This study aimed to examine the association between Family Adaptability, Partnership, Growth, Affection and Resolve (Family APGAR) and HIV treatment outcomes.A cross-sectional study using the Family APGAR questionnaireThe study was conducted in Kumasi, Ghana, at the Komfo Anokye Teaching Hospital and the Kwame Nkrumah University of Science and Technology HospitalConsenting HIV-positive patients who had been on treatment for at least 12 months were recruited.® software. The relationship between Family APGAR and treatment outcomes was determined using Chi-squared tests or Fisher's exact test.The Family APGAR questionnaire was administered, and relevant data were extracted from hospital records and analysed using STATA3. Females were less likely  to report late for treatment compared with the males. After 12 months of treatment, approximately 70% recorded undetectable viral load. Patients with functional families constituted 70.4%, which had a statistically significant relationship with viral load (p = 0.041).Approximately 70.1% of 304 participants were females with a mean age of 41.8 years (±9.9). At treatment initiation, 47.4% of the patients presented at World Health Organisation (WHO) clinical stages I and II and had a CD4 count ≥ 200 cells/mmHIV care providers should incorporate family functionality evaluation into clinical practice and provide early essential support to enhance treatment outcomes.None declared By 2020, the 90-90-90 agenda to end the Human Immunodeficiency Virus/Acquired Immunodeficiency Virus pandemic was targeted by the Joint United Nations Programme on HIV/AIDS (UNAIDS).3There is a growing need to consider other factors influencing HIV/AIDS outcomes apart from drug treatment and adherence.The primary objective in initiating highly active antiretroviral therapy (HAART) is to achieve viral suppression and undetectable HIV Ribonucleic Acid (RNA) viral load.5Within 8 to 24 weeks, this is expected to be achieved by patients who adhere to antiretrovirals (ARVs), provided they do not harbour any resistant strains of HIV.5The World Health Organisation (WHO) defines treatment failure as persistently detectable viral load exceeding 1000 copies/ml after at least six months of using ART8Every individual belongs to a family and derives support from the family during ill health, incapacitation or hospitalisation.12Commonly, HIV research has focused on prevalence,The study was conducted at the HIV Clinic, Komfo Anokye Teaching Hospital (KATH) and the Infectious Disease Unit (IDU) of the University Hospital, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana. Both institutions have a patient population with varied socio-demographic characteristics. Though located in Kumasi, a cosmopolitan city, both study sites receive referrals from towns and villages beyond Ashanti Region. KATH is a public institution owned by the Ministry of Health and provides tertiary-level care as a teaching hospital. Its HIV clinic, the first in Kumasi, was set up in 2003 and attends to an average of 1000 patients monthly. The IDU, established in the year 2010, is located on the campus of KNUST and provides services for students, staff, and their dependents, as well as patients who are not members of the University community. An average of 240 patients a month are seen at the IDU. Study participants were people living with HIV (PLWH) who were 18 years old and above, registered at either of the two study sites and had been on ART for at least 12 months. Participants could understand the study protocol and provided informed consent. Those excluded were HIV-positive patients on hospital admission or those who were too ill to participate.This was a cross-sectional study involving PLWH who visited the health facilities and collected their data at treatment initiation and 12 months after treatment. The study period was three months. Study participants were patients who reported to the study sites on clinic days for a refill of medications or to be seen by a doctor. A systematic random sampling method was used. Selected patients were screened to ensure the eligibility criteria were met. Data on clinical parameters such as HIV serotypes, WHO clinical stage, co-infections, CD4 count, and viral load were extracted from participants' hospital folders. CD4 count and viral load results of patients at both KNUST and KATH were derived from the serology laboratory at KATH. Data on participants' socio-demographic characteristics and family functionality were obtained by administering a structured questionnaire which included the Family APGAR. Hence, family functionality was assessed in participants who had been on treatment for at least 12 months. The Family APGAR is a validated tool which assesses five domains of family function: a respondent's satisfaction with family support in troubling times (Adaptability); satisfaction with family communication and problem sharing (Partnership); satisfaction with family support when pursuing new activities (Growth); satisfaction with family's expression of affection and satisfaction with family time spent together (Resolve). There are three types of responses which are graded as ‘almost always’ (2), ‘some of the time’ (1) and ‘hardly ever’ (0) It has a total score of 10 and each respondent is categorised into a severely dysfunctional family (score 0 – 3), a moderately dysfunctional family (score of 4 - 6) and a highly functional family (score of 7 – 10).3,An estimated 76.8% of adults living with HIV had a baseline CD4 count of less than 200 cells/mmThis study estimated viral load in 1.1ml of plasma based on a procedure recommended by the reagents manufacturers .Those who recorded viral load ≤ 1000 copies/ml were classified as viral suppression, and viral load > 1000 copies/ml was considered a virologic failure. Those who recorded viral load < 20 copies/ml were considered undetectable levels based on WHO recommendation.21Means, standard deviations, frequencies, and percentages were used to describe the data. Chi-square or Fisher's exact tests were used to examine factors associated with the treatment outcome variables . Binary logistic regression was used to assess the magnitude of association of factors that showed some level of association (minimum of p<0.05) with the treatment outcomes. Crude Odds ratios (OR) and adjusted odds ratio (aOR) at 95% confidence intervals were estimated. To assess the determinants of family functionality, the outcome variable  was binary coded as ‘1’ for those who rated their families as dysfunctional  and ‘0’ for those who rated their families as functional. The logistic regression model included only statistically significant variables (p<0.05). After at least 12 months of treatment, the treatment outcome variables consisted of patients with CD4 count decreased below baseline or above baseline and HIV viral load, categorised as undetectable, 20 – 1000 and >1000 copies/ml.Approval was obtained from the Committee on Human Research, Publication and Ethics (CHRPE), School of Medical Sciences (KNUST-SMS), Kwame Nkrumah University of Science and Technology and the Komfo Anokye Teaching Hospital, Kumasi, Ghana (CHRPE/AP/014/18). Participants voluntarily agreed to be recruited into the study and signed or thumb-printed an informed consent form. Their privacy and confidentiality were safeguarded throughout the study period and beyond.A total of 304 study participants were recruited into the study. The mean age of participants was 41.8 (SD ± 9.9), with a minimum age of 22 years and maximum age of 78 years. Those who were females were 213 (70.1%). All the participants had a partner and were either married  or cohabiting . Participants with basic education were 198 (65.1%) and 237 (75.5%) in informal employment. The majority were Christians . . 3 (non-AIDS stage). Participants' gender (p = 0.018), age (p = 0.002) and WHO Staging (p <0.001) were significantly associated with CD4 count at treatment initiation  tested positive for HIV 1 serotype . At treaitiation .3 (AIDS) at treatment initiation was lower  when compared with their male counterparts  compared with patients who reported to the health facility at WHO stage I. The odds of a patient who is >60 years old recording a CD4 count < 200 cells/mm3 (AIDS) at treatment initiation was also higher  when compared with patients who reported to the health facility between the ages of 18 – 30 years  of the participants' CD4 count increased above baseline, suggestive of good immunologic response, while 10.5% (n = 32) of the participants` CD4 count decreased below baseline (suggestive of immunologic failure).Approximately 71.7% (n = 218) of the participants attained the desired endpoint of undetectable viral load after 12 months of treatment. Those who recorded virologic failure  were 11.8% (n = 36) of study participants . ParticiHowever, participants' gender (p = 0.329), age (p = 0.605), relationship status (p = 0.160), and HIV serotype (p = 0.068) had no significant association with CD4 count. The co-infection with the highest frequency was tuberculosis , whilst approximately 74.3% (n = 226) of participants were not diagnosed with any co-infection .Participants who rated their families as functional (Family APGAR score ≥ 7) were 214 (70.4%), and those who rated their families as severely dysfunctional (Family APGAR score < 3) were 49 (16.1%) .After at least 12 months of treatment, there was a statistically significant relationship between family functionality and viral load (p = 0.041) but no significant relationship between family functionality and CD4 count (p = 0.637) .The outcome of interventions for any illness largely depends on how early patients report and if appropriate therapy is initiated. Generally, HIV-positive patients report late to ART centres.In Europe (excluding Russia) the mode of HIV transmission includes but is not limited to the following; 46% through heterosexual sex, 26% from MSMs, 13% in drug users and less than 1% vertical transmission.24One of the factors that promote early access to ART by women is active screening to prevent mother-to-child transmission of HIV.26A patient's clinical stage at treatment initiation is related to the CD4 count. CD4 cells belong to a group of lymphocytes, also called CD4+ T cells, fighting infections within the human body.At treatment initiation, factors significantly associated with CD4 counts were WHO clinical stage, age and sex. Even though females tended to have a higher CD4 count at treatment initiation than men, there was no significant relationship at six months after treatment. However, after 12 months of treatment, male participants were more likely to have CD4 counts above baseline. We surmise that this may be explained by decreased immunity because of changes in women's hormonal cycle during menstruation and pregnancy.Since several factors influence CD4 count, viral load testing has overtaken its usefulness in clinical practice. Virologic response is, therefore, the major prognostic factor for ART outcomes.6In this study, 12% of participants had a viral load > 1000 copies/ml after at least 12 months of treatment. Approximately 88.2% recorded viral ≤1000 copies/ml, which is higher than the 66% viral suppression in the general Ghanaian HIV population but below WHO's target to achieve 90% viral suppression among patients on ARTs.33Apart from the WHO clinical stage, our participants' viral suppression had no significant association with their socio-demographic characteristics and other clinical parameters. A persistently high viral load may be due to treatment resistance, re-infection or drug-drug interactions; however, our study did not assess these.We established that 70% of participants assessed their families as functional, which was associated with the viral load after 12 months of treatment. This highlights the importance of regular viral load testing in HIV care and that strong family support and good family function are essential in ensuring positive disease outcomes. This study considered participants' family functionality, an important but often neglected dimension of patient care. A functional family is associated with a high adherence to antiretroviral therapy, reduced incidence of loss to follow-up and improved treatment outcomes.This study was limited because data relied on participants' medical records including CD4 count, HIV clinical stage and viral load reports, some of which were unavailable. This was largely because of frequent stock out or laboratory equipment breakdown.This provides useful feedback for the need to address health systems-related problems. The administration of Family APGAR was done once, after all the participants had been on treatment for a minimum of 12 months.We recommend a future study that will assess patients' family functionality at the initiation of treatment and at the different stages of treatment to determine whether their APGAR scores vary with time and the associated factors.Our study participants' determinants of treatment outcomes were gender, WHO stage at treatment initiation and family functionality. The latter can be assessed using the Family APGAR, a simple tool, at the outpatient department and should be encouraged. When family dysfunction is detected, health care workers should try to reduce or eliminate it to mitigate any negative effects on ART outcomes. The ever-changing dynamics of HIV management call for a holistic approach which includes the entire family.


