At baseline, no PDR to DTG was found. However, as previously reported, PDR to non-nucleotide reverse transcriptase inhibitor (NNRTI) was high (15%) whilst PDR to NRTI was low (4%). After a median duration of 27 (25–30) weeks on TLD, virological suppression (VL < 1000 copies/mL) was 98% and among the 2 participants with VL ≥ 1000 copies/mL, no ADR was found. HIVDR to DTG is rare among ART naïve individuals. DTG is more likely to address the problems of HIVDR in Africa.Dolutegravir (DTG) use in combination with tenofovir and lamivudine (TLD) is scaling up in Africa. However, HIV drug resistance (HIVDR) data to DTG remain scarce in Zimbabwe. We assessed the prevalence and genetic mechanisms of DTG resistance in people living with HIV initiating on TLD. A prospective cohort study was conducted between October 2021 and April 2023 among antiretroviral therapy (ART) naïve adults (≥18 years) attending care at an HIV clinic in Zimbabwe. Pre-treatment drug resistance (PDR) was assessed prior to TLD initiation and viral load (VL) outcome and acquired drug resistance (ADR) to TLD were described after 24 weeks follow-up. In total, 172 participants were enrolled in the study. The median (IQR) age and log Despite the great achievements reported since the introduction of antiretroviral therapy (ART) and the efforts galvanized towards HIV/AIDS control and eradication by 2030, HIV drug resistance (HIVDR) may still pose an obstacle to the success of ART. Previously reported high levels of pre-treatment drug resistance (PDR)  to nucleThe WHO recommends that surveillance of drug resistance mutations (SDRMs) should accompany the scale-up of DTG-containing ART in HIV programmes and emphasizes the importance of estimating the extent to which acquired drug resistance (ADR) to DTG emerges in populations receiving DTG. Although cases of PLHIV developing VF and integrase strand transfer inhibitor (INSTI)-associated resistance mutation while on DTG-based regimens have been extremely rare ,4,5, DTGZimbabwe has adopted the use of DTG in combination with tenofovir and lamivudine (TLD) as the preferred first-line regimen for HIV treatment . HoweverThis was a prospective cohort study investigating the prevalence and genetic mechanisms of DTG resistance among PLHIV in Zimbabwe. Participants were PLHIV initiating DTG-based ART between October 2021 and April 2023. Consenting participants were ART-naive adults (aged ≥18 years) initiating TLD or patients re-initiating first-line TLD after defaulting for at least 3 months. Participants were attending care at the Parirenyatwa Hospital Family Care Centre (PHFCC), a tertiary level setting, in Harare, Zimbabwe.We consecutively invited individuals to participate in the study and obtained written informed consent prior to recruitment. Through an interview-based questionnaire, we extracted socio-demographic and clinical data  as well as ART data (ART naïve or prior ART exposure). Upon enrolment, whole blood was collected in two ethylenediamine tetra acetic acid (EDTA) tubes; one tube for VL measurement and the other one for baseline GRT, respectively. These participants were followed up to or after 24 weeks when, besides routine laboratory tests, whole blood was collected for VL quantification and GRT for those with virological failure (VL ≥ 1000 copies/mL).Prior to HIV-1 VL quantification, the frozen plasma samples were allowed to thaw at room temperature for 30 min and then centrifuged. Plasma VLs were measured using the Xpert HIV-1 VL assay with a linear range of 40–10,000,000 HIV-1 ribonucleic acid (RNA) copies/mL at the Biomedical Research Training Institute (BRTI), Harare, Zimbabwe. The Xpert HIV-1 VL in vitro diagnostic assay is based on reverse transcriptase polymerase chain reaction (RT-PCR) technology. The Xpert HIV-1 VL automates the test process including RNA extraction, purification, reverse transcription and complementary deoxyribonucleic acid (cDNA) real-time quantitation in one fully integrated cartridge. Following the manufacturer’s instructions, in brief, 1000 μL of plasma sample was added to the cartridge, which was loaded into the instrument. This was followed by the automated process of nucleic acid purification and the simultaneous amplification and detection with the GeneXpert machine . Some plasma samples were also measured at the Infectious Diseases Research Laboratory (IDRL), University of Zimbabwe with the Cobas Ampliprep/TaqMan48 HIV-1 Test quantification system, V2.0  with the detection limit of 20 copies/mL. Following the manufacturer’s instructions, in brief, 1050 μL of plasma was centrifuged and loaded onto the machine with the high and low positive controls and the negative control. This was followed by the automated process of extraction on the COBAS Ampliprep and real-time amplification and detection on the Taqman48 analyser. All tests were conducted in accordance with the manufacturer’s instructions.pol gene genotyping, HIV viral ribonucleic acid (RNA) was extracted from stored plasma samples using a column-based extraction kit, the QIAamp Viral RNA Mini kit protocol . Following the manufacturer’s instructions, plasma samples were thawed, allowed to equilibrate to room temperature (15–25 °C) and thoroughly mixed by vortexing for 20 s. Lysis buffer AVL (560 μL) containing carrier RNA (1 ng/μL) was added to 140 μL of the plasma sample. The reaction was mixed by pulse-vortexing for 15 s and incubated at room temperature for 10 min. Absolute ethanol (560 μL at 96%) was added to the reaction and mixed by pulse-vortexing for 15 s in preparation for binding of the viral RNA onto the QIAamp mini-column membrane. The lysate obtained was transferred to a QIAamp mini-column membrane and centrifuged at 8000× g rpm for 1 min. The column was then washed twice with 500 μL each of buffer 1 and 2 respectively, followed by a centrifugation at full speed  for 1 min in order to discard the flow through. Finally, 60 μL of elution buffer was added to the column and placed into a clean 1.5 mL microcentrifuge tube, which was incubated at room temperature for 1 min and centrifuged at 8000× g rpm for 1 min. The eluted viral RNA was immediately stored at −80 °C prior to RT-PCR. All tests were conducted in accordance with the manufacturer’s instructions.In preparation for HIV TM TaqPathTM Seq HIV-1 Genotyping Assay Kit . The assay is a Sanger sequencing based-assay that enables the detection of genomic mutations in the protease (PR), reverse transcriptase (RT) and integrase (IN) regions of the HIV-1 pol gene. Briefly, for RT-PCR, 10 μL of RNA was denatured in a thermocycler for 10 min at 65 °C and added to a 40 μL Master reaction comprised of 39 μL of RT-PCR Master Mix, PR/RT or IN and 1 μL of enzyme (SuperScriptTM III One-Step RT-PCR with PlatinumTM Taq High Fidelity Enzyme). The mixture was then loaded onto the MIniamp thermal cycler  under the following conditions: 1 cycle of 45 min at 50 °C for reverse transcription, 1 cycle of 2 min at 94 °C for enzyme inactivation, 40 cycles of 15 s, 20 s and 2 min at 94 °C, 50 °C and 72 °C for denaturation, annealing and extension, respectively and 1 cycle of 10 min at 72 °C for the final extension. Then, 2 μL of the resultant RT-PCR product was amplified immediately by nested PCR. For PR/RT and IN regions, nested PCR conditions were: 1 cycle of 4 min at 94 °C for enzyme inactivation, 40 cycles of 15 s, 20 s and 2 min at 94 °C, 53 °C and 72 °C for denaturation, annealing and extension, respectively, and 1 cycle of 10 min at 72 °C for the final extension. The resultant RT-PCR product was amplified immediately by nested PCR. All tests were conducted in accordance with the manufacturer’s instructions. The quality of the nested PCR product was assessed on a 1% agarose gel. The PR/RT and IN nested PCR product was purified using the Purelink Pro 96 viral RNA purification kit  per the manufacturer’s instructions. The purified product was sent to MCLAB, Molecular Cloning Lab, CA, USA for Sanger sequencing.The extracted viral RNA was reverse-transcribed and amplified using the Applied BiosystemsThe AB1 files were exported from the instrument into a working folder on Geneious software version 11.0 , which aPre-treatment drug resistance was classified as surveillance drug-resistance mutations (SDRMs) using the calibrated population resistance (CPR) tool on the online Stanford HIV database. Genotypes were classified as wild type or SDRMs to NRTIs ; SDRMs to NNRTIs ; SDRMs to PIs  and finally SDRMs to INSTIs  . All sequences were confirmed as HIV-1 subtype C.GRT of the p = 0.271, Fisher Exact test). SDRM to PI and NRTI was low, found in 1% (1/137) and 4% (5/137), respectively, whilst SDRMs to NNRTI was high, 15% (21/137). See The presence of any SDRM was seen in 19% (26/137). See There were no SDRMs to INSTI. However, four participants, all ART naïve, had INSTI accessory mutations .p > 0.05). See None of these factors, i.e., age, baseline VL and CD4, ART status and sex were associated with the presence of SDRMs among the participants (Participants were followed up for a median (IQR) duration of 27 (25–30) weeks on TLD. Of the 131 participants with follow-up VL data available, the majority, 98% (129/131), were virologically suppressed with VL < 1000 copies/mL. The two participants with VL ≥ 1000 copies/mL did not have any SDRM at baseline and neither did they develop acquired drug resistance to DTG.The current WHO treatment guidelines for all PLHIV recommend the use of DTG-based regimens as the preferred first-line regimen because of its high potency and high genetic barrier to resistance. DTG plays a crucial role in the efforts to control the HIV pandemic in many resource-limited settings. In this study, we found no SDRM to DTG whilst finding a high level of SDRMs to NNRTI (15%) and low levels of SDRMs to NRTI (4%) and PI (1%) among ART-naïve participants initiating on TLD. Additionally, virological failure was low (2%), and no emergence of ADR to DTG was seen among the two failures at the follow-up visit.The low prevalence of SDRMs to NRTI (4%) and PI 1%) along with the high prevalence of SDRMs to NNRTI 15%), particularly among ART defaulters is broadly consistent with our previous findings %, partic,17,18. A% along wWe found that, by week 24, virological suppression VL < 1000 copies/mL and VL < 50 copies/mL on DTG was high  among the participants. These findings were consistent with recent studies in LMICs that reported a high rate (>95%) of virological suppression among individuals on DTG ,19. SimiIn the ADVANCE (South Africa) , NAMSAL Unsurprisingly, prior to ART initiation, we found no SDRM to DTG among these ART-naïve and defaulted individuals initiating on TLD in a resource-limited setting (RLS). This is consistent with a previous study conducted in Zimbabwe which reported no SDRM to INSTI among INSTI-naïve individuals prior to the introduction of DTG . FurtherAdditionally, the recent OPTIPRIM2-ANRS 169 and the Gilead’s phase 2 trials (NCT02397694) have reported no emergent INSTI resistance among ART-naïve individuals failing on DTG ,27. In tLastly, in our study, up to 17% of the participants were individuals who had previously defaulted ART. Just under half, or 43% (13/30), of these participants were on a DTG-based regimen as previous ART. Previous studies have shown that ART defaulters had higher levels of PDR to NNRTI which may predispose them to virological failure and further development of HIVDR once on ART . In our Overall, this study has provided baseline SDRMs to the preferred first-line ART (TLD) in a RLS and assessed the extent to which acquired DTG resistance emerges in populations receiving DTG. One limitation of the study is the small sample size. Another limitation is the short duration of follow-up. However, previous studies with longer follow-up duration did not find any emergent INSTI DRMs among ART-naïve individuals failing their treatment.We found no SDRM and acquired drug resistance to DTG among ART-naïve individuals initiating TLD in a RLS following 6-month post-DTG initiation. DTG is more likely to address the problems of virological failure and emergence of HIVDR in Africa. However, as DTG becomes widely available in many RLS, surveillance of HIVDR to DTG among individuals on DTG is warranted so as to preserve its activity.


