Current Antiretroviral Therapy Regimens Research Articles

Impact of Combination Antiretroviral Treatment on Liver Metabolic Health in HIV-Infected Persons.

In the last three decades, there has been a considerable improvement in human immunodeficiency virus (HIV) therapy. Acquired immunodeficiency syndrome (AIDS) is no longer a common cause of death for people living with HIV (PLWH) in developed countries, and co-infections with hepatitis viruses can be effectively managed. However, metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD) are emerging threats these days, especially as the HIV-positive population gets older. The factors for MASLD development in PLWH are numerous, including non-specific (common for both HIV-positive and negative) and virus-specific. We focus on what is known for both, and in particular, on the burden of antiretroviral therapy (ART) for metabolic health and liver damage. We review data on contemporary drugs, including different groups and some particular agents in those groups. Among current ART regimens, the switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide fumarate (TAF) and particularly its combination with integrase inhibitors (INSTIs) appear to have the most significant impact on metabolic disturbances by increasing insulin resistance, which over the years promotes the evolution of the cascade leading to metabolic syndrome (MetS), MASLD, and eventually metabolic dysfunction-associated steatohepatitis (MASH).

Increased prevalence of pretreatment drug resistance mutations in treatment-naïve people living with HIV-1 in Henan Province, China (2022/23)

Human deficiency virus type 1 (HIV-1) harboring drug resistance mutations (DRMs) before the initiation of antiretroviral therapy (ART) poses a serious threat to the efficacy of current ART regimens. Currently, the prevalence of pre-treatment drug resistance mutations (PDRMs) including transmitted DRMs (TDRMs) is not completely clear. Understanding this prevalence better should offer valuable data for clinical- and government-level decision-making. To closely monitor the PDRM trend in treatment-naïve people living with HIV/AIDS (PLWHA) in Henan Province, China, plasma samples from the patients seeking treatments at our hospital from January 2022 to February 2023 were collected for genotypic drug resistance testing. From the 645 patients whose samples were collected, partial pol and integrase gene sequences were obtained from 637 patients. Subtyping analysis indicated that the top-three most common subtypes, in descending order, were CRF07_BC (41.76%, 266/637), CRF01_AE (28.26%, 180/637), and B (20.41%, 130/637). PDRMs were observed in 5.18% (33/637), 6.28% (40/637), 0.31% (2/637), and 2.83% (18/637) cases for nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs), respectively; all these medications contributed to an overall PDRM prevalence of 11.93% (76/637). On analyzing individual PDRMs, we noted that the most commonly observed mutation(s) were K103S/N (3.77%, 24/637), M184I/V (3.14%, 20/637), followed by K65R (1.26%, 8/637), and V106A/M (1.10%, 7/637). PDRM prevalence in ART-naïve PLWHA of Henan Province is high and increased compared with that noted in previous years. However, evidence of cluster-linked outbreaks of PDRMs is lacking, suggesting that measures such as education about adherence and improved treatment strategies with a low incidence of failure can effectively reduce PDRM prevalence.

Microbiota in the oral cavity of school-age children living with HIV who started antiretroviral therapy at young ages in South Africa.

Infancy is an important developmental period when the microbiome is shaped. We hypothesized that earlier antiretroviral therapy (ART) initiation would attenuate HIV effects on microbiota in the mouth. Oral swabs were collected from 477 children living with HIV (CLWH) and 123 children without (controls) at two sites in Johannesburg, South Africa. CLWH had started ART <3 years of age; 63% <6 months of age. Most were well-controlled on ART at median age 11 years when the swab was collected. Controls were age-matched and recruited from the same communities. Sequencing of V4 amplicon of 16S rRNA was done. Differences in microbial diversity and relative abundances of taxa were compared between groups. CLWH had lower alpha diversity than controls. Genus-level abundances of Granulicatella, Streptococcus and Gemella were greater and Neisseria and Haemophilus less abundant among CLWH than controls. Associations were stronger among boys. Associations were not attenuated with earlier ART initiation. Shifts in genus-level taxa abundances in CLWH relative to controls were most marked in children on lopinavir/ritonavir regimens; with fewer shifts seen if on efavirenz ART regimens. A distinct profile of less diverse oral bacterial taxa was observed in school-aged CLWH on ART compared to uninfected controls suggesting modulation of microbiota in the mouth by HIV and/or its treatments. Earlier ART initiation was not associated with microbiota profile. Proximal factors, including current ART regimen, were associated with contemporaneous profile of oral microbiota and may have masked associations with distal factors like age at ART initiation.