The concept of “undetectable = untransmittable (U = U)” has been revolutionary in both the prevention and treatment of persons with human immunodeficiency virus (HIV). Most studies proving the concept of U = U used an HIV RNA  cutoff of 200 copies/mL to define being undetectable. Since then, increasingly sensitive commercial VL assays, sometimes down to a lower limit of detection (LLD) of 20 copies/mL, lead to confusion about the definition of “undetectable” and when someone is truly considered untransmittable. VLs between the LLD and 200 copies/mL have been associated with future virologic failure; however, no data exist to suggest that intervening in those patients leads to any meaningful benefits. In the absence of a demonstrable benefit of reporting such low VLs, we view this practice as harmful. We suggest recommendations for adjusting VL reporting and improving provider counseling, and call for research designs to mitigate the harms of overly sensitive VL testing. Overly sensitive HIV viral load assays complicate the straightforward, transformative concept of “U=U”. In the absence of demonstrable benefits of reporting low viral load values (<200 copies/mL), we consider this to be a harmful practice and suggest mitigation strategies. A young woman presented to a human immunodeficiency virus (HIV) primary care clinic for the treatment of newly diagnosed HIV infection. She was started on antiretroviral therapy (ART) and was counseled that with time and high adherence, she would achieve an “undetectable” HIV RNA level  and would be noninfectious to sexual partners. Over the subsequent 2 years, the patient's VL remained detectable, based on the laboratory's lower limit of detection (LLD) of 20 copies/mL, with measures between 20 and 200 copies/mL and a normal absolute CD4 lymphocyte count. She reported near-perfect adherence, which was confirmed by pharmacy refill records. Her physician explained that a sustained VL of <200 copies/mL meant that the virus was untransmittable; despite this explanation, she became increasingly frustrated about being unable to achieve an “undetectable” status based on reported laboratory values. She was skeptical about her lack of infectiousness, was dissatisfied with her ART, and was reticent to engage in sexual relationships, which she had avoided since her diagnosis.“Undetectable = Untransmittable (U = U)” is the concept that persons with HIV (PWH) with an undetectable VL cannot transmit the virus to sexual partners , 2. ThisPrior to the widespread consensus on U = U and the advent of HIV preexposure prophylaxis, HIV prevention in serodiscordant sexual partners relied upon counseling, frequent HIV testing, and emphasis on reduction of “risky behaviors” . These oundetectable VL has evolved over the years as clinical laboratory detection of HIV has advanced. Increasingly sensitive VL testing will inevitably lead to more PWH being labeled as “detectable,” when defined as “above the LLD of the assay” or even when the VL is below the LLD but still present and reported as detectable. Many commercial laboratories now detect as few as 20 viral copies/mL depending on which polymerase chain reaction (PCR) assay is used  display of results to patients and providers . One posundetectable is equated specifically to a VL <200 copies/mL rather than looking for the words “not detected” or a “<” symbol in laboratory results. Another option is to focus on the number 200 as being an important number to remember for PWH to understand the status of their HIV. Patients can be counseled that “our goal for treatment is a VL less than 200 and CD4 count above 200.”Providers should adjust patient education and counseling to preempt confusion about U = U and detectable VLs <200 copies/mL. One approach is to spend extra time ensuring that the term Finally, we call for further research into the value of patient and provider awareness of VL values between the LLD and 200 copies/mL. Studies facilitated through the EHR could randomize patients to having quantitative values between the LLD and 200 copies/mL displayed in their results compared to having all values <200 copies/mL hidden and reported only as “undetectable” or “<200.” The outcomes of interest would be to investigate if either approach is associated with a lower incidence of virologic failure and differences in quality of life or perceived health status. Additionally, studies evaluating adherence support programs might evaluate if the magnitude of benefit is higher for preventing virologic failure among those with LLV compared to those who have VLs less than the LLD.undetectable, and call for pragmatic research to determine the value—or harm—of highly precise VL reporting.The establishment of U = U and the evidence showing near-zero risk of sexual transmission even with LLV has been transformative and empowering for PWH. It also provides an opportunity to destigmatize PWH and promote adherence to ART through dissemination of this positive public health message. Testing and reporting of VL values between the LLD and 200 copies/mL have the potential to sow confusion and further stigma in the absence of evidence that this information is clinically useful or actionable. We advocate for alternative approaches to reporting VL values, suggest adjusting patient counseling to clarify the definition of


Long-Acting cabotegravir/rilpivirine (LA-CAB/RPV) is the first FDA-approved, complete, long-acting injectable antiretroviral therapy (ART) regimen. In clinical trials, LA-CAB/RPV has proven to be highly effective in maintaining virologic suppression in people living with HIV (PLWH) with virologic suppression, on a stable ART regimen, and no resistance to either agent. There is limited published real-world data regarding the efficacy, adherence, and discontinuation rates of LA-CAB/RPV, especially in populations underrepresented or excluded from clinical trials. The purpose of this study is to evaluate the real-world efficacy of LA-CAB/RPV in achieving and maintaining virologic suppression in PLWH.We conducted a single-center retrospective chart review of HIV-1 positive adults receiving care at the Ruth M. Rothstein CORE Center, a safety-net system in Chicago. Patients were included if they received at least one dose of LA-CAB/RPV between January 1, 2022 and October 31, 2022.2. Baseline HIV viral load was < 50 copies/mL in 97.9% of patients. Additional baseline characteristics are described in Table 1. Most (86.5%) patients initiated direct-to-inject LA-CAB/RPV with 98% solely initiating every 2-month dosing schedule. The median number of LA-CAB/RPV doses received was 4 . Virologic suppression was defined as HIV viral load < 50 copies/mL. Of the 96 patients, 79 had HIV viral load data at week 4 with 99.7% of those being undetectable, 37 had data at week 12 with 100% of those being undetectable, and 62 had data at week 24 of which 96.8% were undetectable. Adherence rates to injections were high, with 96.3% given on-time and the discontinuation rate was 18.8%A total of 96 patients met inclusion criteria and were included in the study. Of these patients, the median age was 42.5, 79.2% were Black/African American, 54.2% were cisgender men, and 46.9% had a BMI of ≥ 30 kg/mLA-CAB/RPV was highly effective in achieving and maintaining virologic suppression among a large number of patients at an urban HIV clinic. This study is limited by short follow-up time during the program's initial scale-up phase. Additional long-term data are needed to determine long-term real-world efficacy, adherence, and discontinuation rates.Gregory Huhn, MD, MPHTM, Clinical Care Options: Advisor/Consultant|Eli Lilly: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Medscape: Advisor/Consultant|Merck: Advisor/Consultant|Practice Point Communications: Advisor/Consultant|Ridgeback: Grant/Research Support|Trio Health: Advisor/Consultant|Viiv: Advisor/Consultant|Viiv: Grant/Research Support


Cabotegravir + rilpivirine (CAB+RPV) injections, the first complete long-acting (LA) antiretroviral therapy (ART) regimen, was approved by the FDA in January 2021 for ART-experienced people with HIV (PWH) who are virologically suppressed (VL < 50 copies/mL). Among individuals virologically non-suppressed (VL ≥ 30 copies/mL) at initiation, high rates of virologic suppression were observed in the demonstration project at Ward 86 for CAB+RPV LA. We observed CAB+RPV LA real-world utilization and effectiveness over the first 2 years of availability in the United States (US) in individuals with VL ≥ 50 copies/mL at initiation in the OPERA® Cohort.All ART-experienced adults with VL ≥ 50 copies/mL at initiation who received their first CAB+RPV LA injection between 21Jan2021 and 28Feb2023 were followed until 25Mar2023. Discontinuation (ART switch or 2 consecutive missed doses) and confirmed virologic failure  were described, for all individuals with VL ≥ 50 copies/mL and for the subset with VL ≥ 200 copies/mL.Of 1843 ART-experienced PWH with ≥ 1 CAB+RPV injections, 229 (12%) had a VL ≥ 50 copies/mL at initiation. At baseline, they were a median of 41  years of age, 31% female, 57% Black and 20% Hispanic. Injections started a median of 9  years after HIV diagnosis with a median viral load of 2.1  log copies/mL and median CD4 count of 579  cells/μL (Table 1). Over a median of 6.1  months of follow-up, 83% were still on CAB+RPV LA at study end. Among the 80% with ≥ 1 VL over follow-up, 94% had a VL < 200 copies/mL and 75% had a VL < 50 copies/mL at study end. CVF was observed in 7 (4%) individuals (Table 2). Similarly for the subset of 93 individuals with a VL ≥ 200 copies/mL at initiation, 90% and 74% had a VL < 200 or < 50 copies/mL at study end, respectively, when follow-up VLs were available (Table 2).In a large, diverse cohort of real-world, routine clinical care in the US, CAB+RPV LA injections were observed in individuals with viral loads ≥ 50 copies/mL at initiation. Most of these individuals were able to suppress to VL < 50 copies/mL and maintain suppression through study end.Ricky K. Hsu, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Janssen: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Honoraria Michael Sension, MD, Gilead: Advisor/Consultant|Gilead: Honoraria|Viiv: Advisor/Consultant|Viiv: Grant/Research Support|Viiv: Honoraria Jennifer S. Fusco, BS, Epividian, Inc.: Salary|Epividian, Inc.: Ownership Interest|Epividian, Inc.: Stocks/Bonds Laurence Brunet, PhD, Epividian, Inc.: Salary|Epividian, Inc.: Stocks/Bonds Gayathri Sridhar, MBBS, MPH, PhD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Full Time Employee Vani Vannappagari, MBBS, MPH, PhD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employee Jean A. van Wyk, MBChB, MFPM, ViiV Healthcare Ltd: Stocks/Bonds Michael B. Wohlfeiler, JD, MD, AAHIVS, ViiV Healthcare: Serves as a PI on clinical trials, but does not receive personal compensation for this work  Gregory P. Fusco, MD, MPH, Epividian, Inc.: Board Member|Epividian, Inc.: Ownership Interest|Epividian, Inc.: Stocks/Bonds


