the full model.Among the patients with advanced HIV infection . Therefore, intensive adherence counseling, follow-up and support should be focused on patients with viral non suppression to enhance immunological recovery. Globally, around 36.9 million people were living with HIV and about 21.7 million people were on HAART in 2017. There were 1.8 million people who were newly infected with HIV and 940,0000 people died from Acquired Immune Deficiency Syndrome (AIDS) related illnesses in 2017 . CurrentPeople living with HIV infection require an ongoing HIV care and access to medications to allow immune reconstitution, minimize the risk of resistance emergence ,7, preveDespite the benefits of ART, there is a growing concern about treatment failure, drug resistance and late drug toxicities associated with long-term use of ART , 14, maiA retrospective cross sectional study was conducted from April, 2015 to January, 2019 at Tigray Health Research Institute (THRI) which is the only center for VL determination specifically for Tigray region and some parts of Northern Ethiopia. Tigray region is the 6th largest by area and the 4th most populous of the 9 Regional States of Ethiopia . The RegBlood samples are sent to the regional laboratory for VL determination from all the health care facilities offering HIV ART services. The sample referral form contains the following information: name of the patient, Medical Registration Number (MRN), Unique ART number, name of the health facility, some demographic data, clinical, treatment, baseline and recent CD-4 count and reason for determining viral load. The source of the data was from all the people living with HIV, enrolled in ART care for at least 6 months whose blood sample was sent for VL determination through standard sample transportation technique to the regional laboratory/THRI from April, 2015 to January, 2019. The study was done among 19525 patients which had complete data on demographic, clinical, immunological, and viral load in the database of THRI.To come up with the final sample, all records of patients from the Tigray regional state available in the database of THRI were reviewed and then all the study participants which fulfilled the eligibility criteria were included in the study .The data were collected from the database of THRI using a data retrieval checklist. All the data in the database were exported to Microsoft excel 2010 and then data verification and filtration were done before exporting to STATA 14.0.CD4+ T-cells count was measured at baseline and every six months during follow up at the respective health care facilities or at the nearby referral laboratory where blood samples were transported. Nevertheless, only the results of the baseline and recent CD-4 count of each client was sent via the request form for VL determination to THRI by the health care facilities regardless of the time of initiation of ART. Hence, baseline and recent CD-4 counts were taken for analysis in this study as an independent and dependent variables respectively.Data completeness and consistency was checked using Microsoft excel. Data cleaning was done with box plot and running frequencies for each variable in STATA version 14.0 to check outliers and inconsistencies for accuracy purpose. The normality of the continuous variables was checked by scatter plot matrix and/or normal probability plots. Low and high positive controls were checked during VL determination. During the CD4+ T-cells count determination by each machine; low, medium and high quality controls were done to evaluate run validity in each laboratory, where the CD-4 count was done.Analysis was done using STATA-14.0 to estimate the proportion of patients with immunological failure or recovery and to identify factors associated with CD-4 T-cells progression over time. Univariate analysis was used to determine the socio-demographic and clinical characteristics of the study population.Number of recent CD-4 T-cell counts after initiating ART was modeled by using Generalized Linear Model (GLM) with a family of Poisson with a log link function and a robust standard error. Generalized Linear Model (GLM) is an extension of the linear modeling process that allows the model to be fit to data that follow probability distributions other than the normal distribution. Poisson regression model is a special case of a generalized linear model (GLM) with a log link, the reason why the Poisson regression also called Log-Linear Model. . GLM PoiAll significant variables in the bivariable analysis were entered into the multivariable GLM Poisson regression models based on biological plausibility, previous literature, and statistical significance in bivariable analyses. As pregnancy and lactating status applies to females, both variables were excluded from statistical model building of the multivariable analysis. Multivariable analysis was also done by stratifying the WHO stages to check whether the coefficients of variation remain constant or differ compared to the full model. Collinearity was omitted in the statistical modeling.Ethical clearance and approval was obtained from Tigray Health Research Institute (THRI) Institutional Review Board (IRB) / Ethical Review Committee with the reference no of THRI/00132/19. Permission to use the data was obtained from the Tigray Regional Health Bureau and THRI. The data were from a secondary database on HIV infected patients for viral load monitoring while on combination of antiretroviral treatment. All the baseline and recent CD4 counts were extracted from the database retrospectively, which were entered from the sample referral form. The data were not accessible by any other third party other than the study team. All the data did not carry personal identifiers. Informed consent was waived from the ethics committee.A total of 19,525 patients were included in the study. The median age (IQR) of the study participants was 38 (31–45) years. Females accounted for 65.90% of the study participants. About 11,959 (61.25%) of the patients had VL determined as part of routine first VL (6 months or more on ART) determination. Only 95 (0.74%) and 202 (1.57%) were pregnant and lactating mothers respectively. A total of 18,671 (95.63%) people living with HIV were getting ART service at governmental health care facilities. Most of the patients, 18,517 (94.84%) had a good drug adherence. The median (IQR) of the baseline CD-4 T-cells count was 201 (112–341). Similarly, the median (IQR) of the recent CD-4 count was 423 (264–611). The median increase of CD-4 T-cells count from the baseline to the recent CD-4 T-cells count was 222 cells/micro Liter. The immunological response after initiation of ART based on the recent and baseline CD-4 T-cells count showed that 15,736 (80.59%) of them had positive immunological response. Most of the clients, 9,390 (48.09%) were on 1e (TDF-3TC-EFV) regimen and 19,284 (98.77%) patients were on first treatment line .Among the patients with advanced HIV infection (< 200 CD-4 T-cells / mm3) at baseline, only 28.35% of them had immunological recovery (≥ 500 CD-4 T-cells /mm3). Based on the WHO definition, only 2.14%, 95%CI (1.94%- 2.35%) of the patients had immunological failure .Bivariable analysis. The bivariable analysis showed that the Incidence Rate Ratios (IRRs) of the independent variables were associated with CD-4 T-cells progression over time. At bivariable analysis level, CD-4 T-cells count at baseline , Males , and lactating mothers  were significantly associated with the recent CD-4 T-cells count. Similarly, patients’ age categories were significantly associated with the recent CD-4 T-cells count. However being pregnant was not statistically associated with the recent CD-4 T-cells count over time  were significantly associated with the recent CD-4 T-cells count. Similarly, patients with VL suppression  were significantly associated with the recent CD-4 T-cells count. However, patients with a regimen of 1f were not significantly associated with the recent CD-4 T-cells count , patients served in a military health care facility , Patients with a recent WHO stage II  and patients with poor adherence  were significantly associated with the recent CD-4 T-cells count. Patients with a virological test reason of suspected ART failure clinical , patients with a current regimen of 2f , Patients with a 2ls count .A multivariable analysis using the GLM showed that the initial model without any predictor variables have an AIC of 159.3391. The constant was significant with p-value< 0.01 .After including all predictors to explain the variability of CD-4 T-cells count in the final model, the AIC has decreased from 159.3391 at the null model to 126.0423. The multivariable analysis showed that, as CD-4 T-cells count increases by one unit, the recent CD-4 T-cells count increases by a factor  while holding all other variables in the model constant. Males compared to females, while holding