Dramatic Improvement of MRI Abnormalities of HIV Dementia after Suppressive Antiretroviral Therapy (S25.002)

<h3>Objective:</h3> Not applicable. <h3>Background:</h3> A 59-year-old man diagnosed with HIV 26 years prior and a long history of antiretroviral therapy (ART) non-adherence presented with subacute cognitive decline. A neurologic workup including cerebrospinal fluid testing showed no evidence of opportunistic infections. He was admitted to an assisted care facility where he restarted ART. However, he remained viremic and was referred to the National Institutes of Health (NIH). On admission to the NIH, he had an HIV plasma viral load of 28,056 copies/mL and CD4 T-cell count of 5 cells/μL. He was started on a new ART regimen with increased central nervous system penetration (etravirine, dolutegravir, darunavir/cobicistat, tenofovir/emtricitabine). MRI revealed extensive leukoencephalopathy and volume loss, consistent with HIV encephalopathy. Comprehensive neuropsychological testing revealed significant deficits in all cognitive domains, including learning, memory, attention, executive function, and psychomotor speed. The patient was followed for two years, during which time he achieved and sustained viral suppression (&lt;40 copies/mL) and reached a CD4 T-cell count of 197 with ART. A repeat MRI showed profound improvement in the white matter signal abnormality. Repeat neuropsychological testing demonstrated notable improvements in several tests of attention, information processing, and psychomotor speed, but continued difficulty in most other cognitive domains. <h3>Design/Methods:</h3> Not applicable. <h3>Results:</h3> Not applicable. <h3>Conclusions:</h3> While current ART regimens are highly effective in reducing the incidence of HIV-associated neurologic complications, their role in reversing the MRI abnormalities seen in HIV encephalopathy remains unclear. In this case, we tracked HIV encephalopathy in the current era of effective ART with serial MRI evaluations. Our results provide a rare example of dramatic reduction of periventricular white matter hyperintensities and improved performance in a subset of cognitive domains. Providers encountering white matter abnormalities in patients with treated HIV should consider this legacy effect in evaluating whether disease is progressive, or as in this case, improved. <b>Disclosure:</b> Ms. Dietrich has nothing to disclose. Miss Laidlaw has nothing to disclose. Dr. Hammoud has nothing to disclose. Dr. Pau has nothing to disclose. Dr. Smith has nothing to disclose.

Point-of-care urine tenofovir testing to predict HIV drug resistance among individuals with virologic failure.

We sought to evaluate the utility of a point-of-care (POC) urine tenofovir (TFV) assay, developed to objectively assess adherence, to predict HIV drug resistance (HIVDR) in people failing first-line antiretroviral therapy (ART). We retrospectively analyzed TFV levels as a biomarker of adherence in urine specimens collected during a clinical trial that enrolled adults with virologic failure on first-line ART in Uganda and South Africa. Urine specimens were analyzed from participants on TFV-containing regimens who had a viral load >1000 copies/ml and paired genotypic resistance test (GRT) results. We assessed recent ART TFV adherence with a qualitative POC lateral flow urine assay with a cut-off value of 1500 ng/ml. We then calculated performance characteristics of the POC urine TFV assay to predict HIVDR, defined as intermediate or high-level resistance to any component of the current ART regimen. Urine specimens with paired plasma GRT results were available from 283 participants. The most common ART regimen during study conduct was emtricitabine, tenofovir disoproxil fumarate, and efavirenz. The overall prevalence of HIVDR was 86% ( n = 243/283). Of those with TFV detected on the POC assay, 91% ( n = 204/224) had HIVDR, vs. only 66% ( n = 39/59) among those with no TFV detected ( P- value < 0.001). Positive and negative predictive values of the assay to predict HIVDR were 91% and 34%, respectively. In populations with a high prevalence of HIVDR, the POC urine TFV assay can provide a low-cost, rapid method to guide requirements for confirmatory resistance testing and inform the need for regimen change.

Closing the HIV Treatment Gap for Adolescents in Windhoek, Namibia: A Retrospective Analysis of Predictors of Viral Non-Suppression.