Interferon-inducible protein-10 (IP-10) and monokine induced by interferon-gamma (MIG) are chemokines recognized as inflammatory biomarkers during HIV-1 infection. We assessed their early and long-term dynamics after initiation of antiretroviral treatment (ART).Persons with HIV-1 (PWH) aged>18 years starting their first ART in 2015-2021 in a prospective cohort (n=73) were included. IP-10 and MIG plasma levels were quantified using a multiplexed bead-based assay.3 had higher levels of IP-10  and MIG . All of them matched their counterparts several months following ART initiation. MIG levels showed a greater decrease at day 10 in those treated with INSTI (p=0·038). Low-level HIV-1 viremia did not impact MIG or IP-10 levels.IP-10 and MIG plasma levels showed a significant and consistent reduction following ART (80% integrase inhibitor [INSTI]-based) initiation, starting at day 20 and maintained throughout the study period (48 months), paralleling the HIV-1 RNA decay and CD4+ count recovery (p<0·001). At baseline, PWH≥ 50 years, CDC stage C and CD4+ count<350cells/mmPlasma IP-10 and MIG showed an early significant decline following ART initiation, with greater early declines in MIG levels in INSTI-based regimens. These findings suggest a strong impact of HIV-1 viremia on IP-10 and MIG levels. Interfe3 , 12, 16.3 .After HIV-1 infection, a strong positive correlation of IP-10 with HIV-1 RNA and a negative correlation with CD4+ T cell count has been reported . In turnWe aimed to assess the dynamics in plasma IP-10 and MIG levels throughout the study period in a well-characterised cohort of PWH initiating current antiretroviral regimens including integrase inhibitors. Analyses were focused on particular scenarios of interest, stratifying according to age, AIDS-defining events, and CD4+ T cell count at baseline and HIV-1 RNA at month 12 after ART initiation.We used frozen plasma samples stored at -80°C that were prospectively collected from 32 HIV-1-infected treatment-naïve individuals in clinical follow-up at the Spanish HIV-1/AIDS Research Network Cohort (CoRIS), a nationwide multicentre cohort launched in 2004, including individuals with confirmed HIV-1 infection who were recruited in 46 HIV-1 care units of the Spanish Public Health System. A complete description of CoRIS has been published previously , who started ART in April 2017. Blood samples were processed at the Galicia Sur Health Research Institute to obtain plasma and peripheral blood mononuclear cells and stored at the Biobank of Vigo for subsequent analysis. Overall, 73 individuals aged > 18 years and who initiated ART from February 2015 to July 2021 were included in the current analysis according to their sample availability in the time points of interest for plasma cytokine measurements.All individuals participating in the study gave their informed consent and protocols were approved by institutional ethical committees.3 vs. CD4+ T count ≥350 cells/mm3, and the initial antiretroviral (ARV) regimen (two nucleos[t]ide reverse transcriptase inhibitors [NRTIs] plus a third drug including boosted-protease inhibitors [b-PI] or integrase strand transfer inhibitors [INSTI]).We assessed changes in plasma chemokine profiles (IP-10 and MIG) pre- and post-ART initiation in the study population, at the following sampling time points: baseline and months 6 and 12 after ART initiation. For the Ferrol cohort, it was possible to assess earlier time points including day 10, day 20, and months 1 and 3 after ART initiation. In turn, within the CoRIS cohort, it was also possible to evaluate longer time points including months 24, 36, and 48 after ART initiation. Plasma chemokine changes were compared with HIV-1 RNA and CD4+-T cell dynamics. Several particular scenarios were assessed: the subset of individuals aged ≥50 or <50 years, baseline CDC category , baseline CD4+ T count <350 cells/mmIn addition, within the Ferrol cohort, we were able to explore the IP-10 and MIG levels in individuals with low-level viremia (defined as HIV-1 RNA 20-199 copies/mL), and target detected (TD) or not detected (TND) HIV-1 RNA below 20 copies/mL, at month 12 after ART initiation.® MAP human high-sensitivity T cell magnetic bead panel; Merck EMD Millipore, Billerica, MA, US).Determinations of IP-10 and MIG (pg/mL) were performed using a multiplex bead-based immunoassay  among continuous variables  at different time points. We used the Mann-Whitney U test to compare the median concentrations of plasma determinations among groups. In addition, we utilized Spearman’s correlation coefficient to correlate quantitative variables.a priori, before the ART initiation date. Models were adjusted for sex, age, comorbidities, CD4 cell count <350 cells/mm3 at ART initiation, and CDC stage C at HIV infection.Finally, we used a logistic regression model to assess the impact of multiple baseline predictor variables on high concentrations of plasma IP-10 and MIG at month 12 after ART initiation, defined as >370pg/mL and >955pg/mL, respectively, based on cutoffs used in a previous analysis . Values 3, 36 (49.3%) participants had CD4+ counts <350 cells/mm3, 38.3% had HIV-1 RNA >100,000 copies/mL at ART initiation, and 80.8% had initiated an INSTI-based regimen.The baseline characteristics of participants are shown in IP-10 and MIG plasma levels showed a significant and consistent decrease vs. baseline throughout the study period following ART initiation (p<0·001)  preceded the CD4 cell count increase   parallelism of IP-10 and MIG decrease with CD4+ count recovery (p<0·001) and the HIV-1-RNA decay (p<0·001) at month 12  and MIG (p<0.001) than PWH aged <50 years. Upon ART initiation, IP-10 levels in PWH aged ≥50 years showed a sharp reduction and at month 12, IP-10 levels matched PWH aged <50 years. Similarly, MIG levels showed a sharp decrease in PWH aged ≥50 years, but the late decline was slower, and at month 12, differences were still significant vs. PWH aged <50 years (p=0·021) . Although, the median time from HIV diagnosis until ART initiation was higher in individuals who were aged ≥50 years than in individuals with ages <50 years, this difference was not statistically significant .PWH with CDC stage C had higher baseline IP-10 levels (p=0·001) and MIG levels (p=0·024) than those with a CDC stage A. After ART initiation, both cytokines decreased, and no significant differences were observed among PWH with a CDC stage C vs. A after month 6 for MIG. However, IP-10 levels were higher in PWH with CDC stage C vs. A at month 12 (p=0·021)  and MIG levels  than those with CD4+ T count ≥350 cells/mm3. Subsequently, both cytokines decreased and matched those with CD4+ count ≥350 cells/mm3 at month 6  at month 12 after ART initiation  in individuals who initiated two NRTIs plus INSTI vs. two NRTIs plus b-PI (p=0·038)  reported similar baseline levels of IP-10 and MIG among age strata, but groups were defined as those aged ≤35 years, those with ages ranging from 35 to 44 years, and those aged ≥44 years . Of noteIn our study, PWH with CDC stage C had higher baseline IP-10 and MIG levels than those with CDC stage A. According to our data, IP-10 increases have been described in PWH with opportunistic infections (tuberculosis and cryptosporidiosis) . Baselin3 at ART initiation had higher baseline IP-10 and MIG levels than those with CD4+ count ≥350 cells/mm3. The difference was significant for IP-10 and borderline significant for MIG. Upon ART initiation, both cytokine levels decreased and matched those of PWH with CD4+ count ≥350 cells/mm3 at month 6 and thereafter. A Brazilian cohort found that individuals with CD4+ count <350 cells/mm3 at ART initiation showed higher IP-10 levels compared to those with CD4+ count >350 cells/mm3. In that cohort, individuals who initiated ART with CD4+ count >350 cells/mm3 achieved normalization of plasma IP-10 to levels similar to those of healthy individuals after undergoing ART for a median of 12 months. However, the evolution of IP-10 at 12 months was not compared between PWH with CD4+ count < or > 350 cells/mm3 at ART initiation  at month 12 after ART initiation. This is in agreement with data retrieved from a Swedish case-control study, where IP-10 did not show significant differences between individuals with detected viremia (50-999 copies/mL) and those with persistent virological suppression (HIV-1 RNA <50 copies/mL) after 12 months following ART initiation . HoweverInterestingly, on day 10 after ART initiation, MIG (but not IP-10) levels showed a significant decrease in individuals who initiated an INSTI-based regimen (vs. a b-PI-based one). This could be influenced by the well-documented significantly faster initial HIV-1 RNA decay kinetics of INSTIs , 25. ImpDespite both IP-10 and MIG being pro-inflammatory biomarkers, the subtle differences found in their plasma dynamics in the present study could suggest potentially diverse pathophysiological underlying mechanisms. In contrast to MIG, IP-10 (known as being impacted as prematurely as 6 days after primary HIV-1 infection) showed significant declines as early as 20 days after ART initiation. Intriguingly, IP-10 levels remained high at month 12 in PWH with CDC-stage C at HIV diagnosis. A higher reservoir size (partly mediated by IP-10)  could co3) and achieve levels of HIV-1 viremia below 200 copies/mL after undergoing ART for 12 months, have limited levels of chronic inflammation to impact MIG and IP-10 12 months after ART initiation. Nearly half of PWH in this cohort had CD4+ counts <350 cells/mm3 at baseline. Initiating ART during the first year of HIV infection reduces numerous biomarkers of inflammation and immune activation that are impacted by different inflammatory pathways. This response is more remarkable during acute HIV infection, potentially because of an early effect on attaining a smaller HIV-1 latent reservoir (partly mediated through IP-10)   and virah IP-10) . A baselOverall, these findings reinforce the recommendation of early ART, prioritizing INSTI-based regimens, resulting in a decrease in chronic immune activation and inflammation.3 had higher levels of both IP-10 and MIG levels. All these variables are associated with late HIV diagnosis. This finding reinforces the need to achieve timely diagnosis of individuals with occult or unknown HIV infection. This study adds information regarding early and late time points in the dynamics of IP-10 and MIG plasma levels, as well as in current scenarios in clinical practice: PWH aged ≥50 years, INSTI-based ART, and low-level and TND viremia.At baseline, PWH aged >50 years, a CDC-stage C, or CD4+ T count <350 cells/mmFurther analyses are