While South Africa’s national HIV program is the largest in the world, it has yet to reach the UNAIDS 95–95-95 targets. To reach these targets, the expansion of the HIV treatment program may be accelerated through the use private sector delivery models. This study identified three innovative non-governmental primary health care models (private sector) providing HIV treatment, as well as two government primary health clinics (public sector) that served similar populations. We estimated the resources used, and costs and outcomes of HIV treatment across these models to provide inputs to inform decisions around how these services might best be provided through National Health Insurance (NHI).A review of potential private sector models for HIV treatment in a primary health care setting was conducted. Models actively offering HIV treatment (i.e. in 2019) were considered for inclusion in the evaluation, subject to data availability and location. These models were augmented by government primary health clinics offering HIV services in similar locations. We conducted a cost-outcomes analysis by collecting patient-level resource usage and treatment outcomes through retrospective medical record reviews and a bottom-up micro-costing from the provider perspective (public or private payer). Patient outcomes were based on whether the patient was still in care at the end of the follow up period and viral load (VL) status, to create the following outcome categories: in care and responding (VL suppressed), in care and not responding (VL unsuppressed), in care (VL unknown) and not in care (LTFU or deceased). Data collection was conducted in 2019 and reflects services provided during the 4 years prior to that (2016–2019).Three hundred seventy-six patients were included across the five HIV treatment models. Across the three private sector models there were differences in the costs and outcomes of HIV treatment delivery, two of the models had results similar to the public sector primary health clinics. The nurse-led model appears to have a cost-outcome profile distinct from the others.The results show that across the private sector models studied the costs and outcomes of HIV treatment delivery vary, yet there were models that provided costs and outcomes similar to those found with public sector delivery. Offering HIV treatment under NHI through private delivery models could therefore be an option to increase access beyond the current public sector capacity. Globally, UNAIDS has set the 95–95-95 targets for HIV testing, treatment and viral suppression by 2030 . While SSouth Africa has a diverse mix of non-governmental providers who provide primary health care services, including HIV treatment. The traditional private sector general practitioner (GP) model of primary health provision caters largely for the 16% of South Africans who have private medical insurance through one of the 78 registered medical insurance schemes. However, nearly double this proportion 29%) of South Africans have said that the first health care facility that they would consult would be a private healthcare facility , 6. This% of SoutTo our knowledge, there is almost no work that describes the cost of private sector primary health care in South Africa as it pertains to the provision of HIV treatment . If the We conducted a cost outcomes analysis by collecting patient-level resource usage and treatment outcomes through retrospective medical record reviews and a bottom-up micro costing from the provider perspective (public or private payer). Data collection was conducted in 2019 and reflects services provided during the 4 years prior to that (2016–2019).Private sector sites (Prv) were eligible if they were: a) a direct provider of primary health care (PHC) services , b) offered a spectrum of PHC services that included at least one among HIV, TB, diabetes or hypertension treatment; c) focused primarily on low-income, uninsured populations and d) had a potentially sustainable model that was not completely reliant on donor funding. These were initially identified through purposeful sampling following desktop research and later expanded to include organizations identified through interviews with key informants. Further details of the models identified are outlined in an exploratory, descriptive study . Those mPublic sector PHC sites (Pub) were initially selected based on their physical proximity to the private sector PHC sites. However, two of the private sector clinic models had multiple physical sites and we used the entire dataset to reach the sample size. The public sector PHC sites included are all in Gauteng province and set in a similar urban setting to those of the private sector sites but are not necessarily in close physical proximity to all private sector sites. Setting was considered important as a proxy for the patient population that each site was serving. Public sector PHC facilities provide a full spectrum of PHC services and therefore were not selected based on service offering.All adults (≥18 years old) living with HIV and seeking HIV treatment at the study sites were considered eligible if, at the time of data collection, they had initiated antiretroviral treatment (ART) or, if already on ART, presented to the site for the first time at least 15 months (12 + 3-month window) before start of data collection. The follow-up window was between January 2016 and December 2019. The study population was patients who started ART at the study site at least 15 months prior to data collection, which included both treatment naïve (i.e. patients who initiated at the study site) and ART experienced patients (i.e. patients presenting at the study site for the first time seeking continuation of HIV treatment). Any patient who formally transferred out of the study site during the 15-month follow-up period or who had a missing medical record was excluded. Patient records were then extracted starting with the most recent eligible patient and moving backwards until a sample of 75 patients per site was reached. The sample size was estimated based on prior cost estimates made at a typical primary health clinic in South Africa and was set to be able to detect a 10% difference in mean cost .Patient-level data included all resources used during a 12-month period to provide HIV treatment to the patient. These included medicines dispensed, laboratory tests performed, and visits made to the facility. This information was extracted from the patient medical records at the study sites. Some facilities had electronic medical records that allowed this to be extracted directly into the study database, while other sites used paper medical records and data capturers had to review and extract the data from these files into the study database. Patient outcome data was also obtained from the medical records. Patients were considered “not in care” if they died during the study period or had a gap in ART coverage > 90 days at 12 months. If patients were “in care” at 12 months, they were classified as responding based on the presence and value of a viral load. When these terms are used to reference these outcome definitions in the manuscript, quotation marks are used . Viral load suppression was defined as having a viral load of ≤400 copies per ml between 9 and 15 months after enrollment. The 3-month window before and after 12 months allowed for variable timing in the routine 12-month viral load. The primary patient outcome at 12 months after enrollment was a composite measure based on retention “in care” and response to treatment (In care and responding). Secondary outcomes included; “in care” but not responding , “in care” with an unknown viral load  and “not in care” (not retained).Costs were estimated from the provider perspective for the study period (12 months at the study site). For the public sector PHC facilities, variable costs were calculated by taking the individual level resource utilization  and multiplying it with the appropriate unit prices. We use two metrics to describe resource utilization, the ARV medicine possession ratio (MPR) and time in care. The ARV MPR measures the proportion of days in the 12-month period (365 days) that the patient was covered by antiretroviral (ARV) medication. Time in care measures the time from ARV treatment initiation at the study site or presentation at the site on treatment to the first of either the end of the follow up period (12 months) or the last day that they were covered by ART based on the last prescription filled in the study period. Fixed costs such as clinic space, administrative staff and utilities were estimated from site financial records and then allocated across the patient population, based on all patients’ visits at the respective study site. For the private sector models, the same approach was used unless the model was a fixed fee per visit model (study site Prv2 and Prv3) in which case the fee was used to reflect the cost to the government of offering public services through this model. If there were any additional resources that were not captured in this fee , these were added to the model fee using the unit cost of that model. These costing methods are described by cost category in more detail in Table This was a retrospective record review without any direct patient interaction by the study team. The ethics boards of the University of the Witwatersrand and Boston University reviewed and approved the study protocols and provided a waiver of informed consent.The list of potential private sector PHC providers was finalized in August 2018. Of the seven distinct private models identified, six were active and offered HIV treatment in 2019, but only three were included in this study. Two were excluded because the necessary data were not available, and one was excluded because it was outside of Gauteng and primary data collection was not feasible. Table 3, while other sites that had median baseline CD4 counts above 300 cells/mm3. The majority of patients were ART naïve (Prv3 (Nurse) did not report this), and overall, approximately one tenth reported having either tuberculosis, hypertension or diabetes  appeared to be distinct from the others (Prv1 (NGO) and Prv2 (GP)). The differences reported across the private models might be partially explained by differences in the patients accessing care and treatment at these facilities, which are not captured by the basic demographics data we have from medical records. In patient interviews that were carried out across public and private primary health care sites, including our study sites, some differences were reported . Namely The variation in the sample population and the differences in outcomes and costs across models indicates that it would be incorrect to treat public primary health clinics and private delivery models as homogenous groups, respectively. There appear to be two clear distinctions between the private sector models presented which may also contribute to the results we see. Two of the private models (Prv1 (NGO) and Prv2 (GP)) had access to government-procured and -supplied antiretroviral medicines and laboratory tests, while the nurse-led model (Prv3) accessed both commodities through the private sector. In addition to this, the nurse-led model is the only model that charges a patient fee for each consultation and service provided aimed at full cost recovery. The NGO model charges a nominal user fee per visit (excluding the first visit which is free to patients), but it is lower and designed to cover only administration costs. It is possible that patients in the Prv3 (Nurse) model manage their HIV treatment through a combination of public sector and private sector care. In the individual level data from Prv3 (Nurse), it is seen that some individuals come back during the 12 month follow up period for other services, but not consistently for HIV treatment. The targeted use of private sector health care for certain conditions was reported by Grépin who showed, using Demographic and Health