Windhoek joined the Fast-Track Cities Initiative in 2017 to optimize HIV service delivery for adolescents, promoting adherence and sustaining viral suppression. Recent surveys and programmatic data show that the treatment gap remains greatest among children and adolescents living with HIV. A retrospective cohort analysis of adolescents living with HIV (ALHIV) receiving antiretroviral therapy (ART) at Windhoek healthcare facilities was conducted. Routine clinical data were extracted from the electronic Patient Monitoring System (ePMS). The SPSS statistical package was used to determine viral non-suppression and perform inferential statistics. 695 ALHIV were analysed with median age of 16 years (IQR = 13-18). Viral non-suppression at 1000 copies/mL threshold was 12%. Viral non-suppression was associated with age at ART initiation, duration on ART, current ART regimen and WHO Clinical Stage. In multivariate analysis, longer duration on ART was a protective factor for viral non-suppression (13-24 months vs. &gt;24 months: aOR = 8.92, 95% CI 2.60-30.61), while being on third line regimen (vs. first line) was protective against viral non-suppression (aOR = 0.11, 95% CI 0.03-0.49). A significant treatment gap is evident for ALHIV with high viral non-suppression levels. Interventions are required to counter treatment fatigue to keep adolescents engaged in ART, and timely switching to rescue regimens for failing adolescents.

Acquired HIV drug resistance among adults living with HIV receiving first-line antiretroviral therapy in Rwanda: A cross-sectional nationally representative survey.

Background:We assessed the prevalence of acquired HIV drug resistance (HIVDR) and associated factors among patients receiving first-line antiretroviral therapy (ART) in Rwanda.Methods:This cross-sectional study included 702 patients receiving first-line ART for at least 6 months with last viral load (VL) results ≥1000 copies/mL. Blood plasma samples were subjected to VL testing; specimens with unsuppressed VL were genotyped to identify HIVDR-associated mutations. Data were analysed using STATA/SE.Results:Median time on ART was 86.4 months (interquartile range [IQR], 44.8–130.2 months), and median CD4 count at ART initiation was 311 cells/mm3 (IQR, 197–484 cells/mm3). Of 414 (68.2%) samples with unsuppressed VL, 378 (88.3%) were genotyped. HIVDR included 347 (90.4%) non-nucleoside reverse transcriptase inhibitor- (NNRTI), 291 (75.5%) nucleoside reverse transcriptase inhibitor- (NRTI) and 13 (3.5%) protease inhibitor (PI) resistance-associated mutations. The most common HIVDR mutations were K65R (22.7%), M184V (15.4%) and D67N (9.8%) for NRTIs and K103N (34.4%) and Y181C/I/V/YC (7%) for NNRTIs. Independent predictors of acquired HIVDR included current ART regimen of zidovudine + lamivudine + nevirapine (adjusted odds ratio [aOR], 3.333 [95% confidence interval (CI): 1.022–10.870]; p = 0.046) for NRTI resistance and current ART regimen of tenofovir + emtricitabine + nevirapine (aOR, 0.148 [95% CI: 0.028–0.779]; p = 0.025), zidovudine + lamivudine + efavirenz (aOR, 0.105 [95% CI: 0.016–0.693]; p = 0.020) and zidovudine + lamivudine + nevirapine (aOR, 0.259 [95% CI: 0.084–0.793]; p = 0.019) for NNRTI resistance. History of ever switching ART regimen was associated with NRTI resistance (aOR, 2.53 [95% CI: 1.198–5.356]; p = 0.016) and NNRTI resistance (aOR, 3.23 [95% CI: 1.435–7.278], p = 0.005).Conclusion:The prevalence of acquired HIV drug resistance (HIVDR) was high among patient failing to re-suppress VL and was associated with current ART regimen and ever switching ART regimen. The findings of this study support the current WHO guidelines recommending that patients on an NNRTI-based regimen should be switched based on a single viral load test and suggests that national HIV VL monitoring of patients receiving ART has prevented long-term treatment failure that would result in the accumulation of TAMs and potential loss of efficacy of all NRTI used in second-line ART as the backbone in combination with either dolutegravir or boosted PIs.

High Rate of HIV-1 Drug Resistance in Antiretroviral Therapy-Failure Patients in Liaoning Province, China.