other variables constant in the model, are expected to have a rate  times lower for the recent CD-4 T-cells count. Age category in 20–24 years compared to 15–19 years, while holding the other variables constant in the model, are expected to have a rate  times lower for the recent CD-4 T-cells count .Patients from military health care facilities compared to patients with non-military health care facilities, while holding the other variables constant in the model, are expected to have a rate  times greater for the recent CD-4 T-cells count. Patients in WHO stage II and III compared to WHO stage I, while holding the other variables constant in the model, are expected to have a rate  and  times lower for the recent CD-4 T-cells count respectively. Patients with good adherence compared to poor adherence level, while holding the other variables constant in the model, are expected to have a rate  times greater for the recent CD-4 T-cells count respectively .On the other hand, patients whose viral load was determined for suspected ART failure initial VL compared to routine first VL is expected to have a rate  times lower for the recent CD-4 T-cells count. Patients with a regimen 1e (TDF-3TC-EFV) compared to a 1c (AZT-3TC-NVP) regimen, while holding the other variables constant in the model, are expected to have a rate  times lower in the recent CD-4 T-cells count. Similarly, patients with viral load suppression compared to patients with virological non suppression, while holding the other variables constant in the model, are expected to have a rate  times greater for the recent CD-4 T-cells count .We made a stratified analysis by WHO stage to find out whether the strength of association of independent variables with the recent CD-4 T-cells count remain same or differ. Based on the analysis, baseline CD-4 T-cells count and VL suppression were positively associated and remain the same with the recent CD-4 T-cells count in all the WHO stages compared to the full model (without stratification by the WHO stage). However, being male in gender, age category in 40–44 and 45–49, and suspected ART failure initial VL for VL determination reason were negatively associated and remain almost the same with the recent CD-4 T-cells count in all the WHO stages. Despite these variables, there were differences after the stratified analysis in variables such as: age categories, service provided in military health care facility, facility type, adherence, in some of the virological test reasons and in some of the regimen types. Service provide in military health care facility was only significant in the WHO stage I sub cluster analysis .Antiretroviral treatment began in 2003 and free ART was launched in Ethiopia in 2005. An estimated 738,976 Ethiopians are currently living with HIV and all of them require antiretroviral treatment (ART). However, only 426,000 are currently taking ART . MonitorThe median baseline CD4+ count of this study was 201cells/μL. This finding was similar to a study conducted in Jimma, Ethiopia, which was 191 cells/μL . However3, 200–499 cells/ mm3 and ≥ 500 cells/ mm3 was 49.61%, 38.95% and 11.44% respectively in this study. A study conducted in Somali region, Ethiopia showed that 57.6% of the patients had a baseline CD4+ count ≤ 200 cells/ mm3 and 42.4% had >200 cells/ mm3 [3, 200–499 cells/ mm3 and ≥500 cells/ mm3 respectively. A study conducted at the Felege Hiwot Referral Hospital reported that 30.8% of the patients had recent CD-4 count of ≥ 500 cells/ mm3 [3), the current study was similar to the study conducted in the Felege Hiwot referral Hospital where 37.6% of them reached a CD4 count of 500 or more cells/mm3 [3. This was lower compared to the mean CD4 count of healthy HIV negative Ethiopians which was 820 (±270) [The proportion of patients with a baseline CD-4 count of <200 cells/ mmlls/ mm3 . Similarells/mm3 , while oells/mm3  and 59% ells/mm3  of the p0 (±270) . This inImmunologic recovery was attained by only 28.35% of the patients, which was lower when compared with another study 45.2% . This stGood adherence compared to poor adherence was positively associated with CD-4 count in this study. Similar studies from Ethiopia, Kenya, Colombia and France have reported that patients with non-adherence to treatment were associated with immunological failures when compared with good adherence , 35, 36.Higher baseline CD4 count was positively associated with the recent CD-4 count during treatment. Different studies have also supported this finding that higher baseline CD4 count was positively associated with the time to immunologic recovery , 31. AnoAge 15–19 years was positively associated with an increase of the recent CD4 count. There was some evidence which showed that commencing HAART at a younger age may be associated with an improved immunologic response , 41. On Females compared to males have positive associations with the recent CD-4 cell count. This finding did not agree with the finding , however3 in this study were classified in WHO stage I and II respectively. However, patients with <200 CD-4 T-cells count are more likely to have advance HIV infection that might be classified into WHO staging IV or III. This shows that there was wrong way of classifying patients into WHO stages at baseline and hence affects the association.This study showed that patients in WHO stage II and III were negatively associated with increment in the recent CD-4 count compared with the WHO stage I. Different other studies have also shown that WHO clinical stage and classification of HIV/AIDS correlates well with CD4+ T-lymphocyte counts , 49. AltPatients with viral suppression were positively associated with the recent CD-4 T-cells count. A similar other studies from Ethiopia, Nepal, Thailand and India reported that patients with HIV RNA level ≥1000 copies/ml were more likely to experience immunological failure in ART follow up as compared with those who had an HIV RNA level less than 1000 copies/ml ,51,52,53Patients from military health care facilities had a higher CD-4 cells count as compared to patients from non-military health care facilities. Even though there were no similar studies which support or contradict this finding, patients from military health care facilities were mostly military staff that might have relatively higher adherence to treatment and nutritional status as compared to civil patients from non-military facilities which then results in a boost of CD-4 cells count after Antiretroviral treatment.Patients with a first line regimen 1e (TDF-3TC-EFV), and second treatment line regimens 2f (AZT-3TC-ATV/r) and 2h (TDF-3TC-ATV/r) were negatively associated with recent CD-4 count as compared to 1c (AZT-3TC-NVP). Though there were no similar studies in relation to recent CD-4 count and antiretroviral regimens, there was reported finding that initiating ART using any one of the following ART regimens: 1c (AZT-3TC-NVP), 1d (AZT + 3TC + EFV) and 1e (TDF + 3TC + EFV) prevented treatment failure . Even thCompared to routine first Viral Load (6 months or more on ART); suspected ART failure initial Viral Load, suspected ART failure immunological and suspected ART failure clinical were negatively associated with the recent CD-4 count. There was a similar finding from Uganda, where being a suspected treatment failure patient and repeat test after suspected failure were positively associated with viral non suppression . This caThis study was not without limitation. Due to the nature of secondary data, there were no data when the baseline and recent CD-4 T-cells count was conducted and hence the time when the immunological failure/ recovery had occurred is not known. In addition to the time of ART exposure the analysis misses some important variables such as the existence of co-infection and grade of ART experience in the HIV infected patients. Despite these limitations, this study was done on a large sample size with appropriate statistical analysis techniques that provides important information regarding viability of ART treatment program in Tigray, Northern Ethiopia.Immunological recovery was lower, only one third of the patients achieved immunological recovery despite being on highly active ART (HAART). Sex, CD4 baseline, age, ART clients served in defense facility, WHO Stages II and III, adherence, virological test reasons of suspected ART failure clinical, suspected ART failure immunological and suspected ART failure initial Viral Load, regimen type of 1e, 2f and 2h and viral load suppression were significantly associated with CD-4 T-cells progression over time, among HIV patients on ART in Tigray region. Therefore, intensive adherence counseling, follow-up and support should be provided focusing on patients with virally non suppressed individuals so as to enhance immunological recovery. In addition, determinants of immunological recovery need to be investigated in detail to design an appropriate intervention.