Surveys from 70 low and middle income countries, that care for a child’s diarrhea or fever was likely to be sought in the private sector while care for child birth, ante natal care and contraception was sought predominantly in the public sector . In our Given these significant differences in the private sector delivery models that have implications for both costs and outcomes, we should not draw direct comparisons between individual private sector models, but rather understand how each model can be leveraged in conjunction with the current public sector PHC models to attain the UNAIDS goals within this resource limited setting. Previous systematic reviews that examined the provision of ambulatory care offered by public and private providers in low- and middle- income countries have drawn different conclusions , 18. OneThis study has several limitations. Only three distinct private sector delivery models were included, and there are other variations of these models in South Africa now. These results should be used to understand the possible drivers of differences the cost per outcome in these models, but it may be inappropriate to generalize the results directly to other sites. The sample sizes were modest, and certain outcome categories became very small when calculating the average cost per category. The study data was reliant on standard patient medical records at each of the sites, which meant that data availability, which was not consistent across sites, in part drove outcome assessments. For example, we do not know the number of comorbidities for site Prv2 or the baseline CD4 count or ART naïve status at Prv3. The study deliberately took the perspective of the Department of Health and what their costs might be to expand services using these models; as a result, it specifically excluded the costs to the patients of accessing care  through these models. Differential patient costs combined with the user fees may be a factor in explaining why certain populations  were drawn disproportionately to certain models. Lastly, we have hypothesized that differences in patients accessing care may partly explain why there were differences in the outcomes across models, but the data presented here is not sufficient to fully explain why these outcomes differed across models except for baseline CD4 count and how that may influence treatment success. Ideally, we would have liked to understand some of the socio-economic characteristics of the patients accessing these models, but that was not available in the routine medical data.Despite these limitations, the results presented here provide some of the first evidence showing the cost associated with providing treatment to uninsured, low income patients outside of the traditional primary health clinics in South Africa using three distinct models. For these models it appears that requiring patients to pay for services (Prv3 (Nurse)) may result in less consistent retention for HIV treatment, while providing services with limited or no cost to patient at the point of care (Prv1 (NGO) and Prv2 (GP)) provided outcomes similar to those found in the public sector. Costs in the private models are similar to those found in the public sector sites, but sites that offered comprehensive services (Prv1 (NGO)) in addition to HIV care and treatment had higher costs. The results suggest that offering HIV treatment under NHI through delivery models similar to these may be able to expand access with similar outcomes and costs to those currently found in the public sector. Further research is required to understand how removing patient costs at the point of care as planned under the NHI might change the outcomes seen here.


Nearly four decades after the first case of AIDS was described, the global number of AIDS-related deaths has steadily declined but falls short of the elimination targets, especially in sub-Saharan Africa. Despite interventions to promote early HIV diagnosis and treatment, hospitalization and mortality related to advanced HIV disease (AHD) remains a significant public health problem in Uganda. We assessed the HIV treatment history and causes of hospitalization among in-patients with AHD at a tertiary hospital in Uganda. In this cross-sectional study, pre-hospitalization HIV treatment history and clinical characteristics of HIV-positive in-patients with CD4<200 cells/μL or WHO stage 3 or 4 clinical events were assessed. Descriptive data were summarized using percentages and medians. Among hospitalized adults with AHD from November 2021 to June 2022, 74% (260/353) knew their HIV status prior to hospitalization and 62% (219/353) were ART experienced at presentation. The median time since ART initiation was 28 months . Overall, 73% (258/353) had at least two etiological diagnoses and the majority  were diagnosed with tuberculosis (61.2%), cryptococcal meningitis (20.7%), mucosal candidiasis (16.1%) and bacterial infections (15%). In conclusion, nearly two-thirds of in-patients with advanced HIV disease were ART experienced prior to hospitalization and tuberculosis was the most common cause of hospitalization. Innovative strategies to strengthen HIV diagnosis, linkage, and retention in HIV care and to increase coverage of TB preventive therapy are urgently needed. Access to early HIV treatment has improved markedly since 2015 following the global commitment to end the AIDS epidemic by 2030, through the UNAIDS 90-90-90 and subsequent 95-95-95 targets . As a reWhile it is clear that the number of AIDS-related deaths, a measure of Advanced HIV disease (AHD) burden in sub-Saharan Africa is not declining as rapidly as expected the reasons for this in an era of universal HIV treatment and expanded access to ART are less clear. One plausible explanation is missed opportunities for early testing and/ or linkage to care , 7. AlteHospitalized patients with AHD face a greater mortality risk due to opportunistic infections such as tuberculosis –16 than Between November 2021 and June 2022, we conducted a cross-sectional study in which we enrolled hospitalized HIV-positive adults from Kiruddu National Referral hospital  in Uganda. Kiruddu hospital is a 200-bed capacity hospital located ten kilometers from the center of Kampala, the capital City of Uganda. The hospital has a high in-patient turnover with approximately 200 HIV- related admissions per quarter. Of these, up to 80% present with advanced HIV disease [We screened hospitalized HIV-positive patients admitted on the medical wards using CD4 or clinical criteria for advanced HIV disease . PatientAt enrolment, participants or next of kin were interviewed to obtain information on socio-demographics and HIV treatment history prior to hospitalization, including adherence to ART. Adherence was assessed using self-reported number of days missed during the one-month period prior to hospitalization. Missing at least two days in a month was equivalent to 93% adherence yet adherence of 95% or more is associated with optimal virologic outcomes . We assuA pre-tested case report form was used to collect demographic (age and sex) and clinical data  status, duration on ART before admission, ART regimen and adherence, baseline vitals, baseline lab parameters including CD4 count, hemoglobin concentration, serum creatinine, random blood sugar and serum albumin). Laboratory values were graded using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Published: November 27, 2017. Data were entered into Open Data Kit (ODK) then imported into Stata version 13  for analysis.Clinical data were compared by ART status at admission (ART experienced versus ART naïve) using chi-square or Fisher’s exact and Wilcoxon-Mann Whitney test for categorical variables and continuous variables respectively. Further, we compared ART regimen at admission, adherence level in the month preceding admission and proportion of men across three ART duration categories. ART duration categories were defined by the duration of antiretroviral therapy at admission . The six months cut-off was selected because virological suppression is expected by six months of consistent ART use and sooner (by three months) with dolutegravir-based regimens. At the time of study implementation, dolutegravir had been widely rolled out and most ART-experienced participants were expected to be on dolutegravir.Regarding in-patient diagnoses other than TB, conditions with a prevalence of less than 1% of the study population were aggregated as ‘other.’ To account for duplicates and minimize the number of categories, some diagnoses were aggregated as follows:1) alcohol intoxication and alcohol withdrawal as alcohol-related central nervous system (CNS) syndrome, 2) oral candidiasis and esophageal candidiasis as mucosal candidiasis, 3) bronchopneumonia (without a TB diagnosis), sepsis, urinary tract infection, community-acquired pneumonia, empyema thoracis and pelvic inflammatory disease as bacterial infections, 4) acute kidney injury and chronic kidney disease as renal dysfunction and, 5) HIV encephalopathy, HIV induced psychosis, clinically diagnosed viral meningoencephalitis as unspecified encephalopathy.All study participants or legal representatives provided written informed consent. Ethical approval was obtained from the Makerere University School of Medicine Research and Ethics Committee (Mak-SOMREC-2021-110).Table 1 shows the overall summary of clinical characteristics of the study population and comparison by ART status at admission. Of note, ART experienced individuals had significantly higher median CD4 count than those who were ART naïve; 101 cells/μL (IQR29-187) versus 32 cells/μL (IQR:9–102), P<0.001.From November 2021 to June 2022, 353 participants with advanced HIV disease were enrolled and over half, 55% (195/352) were male and the overall median age was 37 years . The median age of men was 40 years  whereas that of women was 34 years . Nearly two thirds of study participants; 62% (219/353) were ART experienced and the median time since ART initiation was 28 months (IQR: 2 months to 8 years). Proportions of ART-experienced participants across ART duration categories are illustrated in Thirty-eight percent (133/353) of the study population were ART naïve at the time of hospitalization . Of thesFig 2.Seventy three percent of participants (257/353) had more than one diagnosis, and 2% (7/353) were unclassified. All unclassified participants died during hospitalization. TB accounted for the majority  of admissions followed by cryptococcal meningitis (20.7%), mucosal candidiasis  (16.1%) and bacterial infections (15%). The prevalence of other diagnoses is summarized in Tuberculosis was bacteriologically confirmed in 71% (153/216) of participants and clinically diagnosed in 29%(63/216). Among participants diagnosed with bacteriologically confirmed TB, the basis of diagnosis was positive Urine LAM only in (78%(119/153),), followed by sputum Xpert MTB/RIF Ultra , urine LAM combined with urine Xpert MTB/RIF Ultra , urine Xpert MTB/RIF Ultra only  and lastly, cerebrospinal fluid Xpert MTB/RIF Ultra . Among patients with clinically diagnosed tuberculosis, the basis of diagnosis was symptoms combined with an abnormal chest X-ray in 57% (36/63). Thirteen percent (27/216) of all TB diagnoses were based on symptoms and signs only and chest X-ray was either not done or was reported as normal.In this study, we characterized HIV testing and treatment history and co-morbidities of hospitalized patients with AHD in Uganda.First, we observed that nearly two thirds of in-patients with advanced HIV Disease were ART experienced and presented with a relatively higher CD4 count compared to ART naïve patients. Presentation to in-patient care with advanced HIV disease and prior ART exposure could be attributed to retention failure, immune reconstitution inflammatory syndrome (IRIS) or initiation of ART with profound immune suppression. This is similar to what was observed recently among hospitalized patients with AHD elsewhere in sub-Saharan Africa where