required on the potential impact on plasma IP-10 and MIG and subsequent chronic immune dysfunction of new ART regimens, including dolutegravir-based two-drug regimens and long-acting formulations, as well as in people with persistent immune discordance.Our study has limitations. The small sample size could underpower some of the analyses, especially those evaluating particular scenarios. Despite internal quality control and the prospective design, in a real-life cohort study, errors and heterogeneity in data gathering and recording cannot be ruled out. Finally, IP-10 and MIG could be impacted by other simultaneous uncontrolled conditions, such as viral or bacterial coinfections, which could act as potential confounding factors.3 had higher baseline IP-10 and MIG levels, with sharp subsequent declines. All of them matched their counterparts several months following ART initiation. PWH treated with INSTI-based regimens had faster declines of MIG as early as day 10. Overall, these findings suggest that both IP-10 and MIG are sensitive biomarkers of early antiretroviral treatment response, and are mainly impacted by plasma HIV-1 viremia, low CD4+ counts, and late ART initiation. Starting ART with CD4+ T cell count >350 cells/mm3 had limited impact on MIG or IP-10 levels. Once ART has been initiated, having TD HIV-1 RNA below 20 copies/mL or even low-level viremia (<200 copies/mL) did not impact MIG or IP-10 levels. These issues merit further investigation in larger cohorts and evaluation of new antiretroviral treatment strategies.In conclusion, in this prospective cohort, IP-10 and MIG arise as soluble plasma biomarkers that showed an early, significant, and consistent decline in their plasma levels just a few days after ART initiation, paralleling the HIV-1 RNA decay and CD4+ T cell recovery. PWH with ages ≥50 years, CDC stage C, or PWH with CD4+ count <350 cells/mmThe original contributions presented in the study are included in the article/The study was approved by the regional Ethic Committee (CAEIG), an external scientific and ethics committee of the HIV Biobank (Spanish HIV/AIDS Research Network).The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.HÁ: Conceptualization, Writing – original draft, Writing – review & editing. AG-V: Writing – review & editing. AM: Writing – review & editing. AS-A: Writing – review & editing. BC-C: Methodology, Writing – review & editing. AP-G: Writing – review & editing. JA-D: Methodology, Writing – review & editing. IM-B: Methodology, Writing – review & editing. MG-R: Writing – review & editing. SM: Writing – review & editing. TA: Writing – review & editing. MM-A: Writing – review & editing. EB: Writing – review & editing. CG: Writing – review & editing. JML: Conceptualization, Writing – original draft, Writing – review & editing. EP: Conceptualization, Writing – original draft, Writing – review & editing.Please see the


Interruption in Treatment (IIT) is a challenge in HIV care and treatment programs in sub- Saharan Africa. High IIT among HIV adolescents has both individual and potential public health consequences including discontinuation of treatment, increased HIV transmission and risk of death. In this era of test and treat policy it is important to ensure that patients remain connected to HIV clinics to enable achieve UNAIDS 95-95-95 targets timely. This study aimed to assess risk factors for IIT among HIV-positive adolescence in Tanzania.We conducted retrospective longitudinal cohort study using secondary data of adolescent patients enrolled in care and treatment clinics in Tanga from October 2018 to December 2020. We defined Interuption in Treatment as missing clinic visits for 90 consecutive days after the last scheduled appointment date on anti-retroviral therapy (ART). Cox proportional hazard regression models were employed to identify risk factors of the outcome variable.Among 2,084 adolescents of age between 15 and 19 years were followed for two years, whereby 546 (26.2%) had interrupted treatment. The median age of the participants was 14.6 years , with age between 15 and 19 years, male sex, with advanced HIV disease and were not on Dolutegravir (DTG) related regimens were associated with interruption in treatment; (Hazard ratio (HR) 1.43, 95% CI: 1.23–1.66, p < 0.0001, HR 2.47, 95% CI: 1.62–3.77, p < 0.0001, HR: 2.47, 95% CI: 1.91– 3.21, p < 0.0001 and HR: 6.67, 95% CI: 3.36– 7.04, p < 0.0001 respectively). Adolescents who were on ART for less or equal one year compared to those on ART for more than one year were protective toward interruption in treatment .The risk of interruption in treatment was high among adolescents in HIV care and treatment facilities in Tanga. This might lead to poor clinical outcomes, and increased drug resistance among ART-initiated adolescents. Placing more adolescents with DTG based drug, strengthening access to care and treatment and rapid tracking of patients is recommended to improve patient outcomes. Adolescents are among the populations most impacted by the global Human Immunodeficiency Virus (HIV) epidemic. Accoding to UNAIDS report an estimate of 1.6 million adolescents aged 10 to 19 were living with HIV worldwide by 2018 [While the rollout of antiretroviral therapy (ART), and now including immediate access to all who test positive (test and treat), has brought much excitement and hope to both patients and practitioners, it has also brought many new questions and challenges, particularly regarding interruption in treatment(IIT). Interruption in treatment commonly known as Loss to follow-up among patients with HIV infection has both individual and potential public health consequences including discontinuation of treatment, increased HIV transmission and risk of death –4.Studies show that interruption in treatment rate in Sub-Saharan African countries among adolescents ranged between 15% and 54% . A similIn Tanzania, various studies and routine assessments of HIV services have been done among adults but limited studies exist among adolescents group . A recenRoutine HIV care and treatment implementation program indicates a high rate of loss to follow-up among adolescents in various regions of Tanzania . To achiThe current study used secondary data analysis from the study that was conducted from October 2018 to December 2020 among serologically confirmed HIV-infected adolescent patients. Inclussion criteria involved adolescents aged 10–19 years on antiretroviral therapy (ART) in the selected care and treatment districts health services facilities in Tanga supported by Amref Health Africa in Tanzania (Amref Tanzania), and who had at least one clinic visit after enrolment or ART initiation.From the CTC2 database, we first extracted all HIV positive patients on ART, then obtained adolescents aged 10–19 years. A total of 2104 adolescent patients on ART from 86 districts in Tanga region were obtained. Twenty participants whose follow up visits data was not available were excluded from the study. After data cleaning, a total of 2084 adolescents were included in the final analysis.The primary outcome of interest was interruption in treatment (IIT). IIT among patients on ART defined as missing clinic visits for 90 consecutive days or more after the last scheduled appointment date. Data from patients known to have died or been transferred out to a clinic not affiliated with Amref Tanzania were considered censored. These definitions are consistent with the 2011 World Health Organization (WHO) working group definitions .The IIT variable was a binary variable categorized as clients who interrupted treatment by not appearing consecutively to their next scheduled appointments for more than 90 days and those who did not interrupt treatment. We considered the following variables as potential predictors of interruption in treatment: ART duration ; sex ; age ; married ; WHO HIV disease stage ; BMI ; pregnant (no/yes); district of residence ; ART regimen ; Viral load supreesion; DTG based drug (no/yes). The cut points for some covariates were determined based on the distribution of data to ensure that each category had enough data.Descriptive statistical analyses were carried out to report demographic and clinical characteristics and baseline and last clinic visit for the whole study population. Categorical variables are described by number and percent for each category whereas continuous variables are described by medians and interquartile ranges (IQR).Cox proportional hazard regression models were employed to determine hazard ratio of patients interruption in treatment with associated 95% confidence interval (CI). Kaplan-Meier (KM) curves were used to estimate the cumulative incidence of loss to follow-up from the date of ART initiation. Follow-up time ended at the minimum of the dates of death and last clinic visit. Patients were considered censored if they died or transferred out, or if the time from their last visit to the administrative cutoff of the study was less than that required by the definition of loss to follow-up. Potential risk factors that were statistically significant at a p-value of 0.2 or less in univariate analysis were included as potential confounders in multivariate models. All significance tests were two-sided, and differences were considered significant at p-value less than or equal 0.05. The wald p-value is a test for trend. The missing indicator method was used to handle missing data. Statistical analysis was performed using the SAS ® statistical software package, Release 9.3 .A total of 2104 adolescent patients were enrolled in a study and all were receiving ART during the study peiod. Of them, 20 (0.9%) were excluded because they never came back after enrollment leaving 2084 adolescents who attended clinic at least once after enrolment. A total of 546 adolescents (26.2%) had interrupted treatment during the two years study period.The median age of the participants was 14.6  and 53% of the study population were female.Majority of the adolescence came from Korogwe and Tanga districts about 22% and 21% respectively, where Pangani region had only 5% of the participants. At the time of study, more than 61% of the participants were in WHO stage 3 or 4, and 85.2% had a normal BMI (18.5 - <25) where 91.4% had a successful viral load suppression. Among the study partcipants 1741 (83.4%) were initiated on ART for more than one year from the time of enrolment. At the time of study, 77% of the participants had placed in DTG based drug combination. Among the adolescents, 11(0.5%) had a history of tuberculosis infection during their life time. 17% (17%) of the adolescents were cohabiting, and 3.3% were married while 2.3% were pregnant at the time of study. Of the participants 180 (8.6%) presented with viral load suppression failure, and 98% of the participants were in first line regimen. Additionally 