Long-term combination antiretroviral therapy often results in toxicity/tolerability problems, which are one of the main reasons for switching treatment. Despite the favorable profile of raltegravir (RAL), data on its combination with abacavir/lamivudine (ABC/3TC) are scarce. Based on clinical data, we evaluated this regimen as a switching strategy.Multicenter, non-controlled, retrospective study including all virologically suppressed HIV-1-infected patients who had switched to RAL+ABC/3TC.We evaluated effectiveness (defined as maintenance of HIV-1-RNA <50 copies/mL at 48 weeks) safety, tolerability, laboratory data, and CD4+ count at week 48 of this switching strategy.The study population comprised 467 patients. Median age was 49 years (IQR: 45–53). Males accounted for 75.4%. Median CD4+ count at baseline was 580 cells/μL . The main reasons for switching were toxicity/tolerability problems  and physician’s criteria . At week 48, HIV-1 RNA remained at <50 copies/mL in 371/380  when non-virological failure was censured. Virological failure was recorded in 1.9% patients and treatment failure in 20.5% of patients . The main reasons for treatment failure included switch to fixed-dose combination regimens , toxicity/poor tolerability , and physician’s decision . A total of 73 adverse events were detected in 64 patients (13.7%). These resolved in 43 patients (67.2%). Of the 33 cases related or likely related to treatment, 30 were Grade-1 (90.9%). CD4+ count and renal, hepatic, and lipid profiles remained clinically stable over the 48 weeks.Our findings suggest that RAL+ABC/3TC could be an effective, safe/tolerable, and low-toxicity option for virologically suppressed HIV-1-infected patients. The availability of highly effective combination antiretroviral therapy (cART) over the last 2 decades has made HIV-1 infection a treatable chronic disease. However, the need for continued use of cART has generated problems such as toxicity, lack of tolerability, and drug interactions, which have forced clinicians to seek new treatment regimens. These regimens are not always adequately represented in clinical trials or observational studies [Toxicity has been a major concern for clinicians engaged in managing HIV-1 infection, and despite the good safety and tolerability profiles of new drugs, it remains a problem in some patients. . In manyRaltegravir (RAL) is an integrase strand transfer inhibitor (INSTI) with a very good safety/tolerability profile. It was approved on July 8, 2009 by the US Food and Drug Administration for the treatment of naïve HIV-1-infected patients in combination with 2 nucleoside analogues . AbundanTherefore, the objective of the present study was to determine the effectiveness and safety of RAL plus ABC/3TC as a switching strategy in virologically suppressed HIV-1-infected patients based on real-life data.We performed a multicenter, non-controlled, retrospective study of virologically suppressed HIV-1-infected patients switching to RAL (400 mg bid or 800 mg qd) plus ABC/3TC in 14 hospitals across Spain. All patients included fulfilled the following criteria: i) age ≥18 years, ii) documented HIV-1 infection, iii) switch from another regimen to RAL+ABC/3TC for any reason, iv) serum HIV-1 RNA <50 copies/mL for at least 24 weeks before switching to RAL+ABC/3TC, and v) availability of HIV-1 viral load records during follow-up including baseline, intermediate, and week-48 values when appropriate. The study data were collected between January and February 2017 from patients who had switched from December 2007 to January 2016 to ensure that at least 48 weeks of clinical follow-up were available. Eligible individuals were identified through the records obtained from clinical databases and/or from the hospital pharmacy unit.Data for the study were collected retrospectively from the patient’s medical records, anonymized, and entered into an on-line electronic database  . BaselinThe study protocol was approved by Hospital Universitario Gregorio Marañón Ethics Committee (code LEO-RAL-2015-01) in accordance with the principles of the Declaration of Helsinki (2013). The study was also approved by the individual ethics committees in some centers . The data analysis was based on retrospective and anonymized routine clinical data, thus obviating the need for written informed consent.The primary endpoint was the percentage of patients who maintained virological suppression (HIV-1 RNA <50 copies/mL) after 48 weeks of treatment. Virological failure was defined as 2 consecutive HIV-1 RNA measurements >50 copies/mL or a single measurement of >50 copies/mL if treatment was subsequently changed. Viral load was evaluated 3 or 4 times, when available, during the 48-week period of the study to ascertain virological control, according to the routine clinical protocols at each hospital. If viral load was not available in the records at week 48, or in the following 4–8 weeks, patients were considered treatment failures.The secondary endpoints included the proportion of patients with treatment failure due to any cause, clinical/laboratory AEs, description and severity of AEs, and changes from baseline in the following: a) serum total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides; b) serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (AP) levels; and c) estimated glomerular filtration rate (eGFR) according to the CKD-EPI equation.Treatment was considered to have failed when any of the following events occurred: 1) virological failure; 2) interruption of treatment by the patient or the physician; 3) change of treatment regimen for reasons not related to virological failure including simplifications or AEs; and 4) incomplete data or missing patients.We also conducted a survival analysis, in which patient data were censored if the cause of treatment failure was not virological failure or treatment toxicity.2 test when the sample was sufficiently large or Fisher’s exact test when it was not; a Yates correction was used when necessary.Nominal variables were described as numbers and percentages. Variables that did not follow a normal distribution were described using the median and interquartile range (IQR: 25–75). The association between qualitative variables was assessed using the χThe percentage of patients who maintained virological suppression was analyzed using Kaplan-Meier curves, and including all treatment failures. The 95%CI for the proportion of patients at risk of treatment failure at 48 weeks was derived from the Kaplan-Meier curve.Continuous variables were homoscedastic and were normally distributed according to the Levene and Kolmogorov-Smirnov tests. The values of each continuous variable at the different time points were considered dependent measures. Thus, changes in these variables over the 48 weeks of treatment were analyzed using mixed linear models (MLM) with an autoregressive covariance structure, and results were confirmed by general linear models (GLM) with repeated measures. The significance of differences time points for each continuous variable was determined by least significant difference analyses.All analyses were performed using R v.3.3.2 (R Development Core Team 2014) [The study population comprised 467 patients. The baseline characteristics of the study population are summarized in Prior to switching, the treatment regimen included a protease inhibitor (PI) in 225 patients (48.2%), an INSTI in 121 patients (25.9%), a non-nucleoside reverse transcriptase inhibitor (NNRTI) in 104 patients (22.3%), and a regimen with only nucleoside reverse transcriptase inhibitors (NRTI) containing AZT/3TC/ABC in 22 patients (4.7%). Monotherapy with boosted PIs was used in 18 patients and dual therapy in 17 patients including PIs plus 3TC (8), PIs plus INSTI (4), PIs plus NNRTIs (3), and INSTI plus NNRTIs (2). ABC/3TC was the most frequent NRTI backbone co-formulation before switching , followed by FTC/TDF . In 83 patients (17.8%), the NRTIs were not co-formulated .Data on historical resistance from all previous genotypic studies was available for the 467 patients included in the study. Analyses of these genotypic studies indicated that, before switching, 91 patients had pre-existing resistance mutations; these were to PIs , NNRTI , and NRTIs . Resistance mutation M184I/V had been registered in 23 patients and was detected with L74I/V in 7 patients.The main reason for switching antiretroviral therapy was drug toxicity/tolerability , followed by physician’s criteria , and other, unknown reasons . Among the 197 patients who switched owing to toxicity/tolerability, the specific