the majority were ART-experienced .Regarding individuals who were ART naïve at presentation, 68% were unaware of their HIV status indicating system failures to test some populations early. Contrarily, 32% had been previously diagnosed with HIV but never initiated ART, suggesting failure of linkage to ART initiation.Finally, we observed that tuberculosis is the commonest co-morbidity in the in-patient setting suggesting that innovative implementation strategies for TB preventative therapy in this population are needed.ART-experienced individuals presenting with AHD may have treatment failure, or immune reconstitution inflammatory syndrome or sub optimal immune reconstitution after ART initiation , 27. We A relatively small proportion (Five percent) of the study population were receiving ART for 3 to 6 months (median time of 4 months) prior to hospitalization and less than a quarter (21%) reported suboptimal adherence. We hypothesize that this ‘3 to 6 months’ category received sufficient ART for immune reconstitution and may be categorized as possible immune reconstitution inflammatory syndrome (IRIS) . The proThe third category of ART experienced patients were receiving ART for six months or more (40% of our study population) and half reported sub-optimal adherence, therefore we suggest that this population may be classified as possible treatment failure and/or ART non-adherence. Beyond six months of effective ART, viral suppression and immune recovery are expected except in a few isolated cases of sub optimal CD4 recovery despite virological suppression , 30. Of Over a third of the study population were ART naïve at presentation, indicating gaps in early HIV diagnosis and linkage to care. The majority of ART naïve patients were not aware of their HIV status prior to hospitalization, and this implies that lack of early HIV diagnosis remains a barrier of eliminating AHD. Similarly, the 2022 UNAIDS report indicated that no country in sub-Saharan Africa was able to meet the ‘first 95% target’ for 95% of all people living with HIV knowing their HIV status . This caOur study suggests that tuberculosis accounts for most of the morbidity associated with advanced HIV disease among in-patients. This is consistent with what has been observed elsewhere in sub-Saharan Africa, however the prevalence of TB in our study was relatively higher than expected (61% versus 40%) , 35. ThiTB preventative therapy is recommended by WHO for all people living with HIV (PLHIV) with a target of 90% of all PLHIV by 2025, however implementation is suboptimal globally , 39. AmoThe main limitation of this observational study is related to the assessment of HIV treatment history. ART status and adherence were assessed by self-report, potentially leading to social desirability bias and risk of misclassifying individuals who are ART experienced as ART naïve. This bias was mitigated by asking the question in a non-judgmental manner with preceding empathetic statements. Additionally, the assessors were not directly involved in clinical care of the study participants. Our findings showed that ART-experienced patients had higher CD4 counts than ART naïve, therefore we believe that the assessment of ART status was reliable.Second, in-patient diagnoses were collected by chart review and data were insufficient to categorize diagnoses as confirmed versus clinical/ presumptive. This was only possible for TB diagnosis, therefore our discussion on causes of hospitalization is focused on TB which is also the most prevalent.Finally, documentation of viral loads was challenging because attaining a viral load required a linked clinic ID, which many participants did not have. Viral load testing would have complemented interpretation of HIV treatment history, which is important for diagnosis of treatment failure and IRIS. For instance, diagnosis of IRIS was challenging in the absence of viral load as IRIS can occur across all three ART duration categories. Patients with unmasking IRIS more likely in the <3 months group, those with unmasking/paradoxical IRIS could fall in the 3–6-month group and some patients in the >6months group could have paradoxical IRIS. Considering challenges in access to plasma viral load, we recommend that point-of-care viral load testing should be added to the advanced HIV disease package of care for hospitalized patients.In summary, our findings suggest that the prevalence of advanced HIV disease among hospitalized adults is attributable to clinical failure reflected by opportunistic infections and poor adherence in a predominantly ART-experienced population. Slow change to near universal DTG regimen may have contributed to treatment failure. Long-acting ART formulations such as 2-monthly cabotegravir plus rilpivirine should be evaluated in effectiveness trials for ART experienced adults with suboptimal virological control. This regimen may improve adherence and modelling studies have shown low risk of emergent resistance . AdditioS1 Dataset(XLS)Click here for additional data file.S1 File(DO)Click here for additional data file.S2 File(XLSX)Click here for additional data file.


Background: Women are disproportionally affected by HIV and are at greater risk of OIs and malignancies. This study investigated the spectrum of OIs and malignancies among women living with HIV (WLHIV) in Ethiopia. Methods: A retrospective longitudinal study was conducted among 3,817 WLHIV on Antiretroviral Treatment (ART) from 2007 to 2019 in Ethiopia. Data on OIs, malignancies, and clinical characteristics were retrieved from medical records. Prevalence, incidence, and mortality rates were measured over 13 years of follow-up. The Kaplan-Meier survival curve and multivariable Cox-proportional hazard regression were used to estimate incidence and identify predictors of OIs and malignancies, respectively. Result: The pooled prevalence of OIs or malignancies was 47%. OIs accounted for 39% and malignancies were 23.3%. The incidence of OIs and malignancies were 19.4 (95%CI:9.2-29.5) and 11.5 (95%CI:2.2-20.8) per 100 person-years of observation, respectively. Incidence of candidiasis was 14.1 per 100 person-years followed by Lymphoma (11.9), Cervical Cancer (11.5), and TB (10.9). The risk of OIs was higher in patients with baseline CD4 count ≤500 cells/mm3 [AHR (95%CI): 2.0 (1.8-2.3)] and VL>1000 copies/ml [AHR (95%CI): 1.5 (1.1-1.9)]. Overall, 24.6% died, and of them, 62.2% had a history of OIs or malignancies. The risk of death was higher among WLHIV with a history of Toxoplasmosis, TB and PCP. Conclusion: OIs and malignancies was recently increasing and two-thirds of all deaths were associated with these co-morbidities. The high rates of OIs and malignancies were attributed to poor treatment outcomes. The finding calls to enhance the diagnosis and treatment of these co-morbidities.AIDS: acquired immune deficiency syndrome; CI: confidence interval; EPHI: Ethiopian Public Health Institute; HAART: highly active antiretroviral therapy; HIV: human immunodeficiency virus; HR: hazard ratio; Mg/dl: milligram per deciliter; TB: tuberculosis; PCP: pneumocystis carinii pneumonia; ZJU: Zhejiang University Opportunistic infections (OIs) and malignancies are common in individuals with weakened immune systems, mainly among people living with HIV (PLWHIV) and malnourishment . These cPneumocystis Pneumonia (PCP), remain major causes of morbidity and mortality in HIV/AIDS patients in LMICs  and malignancies [AHR (95% CI) = 1.2 (1.04–1.4)]. Patients with VL > 1000 copies/ml had also a higher risk of OIs [AHR (95% CI) = 1.4 (1.1–1.7)] and malignancies [AHR (95% CI) = 1.8 (1.4–2.4)] ] .Table 3p < 0.05. Toxoplasmosis was the most prevalent infection among dead cases (41.2%) followed by TB (37.3%) and PCP (34.9%). Among OIs or malignancies associated with death, 32.5% had a history of oral candidiasis followed by TB (32%) and Lymphoma (28%) , ma (28%) . The risma (28%) . As indi3 and VL > 1000 copies/ml had a higher risk of acquiring OIs and malignancies. A quarter of patients died during follow-up and significantly associated with Toxoplasmosis, TB, and PCP.This study showed that the pooled prevalence of OIs or malignancies among WLHIV during the 13 years of follow-up was 47% . The most prevalent OIs were oral candidiasis (14.2%), TB (11.3%) and Herpes zoster (9.6%), whereas the prevalence of cervical cancer and Lymphoma was 11.9% and 13.3%, respectively. The Incidence of OIs or malignancies was 19.7 per 100 person-years observation, respectively. Oral candidiasis was the most incident case with 14 per 100 person-years followed by lymphoma (12), Cervical Cancer, and TB (11). Patients with CD4 count <500 cells/mmThe overall prevalence of OIs in the current study was almost double the findings from Northwest Ethiopia  but muchThe overall prevalence of malignancies was relatively higher compared to the findings ,18,20,213 had a two-fold higher risk of developing OIs which is consistent with previous studies [3 and VL > 1000 copies/ml were also supported by many studies [Our analysis shows that WLHIV with CD4 count <500/mm studies ,18,25,26 studies ,25,27. T studies . The hig studies ,18,24,29The rate of mortality among WLHIV was consistent with previous studies in Ethiopia ,31, and Due to the limited information in the recordings, the different stages of cervical cancer and the types of lymphoma were not characterized. Nearly 20% of records were excluded due to lost-to-follow-up or incomplete records. This would affect the generalizability of findings since the missed cases would have special features that would affect the occurrence of OIs and malignancies. Moreover, this study was conducted at referral hospitals and university hospitals where most patients are urban and relatively high economic compared to rural WLHIV. The facilities had limited capacity during the earlier times to diagnose OIs and HIV-related malignancies and hence misclassification or misdiagnosis might happen. Since this study was concluded by the end of 2019, the burden of OIs and malignancies during after the era of COVID-19 was not part of this study.Nearly half of WLHIV develop either OIs or malignancies while the incidence rate was also increasing, particularly for TB and Toxoplasmosis. A quarter of WLHIV died during the 13 years of follow-up, of whom two-thirdss were associated with OIs or malignancies. The high rates of mortality associated with opportunistic infections were attributed to immunologic and virologic failures. The finding calls to enhance the diagnosis and treatment of OIs and malignancies particularly TB, Toxoplasmosis, and cervical cancer during the clinical management of WLHIV.OIs: common opportunistic infections . TB was diagnosed using AFB microscopic or GeneXpert. Moreover, oral candidiasis, Toxoplasmosis, PCP, and Herpes zoster were defined per the clinical definitions according to the national comprehensive ART guideline on Ethiopia [Ethiopia .Malignancies: common malignancies among WLHIV . Cervical cancer was determined using Visual Inspection with Acetic Acid (VIA) or PAP smear complemented with clinical evidence as recorded by the attending physician. Lymphoma was also defined per the clinical definitions according to the national comprehensive ART guideline on Ethiopia [Ethiopia .Lost to follow-up: Patients missing their follow-up visits according to their appointment schedule for more than 3 months as recorded on the appointment schedule.WHO clinical stages, CD4 count, and VL suppression were described as per the national compressive ART guideline .Ethical approval was obtained from the Ethiopian Public Health Institute Scientific and Ethical Review Office (SERO) with approval number; EPHI-IRB-19110-2019. Confidentiality was respected during the abstraction of data by the use of a specific identification code for each enrolled patient number. Given the nature of the data collection was a medical record review, informed consent from the study participants was not applicable.Click here for additional data file.