This study aimed to monitor the prevalence of HIV-1 drug resistance and risk factors associated with drug resistance in antiretroviral therapy (ART)-failure individuals in Liaoning Province, China. Plasma samples were collected from HIV-1-positive individuals who experienced ART failure in Liaoning Province between April 2018 and September 2019. Genotype resistance test was performed using an in-house assay on these collected samples. Factors associated with drug resistance were identified by logistic regression analysis. We collected a total of 468 ART-failure individuals, of which 256 were successfully included in the final study. Of these, the most predominant genotype was CRF01_AE, accounting for 77.73%. The resistance rate to any of the three classes of antiretroviral drugs (non-nucleoside reverse transcriptase inhibitors [NNRTIs], nucleoside reverse transcriptase inhibitors [NRTIs], and protease inhibitors [PIs]) was 64.84%. Among 256 ART-failure patients, 62.89% showed drug resistance to NNRTIs, 50.39% to NRTIs, and 3.13% to PIs. G190S (31.25%) and Y181C (25.78%) mutations were the most common NNRTIs resistance mutations. K65R (29.69%), M184V (28.52%) were the most common NRTIs resistance mutations. Factors associated with drug resistance included current ART regimen and viral load. The high drug resistance rate among ART-failure individuals in Liaoning Province needs more attention. Corresponding strategies for the risk factors associated with HIV drug resistance can better control and prevent the prevalence of resistance.

The risk of hyperglycaemia associated with the use of dolutegravir among adults living with HIV in Kampala, Uganda: a case-control study

BackgroundEmerging evidence suggests a possible association between hyperglycaemia and use of dolutegravir, a preferred first-line antiretroviral agent in sub-Saharan Africa. Rigorous studies are needed to validate this association in the light of increasing dolutegravir use and burden of non-communicable diseases among people living with HIV. MethodsWe conducted a case-control study in Kampala, Uganda to assess the risk of hyperglycaemia associated with dolutegravir-based antiretroviral therapy (ART). Cases were people living with HIV with hyperglycaemia and controls were people living with HIV without hyperglycaemia, confirmed by fasting plasma glucose and 2-hour oral glucose tolerance tests. Data were collected by interviewer-administered questionnaires and medical record abstraction. Analysis compared cases and controls on dolutegravir use before diagnosis of hyperglycaemia while controlling for potential confounders through multivariable logistic regression. FindingsA total 435 participants were included (204 cases, 231 controls). At bivariate analysis, significant differences in age, education, current body-mass index, hypertension as a comorbidity, previous ART regimen, and current ART regimen existed between cases and controls. Among the 204 cases, 54 (27%) had hyperglycaemic levels that were diagnostic of prediabetes, with 150 (74%) being diagnostic of diabetes. Of note, 75 (40%) participants previously treated with dolutegravir changed to other ART regimens after being diagnosed with hyperglycaemia. In multivariable analysis, patients with previous dolutegravir use had nearly 30-times greater odds of hyperglycaemia compared with those who had non-dolutegravir based regimens (adjusted odds ratio [aOR] 29·06 [95% CI 9·86–85·70]). The odds of hyperglycaemia also increased with age (56 years and older vs 18–35 years, aOR 7·53 [95% CI 2·65–21·38]), and hypertension (aOR 5·64 [2·60–12·21]). InterpretationOur study shows a strong association between previous dolutegravir exposure and hyperglycaemia. Given the benefits of dolutegravir, its wide-scale roll-out in sub-Saharan Africa, and the growing burden of diabetes, systematic screening of hyperglycaemia before initiation of dolutegravir, routine glucose monitoring, and the consideration of alternate regimens for those at risk for diabetes are needed. FundingThis research was supported by the US National Institutes of Health, Fogarty International Center and Global Health Equity Scholars (grant D43TW010540).