cause was available in 129 patients, with renal toxicity being the most frequent type , followed by bone toxicity  and gastrointestinal disorders . Most toxicity/tolerability problems were resolved after switching ; they remained unresolved in 39 patients (19.8%). No data were available for the other 28 patients.The primary endpoint was achieved by 371/380 patients  after censoring non-virological failures, with virological failure in 1.9% of patients. At 48-week the proportion of patients at risk of treatment failure was 20.5% . A survival analysis was performed because more than 10% of failures were for reasons not directly associated with regimen safety or effectiveness. The 48-week overall survival rate was 80% . Of the There were 96 failures, and the most frequently reported reasons included switch to fixed-dose combination regimens , toxicity/poor tolerability , physician’s decision , and virological failure . Less frequent reasons were loss to clinical follow-up or patient’s decision , death not associated with treatment , and other .Overall, 64 patients (13.7%) experienced 73 AEs . The mosP>0.068).Variables related to lipid, hepatic, and renal profiles and CD4+ count  did not P<0.003). More data can be found in The exceptions were AST, AP, total bilirubin, and HDL cholesterol. HDL cholesterol values were higher at 48 weeks than at any other time  were detected in some patients. These generally did not return to normal when they were due to the effect of previous ARTs or preexisting comorbidities, as reflected in patients with previous renal impairment .Although RAL+FTC/TDF has been shown to be highly efficacious and safe as a switching strategy in clinical trials and cohort studies ,16, equiOur findings revealed a high percentage of treatment success, thus indicating that RAL+ABC/3TC has a high virological suppression rate that is in the same range as other switching therapies –22. ViroFurthermore, 4 of the virological failures were with RAL once daily at the off-label dose, and, as demonstrated in previous studies with naïve patients, this dose could have compromised efficacy .Switching to fixed-dose combination regimens was the main reason for treatment failure, probably because twice-daily dosing of RAL could have hampered adherence to the regimen, especially in recent years, with the increasing availability of new single-tablet options , 24,25.The safety profile of RAL+ABC/3TC is in line with other INI switching studies ,26, withIt is also important to note that most toxicity/tolerability problems related to previous regimens were resolved after the switch to RAL+ABC/3TC.No significant changes in lipids were observed, including in the subgroup of patients who had previously taken boosted PI–based regimens, although significant changes in lipid values have been reported in other cohorts. These findings could have 2 explanations. On the one hand, most of the patients who switched from PIs (69%) were taking darunavir or atazanavir. These drugs have a much more neutral lipid profile than lopinavir or fosamprenavir, which are more common in previous cohort studies. On the other hand, 25% of patients were already taking RAL and 50% were taking ABC/3TC, 16.P<0.975). These findings differ from those of other studies on switching from TDF to ABC, which reported a slight increase in eGFR [Renal function parameters also remained stable during the study period, even in the subgroup of patients who switched from a regimen containing TDF Click here for additional data file.


We aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen.We analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen.Among 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%).Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4<200 cells/μL and HIV-RNA>100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4<200 cells/μL and HIV-RNA>100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4<200 cells//μL and with transmission categories other than men who have sex with men. Compared with ABC/3TC/DTG, the prescription of other initial ART regimens decreased from 2014–2015 to 2016–2017 with the exception of TDF/FTC+DTG. Differences in the choice of the initial ART regimen were observed by hospitals’ location.The choice of initial ART regimens is consistent with Spanish guidelines’ recommendations, but is also clearly influenced by physician’s perception based on patient’s clinical and sociodemographic variables and by the prescribing hospital location. International and local guidelines for the treatment of HIV-infection provide recommendations on the preferred drug combinations for initial antiretroviral therapy (ART) of treatment-naïve patients ,2. AlthoPrevious studies have shown that the decision on what specific ART regimen is prescribed to each patient can be influenced by a variety of factors, not only dependent on the patient  but also on the prescribing physician  ,6. The fIn this study, we aimed to describe the most frequently prescribed initial ART regimens in recent years in HIV-positive patients in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of initial ART.CoRIS is an open, multicentre, prospective cohort of ART-naïve HIV-positive adults recruited in 45 centres from 13 of the 17 Autonomous Regions of Spain. Patients are followed periodically in accordance with routine clinical practice. Data are subject to internal quality control. A complete description of the cohort has been published elsewhere ,11.st September 2014 (when DTG became available in Spain) and 30th November 2017 with the most commonly used first-line antiretroviral regimens. In order to facilitate the analyses, only regimens prescribed in >5% of individuals were considered. Patients with no follow-up after initiation of ART were excluded.Patients included were antiretroviral-naïve, aged ≥ 18 years, and had started ART between 1The primary endpoint was the choice of the initial ART according to the most frequently prescribed regimens: abacavir (ABC) /lamivudine (3TC) /dolutegavir (DTG) was the most frequently prescribed ART, followed by tenofovir disoproxil fumarate (TDF) /emtricitabine (FTC)/ elvitegravir (EVG)/ cobicistat (COBI), TDF/FTC/rilpivirine (RPV), tenofovir alafenamide(TAF)/FTC/EVG/COBI, TDF/FTC+DTG, TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) and TDF/FTC+raltegravir (RAL).Possible explanatory variables included sex , age at ART initiation , transmission category , educational level , origin , CD4 T-cell count  and viral load , presence of hepatitis C virus antibodies , presence of hepatitis B virus surface antigen (HBVSA) , triglycerides , HDL  and total cholesterol  within 6 months previous to ART initiation, AIDS diagnosis at ART initiation , presence of comorbidities , period of ART initiation  and hospital characteristics .Descriptive analysis of patients’ characteristics was carried out using frequency tables for categorical variables and median and interquartile range for continuous variables. Differences in socio-demographic and clinical characteristics according to initial regimen were assessed with the non-parametric Kruskal-Wallis test for continuous variables and the chi-squared test for independence for categorical variables. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between explanatory variables and the choice of the initial regimen. All variables that retained a significant independent association (p <0.05) were included in the final model.Heterogeneity introduced by different hospitals was accounted for by including the study hospital as a fixed effect in the model and by using robust methods to estimate standard errors and, thus, to calculate 95% confidence intervals and p-values.All statistical analyses were performed using Stata software .Ethics approval was obtained from all hospitals’ Ethics’ Committees and every patient provided written informed consent to participate in the cohort. This study was approved by the Ethics Committee of Instituto de Salud Carlos III (CEI PI 63_2017-v2).Between September 1, 2014 and November 30, 2017, 3,575 patients aged ≥18 years initiated treatment; among these, 147 (4.1%) with no follow-up after ART initiation and 554 (15.5%) who initiated a treatment prescribed in <5% of patients were excluded. The final analysis included 2,874 (80.4%) subjects who initiated ART during the period of study. They were predominantly male (88.5%) and 59.7% were from Spain. Transmission route was heterosexual contact in 23.5% and MSM in 68.9%. At treatment initiation, median age was 36 years (interquartile range [IQR]: 30–44), median CD4+ T-cell