Several studies have described the rapid decline and clearance of hepatitis B surface antigen (HBsAg) in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfection after initiating combined antiretroviral therapy (cART). Early decline of HBsAg levels is associated with HBsAg seroclearance in the treatment of chronic HBV infection. This study aims to evaluate the HBsAg kinetics and the determinants of early HBsAg decline in patients with HIV/HBV coinfection during cART.10 IU/ml at 6 months from the baseline after initiation of cART.A total of 51 patients with HIV/HBV coinfection were enrolled from a previously established HIV/AIDS cohort and followed for a median of 59.5 months after cART initiation. Biochemical tests, virology and immunology assessments were measured longitudinally. The kinetics of HBsAg during cART were analyzed. Soluble programmed death-1 (sPD-1) levels and immune activation markers (CD38 and HLA-DR) were measured at baseline, 1-year and 3-year during treatment. HBsAg response was defined as a decline of more than 0.5 log10 IU/mL) in the first six months and attained a decrease of 1.39 log10 IU/mL after 5-year therapy. Seventeen (33.3%) participants achieved a decline of more than 0.5 log10 IU/ml at the first 6 months of cART(HBsAg response) of which five patients achieved HBsAg clearance at a median of 11 months (range: 6-51 months). Multivariate logistic analysis showed the lower baseline CD4+ T cell levels  and sPD-1 level  were independently associated with HBsAg response after cART initiation. The alanine aminotransferase abnormality rate and HLA-DR expression were significantly higher in patients who achieved HBsAg response than in those who did not achieve HBsAg response after cART initiation.HBsAg declined faster (0.47 log+ T cells, sPD-1, and immune activation were related to a rapid HBsAg decline in patients with HIV/HBV-coinfection after the initiation of cART. These findings imply that immune disorders induced by HIV infection may disrupt immune tolerance to HBV, leading to a faster decline in HBsAg levels during coinfection.Lower CD4  As a thHepatitis B surface antigen (HBsAg) seroclearance is considered the endpoint in chronic hepatitis B (CHB) functional cure studies; however, it is only achieved in few patients . Early sThe immunoinhibitory receptor programmed death-1 (PD-1) combined with programmed death-ligand 1(PD-L1), can directly contribute to T-cell dysfunction and exhaustion. PD-1 expression on T cell is persistently upregulated during HIV and HBV infection . The sol+ T cell with HBsAg decline in HIV/HBV coinfection after the initiation of cART. Our study also ascertained determinants with a significant HBsAg decline(>0.5 log10 IU/ml) in early treatment in patients with HIV/HBV-coinfected.Recently, several studies have reported a high prevalence of HBsAg seroclearance in HIV/HBV coinfection during combined antiretroviral therapy (cART) . Neverth22.1The study participants were recruited from a longitudinal HIV/AIDS cohort conducted at the Peking Union Medical School Hospital (PUMCH). The inclusion criteria for the HIV/AIDS cohort have been described previously , includiWe recruited patients with HIV/HBV coinfection from the HIV/AIDS cohort. The inclusion criteria of this study were as follows: (1) positive HBsAg or detectable HBV DNA lasting more than 6 months (2) no previous history of anti-HBV treatment. (3) patients who received cART for more than 6 months in the HIV/AIDS cohorts. The exclusion criteria were as follows: (1) coinfection with hepatitis C, (2) existence of alcoholic and autoimmune liver diseases, (3) history of malignancy, and (4) use of corticosteroids, immunosuppressants, or chemotherapeutic drugs in the past 6 months. Overall, 896 adult patients were screened from the HIV/AIDS cohort, and 51 eligible patients were enrolled in this study Figure 1This study was conducted following the Declaration of Helsinki and was approved by the Institutional Review Board of PUMCH. Written informed consent was obtained from each participant.2.2+ and CD8+ T cell counts and the presence of CD38 and HLA-DR markers .Routine liver function tests were performed at PUMCH laboratory. HBV serological markers  were determined using the Abbott Architect platform. HBV viral load was quantified using the COBAS Ampliprep/TaqMan48 real-time polymerase chain reaction (PCR) Test . Furthermore, HBV genotype was determined using PCR for the HBV reverse transcriptase gene. HIV-1 RNA levels were measured using the COBAS HIV-1 assay . Flow cytometry was employed to evaluate CD42.3HBsAg was quantified at baseline and 6, 12, 24, 36, 48 and 60 months in patients after the initiation of cART. Quantification of HBsAg was measured from frozen stored samples (-80°C) using the Abbott Architect HBsAg assay , with a range of 0.05–124,925 IU/ml.2.4Serum sPD-1 levels were measured using a commercial ELISA Kit , with a detection range of 15.6–1000 pg/ml. The sensitivity was 3.27 pg/ml. The intra-assay and inter-assay CV% were <10%. Serum was diluted appropriately when the concentration was outside this range. sPD-1 was quantified in participants at baseline, 1 year, and 3 years after cART.2.510 IU/ml at 6 months from the baseline, which is a significant decline in patients with CHB under NAs therapy , a main effect of time , and interactions between group * time were included in each model. Differences in continuous variables between the HBsAg response and non-response groups were analyzed using the independent samples t-test, and Mann–Whitney U test for normally and non-normally distributed data, respectively. Categorical variables were analyzed using the chi-square test or Fisher’s exact test. Furthermore, binary logistic regression was performed to determine the influence of characteristics on the HBsAg response. Variables with a P<0.10 in the univariate regression were included in multivariate logistic regression analyses. The multivariate logistic regression analyses were fitted based on maximum likelihood estimation. Statistical analysis was performed using SPSS 23.0 and GraphPad Prism 8.0.Serum levels of sPD-1 at baseline were categorized into three groups according to four quartiles: Q4: >908pg/mL, Q1: <417 pg/mL and below and above the median (Q2 and Q3: 417‐908pg/mL). Continuous variables were expressed as mean [standard deviation] or median (25th-75th percentile). Linear mixed-effects modeling was performed to investigate the HBsAg decline across the measured time points. A main effect of group  patients had elevated ALT levels. Regarding HIV infection-related parameters at baseline, the median HIV-RNA was at 4.53 log10 copies/ml. The mean CD4+ T cell was 227 cell/mm3, the mean CD8+ T cell was 830 cell/mm3, and the median CD4+/CD8+ ratio was 0.29. Patients had received cART for 59.5 (36.0–96.3) months. Forty-one (80.3%) patients initiated tenofovir disoproxil fumarate (TDF)+lamivudine (3TC)-based HBV therapy cART schedules, nine (17.6%) used 3TC, and one received tenofovir alafenamide fumarate/emtricitabine. After a median of approximately 5-year treatments, patients with HIV/HBV coinfection achieved HBV viral control, decreased HBsAg levels, decreased fibrosis score, and increased platelet counts. After treatment, the HIV viral load was controlled, and CD4+ T cell counts and CD4+/CD8+ ratio recovered significantly. Generally, these patients were successfully treated.Fifty-one patients were enrolled in this study, and cART was initiated between July 2007 and November 2020. The characteristics of the participants with HIV/HBV-coinfection are presented in 3.210 IU/mL, and achieved a decline of 1.39 log10 IU/mL after five years of therapy. We investigated the effects of HBeAg positivity and baseline HBsAg levels on HBsAg decline. PWH with positive HBeAg results had significantly higher HBsAg levels at baseline and 6 months : 417–908) pg/ml, which decreased dramatically after receiving cART (P<0.001) (3.4Patients with HIV/HBV coinfection were categorized into the following two groups to determine the factors related to early HBsAg decline in coinfected patients: the HBsAg decline response group (sAg-R) and the HBsAg non-response group (sAg-NR), as defined in the Methods  and a decreased count of CD4+ T cell at baseline than sAg-NR group . The sAg-R group was more likely to have CD4+ T cell counts below 200 cells/mm3 than the sAg-NR group, with a significant difference . However, no significant difference was observed in the proportion of sPD-1 levels below Q1 (<417 pg/ml) between the sAg-R and sAg-NR groups .Baseline characteristics and differences are presented in 10 IU/mL), CD4+ T cell counts <200 cell/mm3 , and sPD-1: Q1<417 pg/mL or not  as covariates to assess their influence on HBsAg response. Baseline HBV-DNA (odds ratio (OR)=1.287, P=0.044), CD4+ T cell count below 200 cells/mm3, and low sPD-1 levels  were risk factors for HBsAg decline. As TDF-based ART regimens have been reported to facilitate HBsAg decline  during treatment. The expression of CD38 on CD8+ T cells between the two groups showed a similar trend but was not significantly different  in HIV/HBV coinfection. Our findings suggest that lower CD4HBsAg seroclearance is an essential standard for functional cure evaluation and is an ideal endpoint for treating HBV infection . However+ T cell counts were significantly correlated with a rapid decline in HBsAg levels. Previous studies have reported that CD4+ T cell recovery is associated with HBsAg loss , resulting in a rapid HBsAg decline and liver inflammation, as evidenced by higher ALT abnormalization and immune activation in the sAg-R group. This phenomenon may be more pronounced in coinfected patients with low CD4nfection . However+ T cell levels  in our study, indicating the effects of sPD-1 and CD4+ T cells on HBsAg decline are independent of each other. It also suggests that sPD-1 levels in HIV/HBV coinfection are not only influenced by the HIV-induced immune mechanism, but also by other factors. Given the potential benefits of low sPD-1 levels for HBsAg decline, it is important to explore the possibility of reducing sPD-1 generation through immunotherapy, such as PD-1/PD-L1 inhibitor. Nevertheless, further investigations are required to fully confirm and elucidate the role of sPD-1 in HBsAg decline in more detail.Our study represents the first investigation into sPD-1 profiles in HIV/HBV coinfected individuals and provides novel insights into the role of sPD-1 in this context. Our findings indicate that sPD-1 levels were elevated at baseline and subsequently decreased during long-term antiretroviral therapy. During HIV infection, sPD-1 levels are closely associated with PD-1 expression on T cell surfaces . Therefo+ T cell counts for HBsAg seroclearance. Therefore, a well-designed large-cohort study should be conducted to validate our findings.Our study had some limitations. First, the follow-up intervals were not stringent, which may have induced bias. Second, the sample size was relatively small, which limited the generalizability of our conclusions to other settings. Finally, overall, HBsAg seroclearance was insufficient; therefore, we could not evaluate the diagnostic performance of sPD-1 and CD4+ T cell counts and sPD-1 levels may have implications for HBsAg decline in patients with HIV/HBV coinfection. Notably, patients who experience a significant decline in HBsAg exhibit higher liver inflammation and immune activation. Future exploration of the dynamic changes of the immune system after cART initiation could provide valuable insights for developing novel therapies and designing clinical trials of chronic HBV infection.In conclusion, this exploratory study suggests that monitoring CD4The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Institutional Review Board of PUMCH. The patients/participants provided their written informed consent to participate in this study.XDL, WC and TL contributed to the design, and interpretation of the results and drafts of the manuscript. XS, YL, XXL and WC contributed to regular clinic visits and data collection. XDL, LX, LL, XSL, YY, YW and YH performed experiments, statistical analyses, and validation. WC and TL were involved in the supervision, funding acquisition, and manuscript review. All authors contributed to the article and approved the submitted version.