Resource and infrastructure challenges on the RESIST-2 Trial: an implementation study of drug resistance genotype-based algorithmic ART switches in HIV-2-infected adults in Senegal

BackgroundSecond-line treatment of HIV-2 in resource-limited settings (RLS) is complicated by a lack of controlled trial data, limited availability of HIV-2-active antiretroviral drugs, and inadequate access to drug resistance testing. We conducted an implementation trial of a dried blood spot- (DBS) based, drug resistance genotype-informed antiretroviral therapy (ART) switching algorithm for HIV-2-infected patients in Senegal.MethodsHIV-2-infected adults initiating or receiving ART through the Senegalese national AIDS program were invited to participate in this single-arm trial. DBS from participants with virologic failure (defined as viral load (VL) > 250 copies/mL after > 6 months on the current ART regimen) were shipped to Seattle for genotypic drug resistance testing. Participants with evidence of drug resistance in protease or reverse transcriptase were switched to new regimens according to a pre-specified algorithm. Participant clinical and immuno-virologic outcomes were assessed, as were implementation challenges.ResultsWe enrolled 152 participants. Ten were initiating ART. The remainder were ART-experienced, with 91.0% virologically suppressed (< 50 copies/mL). Problems with viral load testing capability resulted in obtaining VL results for only 227 of 613 (37.0%) participant-visits. Six of 115 participants (5.2%) with VL available after > 6 months on current ART regimen experienced virologic failure, with per-protocol genotypic testing attempted. One additional test was performed for a participant with a VL of 222 copies/mL. Genotypes from three participants showed no evidence of major drug resistance mutations, two showed nucleoside reverse transcriptase inhibitor (NRTI) resistance, one showed both NRTI and protease inhibitor resistance, and one test failed. No integrase inhibitor resistance was observed. Five of six successfully-tested participants switched to the correct regimen or received additional adherence counseling according to the algorithm; the sixth was lost to follow-up. Follow-up VL testing was available for two participants; both of these were virally suppressed (< 10 copies/mL). The trial was terminated early due to the COVID-19 pandemic (which prevented further VL and genotypic testing), planned rollout of dolutegravir-based 1st-line ART, and funding.ConclusionsThe RESIST-2 trial demonstrated that a DBS-based genotypic test can be used to help inform second-line ART decisions as part of a programmatic algorithm in RLS, albeit with significant implementation challenges.Trial registrationClinicalTrials.govNCT03394196. Registered on January 9, 2018.

Patient-Reported Treatment Satisfaction and Quality of Life Among People Living with HIV Following the Introduction of Dolutegravir-Based ART Regimens in Ukraine.

In 2017, the government of Ukraine initiated its ART Optimization Initiative, revising its national antiretroviral therapy (ART) guidelines and embracing Dolutegravir (DTG) as a backbone of first-line ART regimens. A cross-sectional survey of 464 ART patients from 22 large ART clinics was carried out in mid-2019. The survey assessed patient-reported outcomes (PROS) including treatment satisfaction, physical health, mental health, depression, side effects of ART, and adherence. The associations between ART regimen and PROs were assessed using bivariable and multivariable generalized estimating equations (GEE) models. More than half (55.6%) of the patients were satisfied with their current ART regimen. Less than a half (45.3%) considered their physical health as good while only 36.9% rated their mental health as good, 21.3% reported moderate or severe depression, 82.3% reported no side effect in the past 4weeks, and 44.4% reported not missing ART medication in the past month. In adjusted analysis, patients starting ART with DTG had higher treatment satisfaction compared to people continuing LPV-based regimens (aOR = 0.49, 95% confidence interval: 0.22-0.90). Also in adjusted analyses, unemployment, low income, and history of injection drug use were associated with unfavorable PROs. While the results indicate modestly favorable effects of ART Optimization, there is clearly a need for complementary interventions to improve PROs among disadvantaged ART patients in Ukraine.

1036. Persistence of Guideline-Recommended Antiretroviral Therapy Regimens among Persons Living with HIV Newly Initiating Treatment in the US