count was 416 cells/μL (IQR: 243–591), 8.5% of patients had a history of AIDS diagnosis, 34.5% had a viral load >100,000 copies/mL and 89.2% were attending hospitals with more than 500 beds.The most frequently prescribed initial regimens in the study period and the differences in sociodemographic and clinical characteristics of patients according to their initial ART regimen are shown in As expected, rilpivirine was rarely used in patients with high baseline viral load >100,000 copies/mL (2.5%) or CD4 counts <200 cells/μL (4.0%). A higher proportion of the patients starting TDF/FTC+DTG, TDF/FTC+bDRV and TDF/FTC+RAL had a CD4 cell count below 200 cells/μL and an AIDS diagnosis at start of treatment. TDF/FTC+DTG and TDF/FTC+RAL were more frequent in participants with triglycerides >150 mg/dL and cholesterol-HDL ≤40 mg/dL. Large differences in the prescription of initial regimen were noted by hospital location but not by hospital size. There were also differences in the use of initial regimen in relation to HBVSA and previous cardiovascular event; nevertheless they must be interpreted with caution as the number of events was small.We also observed changes over time in the distribution of the most frequent initial ART regimens . In the Results from multivariable analysis are shown in This is, to our knowledge, the first study assessing the factors influencing the choice of initial ART in a reasonable large cohort in recent years, when newer treatment regimens have become widely available. All the regimens analyzed were considered preferred or alternative by the Spanish treatment guidelines during the study period ,12–14, bOverall, ABC/3TC/DTG was the most frequently prescribed regimen. Interestingly, the prescription of initial regimens changed over the calendar period. Over time, the prescription of regimens based in DTG and EVG increased. TDF/FTC/EVG/COBI prescription decreased but this was probably partly due to the introduction of TAF/FTC/EVG/COBI, which became available in Spain in 2016. The prescription of the other regimens  decreased over time. These changes reflect those introduced in the Spanish HIV treatment guidelines. In 2014, all the regimens included in this study were considered preferred treatments . HoweverDifferent regimens were preferentially prescribed to certain groups. The use of integrase inhibitors was more frequent among MSM. This could be in part due to patients’ preference, as MSM frequently have more access to information about HIV  and coulTDF/FTC+RAL, TDF/FTC+bDRV and TDF/FTC+DTG were more likely to be prescribed to patients with low CD4 counts. The use of TDF/FTC is probably due to the need to initiate treatment promptly when results from HLA B5701 are not yet available, and RAL and DTG could probably be used to minimize interactions in patients that might be being treated for other opportunistic diseases. Also, prevalence of resistance to integrase inhibitors is low in Spain ,16 and tThe choice of regimens varied significantly by hospital location. This is not explained by local variations in clinical characteristics of the patients, as these differences were still large after adjusting for all other factors. Possible explanations include regional variations on the physicians’ perceptions of efficacy and safety of different regimens, differeOur study is limited by the lack of information on individual physician’s characteristics, and some clinical variables that could influence the choice of ART such as pregnancy, resistance testing or other drugs that could interact with ART. However, our strengths include the analysis of a reasonably large number of patients from a multicenter well established cohort, and the recent time period which allow us to analyze the newer treatment regimens. Our results suggest that initial ART prescriptions are influenced by clinical and demographic patient variables, and also by the prescribing hospital location.In conclusion, in this multicenter Spanish cohort the prescription of initial ART regimens varied not only with patients’ clinical and demographic characteristics, but also with other variables such as the period of ART initiation and hospital location. Over time, regimens based on integrase inhibitors have become the most frequent choice as initial ART.


Cryptococcal meningitis has a high morbidity and mortality among AIDS population. Cryptococcal antigen (CrAg) detection is considered an independent predictor for meningitis and death. Since 2011, the World Health Organization recommends CrAg screening for people living with HIV/AIDS (PLHAs) with CD4 counts <100–200 cells/μl. Its implementation is still limited in low-middle-income countries. We aimed to estimate the prevalence and predictors of CrAg positivity in PLHAs. We also evaluated outcomes among those who were CrAg-positive.Prospective cohort conducted at an infectious diseases hospital, in Brazil. Adults with CD4 <200 cells/μl, without previous cryptococcal disease and regardless of symptoms, were enrolled from 2015 to 2018. CrAg tests were performed by LFA. Lumbar puncture was done in CrAg+ individuals and pre-emptive therapy was offered for those without meningitis.Of 214 individuals recruited, 88% were antiretroviral experienced, of which only 11.6% with viral suppression. Overall, CrAg prevalence was 7.9% . In CD4 ≤100 cells/μl group it was 7.5%  and 9.1%  in the group with CD4 101 to 199 cells/μl (p = 0.17). Prevalence in asymptomatic subjects was 5.3% . One among 17 CrAg+ participants had documented meningoencephalitis and no subclinical meningitis was detected. Adherence to pre-emptive treatment was 68.7% (11/16). There were no statistically significant differences in sociodemographic, clinical or laboratory characteristics to predict CrAg positivity. No case of cryptococcal disease was diagnosed among CrAg + subjects, followed by a median of 12 months.versus CD4 101–199 cells/μl). No clinical nor laboratory factors predicted CrAg positivity, corroborating the need for the implementation of universal CrAg screening for PLHAs with CD4 <200 cells/μl in similar settings.CrAg screening for severely immunosuppressed PLHAs in Brazil yielded a prevalence of 7.9%. No difference was found in the prevalence of CrAg stratified by CD4 values (CD4 <100  Cryptococcal meningoencephalitis accounts for 70% to 90% of cases of cryptococcal disease in patients with HIV; it is a life-threatening infection and the second leading cause of death in this population , 2. DespLatin America has the third highest rate of HIV/AIDS-related cryptococcal meningitis in the world, with an estimated 7,000 3,600–11,100) people with positive antigenaemia, 5,300 2,600–8,900) with cryptococcal meningitis and 2,400  deaths annually )/E2, where N is the sample size; Z is the level of confidence according to the standard normal distribution , P is the estimated prevalence of CrAg positivity among the participants (we considered P = 0.10), and E is the tolerated margin of error (proportion within 4%), resulting in a required sample of 208 participants.The sample size was calculated using the formula: N = . Descriptive and exploratory analyses were performed to summarize the characteristics of the individuals. Central measures (mean or median) and dispersion measures (standard deviation and interquartile rage) were calculated for continuous variables, and percentage for categorical variables. We estimated CrAg prevalence considering CD4 ≤ 100 and 101–199 cells/μl, with 95% confidence interval (CI).Univariate analysis was performed to investigate sociodemographic, clinical, and laboratory factors potentially associated with serum CrAg positivity. Chi-squared test or the Fisher exact test were used for comparison of categorical variables and the t test for continuous variables. All tests were two-tailed, with the significance level set at <0.05This study was approved by the institutional review board of Tropical Diseases State Hospital “Dr. Anuar Auad” (CAAE: 42429715.5.1001.0034). All participants gave written informed consent (as outlined in PLOS consent form) to publish these case details. The data collected were considered confidential and are presented in anonymous manner. The consent form used is available in an online repository.A total of 214 individuals with CD4 cell counts < 200 cells/μl were enrolled, of whom 72.4% were male. The median age was 40 (interquartile range (IQR) 33–49) years. Most of the individuals (78.5%) were interviewed on an outpatient basis. About half of the participants were diagnosed with HIV within the previous 12 months, 40.2% had been diagnoses for more