Patients younger than 40 years old were more likely to be lost to follow-up when compared to those aged >50 years old, as well as patients who were unemployed and patients with a CD4 count < 350 cells/mm3. Patients with haemoglobin levels lower than 10 g/dL and with a CD4 count < 350 cells/mm3 were more likely to have virological failure. Conclusions: We have identified clinical and sociodemographic determinants of loss to follow-up and in the development of virological failure for HIV-positive patients in clinical care in the MMH. Therefore, HIV programs must consider these factors to increase the screening of patients at high risk of poor outcomes and particularly to strengthen adherence counselling programs.Introduction: Access to antiretroviral treatment (ART) is increasingly available worldwide; however, the number of patients lost to follow-up and number of treatment failures continue to challenge most African countries. Objectives: To analyse the retention in clinical care and the virological response and their associated factors of HIV-1 patients from the Maputo Military Hospital (MMH). Methods: A cross-sectional observational study was conducted to analyse data from patients who started ART between 2016 and 2018 in the MMH. Results: At the end of 12 months, 75.1% of 1247 patients were active on clinical follow-up and 16.8% had suspected virologic failure (VL > 1000 copies/mm Human immunodeficiency virus (HIV) is still one of the major public health problems worldwide, especially in low–mid-income countries (LMIC). It is estimated that in 2021, worldwide, around 38.4 million individuals were living with HIV [In Mozambique, in 2021, the estimate of inhabitants living with HIV was 2.101 million, with around 35.463 deaths recorded from HIV [To address the pandemic, the World Health Organization (WHO) with the Joint United Nations Program on HIV/AIDS (UNAIDS) launched the 95-95-95 targets to be achieved in 2030, which propose achieving 95% diagnosis among all people living with HIV (PLHIV), and of those, 95% of patients on antiretroviral therapy (ART), and of those, 95% patients should achieve viral suppression (VS) .Mozambique has adopted this 95-95-95 strategy to improve the access to treatment for HIV-positive people. However, the massive expansion of units offering ART has become challenging, making it difficult to keep the balance between ART demand and availability, as well as the quality of clinical care . In 2021Several studies have shown evidence that with an adequate ART regimen, an increase in survival and an improvement in the quality of life of these patients is observed . HoweverThis is a cross-sectional observational study conducted at the Maputo Military Hospital (MMH) in Mozambique. The MMH belongs to Mozambique’s national health system and is the largest military health facility in the country. It has an Integrated Care and Treatment Centre (CICTRA), where ART services are offered, with about 16,244 HIV+ patients registered in its database (openMRS). The follow-up of HIV-positive patients started in 2005 and the test and treatment strategy was adopted in 2016. It has an average daily observation of 90 HIV-1 patients and an average annual ART initiation of 780 patients.All patients who started treatment at the HMM between the 1st of January 2016 and 30th of December 2018 and who were older than 18 years old were selected from the HMM database (openMRS). Pregnant and lactating women, patients co-infected with tuberculosis and deceased patients were excluded from this study. Moreover, those who were transferred to and from other health facilities during the period of analysis and from whom clinical information and follow-up were lost were also excluded from this study. Overall, 1773 newly diagnosed patients were retrieved from the openMRS database and 1247 were included in the analysis, according to the flowchart presented below .3 and good virological response as patients with a viral load below 1000 copies/mm3 6 months after starting ART [3 (late presenters) and CD4 ≥ 350 cells/mm3 (non-late presenters). The haemoglobin level was stratified into ≥10 g/dL and <10 g/dL [The Ministry of Health of Mozambique defines virological failure as patients with a viral load above 1000 copies/mmting ART . The lev<10 g/dL .The two main outcomes were retention in care at 12 months and virological failure and the independent variables were sex, age at the start of treatment, distance between residence and health care facility, employment, education, WHO clinical stage, body mass index, haemoglobin, CD4 count and ART regimen.Data were entered, cleaned, coded and checked for missing values, outliers and inconsistencies.Descriptive analysis was used to characterize the sociodemographic and clinical characteristics of patients included in this study.2) or Fisher tests were used. To compare age at the start of the treatment between the two groups, the Mann–Whitney test was used. To analyse the association between the outcome and qualitative variables, chi-square tests  and respective 95% confidence interval (CI). Factors that were associated with outcomes at the 20% significant levels in the bivariate model were included in the multivariable analysis.SPSS Statistic Version 28 software was used for statistical analysis.The protocol was in accordance with the declaration of Helsinki and approved by the National Bioethics Committee of Mozambique ref: 362/CNBS/20. All the variables included in this study were anonymized and no patient information was disclosed to any third person.The characteristics of the study population according to the level of retention in care at 12 months are described in p < 0.001) and younger patients <39 years presented higher levels of dropouts (p < 0.001). In total, 75.0% (311/1246) of the study population lived more than 5 km away from the Health Care Facility , with higher loss to follow-up for those who lived above 5 km distance (p < 0.001). In total, 50.9% (551/1082) of the population had completed high school. The majority of the population was employed (83.1%) and these patients presented a higher level of retention in health care (84.6% actives vs. 73.1% dropouts) (p < 0.001). Moreover, patients with CD4 counts < 350 cells/mm3 presented significantly more dropouts of follow-up compared to patients with CD4 counts > 350 cells/mm3 (p < 0.001) . Regarding age, most of the participants, 32.2% (401/1247), were aged between 30 and 39 years (< 0.001) .p = 0.002 for patients between 18 and 29 yo and OR: 2.389, 95%CI: 1.397–4.087 p = 0.001 for patients between 30 and 39). Unemployed patients also presented a higher probability of dropouts of follow-up  compared to those who were employed. Also, patients who started treatment with a CD4 < 350 cells/mm3 were more likely to drop out  when compared to those with CD4 > 350 cells/mm3. Adjusted ORs suggested that patients younger than 39 years old were more likely to be lost to follow-up when compared to those over 50 years old , patients with higher haemoglobin levels were less likely to drop out when compared to those with levels of haemoglobin less than 10 g/dL and those that resided more than 5 km away from the health care unit were more likely to drop out of care when compared to those that lived nearer to the hospital   . Despite3 , a slightly higher number of females was observed , with most individuals being more than 50 years old (32.4%). Most patients (70.3%) with virological failure lived more than 5 km away from the HCF, were employed (84.7%) and presented a WHO clinical stage of 1 or 2 (82.8%)  . 3 presented higher prevalence of high-level education (p = 0.010), higher prevalence of body mass index between 18 and 30 kg/m2 (p = 0.050), lower haemoglobin levels (p = 0.050) and lower CD4 counts at the start of treatment (p = 0.010)  .p = 0.025) when compared to patients presenting haemoglobin levels ≥ 10 mg/L. Also, patients with CD4 counts < 350 cells/mm3 at the start of treatment were more likely to have virological failure  when compared to those with a CD4 count ≥350 cells/mm3 at the start of treatment (Adjusted ORs  suggestereatment .p = 0.140) when compared to patients with primary education levels, that patients with a higher body mass index were less likely to develop virological failure when compared to those with a lower body mass index  and, strikingly, that patients taking regimens with a backbone of AZT + 3TC were less likely to develop virological failure  when compared to those taking regimens with a backbone of TDF + 3TC.On the other hand, education, body mass index and ART regimens, which were associated with virological failure in the bivariate model, did not show any association in the multivariable model. However, it suggested that patients with higher education levels were less likely to develop virological failure , but some developed virological failure (16.8%). When comparing our results with previously reported levels of retention in care in Mozambique (68%) , we founIn this study, around 25% of patients on ART were lost to follow-up at 12 months. These patients may experience higher morbidity, mortality and resistance to antiretrovirals, contributing to progression to AIDS and increasing HIV transmission, according to Stricker and colleagues 2014) . However . HoweveOur results also suggest that younger age groups less than 40 years old were more likely to drop out of follow-up in the first 12 months when compared to the age group of those over 50 years old. This could be related to stigma and fear of disclosure of their HIV status to their partner . These rIn our study, we also found an association between loss to follow-up and unemployment. This can be related to the socioeconomic limitations that unemployed individuals face and lower access to HCFs, related to language barriers or transportation difficulties . This coRegarding CD4 cell count, our study showed that patients with low CD4 counts were more likely to drop out of follow-up, having more difficulties in improving their clinical status, suggesting that a worse health condition might be an obstacle to accessing the HCF . HoweverDespite there being no statistically significant differences in the distance to the health facility, we found that patients who lived far from the hospital (≥5 km) were more likely to drop out, which can be justified by the socioeconomic difficulties these patients face to reach the heath facility; often, they need to pay for transport and it takes a long time to get to the hospital. Similar results were found in a systematic review of 66 studies across 15 countries in sub-Saharan Africa where geographic and transportation-related barriers were associated with worse outcomes throughout the continuum of HIV care and treatment services .Virological failure among the patients enrolled in this study was 16.8%. This might be due to the strong involvement of health care professionals in the follow-up of HIV-positive individuals. At the MMH, health care workers (i) carry out adherence counselling every day in the morning before medical appointments to raise awareness about the importance of taking the ARV regimen correctly and (ii) contact peer educators and psychologists who help patients with questions related to adherence to the ARV regimen. 