60 (3%) participants were poorly adhering to care and treatment.Covariate-adjusted Kaplan Meir plots for the overall interruption in treatment by sex and age group suppression categories, are presented in Fig. 2) compared to those with normal BMI (18.5 -<25 kg/m2) .Table Patients who were initiated ART within one year were more likely to be significantly protective toward interruption in treatment compared to patients who were on ART for more than one year . It was found that married adolescents had an increased risk of interruption in treatment compared to single with , however these results were not statistically significant. There was no association of interruption in treatment among those with poor adherence to treatment and adolescents who have ever had TB history ,  respectively.Adolescents patients placed in second line regimen were significantly independently less likely to become interrupted in treatment . Patients who were not placed in Dolutegravir (DTG) based drug were more likely to interrup treatment  compared to those who were taking DTG drug combination. Viral load suppression failure was not significantly found to be a risk factor for interruption in treatment among adolescence in the region .This is a retrospective longitudinal cohort study conducted among HIV-infected adolescents in Tanga, Tanzania. Results showed that the overall interruption in treatment rate was high (26.2%), much higher than required to meet the 95-95-95 targets. Adolescents aged between 15 and 19 years, male sex, those residing from Mheza district, advanced HIV disease, being on ART for long time and those placed in non DTG based drug had significantly higher risk for interruption in treatment. Our study population of HIV-infected adolescents in Tanga was higher enough for whom detailed longitudinal clinical and demographic were available.The interruption in treatment rate observed in this study population were high and somewhat consistent with other studies carried out in some African countries and even outside the continent. Other estimates of interruption in treatment among HIV-infected adolescents in Sub-Saharan African countries including Cameroon, Kenya, Tanzania and South Africa have been reported ranging from 13.4 to 42.2% –16. HoweThe current study found that the determinants of interruption in treatment were generally similar to those in other African settings. Adolescents aged 15–19 years had a higher risk of interruption in treatment from ART uptake. The finding was inline with previous studies conducted in Ethiopia, South Africa, and sub-Saharan Africa . Fear ofWe also identified increased risk of interruption in treatment among male adolescents in our study which was consistent with some previous studies conducted in Tanzania, Ethiopia and Malawi –25. NeveOur study found that sicker patients were more likely to interrupt treatment. Increased risk of interruption in treatment with advanced WHO clinical staging (stage IV) observed in our study was consistent with previous study conducted in Tanzania, India, Kenya and Nzimbabwe , 16–18, This study, like other studies, has found that adolescence placed in second-line ART regimen had reduced risk of of interruption to treatment, our findings agree with studies conducted in Tanzania and Ethiopia , 30. HowStudies in South Africa and USA show that among adolescents who virally unsupressed the risk of interruption in treatment is high , 33. HowOther noteworthy findings were increased risk of interruption in treatment among adolescence who have been placed in non-DTG based regimen of which we have observed limited report of related studies and among adolescents who have been on ART for long time (at least one year from enrollment or ART initiation date). This finding contradict with other studies in African countries. For instance, a study conducted in South Africa show that shorter time on ART (≤ 12 months) was independently associated with higher interruption in treatment . MoreoveIt is important to note that clinics may tend to invest their limited resources in educating patients who are initiating ART about adherence, rather than in efforts to track patients who have interrupted treatment in their communities and return them to care, further exascerbating the impact of non-retention. Finally, in order to reach the recommended 95-95-95 goals to end the AIDS epidemic by 2030, it is essential that adolescent patients who are initiated with ART remain in care and virally suppressed, the final step of the treatment/prevention cascade . With thMajor strengths of this study is the relatively large sample size with inclusion of all the 86 health facilities in the region, providing us substantial power to obtain accurate and reliable estimate over a large number of potential risk factors, adjusted for one another, and the sufficient follow-up time of 24 months. Additionally, the longitudinal nature of this analysis provided an opportunity to assess rate and time of interruption in treatment and associated predictors. The major limitation is that our analysis based on the secondary data from the existing database. It is possible that not all clinical data were correctly captured and that some data were not captured at all, resulting in missing data which however was handled during data analysis but this is a general limitation of using routine data.Our study has shown a high incidence of interruption in anti-retroviral treatment among adolescents living with HIV in Tanga region which is still a major concern and likely leading to poor clinical outcomes, and increased drug resistance among ART-initiated adolescents in the region. In addition we found that a high risk of ART treatment interruption is significantly attributed to either among Adolescents aged between 15 and 19 years, a male gender, advanced HIV disease, Muheza district, being on ART for long time and being on a non DTG based drug. Our results highlight the needs for multi-intervention and cross-cutting strategies to address the identified attributing factors among adolescents in care and treatment facilities in the region. This can include designing integrated clinics and youth clubs and camps for adolescents, especially in primary health facilities to increase retention in HIV care services.


The types of pharmacist-provided medication therapy management (MTM) services provided to patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and the effects of MTM on medication adherence and patient outcomes have only recently begun to be studied. Although available studies suggest that patients receiving MTM services have better antiretroviral therapy (ART) adherence and outcomes, only 1 study has examined a large group of patients with HIV/AIDS, and none has examined adherence or outcomes for more than 1 year. A pilot program conducted by the California Department of Health Care Services (DHCS) and Medi-Cal  provided an opportunity to examine ART adherence and outcomes in a large patient population receiving MTM services in community pharmacies over 3 years.To examine an HIV/AIDS pharmacy MTM compensation pilot program over a 3-year period (2005-2007) in a sample of Medi-Cal beneficiaries by describing the associations between use of pilot pharmacies and (a) adherence to ART regimens; (b) medication utilization, including number and type of ART medication regimens and use of contraindicated ART regimens; (c) occurrence of opportunistic infections; and (d) all-cause pharmacy and medical costs.This was a cohort study examining Medi-Cal pharmacy and medical claims data (2005-2007) for patients with HIV/AIDS who were served by pilot pharmacies versus other (nonpilot) pharmacies. The study groups, pilot and nonpilot pharmacy patients with HIV/AIDS, consisted of Medi-Cal beneficiaries aged 18 years or older as of January 1, 2005, who were continuously enrolled from January 1, 2004, through December 31, 2007, and who received both a diagnosis of HIV/AIDS and at least 1 ART pharmacy claim during both the index period (2004) and the study period . Pilot pharmacy patients were identified as having filled 50% or more of their ART prescriptions each year at 1 of the 10 pilot pharmacies. Patients, for whom comprehensive medication data were not available, including those enrolled in managed care plans and/or Medicare, were excluded. Adherence was defined as a medication possession ratio (MPR) of 80%-120% and excess medication fills as MPR greater than 120%. Logistic regression was used to investigate the factors associated with adherence. Comparisons were made between groups using bivariate statistics . For comparisons of costs, generalized linear models were used including predictor variables for age, gender, and race/ethnicity.The study sample consisted of 2,234 patients meeting the study inclusion criteria. The proportion of study patients receiving the majority of their prescription medications (ART plus non-ART) at pilot pharmacies was 19.7% in 2005 and increased to 27.6% in 2006 and 28.1% in 2007. The demographic profile of pilot pharmacy patients was similar to that of patients receiving medications at nonpilot pharmacies, except that pilot pharmacies had a higher proportion of Latino patients . A greater percentage of pilot than nonpilot pharmacy patients were adherent to their ART medication regimens . After controlling for age, gender, and ethnicity/race in logistic regression analysis, use of a pilot pharmacy  was the most important factor associated with likelihood of adherence. Each year, pilot pharmacy patients were more likely than nonpilot pharmacy patients to remain on a single type of ART regimen  and less likely to have excess fills  and to use contraindicated regimens . The percentages of patients experiencing opportunistic infections were similar between groups each year, approximately 35% (P = 0.809-0.945). In the generalized linear model analyses, the between-group differences in predicted mean (standard error [SE]) total health care costs per patient were not significantly different in any year . In each year, predicted non-ART medication costs were approximately 30%-40% greater in the pilot pharmacy than nonpilot pharmacy group ; however, predicted expenditures for inpatient services were significantly lower . Payment from the DHCS Medi-Cal program for MTM services was approximately $1,000 per pilot pharmacy patient per year.Over a 3-year period, patients at pilot pharmacies consistently had higher medication adherence rates, were more likely to remain on a single type of ART regimen throughout the year, had fewer excess fills, and used fewer contraindicated regimens than nonpilot pharmacy patients. There were no significant differences in mean total cost per patient per group, and the additional MTM services payment added less than 3% to the total cost.