than 5 years and 68.2% had previous opportunistic disease. Before enrolment, 88.8% of the participants had started ART at some time, of whom 51.4% were regular users of this medication in the last 3 months, but only 11.6% were viral suppressed. The sociodemographic, and clinical characteristics, including the use of ART, are shown in Overall, 73.3% had CD4 count < 100 cells/μl, 53.3% had up to 50 cells/μl, with median of 47 (IQR 20–102) cells/μl. In the CrAg-positive group, the median CD4 was 56 (IQR 27–128) cells/μl and 47 (IQR 19–102) cells/μl in the CrAg-negative group (p = 0.466). Regarding viral load, 51.4% had > 100,000 copies/ml and 25 participants had a viral load below the detection threshold (< 40 copies/ml). Characteristics related to the laboratory tests are described in Among the 214 participants, 17 presented with positive cryptococcal antigenaemia, resulting in an overall prevalence of 7.9% . The prevalence of CrAg was 7.5%  in individuals with CD4 ≤ 100 cells/μl and 9.1%  in those with a CD4 count between 101 and 199 cells/μl (p = 0.77).Sixteen individuals who were CrAg positive had experience of ART but only one had an undetectable viral load. In the outpatient group , the prevalence of cryptococcal antigenaemia was 7.7% , and in the hospitalized group  it was 8.7% , without a significant difference between the groups (p = 0.76). The prevalence of CrAg among asymptomatic participants was 5.3% , and 9.3%  among symptomatic participants, with no significant difference between the groups (p = 0.316).Cryptococcus spp in CSF. This patient presented severe intracranial hypertension , which improved without need for shunt, after 5 weeks of regular lumbar punctures. He received treatment with amphotericin B  associated with fluconazole 800 mg for 6 weeks. Regular outpatient follow-up was maintained at another facility. Thirteen out 16 individuals with positive CrAg received pre-emptive induction therapy with fluconazole. Four individuals received itraconazole at a dose of 400 mg in the induction phase and maintained this antifungal therapy during consolidation and maintenance, three because of a history of histoplasmosis and one as aspergillosis treatment. Adherence to pre-emptive treatment was 68.7% (11/16).All individuals with positive antigenaemia underwent lumbar puncture. No subclinical cryptococcal meningitis was detected. One among 17 CrAg+ had documented symptomatic meningoencephalitis. This was demonstrated by positive India ink microscopy, positive CrAg LFA and positive culture for After median follow-up of 12 months , no further cases of cryptococcal meningitis or cryptococcosis were reported in the CrAg-positive group. The overall mortality rate was 11.7% (2/17), with no cryptococcal disease as cause of death. Even though the majority of CrAg+ was ART experienced by the time of recruitment, 94.1% were no viral suppressed (< 40 copies/ml). The median time without effective treatment was 31 (IQR 5–129) months. 10 out 17 CrAg+ individual had to change the initial ART regimen due to virological failure. Six of them had viral resistance confirmed by HIV genotyping and achieved viral suppression after switch of ART regimen. The most common antiretroviral regimens after switch were: tenofovir desoproxil and lamivudine associated with dolutegravir and / or protease inhibitors. The median time to achieve viral suppression after recruitment was 4 (IQR 2–10) months.Most of the CrAg+ patients (88%) remained under care, and 76.4% (13/17) achieved undetectable viral load. The median CD4 count increased from 56 (IQR 27–128) cells/μl to 140 (IQR 98–140) cells/μl and 23.5% (4/17) remained with a CD4 count < 100 cells/μl. Details of the follow-up of CrAg-positive individuals are presented in In the present study, the overall prevalence of cryptococcal antigenaemia was 7.9%  and is considered high. There was no difference in the prevalence of CrAg among individuals with CD4 lower than 100 cells/μl compared with those with CD4 counts between 101 and 199 cells/μl. Most individuals were experienced with ART, however only 11.6% had an undetectable HIV viral load, reinforcing the relevance of CrAg screening among severe immunocompromised HIV individuals, regardless of ART status. The study contributed to the fact that there were no new cases of cryptococcal disease in the CrAg positive group and no death related to this disease during follow-up.Brazil is a large country with varying morbidity profiles and scarcity of data on the prevalence of CrAg among the HIV population. The prevalence of CrAg in Brazil was 2.6%  in the North Region (Pará State) , regardlA systematic review that aimed to assess the prevalence of cryptococcal antigenaemia found values ranging from 0.2% to 22.5%, depending on the geographic area and immune status of the HIV population studied . In the The prevalence of CrAg among those with a CD4 cell count ≤ 100 cells/μl was shown to be higher among hospitalized patients  than among patients treated at outpatient clinics , with similar confidence intervals . We obtaEven in the subgroup of symptomatic participants, the symptoms were mostly mild and non-specific, as in a real-world scenario, and we didn’t find association with CrAg antigenaemia. We did not identify any demographic, clinical or laboratory variables that could assist in predicting CrAg positivity, reinforcing the concept that screening is needed for all individuals with advanced HIV immunosuppression regardless of clinical manifestations.Similar to other studies , 32, 33,No subclinical cryptococcal meningitis was detected and we did not find any new case in CrAg-positive individuals, even in those with low adherence to pre-emptive treatment. This contrasts with a recent study reporting 33%  of asymptomatic cryptococcal meningitis among CrAg-positive individuals and an incidence of cryptococcal meningitis during follow-up of 21.4%  without pre-emptive fluconazole and 5.7%  with pre-emptive fluconazole [Our study has some limitation, due to the use of a convenience sample and lack of the results of follow-up of CrAg negative participants. We did not use a random sampling process to select participants. In order to have a representative sample, we invited hospitalized or outpatient assisted HIV-positive individuals, according to a confidential list provided by the central laboratory. Outpatients were accessed by phone calls. However, individuals who could not be contacted or who did not come to the service, probably because of social issues or clinical status, may generate a population with different characteristics. The prevalence could be underestimated, as this population could be less adherent to ART. Due to financial restriction, titration of the CrAg LFA tests was not performed; only qualitative results were obtained. Thus, there is a risk of false-positives in tests with low titration (≤ 1:5) up to 34% . This maOur strengths are that this is the first study in Latin America that evaluates the outcomes of patients screened for CrAg and pre-emptively treated. The population differs from most studies and is composed of PLHAs already experienced in ART, non-asymptomatic and with a higher threshold for CD4 count. Our recruitment was innovative. We hope that it will be the starting point for a reflex screening strategy, since the Central Laboratory is also responsible for conducting the CD4 count tests.The prevalence of cryptococcal antigenaemia in the Midwest region of Brazil is 7.9%  among PLHAs with CD4<200 cells/μl, regardless of symptoms, and 5.3%  in asymptomatic group. There was no difference in the prevalence of CrAg among individuals with CD4 lower than 100 cells/μl compared with those with CD4 counts between 101 and 199 cells/μl. Pre-emptive treatment associated to ART adherence, viral suppression and CD4 restoration are main protective factors to avoid cryptococcal meningitis. Sociodemographic factors, duration of an HIV diagnosis, ART history, clinical or laboratory characteristics cannot predict positivity of CrAg. Even in HIV population with long time of diagnosis, experienced to ART and with poor adherence to it, the serum CrAg routine is still indicated when reassessing care, including those with a higher CD4 threshold of 200 cells/μl.To date, the CrAg screening strategy is not routinely available in resource constrained countries. Health policies incorporating antigenic diagnostic methodologies, such as the cost-effective LFA, are necessary for the early identification of cryptococcal disease and its treatment, in similar settings.S1 File(PDF)Click here for additional data file.