BackgroundDiscontinuation of first-line antiretroviral therapy (ART) may lead to poor outcomes for persons living with HIV (PLWH). While single-tablet regimens (STRs) have been associated with greater persistence compared to multi-tablet regimens (MTRs), few real-world studies have assessed persistence with current guideline-recommended ART regimens. The study aims to assess persistence among treatment-naïve PLWH initiating guideline-recommended ART regimensMethodsLongitudinal pharmacy claims were extracted from IQVIA’s US LRx database for PLWH initiating ART between Jan 1, 2016 - Jul 31, 2019 (index period), with the observational period up to Jan 31, 2020. Index date was defined as the date of the first ART claim for STRs, or the date of the last filled drug of 1st set of claims for MTRs. Persistence was measured as the number of days until treatment discontinuation (≥ 90-day gap in therapy) and presented via Kaplan-Meier curves. Risk of discontinuation was assessed via Cox proportional hazards models, with BIC/FTC/TAF used as the reference ART regimen.ResultsOverall, 90,949 PLWH initiated STRs and 20,737 initiated MTRs. Average (SD) age was 43 (14) years, 75% were male, and 75% had commercial insurance. At 6 months of follow-up, 71% of PLWH initiating STRs and 56% initiating MTRs remained on their ART regimen. The proportion remaining on their index regimen at 6 months of follow-up was 79% for BIC/FTC/TAF, 73% for EVG/COBI/FTC/TAF, 71% for DTG/ABC/3TC, 69% for DTG + FTC/TAF, 67% for EFV/FTC/TDF, 62% for EVG/COBI/FTC/TDF, and 38% for DTG + FTC/TDF. Risk of discontinuation was higher for MTRs compared to STRs (hazard ratio [HR]: 1.63, 95% CI: 1.61 - 1.66). Compared to the referent BIC/FTC/TAF, risk of discontinuation was higher for EVG/COBI/FTC/TAF (HR: 1.54, 95% CI: 1.48 - 1.60), DTG/ABC/3TC (HR: 1.58, 95% CI: 1.52, 1.65), DTG + FTC/TAF (HR: 1.83, 95% CI: 1.74 - 1.93), EFV/FTC/TDF (HR: 2.31, 95% CI: 2.21 - 2.41), EVG/COBI/FTC/TDF (HR: 2.58, 95% CI: 2.47 - 2.70), and DTG + FTC/TDF (HR: 6.20, 95% CI: 5.83 - 6.59).Table 1. Persistence with ART by regimen for STR and MTR Figure 1. Forest Plot of Hazard Ratios for Treatment Discontinuation ConclusionAmong US adult PLWH, STRs were associated with longer persistence on first-line therapy compared to MTRs. Among STRs, persistence was highest for BIC/FTC/TAF.Disclosures All Authors: No reported disclosures

Implementation and operational feasibility of SAMBA I HIV-1 semi-quantitative viral load testing at the point-of-care in rural settings in Malawi and Uganda.

We monitored a large-scale implementation of the Simple Amplification-Based Assay semi-quantitative viral load test for HIV-1 version I (SAMBA I Viral Load=SAMBA I VL) within Médecins Sans Frontières' HIV programmes in Malawi and Uganda, to assess its performance and operational feasibility. Descriptive analysis of routine programme data between August 2013 and December 2016. The dataset included samples collected for VL monitoring and tested using SAMBA I VL in five HIV clinics in Malawi (four peripheral health centres and one district hospital), and one HIV clinic in a regional referral hospital in Uganda. SAMBA I VL was used for VL testing in patients who had been receiving ART for between 6months and ten years, to determine whether plasma VL was above or below 1000 copies/mL of HIV-1, reflecting ART failure or efficacy. Randomly selected samples were quantified with commercial VL assays. SAMBA I instruments and test performance, site throughput, and delays in communicating results to clinicians and patients were monitored. Between August 2013 and December 2016 a total of 60889 patient samples were analysed with SAMBA I VL. Overall, 0.23% of initial SAMBA I VL results were invalid; this was reduced to 0.04% after repeating the test once. Global test failure, including instrument failure, was 1.34%. Concordance with reference quantitative testing of VL was 2620/2727, 96.0% (1338/1382, 96.8% in Malawi; 1282/1345, 95.3% in Uganda). For Chiradzulu peripheral health centres and Arua Hospital HIV clinic, where testing was performed on-site, same-day results were communicated to clinicians for between 91% and 97% of samples. Same-day clinical review was obtained for 84.7% across the whole set of samples tested. SAMBA I VL testing is feasible for monitoring cohorts of 1000 to 5000 ART-experienced patients. Same-day results can be used to inform rapid clinical decision-making at rural and remote health facilities, potentially reducing time available for development of resistance and conceivably helping to reduce morbidity and mortality.

Determinants of virological failure among adults on first-line highly active antiretroviral therapy at public health facilities in Kombolcha town, Northeast, Ethiopia: a case–control study

ObjectiveTo identify determinants of virological failure among HIV-infected adults on first-line highly active antiretroviral therapy at public health facilities in Kombolcha town, Northeast, Ethiopia, in 2019.MethodsAn unmatched case–control study was...