3 at the beginning of treatment had the highest prevalence of virological failure. This could be related to behavioural determinants that imply that patients who present with lower CD4 counts have lower access to health care services and therefore higher risk of low adherence and worse follow-up. On the other hand, higher CD4 improves the health status of the patient, which contributes to higher access to care, better adherence, better follow-up and therefore reduction in the occurrence of virological failure [Regarding the associations between the studied variables and virological response, our results showed that patients with CD4 counts below 350 cells/mm failure . Similar failure . The sam failure , as well failure ,29,30. We also observed that patients with haemoglobin levels < 10 were more likely to develop virologic failure. Haemoglobin levels are related to disease progression in HIV-1-infected patients. Low haemoglobin levels contribute to reduced immunity, which in turn also may compromise virologic response . SimilarAlthough there were no statistically significant differences in multivariable models, we found that patients who completed higher-level education were more likely to develop virological failure, which may be because these patients do not trust the health system and consequently do not follow the clinic recommendation. Different results were found in a cohort study performed in Italy including 8023 HIV-positive patients that showed that patients with higher educational levels were more likely to reach an undetectable viral load compared with others .While some studies show differences in virological response between age groups, our study did not find a statistically significant association. This could suggest that the effectiveness of treatment in our population is not affected by age, if it is taken regularly. Similar results to ours were found in a cohort from several African countries between 2013 and 2019 . HoweverThe prevalence of HIV at older ages has been increasing significantly in sub-Saharan African countries. Age can be a factor associated with a weaker virologic response, especially in older ages, but previous studies found conflicting results. Several published studies concluded that older patients were more likely to progress to virological failure and mortality, while other studies show the opposite. Some studies carried out in Africa have suggested that the mortality associated with HIV in African countries is higher in older patients compared to in high-income countries. There are also controversies regarding sex and age in relation to the virological response to antiretroviral drugs. Several pharmacological studies have described differences in pharmacokinetics, toxicity and virological response between males and females . AnotherIn summary, the results concerning the potential association of age and sex with retention in care and virological response are conflicting and should be further explored.Our study indicated younger age groups (<40 years), unemployment, CD4 counts below 350 cells/mL and Hb < 10 as risk factors associated with lower retention in care and development of virological failure. Given the high rates of loss to follow-up in Mozambique, we propose investing in focused adherence reinforcement programs for patients in these risk groups. However, other studies involving a greater number of HCFs in different regions of the country are needed.


This article aimed to compare the prevalence of dyslipidemia and determine risk factors associated with lipid levels in a cohort of HIV-infected patients receiving two different antiretroviral therapy (ART) regimens, nucleoside reverse transcriptase inhibitor/non-nucleoside reverse transcriptase inhibitor (NRTI/NNRTI) and nucleoside reverse transcriptase inhibitor/integrase strand transfer inhibitor (NRTI/INSTI).t-test and Mann–Whitney U test. Generalized linear mixed-effects model (GLMM) and value of p < 0.05 were used to determine factors associated with serum lipid profiles.This longitudinal study analyzed 633 HIV-infected patients with complete blood lipid profile records for at least 1 year at the ART clinic of Zhongnan Hospital of Wuhan University, China, from June 2018 to March 2021. Demographic and clinical data, including age, gender, body weight, height, current/former/non-smoker, current drinker, diabetes mellitus, hypertension, were extracted from electronic medical records. Laboratory tests included hematology, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Lipoprotein(a) and CD4 cell count. The observation duration of this study was a maximum of 33 months. Data comparisons were performed using the Chi-square test, Student’s p = 0.008) compared to the NNRTIs group, even after adjusting for other covariates. In addition, GLMM analysis also showed that age, gender, BMI, CD4 count, and ART duration were associated with dyslipidemia.In this study, the effect of the NNRTIs group on the lipid profile over time was mainly an increase in TC and HDL-C, while a decrease in TC/HDL-C and LDL/HDL-C. However, the INSTIs group had higher mean TC and lower HDL-C compared to the NNRTIs group, with significantly increased levels of TC, TG, HDL-C, and LDL-C. In the analysis of dyslipidemia rates, there were significant differences in the prevalence of abnormal TG and TC/HDL-C in HIV-infected patients receiving two different ART regimen groups during different follow-up periods. Dyslipidemia, defined as hypercholesterolemia, hypertriglyceridemia, and low HDL-C, was more prevalent in the INSTIs group, with a higher risk of developing hypertriglyceridemia and a higher TC/HDL-C ratio compared to the NNRTIs group. GLMM analysis suggested significantly higher TG values in the INSTIs group (estimated 0.36, SE 0.14, In conclusion, treatment with both commonly-used ART regimens can increase the mean values of lipid profiles and the risk of dyslipidemia. The findings indicated that TG values were significantly higher in the INSTIs group than in HIV-infected patients receiving the NNRTIs regimens. Longitudinal TG values are independently associated with the clinical types of ART regimens.Clinical Trial Number: ChiCTR2200059861. Due to strong epidemiologic evidence, the benefits of increased application of combined antiretroviral therapy (ART) on life expectancy were well established . ART regAccording to the Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV, it was recommended that initial ART regimens for adults and adolescents generally consists of two nucleoside reverse transcriptase inhibitors (NRTIs) in combination with a third active antiretroviral drug from the following three drug classes: integrase strand transfer inhibitors (INSTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), or protease inhibitors (PIs) . Recent Dyslipidemia, a major long-term adverse effects of current ART regimens, is not only a leading cause of cardiovascular disease (CVD), but also a key risk factor for preventable CVD-related mortality , 6. DespIn HIV-infected patients receiving combination ART regimens, the effect of ART regimens on the lipid profile has been demonstrated, but uncertainty remains about the comparative effects of different ART regimens . SpecifiA monocentric longitudinal observational cohort study.This longitudinal cohort study was conducted in an outpatient cohort of ART clinic of Zhongnan Hospital of Wuhan University, from June 2018 to March 2021, which provides HIV/AIDS interventions including free diagnosis, treatment and monitoring.All HIV-infected patients receiving HAART at the ART Clinic of Zhongnan Hospital of Wuhan University from June 2018 to March 2021.All HIV-infected patients receiving NRTIs in combination with NNRTIs, NRTIs in combination with INSTIs for at least 1 year at the ART Clinic.Inclusion criteria were as follows: (1) HIV-infected patients participating HIV/AIDS prevention treatment control programs at the ART Clinic; (2) follow-up were conducted at six-month intervals on average; (3) having at least two follow-up measurements of blood lipids; (4) receiving first-line ART regimens consisted of 2 NRTIs in combination with 1 NNRTI or 2 NRTIs in combination with 1 INSTI; (5) HIV-infected patients who constantly and regularly maintained the assigned treatment regimen at least during the study period.Exclusion criteria were as follows: (1) Those who has severe liver, kidney, heart, brain and other dysfunctions; (2) Presence of viral hepatitis, active syphilis, tuberculosis, autoimmune diseases and other active infectious diseases; (3) Women who are known to be pregnant, lactating, or intending to become pregnant during the study; (4) Those who modified ART medication between available lipid measurements; (5) Having no follow-up testing for blood lipids within 6 months of ART initiation; (6) Receiving protease inhibitors or other ART regimens; and (7) Those who have poor compliance and cannot cooperate with treatment and intervention .A census sampling was used, in which 633 eligible patients visiting the ART clinic were included for this study .Exposure: ART regimens consisted of 2 NRTIs in combination with 1 NNRTI or 2 NRTIs in combination with 1 INSTI.Independent Variables: Potential confounders of lipid profile such as age, gender, weight, body mass index, drinking habit, smoking habit, hypertension, fasting plasma glucose, duration on HAART, CD4 count, T lymphocyte count and HIV-1 viral load as independent variables were included in the final model.Dependent Variable: Total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Lipoprotein(a), TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C level.Outcomes: Baseline means were estimated first and then the follow-up means subtracted for the baseline were estimated to account for differences in mean values of lipid profiles among HIV patients by type of ART regimen at different follow-up periods and baseline examinations. Prevalence of lipid abnormalities between different ART regimens during each follow-up period. Generalized linear mixed-effects model (GLMM) was used to identify factors affecting serum lipid profiles.Data were extracted from an electronic medical records system, including demographic, clinical characteristics, and laboratory results. Demographic and clinical data comprehensively included age, gender, body weight, height, lifestyle behaviors (smoking and drinking), medical history , duration of ART use and types of ART regimens. Laboratory tests included