Self-reported antiretroviral therapy (ART) adherence measures that are associated with plasma viral load (VL) are valuable to clinicians and researchers, but are rarely examined among groups vulnerable to dropping out of care. One-seventh of all those living with HIV pass through incarceration annually and criminal-justice (CJ) involved people living with HIV (PLH) are vulnerable to falling out of care. We examined the association of self-reported ART adherence with VL in a criminal-justice sample compared to a routine-care sample.n = 414) were examined and compared with the routine-care sample from the Centers for AIDS Research Network of Integrated Clinical Systems’ seven sites .Samples: We examined data from a multisite collaboration of studies addressing the continuum of HIV care among CjJ involved persons in the Seek, Test, Treat, and Retain cohort. Data pooled from seven CJ- studies  outcomes. Interactions by CD4 count and self-reported health status were also tested.P < 0.01) and that in the routine-care sample was − 0.42 . For the logistic regression of binary detectable VL on 10% increments of adherence we found the coefficient was − 0.26  and in the routine-care sample it was − 0.38 . There was no significant interaction by CD4 count level in the CJ sample, but there was in the routine-care sample. Conversely, there was a significant interaction by self-reported health status level in the criminal-justice sample, but not in the routine-care sample.Among the CJ sample, the coefficient for log-VL was − 0.31 (95% CI = − 0.43, − 0.18; The visual analogue scale is valid and useful to measure ART adherence, supporting treatment for CJ- involved PLH vulnerable to falling out of care. Research should examine adherence and VL in additional populations. A high level of adherence to antiretroviral treatment (ART) is essential for achieving viral suppression among people living with HIV, and is critical for both maintaining their health and preventing HIV transmission to others. Valid, yet practical measures of adherence to ART are needed for studies of intervention efficacy and effectiveness in low-resource settings, and are useful for the clinical care of hard-to-reach populations who have extensive barriers to achieving viral suppression. Real-world, self-reported ART adherence measures that are reliably associated with viral load (VL) measures provide many advantages over medication event monitoring system (MEMS) or pill count, namely increased feasibility of use in busy clinical care settings where pill counts and MEMS have numerous logistical hurdles for routine use, as well as lower costs and more complete data , 2. SelfAs 1 in 7 people living with HIV cycle through criminal justice settings each year , cliniciOne of the most widely used measures of self-reported adherence is a single-item, 0–100% rating scale, generally called the visual analogue scale (VAS) , 13. It Although several factors besides ART adherence can affect viral suppression including persistence on ART , genotypThis study had two main goals. First, we sought to examine rates of ART adherence and viral suppression among criminal justice-involved people living with HIV across seven sites in the U.S. Second; we aimed to examine the association between self-reported ART adherence and VL. Additionally, we explored whether the relationship between adherence and VL was modified by level of CD4 count or self-reported general health status. We hypothesized that higher levels of self-reported ART adherence would be associated with lower levels of VL or with viral suppression (VL < 200 copies/mL) . In addin = 414) were compared with data on people living with HIV pooled from seven CNICS sites  [The current study uses baseline data from seven sites within the Seek, Test, Treat, and Retain (STTR) cohort , a large 11,698) . CNICS i 11,698) . The datAt each study site, baseline interviews and laboratory measures were collected and processed by individual studies and the STTR Coordinating Center harmonized the data. We analyzed and compared cross-sectional, baseline data from criminal justice-involved people living with HIV in the STTR studies, and with people living with HIV in routine care in CNICS. Criminal justice-involved participants included those in custody or released but under community supervision. Of 1189 criminal justice-involved (STTR) participants, 414 individuals had complete data on adherence and VL within 30 days of the adherence reference period. Of 15,740 possible people living with HIV in routine clinical care, 11,698 participants had complete data on adherence, or a VL within 30 days of the adherence reference period.In both groups, self-reported adherence data were measured using the VAS, on a scale of 0–100% of ART doses taken in the preceding 30 days. Self-reported general health status was measured using the first item of the SF-12 instrument  on a 5-point Likert-type scale with response options that ranged from “poor” to “excellent.” Study sites also collected self-reported data on age and gender for use in adjusted analyses. We also collected data on ART regimens – Non-nucleoside Reverse Transcriptase (NNRTI), Protease Inhibitors (PI), integrase strand transfer inhibitor (INSTI) , and comP-values were computed for the test of whether the regression coefficient for the given ART type is different than that for NNRTI. Again, the routine care sample was analyzed to provide a normative comparison for the size and direction of effects estimated in the criminal justice sample for all analyses.We first examined descriptive characteristics of ART adherence and VL, and then assessed the associations of adherence with VL in each individual criminal justice-involved study, and the combined criminal justice sample, which were then compared to the overall, CNICS, routine HIV care dataset. Next, we constructed linear and logistic mixed effects regression models with random intercepts and slopes, adjusted for age using the criminal justice sample data. To determine the robustness of the associations of adherence with VL, we used three distinct approaches often used in adherence research , 33, 34.3, and self-reported general health status was categorized as high  vs. low . To test whether the associations between adherence and VL differed significantly by CD4 or health status strata, we conducted linear mixed effect regressions of log-VL outcomes on 10% increments of adherence, age, sex, study site, the effect modifier variable of interest  and the interaction of adherence*effect modifier variable. A sensitivity analysis using different cut points to define the health status strata (excellent/very good vs. good/fair/poor) was also performed, and because the results did not differ greatly, we present results using the original cut-point.CD4 cell count and self-reported general health status were assessed as possible effect modifiers of the adherence-VL association in both the criminal justice and routine care samples. CD4 count was dichotomized as ≤ 500 vs. > 500+ cells/mmP < 0.001) more likely to have a detectable VL (26% vs. 12%), greater mean log-VL, smaller proportion with ART adherence scores ≥ 95% (59% vs. 70%), and smaller proportions of ART regimens containing either PI (28% vs. 41%) or NNRTI (23% vs. 42%), or INSTI regimens , so each 10% increment in adherence was associated with a reduction in VL of 34%.We examined the association between VL (both continuous and binary) and adherence (in 10% increments) using mixed effects regression analyses and found, among the criminal justice sample the relative VL was 0.73 . Similarly in the criminal justice sample, for the logistic regression of binary detectable VL on 10% increments of adherence we found an odds ratio (OR) of 0.77 . In this case, however, there was a significant interaction, indicating that the coefficients in the two samples were significantly different from one another (P = 0.049). Moreover, we examined the associations of optimal adherence (≥95%) with binary detectable VL, and in the criminal justice sample we found that the OR was 0.56  for those with CD4 < 500; it was − 0.25  for those with CD4 ≥ 500  than it was for high health status  and that the interaction was significant  and combination/other ART regimens showed significantly stronger associations than with NNRTI regimens.Although there were no significant differences by regimen in the association of adherence with viral suppression every other regimen compared with NNRTI showed a significantly stronger association with viral