Protease inhibitor effects on prevalence of bacterial vaginosis and human papillomavirus-related lesions.

Antiretrovirals of the protease inhibitor (PI) class tend to achieve low concentrations in biological fluids. This study aimed to analyze possible changes in the vaginal microbiome and frequency of cervical human papillomavirus (HPV)-DNA and HPV-related lesions associated with the use of PI in antiretroviral therapy (ART). Eighty-eight women with human immunodeficiency virus infection were divided in two groups: ART with PI and without PI. All the participants underwent anamnesis with demographic data collection. The total DNA, used as the template in the polymerase chain reaction-based assays for the detection of HPV-DNA, was extracted from cervical samples during cervical cytopathology. There were no differences between the groups with respect to HPV-related lesions. Despite the higher prevalence of bacterial vaginosis (BV) in the PI group (33.96% vs 17.14%), the difference was insignificant when considering all women (P = 0.066). When women with a detectable viral load and a CD4+ T-cell count <200 were excluded in both groups, BV was found to be more prevalent in the PI group (odds ratio, 3.349; 95% confidence interval, 1.113-11.41, P = 0.049). No associations were found between BV and age, condom use, cervical HPV, time with current ART regimen, unprotected receptive anal intercourse and cervical HPV-related lesions. The use of PI did not alter the frequencies of HPV-DNA and HPV-related lesions. However, an increased frequency of BV was found in women using PI after excluding women with a detectable viral load and a CD4+ T-cell count of <200.

Evaluation of weight-based prescription of antiretroviral therapy in children.

ObjectivesThe aim of the study was to investigate the extent of and factors associated with incorrect dosing of antiretroviral therapy (ART) in HIV‐infected children in Harare, Zimbabwe.MethodsAll children aged 0–10 years and children aged 11–17 years who weighed < 35 kg and taking ART were recruited from the paediatric HIV clinic at Harare Hospital. Their current doses of ART drugs were compared against doses recommended by the national guidelines.ResultsAmong 309 children recruited [55% male; median age 7 years (interquartile range (IQR) 5–10 years)], the median CD4 count was 899 cells/μL and the median duration of their current ART regimen was 11.2 months (IQR 4.9–17.1 months). Overall, 110 (35.6%) children were prescribed incorrect doses of at least one drug component within their ART regimen; 64 (20.7%) under‐dosed and 49 (15.9%) over‐dosed on at least one drug. Children receiving a higher than recommended dose of at least one drug were younger compared with correctly dosed children (median 6 versus 7 years, respectively; P = 0.001), had been on their current ART regimen for a shorter time (median 7.2 versus 13 months, respectively; P = 0.003) and were less likely to be receiving a three‐drug fixed‐dose combination (FDC; 42.9 versus 63.3%, respectively; P = 0.009). Those who were under‐dosed were also less likely to be on a three‐drug FDC (25 versus 63.3%, respectively; P < 0.001).ConclusionsOver a third of children were prescribed incorrect doses of ART. Children taking triple‐drug FDCs were likely to be correctly dosed. Our study highlights the importance of weight monitoring at each clinical contact, training of health care providers on paediatric drug dosing and the need for wider availability of FDCs for children.