Transmitted drug resistance (TDR) occurs in people living with HIV infection (PLWH) who are not exposed to antiretroviral drugs but who are infected with a virus with mutations associated with resistance. In Costa Rica, HIV genotyping is performed in PLWH failing their first-line ART regimen, but it is not routinely done for all treatment-naïve PLWH before ART initiation, therefore, little is known about TDR prevalence.The aim of this study was to determine the prevalence of TDR and the HIV mutation patterns. During 2020, 162 cases of newly diagnosed treatment-naïve PLWH from all of the country’s HIV clinics were included for a genotyping study. Viral ARN was extracted from plasma samples obtained from the HIV National Reference Laboratory and protease (PR), reverse transcriptase (RT), and integrase (IN) regions were amplified and sequenced. The HIV database Program (Stanford University) and the World Health Organization (WHO) 2009 TDR surveillance mutation list were used for interpretation of resistance-associated mutations.The overall prevalence of TDR was 36% (N=59/162). According to ART class, TDR was 22% in the nucleoside reverse transcriptase inhibitors (NRTI), followed by 13% in the non-nucleoside reverse transcriptase inhibitors (NNRTI); for the protease inhibitors (PI) and the integrase inhibitors (INI), TDR was 8% and 3%, respectively. . Most common mutations were: in NRTI, M41L (9.9%), and M184I (6.8%); in NNRTI, K103N (7.4%); in PI, M46I (4.3%); in INI, T97A (1.9%). (Table 1). The median age was 32 years-old (range: 16-71), and 91% were male. Median CD4 count was 420 cells/uL (range: 11-1670) and median viral load was 588337 copies/mL (range: 1220-10000000). According to CDC classification, 20% were stage C-3.Source: local databaseSource: local databaseSource: local databaseThis study population has a moderate level of HIV drug resistance (HIVDR) in ART-naïve PLWH and strongly implies the need to introduce HIVDR surveillance in Costa Rica. These findings confirm the TDR and highlight the need for systematic viral load monitoring and drug resistance testing at diagnosis. Continuous surveillance of newly infected individuals is required to help strategize the best ART regimen for these patients, and should prompt a change in current local recommendations for starting ART.Source: local databaseAll Authors: No reported disclosures


Compared with patients harboring a B viral subtype and treated with a DTG-based regimen, patients on DRV had an increased risk of VF, both in subtype B , C , CRF02-AG  and G ; DTG also demonstrated a reduced efficacy in subtypes C  and CRF01-AE . Higher baseline HIV-RNA and a longer time since HIV diagnosis also predicted VF. Conclusions: In line with randomized trials, DTG-based first-line regimens showed an overall superior efficacy compared with DRV-based regimens. GRT may still play a role in identifying patients more at risk of VF and in guiding the choice of an antiretroviral backbone.Background: Dolutegravir (DTG)-based first-line regimens have shown superior efficacy versus darunavir (DRV)-based ones in randomized trials. We compared these two strategies in clinical practice, particularly considering the role of pre-treatment drug resistance mutations (DRMs) and of the HIV-1 subtype. Materials and methods: The multicenter Antiretroviral Resistance Cohort Analysis (ARCA) database was queried to identify HIV-1-positive patients starting a first-line therapy with 2NRTIs plus either DTG or DRV between 2013 and 2019. Only adult (≥18 years) patients with a genotypic resistance test (GRT) prior to therapy and with HIV-1 RNA ≥1000 copies/mL were selected. Through multivariable Cox regressions, we compared DTG- versus DRV-based regimens in the time to virological failure (VF) stratifying for pre-treatment DRMs and the viral subtype. Results: A total of 649 patients was enrolled, with 359 (55.3%) and 290 (44.7) starting DRV and DTG, respectively. In 11 months of median follow-up time, there were 41 VFs  and 15 VFs (5.3 per 100 PYFU) in the DRV and DTG groups, respectively. Compared with a fully active DTG-based regimen, the risk of VF was higher with DRV (aHR 2.33;  The latest European HIV treatment guidelines for drug-naive persons living with HIV (PLWH) recommend the use of two nucleoside reverse transcriptase inhibitors (NRTIs) associated with an integrase strand transfer inhibitor (InSTI) as first-line regimens for most patients. Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens are also considered as alternative regimens in specific clinical situations, as well as darunavir (DRV)-based regimens .INSTIs are effective and well tolerated molecules . DTG, inBoosted protease inhibitors, and particularly DRV, have also demonstrated great virological effectiveness in clinical trials and in clinical practice , and theA GRT is recommended prior to the initiation of antiretroviral therapy (ART), ideally at the time of diagnosis . HoweverDifferent studies compared DTG- to DRV-based regimens as first-line treatments for adult naive PLWH ,13. In FRegarding pre-treatment DRMs and their possible influence on time to virological failure, Kityo et al.  analyzedHamers et al.  similarlConcerning viral subtypes, different studies have tried to analyze the possible influence of the HIV-1 viral subtype on virological responses to antiretroviral therapies, with sometimes discordant results ,17,18,19We undertook this study to assess how DTG-based regimens perform compared to DRV-based ones in the treatment of naive PLWH in clinical practice, focusing on the possible influence of pre-treatment drug resistance mutations and viral subtypes on the time to virological failure.A retrospective study was performed using the Antiretroviral Resistance Cohort Analysis (ARCA) database , which cPatients were considered eligible for the study if they had a concentration of plasmatic HIV-1 RNA at a baseline of 1000 copies/mL or higher, with no previous exposure to antiretroviral treatments and with a genotypic resistance test available prior to starting ART. Major NRTI, NNRTI, PI resistance mutations were identified using the 2019 IAS-USA drug resistance mutation list . ImportaThe primary outcome was to compare three-drug regimens with 2NRTIs plus DTG versus 2NRTIs plus DRV in the time to virological failure (VF), defined as the detection of an HIV-1 RNA of 50 copies/mL or higher after at least three months from the start of the therapy, focusing on the presence of pre-treatment drug resistance mutations (DRMs) and the different viral subtypes.We considered as DRMs those mutations that could cause at least potential low-level resistance to one or both of the NRTIs included in the study regimen, by using the Stanford HIVdb genotypic resistance interpretation system (version 9) .Baseline patients’ characteristics were described as numbers and proportions for qualitative variables and medians and interquartile ranges (IQR) for continuous variables. Differences in baseline characteristics between DTG- and DRV-based regimens were assessed through chi-squared testing for qualitative variables and Student’s t-testing for continuous variables. Estimated probabilities of VF were calculated for both groups through the Kaplan–Meier estimator and compared through the log-rank test. Two multivariable Cox regression models were then performed to detect any differences between DTG and DRV in time to VF: in the first model, the exposure (ART group) was stratified for the presence or absence of any pre-treatment DRMs associated with at least potential low-level resistance to at least one of the 2 molecules of the backbone and adjusted for viral subtype and for any potential confounder; in the second model, the effect of the ART regimen was analyzed by stratifying the ART group for viral subtype (B versus every other subtype) and by adjusting for pre-treatment DRMs  and the same pattern of confounders.A confounder was defined as any demographic and viro-immunological variable that resulted in a statistically different value at baseline between the two ART groups and that could affect treatment outcomes, according to previous knowledge ,25,26,27A total number of 649 patients was eligible for study analysis. Among them, 359 (55.3%) started a DRV-based regimen and 290 (44.7%), a DTG-based one. Dosing of the DRV and type of booster was not reported in the electronic database.The sociodemographic and viro-immunological characteristics of the enrolled patients are listed in Concerning the pre-treatment DRMs, 30 patients (4.6%) had a virus with at least one NRTI-associated potential low-level resistance mutation ; in nine cases (1.4%), pre-treatment DRMs were associated with at least potential low-level resistance to the backbone . All the mutations of the population are listed in Pre-treatment DRMs were associated with VF in two patients on tenofovir/emtricitabine plus dolutegravir, one of whom presented only an M184V mutation and the other showing a combination of M41L and T215C/F/I/L/R/S .During 11 months of median follow-up time, 56 VFs occurred in the overall population: 41 in 488.53 patient-years of follow-up (PYFU) in the DRV group (incidence rate of 8.4 in 100 PYFU) and 15 in 285.7 PYFU in the DTG one (incidence rate of 5.3 in 100 PYFU). The estimated probabilities of VF for the DRV group were 10.9% , 7.7–15.5%) and 16.7%  at 1 and 2 years, respectively. For the DTG group the estimated probabilities of VF were 4.8%  at 1 year and 11.9%  at 2 years, resulting in a borderline significant log-rank for DTG versus DRV (p = 0.016), especially in patients with a history of HIV infection longer than 1 month or a viral load at baseline higher than 100,000 copies/mL. Moreover, DTG-based regimens with a compromised backbone  were at higher risk of VF compared with DTG plus a fully active backbone . Since patients on DRV-based regimens with pre-treatment DRMs to the backbone had no VF, no hazard ratios could be calculated for this group. Interestingly, among viral subtypes, the C subtype  and G subtype  showed an independently increased risk of VF. After adjusting for gender, age, baseline CD4 cells count, zenith HIV HIV-RNA, months since HIV diagnosis and CDC stage C (Cox model 1), starting a regimen with 2 fully-active NRTIs plus DRV was associated with a higher risk of VF if compared with patients starting a DTG-based regimen with a fully-active backbone (adjusted hazard ratio (aHR), 2.33; 95% CI, 1.17–4.66; p = 0.011), C subtype , CRF02-AG subtype  and G subtype . However, DTG also demonstrated a reduced efficacy in C subtype  as well as in the CRF01-AE subtype . Direct comparisons of DRV and DTG for every non-B subtype did not show any difference in effectiveness between the two treatment groups. Particularly, no differences in VF were evidenced when directly comparing DRV-based to DTG-based regimens in the C subtype .In the second multivariable model see , the ARTThis study documents that DTG-based regimens are associated with better virological outcomes than DRV-based regimens in naive PLWH with fully active backbones and harboring a B viral subtype.In the subgroup of patients with a fully active backbone, DTG showed higher rates of virological suppression compared to DRV, with a lower incidence of VF events. However, the efficacy of DTG was affected by the presence of mutations decreasing the activity of the NRTI backbone. It must be noted that all the HIV sequences considered were obtained by population sequencing; thus, the dataset may have included cases with undetected minority drug-resistant species potentially, impacting the response to therapy. It is indeed known that drug resistance mutations are fixed at different levels depending on the balance between the advantage and fitness cost , with thRegarding viral subtypes, PLWH infected by a B viral subtype in antiretroviral therapy with DTG-based regimens showed better outcomes in achieving and maintaining virological suppression than patients in DRV-based regimens with the B, C, CRF02-AG or G viral subtypes or patients on DTG-based regimens infected by the C or CRF01-AE viral subtype. Conversely, no statistical differences were found for DRV versus DTG for non-B viral subtypes.These results seem to be in line with the ones of the FLAMINGO study , which sAn important trial comparing DTG and DRV in a more complex population, the NADIA trial , showed The cohort of PLWH analyzed in this study is quite varied because it comes from the clinical experience of several Italian clinical centers, which provided data to the ARCA database. Clearly, each center had its own population and approach to treatment and this ensured a wide heterogeneity in the study population and therefore a good generalizability of the study results, at least among European countries. Conversely, a major limitation lies in the demographic characteristics of the population, mostly made up of men and Caucasians, making it difficult to generalize the results to other populations. Our study surely presents other limitations, including a lack of information about the presence of a possible booster (ritonavir or cobicistat) used with DRV and possible unknown confounders between the two studied populations. However, after stratifying for all measurable baseline confounders such as viral load, CD4 cell count and disease duration, a more favorable outcome with DTG was confirmed, suggesting a good reliability of our findings. Finally, no data regarding adherence to antiretroviral treatment were reported in the database. This surely represents a significant limitation, considering that a low level of adherence to treatment could affect virological responses and facilitate the development of DRMs.The strengths of our work are the large sample size as well as the availability of real-life data coming from clinical practice and not available from the analysis of clinical trials.In conclusion, from this study, DTG seems to be the best choice for clinicians facing naive people living with HIV starting a first-line ART. However, a possible reduced efficacy of DTG-based regimens is still possible in certain settings and the availability of GRTs prior to the beginning of a first-line antiretroviral regimen is of paramount importance in order to correctly weigh the individual risk of VF.