suppression Table . MoreoveAmong criminal justice-involved persons living with HIV from seven criminal justice-focused studies in STTR, we found consistent associations between higher self-reported ART adherence, using a variety of approaches, with lower VL levels. We compared these findings to people living with HIV in routine clinical care from seven CNICS sites across the US and found similar patterns of association. In addition, the coefficients reflecting the strength of the association were generally in the same direction and of similar magnitude to those among people living with HIV in the routine clinical care sample. These findings have important implications for the care of people living with HIV who cycle through criminal justice settings, and the study of ART adherence in the continuum of HIV care among criminal justice-involved populations. Because criminal justice-involved populations, particularly those recently released from incarceration, are highly transient and hard-to-reach because of frequent unstable housing, substance use, and mental health problems they face greater challenges to ART adherence as well as to accessing HIV care –37. SuitOf particular note, in the criminal justice sample we found that the associations of self-reported adherence with VL were robust in that there was a significant association of high levels of adherence with lower levels of VL, measured in a variety of ways – continuous (log-VL) and dichotomous. It is clinically useful to know that every 10-point increment on the 0–100% adherence scale is associated with approximately a 25–30% decrement in log-VL. The GAM analysis suggests that this association was not significantly different in magnitude at the low or high end of the VAS adherence scale. Together these findings mean that assessing self-reported ART adherence could be useful in detecting patients who are most likely to have uncontrolled viremia at the low end, as well as in detecting those who are likely well controlled at the high end of adherence reports. Comparisons of these associations with the routine care sample provided strong confirmation of the findings in the smaller criminal justice sample because in almost every analysis, the coefficients were of very similar direction and magnitude as those in routine care.The examination of potential effect modification by CD4 cell count and general health status also enhanced the clinical relevance of our findings. In the criminal justice sample, the regression coefficients relating high levels of ART adherence with lower levels of VL were significant in both strata of CD4 count, and the interaction testing difference in the association by CD4 level was not significant, suggesting that the relationship held regardless of stage of illness. However, the point-estimate of this regression coefficient among those with CD4 level < 500 was twice as large as that among those with CD4 level ≥ 500. Furthermore in the routine care sample, the point-estimate of this regression coefficient among those with CD4 level < 500 was more than three times as large as that among those with CD4 level ≥ 500. Thus, with the large sample size the interaction testing differences in the association by CD4 level was highly significant. It is important that the association was strongest among those with the most advanced disease, and for whom clinicians would be most concerned. Nonetheless, the regression coefficients relating high levels of ART adherence with lower levels of VL were significant in both strata of CD4 count in the routine clinical care sample, supporting the robustness of the association.Examination of the associations by self-reported general health status, however, did reveal more variation. Among the criminal justice sample, we found that the regression coefficients relating high levels of ART adherence with lower levels of VL was strong and highly significant among those with low self-reported general health status levels. However, the corresponding coefficient was quite weak (nearly zero) and non-significant among those with high self-reported health status levels. Thus, the interaction testing of the difference in the association by self-reported general health status level was highly significant. This finding supports the association among the most symptomatic, but not among those in best self-perceived health. Interestingly, the same pattern was not observed in the routine care sample. There we found the association of VAS adherence with VL was significant and of similar magnitude regardless of self-reported general health status levels, so the interaction was not significant. Moreover, we found that adherence was associated with viral suppression, especially for combination ART medications.As with all studies, these analyses had several limitations. First, this study was cross-sectional and hence we can only report associations and cannot demonstrate causality. We restricted the criminal justice and routine clinical care samples to only those whose 30-day adherence report window covered the VL test date. While this restriction reduced the sample size substantially, whether the VL overlapped with the adherence timeframe would most likely impart random error, rather than systematic bias in one consistent direction. Inherent to smaller sample size is the reduced power of some analyses, especially the interaction or moderation analyses, such as those we conducted by CD4 and self-reported general health status. As often occurs with secondary data analyses, the data were collected for other purposes and hence did not always align with the design needs of this analysis. The smaller sample size resulting from our attempts to eliminate error reduced our power to detect associations and interactions, widening confidence intervals around the coefficients of associations. The sample size was also smaller for analysis by CD4 count and general health status than that for other variables, so we had limited power for these moderation analyses. We lacked data on barriers to adherence, or objective measures such as MEMs, pill count or number of pills in each ART regimen to make comparisons with the VAS. Despite these limitations in the data we do have viral load data that a strong anchor for adherence for this analysis. Last, although this study includes several major HIV epicenters around the US, and both jail and prison settings, the findings may not generalize to all criminal justice settings, nor to all major metropolitan or smaller areas. It also may not generalize to cases where the time frames of the VAS adherence and VL measures do not match.Overall, we found that relationships between adherence and VL, using a variety of approaches among criminal justice-involved PLWH, were robust and similar to those in routine clinical care. Consequently, the VAS adherence measure is a convenient, valid and useful adherence measure to support treatment for criminal justice-involved people living with HIV who are vulnerable to falling out of care. While we recognize that obtaining VL is essential to assessing the outcomes of care, the VAS adherence measure is useful to clinicians in this situation, where it is often difficult to measure VL regularly. It can provide results more quickly and efficiently for clinical decision-making than more complex adherence measures, or VL tests which often take days to produce results. Findings from this assessment when adherence is suboptimal (<=95%) can direct clinical care in two important ways: 1) providers can quickly intervene to optimize adherence and possibly avoid virologic failure sooner than they could if they waited for VL test results and 2) proactively order HIV-1 genotyping to assess for virologic resistance to current medications. The latter is indicated because the risk of resistance is greater with poor or intermittent adherence that often attends criminal justice-involved people living with HIV who have prevalent substance use disorders and cycles of incarceration and release. This study also provides further evidence of the validity of the VAS adherence measure for use in other survey research. This is, particularly the case in post-release criminal justice-involved populations or other situations where more objective forms of adherence measurement and more frequent VL testing are not feasible. While some research has supported the notion that criminal justice-involved populations can achieve HIV continuum of care milestones as well as those of non-criminal justice-involved populations , it is g