hematology, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Lipoprotein(a), and CD4 cell count. All patients were assigned unique identification numbers to anonymize data. After initiation of ART, patients were evaluated at six-month intervals with the above-described laboratory tests repeated. The observation period for this study was a maximum of 33 months. Data were carefully reviewed by two independent researchers. Discrepancies between the reviewers were resolved by discussion or a third researcher. All methods were performed in accordance with relevant guidelines and regulations.2), normal (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), and obese  (Weight was categorized according to BMI as underweight (less than 18.5 kg/m0 kg/m2) . Accordi0 kg/m2) . In addi0 kg/m2) , 14.p values less than 5% were considered statistically significant. Measurement data were tested using Levene’s method for homogeneity of variance and Shapiro–Wilk (S–W) test for normal distribution. Categorical variables were presented as frequency rates and percentages (%), and Chi-squared tests were used to compare the proportions of categorical variables. Fisher’s exact test was used when limited data were observed. When the measurement data were normally distributed, the mean ± standard deviation (mean ± SD) was used, and the independent group t-test was used to compare the means of continuous variables. Non-normally distributed measurement data were expressed as medians (interquartile range [IQR]), and Mann–Whitney U test was used to test for significant differences between groups, as appropriate. Due to repeat measurements of blood lipids profiles, generalized linear mixed-effects models (GLMM) were used to determine factors associated with each serum lipid profile across all study participants, using coefficient estimates with 95% confidence intervals (CIs). To accommodate unbalanced, unequally spaced observations, the Generalized additive mixed models (GAMM) were used to present the effects of different ART regimens on triglyceride over time after adjusting for covariates of age, gender and BMI. In addition, a sensitivity analysis of associated factors for lipidemia by generalized estimating equation (GEE).All statistical analyses were performed using RStudio (version 2021.09.1.0) and Graphpad Prism (version 8.1 for Windows). All tests were two-tailed and The study was approved by the Institutional Review Board of College of Zhongnan Hospital of Wuhan University (No. 2022122 K), and written informed consent was obtained from the study participants. All research procedures were performed in accordance with the approved guidelines and regulations according to the criteria of the Declaration of Helsinki. The Chinese Clinical Trial Registry number of this work is ChiCTR2200059861.p = 0.919). In addition, there was no difference at baseline in the percentage of smokers, drinkers, and patients with hypertension between the two ART treatment groups . Among all HIV-infected patients participating in this study, 14 HIV patients had the previous history of gout complications, 5 patients had the history of cerebrovascular disease, and only 2 patients had the history of coronary heart disease, and other patients denied baseline comorbidities. It should be noted that complete baseline lipid data were analyzed for only 546 patients, and lipid profiles were not obtained from the remaining 87 patients within the week prior to ART use. There were no significant differences in the baseline characteristics of HIV-infected patients at each ART treatment group  were treated with the NNRTIs regimens, and 211 patients (22%) were treated with the INSTIs regimens. The total follow-up time was 10,794 patient-months (900 patient-years), and the median follow-up duration was 17 months. The mean (± standard deviation [SD]) age of all patients was 35.8 ± 14.8 years, ranging from 11 to 83 years, and 31 patients (4.9%) were female. The average BMI of HIV-infected patients treated with different ART regimens were similar .According to the type of ART regimens, mean differences of lipid profile at different follow-up periods with baseline data of HIV-infected patients were compared. The results were summarized in p < 0.05 for all). In addition, even though there were no statistically significant differences, the mean values of TG/HDL-C were slightly higher than baseline in all HIV-infected patients during the follow-up periods , while there was a significant difference in the prevalence of abnormal TG, LDL-C and TC/HDL-C in HIV-infected patients receiving different ART regimens during different follow-up periods  during follow-up periods were observed between different ART regimens  were applied to assess factors associated with each serum lipid profile . The Akap = 0.008). In addition, high BMI were associated with increased TG and decreased HDL-C. Conversely, lower CD4 count were associated with a raised HDL-C. It was also worth noting that HIV-infected patients with lower T lymphocyte count were more likely to have lower TC and TG. Furthermore, duration on ART was also an independent factor for elevated TC and TG  levels. In addition, a significantly higher risk of Lp(a) elevation was observed in the older HIV-infected patients. Regarding TC/HDL-C, those HIV-infected patients with higher BMI were more likely to have elevated TC/HDL-C as compared with lower BMI. Moreover, older age, smoking habit, and increased CD4 count and T lymphocyte count were associated with increased TC/HDL-C .p = 0.031; In order to avoid potential attrition bias, the lipid profile analyses restricted to HIV-infected patients with 24 months of follow-up was repeated by generalized estimating equation (GEE). The result of sensitivity analyses further supported similar lipid profile changes as the main analysis . Comparep < 0.001; Generalized additive mixed models (GAMM) were used to accommodate unbalanced, unequally spaced observations after adjusting for covariates of age, gender and BMI. The GAMM model showed a significant increase in TG values over time in HIV-infected patients receiving ART regimens . After adjusting for a wide range of confounders in our analyses, the estimates were robust across sensitivity analyses.This study investigated the relationship between two different ART regimens and lipid profiles, and identified risk factors associated with lipid levels using the GLMM in HIV-infected patients. The results showed that HIV-infected patients on INSTIs regimens experienced a larger TG increase than those on the NNRTIs regimens , higher mean values of each serum lipid profiles were observed in HIV patients on INSTIs regimen compared with those on NNRTIs regimen. The present study is inconsistent with earlier studies conducted in Ethiopia, indicating that HIV-infected patients undergoing long-term ART regimen are more likely to have elevated HDL-C as compared with patients undergoing short-term ART regimen , 25. AddAntiretroviral therapy regimens were found to be associated with a high prevalence of dyslipidemia (63.8%) in HIV-infected patients, among which the prevalence of hypercholesterolemia ranging from 8.1 to 16.5%, hypertriglyceridemia ranging from 21.8 to 33.0%, low HDL cholesterol ranging from 42.3 to 63.7% during the 30-month follow-up duration. Previous cross-sectional studies have also reported a high prevalence of dyslipidemia in HIV-infected patients receiving first-line ART , 27. Howp = 0.02) was associated with short-term mortality in HIV-infected patients (p = 0.03) was significantly associated with mortality  and TC/HDL-C ratio; higher BMI was significantly associated with higher TG and TC/ HDL-C ratio and lower HDL-C; smoking habit was significantly associated with higher LDL-C, Lp(a) and TC/ HDL-C; lower CD4 count was significantly associated with higher HDL-C and lower TC/HDL-C and the duration of exposure to ART regimen was significantly associated with higher TC and TG. The results from sensitivity analyses also indicated that older age was an independent risk factor for higher TC. In agreement with the results from GLMM model, higher BMI has also been demonstrated to increase TG and TC/HDL-C ratio and decrease HDL-C; lower CD4 counts have also been demonstrated to increase HDL-C and decrease TC/HDL-C ratio by GEE analyses. The present study in NNRTIs-treated patients showed changes in TG values over time, while the consequences of INSTIs-treated patients showed larger increases in TG values. TG values were independently associated with types of ART regimen. Even though there was a wide range of confounding factors and limited sample size in this study, advanced methods and sensitivity analyses were used to obtain robust analysis results. Our findings confirm and extend the results from previous observational studies, which showed that age, gender, BMI, CD4 count, and ART duration were the predictors of unfavorable lipid profiles alterations in patients on ART , 30, 31.p = 0.002) and high TG  were more likely to have CVD events (p = 0.049) and TG  levels were significantly associated with subclinical atherosclerosis  of all HIV-infected patients, which may have affected the results obtained and be insufficient to detect relevant differences. In addition, due to incomplete data recording in the study and the limited length of the observation periods, which may introduce selection and channeling bias related to missing data into the analysis, more large-scale multicenter studies with sufficient follow-up are warranted to validate the conclusions and optimize ART regimens in the future.In conclusion, treatment with both commonly-used ART regimens can increase the mean values of lipid profiles and the risk of dyslipidemia, with INSTIs primarily affecting TC, TG, HDL-C and LDL-C elevations, and NNRTIs were associated with increased TC and HDL-C, but with decreased TC/HDL-C and LDL-C/HDL-C. The rates of abnormal TG and TC/HDL-C are different over time between two ART regimens. The findings of this study indicated that TG values were significantly higher in the INSTIs group than in HIV-infected patients on NNRTIs regimens. Longitudinal TG values are independently associated with the clinical types of ART regimens.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.http://www.chictr.org.cn/listbycreater.aspx).The study was approved by the Institutional Review Board of College of Zhongnan Hospital of Wuhan University (No. 2022122K), and written informed consent was obtained from the study participants. All research procedures were performed in accordance with the approved guidelines and regulations according to the criteria of the Declaration of Helsinki. The Chinese Clinical Trial Registry number of this work is ChiCTR2200059861 , and the Guiding Project Fund of Hubei Provincial Administration of Traditional Chinese Medicine (grant number ZY2023F047).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.