Background: Filgotinib (FIL) is a selective JAK1 inhibitor with an affinity 30-fold higher than JAK2, approved to treat moderate to severe active rheumatoid arthritis (RA), in adults with inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). Methods: We conducted a retrospective, multicentric study in order to evaluate efficacy and safety of FIL 200 mg daily therapy, after 3 and 6 months, in 120 patients affected by RA, managed in Tuscany and Umbria rheumatological centers. The following clinical records were analyzed: demographical data, smoking status, previous presence of comorbidities , disease duration, presence of anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), number of biological failures, and prior csDMARDs utilized. At baseline, and after 3 (T3) and 6 (T6) months of FIL therapy, we evaluated mean steroid dosage, csDMARDs intake, clinimetric indexes , erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and body mass index (BMI). Results: At baseline, the mean disease duration was 9.4 ± 7.5 years; the prevalence of previous HZ infection, VTE, MACE, and cancer was respectively 4.12%, 0%, 7.21%, and 0.83%, respectively. In total, 76.3% of patients failed one or more biologics . After 3 months of FIL therapy, all clinimetric index results significantly improved from baseline, as well as after 6 months. Also, ESR and CRP significatively decreased at T3 and T6. Two cases of HZ were recorded, while no new MACE, VTE, or cancer were recorded during the observation time. Conclusion: Despite the limitations of the retrospective study and of the observational period of only 6 months, real-life data on the treatment of RA patients with FIL demonstrate that this Jak inhibitor therapy is safe in terms of CV, VTE events, and occurrence of cancer, and is also effective in a population identified as “difficult to treat” due to failure of previous b-DMARD therapy. Since the approval of the first-generation of Janus kinase (JAKi) inhibitors, tofacitinib and baricitinib, the search for new innovative JAK inhibitors with more specific selectivity has started. It has been hypothesized that the inhibition of JAK1 will allow the same clinical efficacy as a non-selective pan-JAK inhibitor (or event better as the dose could be increased), but with a better safety profile potentially guaranteed by the non-inhibition of JAK2-JAK3 . This haThe efficacy and safety of filgotinib 200 mg daily therapy for 3 and 6 months was evaluated in 120 RA patients observed. We retrospectively collected the data of three evaluations three months apart of 120 rheumatoid arthritis patients followed up in the rheumatological centers in common clinical practice in the period June–December 2022. The following clinical records were analyzed: demographical data, smoking status, previous presence of comorbidities  disease duration, presence of anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), number of biological failures, and prior csDMARDs utilized. At baseline, and after 3 (T3) and 6 (T6) months of FIL therapy, we evaluated mean steroid dosage, csDMARDs intake, clinimetric indexes , erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and body mass index (BMI). We also evaluated some laboratory parameters of tolerability , cholesterol LDL (C-LDL), cholesterol HDL (C-HDL), triglycerides, creatinines, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hemoglobin). The study involving human participants was reviewed and approved by the GISEA Project Ethics Review Board on 22 September 2020 (Code of Ethics 6496_OSS). Written informed consent was not required for participation in this study in accordance with national legislation and institutional requirements.p-value less than 0.05 was considered statistically significant. Statistical analysis was performed by © 2023 MedCalc Software Ltd., Acacialaan 22, 8400 Ostend Belgium.Descriptive statistics have been used to describe the basic features of the population and, because the data did not show a normal distribution, we utilized median and Inter Quartile Range (IQR). For comparisons, the Wilcoxon test for paired sample was used. A p = 0.0001; T0 vs. T6 p = 0.0001; T3 vs. T6 p = 0.048). The mean value of DAS28 decreases from 4.76 (4.34–5.55) at baseline to 3.03 (2.67–3.63) at 3 months, reaching 2.7 (2.29–3.1) after 6 months . The CDAI result is very similar, decreasing from 21 (18–22.75) at baseline to 13 (12–15) in the third month, and down to 9 (6–10.25) at the end of the observation. . ESR and CRP show the same evolution: at baseline, the ESR was 35 (18–48) mm/h, at the third month it was 15 (10–29.75) mm/h, and at the sixth month it was 13 (10–28) mm/h ; CRP at baseline was 1.18 (0.5–1.89) mg/dL; after three months, it was 0.47 (02–0.85) mg/dL; and at 6 months, it was 0.28 (0.12–0.49) mg/dL . Tender and swollen joint counts show a substantial reduction: at baseline, tender joints were 6 (5–11); at three months, they were 2 (1–3); and at month 6, they were 1 (0–2) ; swollen joint count was 4 (4–8) at baseline, 1 (1–2) at month 3, and 0 (0–1) at month 6 . The result of the VAS pain value decreased from 7 (5–8) at baseline, to 2.5 (1–5) at month 3, to 2 (1–3) at month 6 , as well as functional scale HAQ which started from 1 (1–1.5) at baseline and reached 0.25 (0–0.5) at month 3 remaining stable at the same value, 0.5 (0–0.5), up to the sixth month . Regarding patient and physician assessment, the results are consistent: patient PGA at baseline was 70 (40–80); at three months, it was 27.5 (15–41.25); and at six months, it was 20 (10–30) . Regarding the PGA physician, the baseline value was 65 (30–70) at three months 20 (10–45) and at six months, it was 20 (10–30) . After three and six months, no statistically significant differences were observed in the lipid profile or in renal or hepatic function. Regarding adverse events, only two cases of Herpes zoster were observed in the first three months, while no cases of VTE and MACE were recorded in six months of treatment with FIL.After 3 and 6 months of treatment with FIL  [In light of current knowledge, this is the first real-life study of FIL treatment in rheumatoid arthritis in a population identifiable as difficult-to-treat (D2T-RA) due to the high proportion of patients who had failed prior b-DMARD therapy. Our patients had failed previous biological therapies in 76.3% of the population . FINCH 2 evaluated the use of FIL in combination with csDMARDs in patients with prior bDMARD failure or intolerance, i.e., as per the third-line therapy recommended in the EULAR treatment algorithm. In this 24-week phase 3 study, patients with IRs or intolerance to >1 prior bDMARD were randomized to receive placebo, FIL 200 mg, or FIL 100 mg. Results of primary and key secondary endpoints supported the superior efficacy of both FIL doses vs. placebo. Subgroup analyses showed that the efficacy of FIL was not affected by the number or mechanism of action (MOA) of prior bDMARDs, as patients with >3 prior bDMARDs or >1 MOA of prior bDMARDs, as well as those previously exposed to IL-6 inhibitors or TNFis, all achieved efficacy outcomes comparable to the overall study population ,18. Despay 2023)  and theyay 2023) ,27,28, aay 2023) . JAK inhay 2023) ,27. Otheay 2023) ,30. Althay 2023) . A recenay 2023) . An impoay 2023) ,34. Curray 2023) . A seconay 2023) . A thirday 2023) .Despite the limitations of the retrospective study and of the observational period of only 6 months, data on the treatment of RA patients with FIL demonstrate that this Jak inhibitor therapy is safe in terms of CV and VTE events, and is also effective in a population identified as “difficult to treat” due to failure of previous b-DMARD therapy. Real-life and long-term observational studies in the light of the CHMP-EMA recommendations  and a pr


Globally, most countries have implemented a test-and-treat policy to reduce morbidity and mortality associated with HIV infection. However, the impact of this strategy has not been critically appraised in many settings, including Zambia. We evaluated the retention and clinical outcomes of adults enrolled in antiretroviral therapy (ART) and assessed the impact of the test-and-treat policy.n = 2,991] and between August 1, 2016 and October 1, 2020  in 12 districts of the Southern province. To assess factors associated with retention, we used logistic regression (xtlogit model).We conducted a retrospective cohort study among 6,640 individuals who initiated ART between January 1, 2014 and July 31, 2016 , and it was significantly higher among the ATT cohort, 90.6 vs. 74.8%, p < 0.001. The reasons for attrition were higher in the BTT compared to the ATT cohorts: stopped treatment (0.3 vs. 0.1%), transferred out (9.3 vs. 3.2%), lost to follow-up (13.5 vs. 5.9%), and death (1.4 vs. 0.2%). Retention in care was significantly associated with the ATT cohort, increasing age and baseline body mass index (BMI), rural residence, and WHO stage 2, while non-retention was associated with never being married, divorced, and being in WHO stage 3.The median age [interquartile range (IQR)] was 34.8 years , and 60.2% (The retention rate and attrition factors improved in the ATT compared to the BTT cohorts. Drivers of retention were test-and-treat policy, older age, high BMI, rural residence, marital status, and WHO stage 1. Therefore, there is need for interventions targeting young people, urban residents, non-married people, and those in the symptomatic WHO stages and with low BMI. Our findings highlight improved ART retention after the implementation of the test-and-treat policy. SeveHowever, the beneficial effects of early ART initiation are overwhelming in the prevention and treatment of HIV infection. Universal testing and treatment (UTT) has been linked to a reduction in HIV-associated morbidity and mortality . In the For countries in SSA to achieve the sustainable development goal (SDG-3.3) of ending the AIDS epidemic by 2030 , retentiIn view of the existing literature, several studies in different settings have demonstrated the beneficial effect of the test-and-treat strategy , 14, 36 2.2.1.We conducted a retrospective cohort study of PWH enrolled in HIV care in 12 President’s Emergency Plan for AIDS Relief (PEPFAR)-supported districts in one province of Zambia.2.2.Clinical data from patient records were extracted for PWH aged 15 years and older who were initiated on ART between January 1, 2014 and October 1, 2020, regardless of their clinical outcome at the time of data abstraction. PWH initiated on ART before the launch of the test-and-treat policy  formed the pre-test-and-treat cohort, and those initiated in the period following the implementation of the test-and-treat policy  formed the post-test-and-treat cohort.All PWHs that enrolled in care but were not initiated on ART by the time of data abstraction were excluded from the analysis. However, the details of those who were not on ART were provided to the ART health providers for further follow-up and counseling with the aim of commencing ART. PWH with either a missing date of birth or age or a missing ART initiation date were excluded from the study.2.3.Clinical data for PWH were abstracted either from HIV paper-based or electronic medical records known as SmartCare in 45 health facilities located in 12 districts of Southern Province onto the Electronic Data Capture (REDCap) software. Patient outcomes were recorded around the follow-up period of 3, 6, 12, and 24 months ±30 days and the last date of contact with the health care provider. In addition to clinical data , laboratory , and pharmacy-related data, including medicine refill dates, were collected from laboratory and pharmacy registers, respectively, in facilities where SmartCare was not fully functional. Where possible, the data were triangulated from both SmartCare and paper registers.A line list of PWH was created from the ART clinic enrollment register per national guidelines. If the site had fewer than 100 patients on ART, data were abstracted from all the patient SmartCare medical records. For sites with more than 100 patient records, a systematic sampling scheme was used. At each site, we determined a sampling interval (X) by dividing the total number of client records at the site by the sample size and taking the whole number only ; this process was done for the allocated sample sizes in the before and after test-and-treat strategies. The first record for review was selected (N) by randomly selecting a number between 1 and X . Data abstractors selected the Nth record and proceeded with selecting record N + X as the first consecutive record for review, which continued with adding X until the quota for that site had been reached. All the selected records were entered into the REDCap application and screened for inclusion and exclusion criteria. If any patient record from the selected list was excluded from the study, the next eligible record fulfilling the inclusion criteria was selected to replace the excluded record.2.4.Data entries from 10% of the selected patient records were re-abstracted by the team facilitator immediately after the needed records were abstracted by the data extraction team using a systematic random sampling method. Once the files had been re-abstracted, any discrepancies between the data initially abstracted and the data that were re-abstracted were discussed, and the option that was unanimously agreed to be correct was selected. We have used guidelines for strengthening the reporting of observational studies in epidemiology , 16 urban health centers (UHC), and eight hospitals] across the 12 districts from 274 ART sites. In the initial step, the 274 ART sites were stratified into rural and urban sites, and then, a probability based on the number of PWH on ART at each health facility was used to select the required number of sites from each stratum.2.8.p value of <0.05 was used.The data were entered in REDCap and thereafter exported to STATA version 15 and R for standard data analysis. Data were described using frequency and percentages for categorical variables and medians (interquartile ranges) for continuous variables. To test for normality, the Shapiro–Wilk test was used. The Wilcoxon rank-sum test was used to ascertain the statistical difference between the two medians. A relationship between two categorical variables was determined using a chi-squared test. Multivariable logistic regression was used to examine the factors associated with retention using generalized estimating equations (GEE) via the logit link function to account for correlation structure within observations. The variables  in the adjusted analysis were selected based on previous literature , 31, 32 2.9.Ethical approval was obtained from the Macha Research Trust Institution Review Board (IRB) and the Zambia National Health Research Authority (ZNHRA). This project was also reviewed in accordance with the Centers for Disease Control and Prevention’s (CDC) human research protection guidelines. In this study, we analyzed de-identified data from healthcare facilities.3.3.1.p < 0.001. Women comprised 60.2%  of PWH in the study sample. The majority of the participants, BTT  and ATT , were from urban areas. There were more married individuals than those who were never married, divorced, or widowed in both the BTT  and ATT  cohorts. The baseline body mass index (BMI) was significantly higher among participants in the ATT than the BTT . BTT participants took 14 days  to be initiated on ART from the time of HIV diagnosis compared with the ATT cohort that took 0 days , p = 0.001. A high proportion of the participants were taking non-nucleotide reverse transcriptase inhibitors (NNRTIs) at baseline (99.7% BTT and 77.6% ATT) and currently (71.4% BTT and 56.8% ATT). At baseline, the majority of patients had WHO stage I HIV, with a higher proportion of patients in the ATT cohort with Stage I (83.9%) vs. those in the BTT cohort  was observed at different time points: 6 months (80.5%), 12 months (92.4%), and 24 months (94.6%).p < 0.001). However, at 12 months, a higher proportion of participants in BTT than ATT had CD4 ≥ 500 cells/μL, 49.6 vs. 45.1%, p = 0.018. A higher proportion of viral suppression was observed among the participants in the BTT cohort at 6 months  and 12 months . At 24 months, the viral load categories were comparable , while attrition was generally high in the BTT cohort as compared to the ATT cohort: death , stopped treatment , transferred out , and LTFU .At the time of data abstraction, 5,543 (83.4%) were actively on ART, 13 (0.2%) had stopped ART, 412 (6.2%) were transferred out, 621 (9.4%) were LTFU, and 51 (0.8%) were dead . There w3.4.p < 0.001), 6 months , 12 months , 24 months , and > 24 months , that is, all time points.Retention was higher in the ATT cohort as compared to the BTT cohort  at 3 mon3.5.3.5.1.n = 3,305) who were retained in care were from the ATT cohort, whereas over two-thirds of the patients  were not retained in care were from the BTT cohort. The individuals who were retained in HIV care were significantly older than the ones who were not retained . There was a higher proportion of urban participants who were not retained (70.1%) compared to those retained in HIV care. Conversely, there was a higher proportion of rural participants who were retained in HIV care (39.0%) vs. not retained in care (29.9%). Baseline BMI (21.5 vs. 21.0 kg/m2) and CD4 count (306 vs. 283 cells/μL) were significantly higher among the participants who were retained in HIV care in comparison to non-retained ones, with a p value of <0.05. The duration from HIV diagnosis to initiation of treatment was significantly lower among the retained participants as compared with those who were not retained . Equally, the viral load at 24 months among the retained individuals in HIV care was lower . A higher proportion of the participants whose dolutegravir (DTG) was their baseline ART regimen were retained in HIV care compared to those who were not retained . Among those in the NNRTI group, the preponderance of them were not retained in care (92.3 vs. 86.6%). A significantly higher percentage of the baseline participants with WHO stage 1 were retained in HIV care compared to those who were not retained . A year increase in age was significantly associated with 1% increased odds of being retained in HIV care . Participants from rural areas had a significantly higher probability (54%) of being retained in HIV care compared to those from urban areas . Individuals who had never been married had 22% reduced odds of being retained in HIV care compared to those who were married . An increase in the number of days from HIV diagnosis to ART initiation was significantly associated with a 1% reduced chance of being retained in HIV care. Participants who were in WHO stage 3 at baseline had 35% reduced odds of being retained in HIV care compared to the ones in stage 1 . Clients on a DTG and protease inhibitor (PI)-based regimen were 2.27 and 2.29 times more likely to be retained in HIV care relative to those on NNRTIs, respectively. A unit increase in baseline BMI was significantly associated with 3% increased odds of being retained in HIV care .In the adjusted analysis, individuals from the ATT cohort were 3.67 times more likely to be retained in care. A unit increase in age was associated with a 1% increase in the odds of being retained in HIV care. Participants from rural areas had 32% higher odds of being retained in care than those from urban areas. Never married and divorced participants had 24 and 16% reduced odds of being retained in HIV care, respectively, compared to married ones. Baseline participants in WHO stage 2 had 18% increased odds of being retained in HIV care . However, baseline participants with WHO stage 3 had 23% reduced odds of being retained in HIV care. A unit increase in BMI increased the chance of being retained in care by 2% .3.8.In the BTT participant group, factors significantly associated with retention upon adjusted analysis included receiving care at a rural health facility  and being never married . In contrast, for the ATT cohort, factors linked to ART retention were increasing age  and being in WHO stage 2 . See 4.This study aimed to determine the differences in retention rates and clinical outcomes for adult PWH enrolled on ART, BTT, and ATT policies. Participants who initiated ART and were enrolled in care after the test-and-treat policy had better retention in HIV care and health outcomes than those enrolled before the test-and-treat program. Our finding showed a higher prevalence of retention under ATT than what was previously reported in SSA  and HaitThe evaluation results suggest that the universal and rapid test-and-treat implementation policy effectively retained clients in care. However, the clinical and immunological outcomes were better than BTT based on the studies conducted in Nigeria  and ZambThe enrollment age was younger for the ATT cohort than the BTT cohort, which is expected to indicate an effective and well-implemented policy. This was even evident with an average ART initiation turn-around time of 0 days compared to the BTT cohort, where the average ART initiation turn-around time was 14 days. This translated into good treatment outcomes, including clinical and immunological outcomes. For example, compared to the BTT cohort, a higher proportion of clients in the ATT cohort were in stage 1 of the WHO stage, had higher baseline CD4 counts, better attrition factors, and their BMI improved remarkably. However, the viral suppression and CD4 count seemed to be better before the test-and-treat policy. This could be because individuals under the ATT policy were relatively younger than those in BTT, and it has been well-studied that young people struggle to achieve viral suppression .The majority of clients in the ATT cohort were retained on ART and still alive, and very few had stopped treatment, transferred out, lost to follow-up, or died. Our findings align with several clinical trials that assessed rapid universal treatment  and demoMortality was significantly reduced during the ATT phase compared to the time before the universal test-and-treat policy, which is in line with what was observed in Ethiopia . One posOur findings are not just the mere effect of implementing the test-and-treat policy among PWH; this program required implementing several programmatic adjustments, financial support, and increasing human resources to enhance care and support all structures involved in the treatment cascade of PWH, including counseling and testing services. In the real world, testing and treating all PWH to achieve viral suppression is possible when the whole ART cascade of care is enhanced.4.1.Missing data led to delays in data abstraction. Some characteristics, such as viral load and CD4 count, were missing. We did not collect data on alcohol consumption, HIV disclosure status, year of enrollment for each participant, distance to the health facility, or adherence counseling, which could have helped explain retention rates among our study participants. Additionally, we could not get the patients’ perspectives regarding UTT policy. However, the study was able to quantify retention in HIV care and clinical outcomes before and after the universal test-and-treat policy.4.2.We used a large sample size in our study compared to similar studies. Hence, this study was highly powered, and the results may be applicable to PWH living in Zambia. The methodology and statistical analysis were rigorous. The multicenter model and sampling methods used strengthened the study and minimized bias, providing a comprehensive overview of the whole program in the province.5.Our data strongly indicate that the test-and-treat policy implemented in 2016 was significantly more effective in improving retention in HIV care and treatment compared to the BTT period. Additionally, clinical outcomes  improved remarkably to acceptable levels in the ATT cohort. Factors that significantly influenced retention included the treatment policy, older age, location of the facility, not being married, high baseline BMI, and worse WHO stages. Hence, interventions targeting young individuals, urban care recipients, non-married people, and those with symptomatic WHO stages and a low BMI are encouraged.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical approval was obtained from the Macha Research Trust Institution Review Board (IRB), and the Zambia National Health Research Authority (ZNHRA). This project was also reviewed in accordance with the Centers for Disease Control and Prevention (CDC) human research protection procedures. In this study, we analyzed de-identified data from healthcare facilities. The ethics committee/institutional review board waived the requirement of written informed consent for participation from the participants or the participants’ legal guardians/next of kin because the study was a retrospective study.BH and SMa drafted the manuscript. BH and IF conducted all statistical analyses. BH, SMu, LS, MS, JM, SKu, SKa, CC, IF, CB, and SMa participated in data collection. BM, KM, and NK guided study design and draft review. All authors contributed to the article and approved the submitted version.