548. Antiretroviral Therapy Regimen Characteristics Within an Urban, Safety-Net Clinic in the United States

BackgroundContemporary antiretroviral-therapy (ART) regimens have simple dosing, low toxicity, minimal side-effects, and few drug interactions. We evaluated ART regimens in an urban, safety-net, adult HIV clinic in the United States to determine proportions of patients on contemporary ART and identify opportunities to optimize ART for patients on older regimens.MethodsData including current ART regimen, HIV-1 RNA level, and age were extracted from the electronic medical record (EMR) for all patients seen in the prior 13 months. Viral suppression was defined as HIV-1 RNA < 200 copies/mL. A patient was “off-ART” if there were no fills within 270 days or ART had a stop date >90 days prior to end of the study. Unclear regimens from the EMR (n = 179) were chart reviewed. ART regimens were assigned the following designations: contemporary first-line, contemporary non-first-line, older three-drug, two-drug, salvage, or off-ART. ART was also categorized as boosted (containing cobicistat/ritonavir) vs. unboosted, by single-tablet regimen (STR) vs. multi-tablet regimen (MTR), and frequency of dosing. Correlations between ART regimen, viral suppression, and age were analyzed.ResultsThe ART review included 1,215 individuals. Most patients (64%) were on contemporary first-line regimens; 20% were on contemporary non-first-line regimens (figure). Patients on salvage regimens had lower rates of viral suppression than those in other ART categories (80% vs. 90%, P <0.05). Most patients (90%) were prescribed once daily regimens, and of those, 39% were prescribed STRs. There were no significant associations between viral suppression and regimen complexity (P = 0.8). There were 447 (37%) patients on boosting agents with no difference in viral suppression rate (88% suppressed on boosted regimens vs. 90% on unboosted, P = 0.3). Patients on older regimens and greater than equal to twice daily MTRs were older than those on contemporary regimens and STRs. Individuals off ART were younger than those on ART (average age 41 vs. 46 years).ConclusionIn a US urban, safety-net clinic, most patients were on contemporary ART regimens and 90% were on once-daily therapy. Despite these encouraging findings, systematic review identified many patients that could be considered for modernization and simplification with intent to minimize toxicity, side-effects, drug interactions, and cost. Disclosures All authors: No reported disclosures.

Predictive factors associated with liver fibrosis and steatosis by transient elastography in patients with HIV mono-infection under long-term combined antiretroviral therapy.

IntroductionNon‐alcoholic fatty liver disease is characterized by the presence of hepatic steatosis and can be associated with fibrosis progression, development of cirrhosis and liver‐related complications. Data on the prevalence of liver fibrosis and steatosis in HIV patients remain contradictory in resource‐limited settings. We aimed to describe the prevalence and factors associated with liver fibrosis and steatosis in patients with HIV mono‐infection under long‐term antiretroviral therapy (ART) in Rio de Janeiro, Brazil.MethodsClinical assessment, fasting blood collection and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by transient elastography were performed on the same day for this cross‐sectional study (PROSPEC‐HIV study; NCT02542020). Patients with viral hepatitis co‐infection, ART‐naïve or missing data were excluded. Liver fibrosis and steatosis were defined by LSM ≥ 8.0 kPa and CAP ≥ 248 dB/m respectively. HIV history, cumulative and current ART regimens were evaluated. Multivariate logistic regression models adjusted for age and gender were performed.ResultsIn total, 395 patients (60% female; median age of 45 (IQR, 35 to 52) years, body mass index = 25.7 (23.2 to 29.4) kg/m2, alanine aminotransferase = 30 (23 to 42) IU/L, duration of ART for 7 (4 to 14) years) were included. LSM and CAP were reliable in 93% (n = 367) and 87% (n = 344) respectively. The prevalence of fibrosis and steatosis were 9% (95% confidence interval (CI), 7 to 13) and 35% (95% CI, 30 to 40) respectively. The following factors were associated with fibrosis (odds ratio (OR) (95% CI)): older age (per 10 years; 1.80 (1.27 to 2.55); p = 0.001) and CD4+ count <200 cells/mm3 (7.80 (2.09 to 29.09), p = 0.002). Type 2 diabetes had a trend towards the presence of liver fibrosis (2.67 (0.96 to 7.46), p = 0.061). Central obesity (10.74 (4.40 to 26.20), p < 0.001), type 2 diabetes (9.74 (3.15 to 30.10), p < 0.001), dyslipidaemia (2.61 (1.35 to 5.05), p = 0.003) and metabolic syndrome (4.28 (2.45 to 7.46), p < 0.001) were associated with steatosis. A dominant backbone ART regimen of zidovudine (AZT), d4T, ddI or ddC was associated with steatosis (1.90 (1.07 to 3.38), p = 0.028) independently of metabolic features.ConclusionIntegrated strategies for preventing non‐communicable diseases in people with HIV mono‐infection are necessary to decrease the burden of liver diseases.Clinical Trial Number: NCT02542020.

Changes in Body Fat Distribution in Antiretroviral-Naive HIV-Positive Individuals Initiating Current ART Regimens.

To describe the changes in body fat distribution (BFD) occurring over 60 months in a group of antiretroviral therapy (ART)-naive individuals starting different antiretroviral regimens. A prospective ongoing fat change assessment including clinical evaluation and dual X-ray absorptiometry scan is being conducted in all consecutive patients initiating ART from January 2008. Arm, leg, trunk, and total fat as well as fat mass ratio were determined. A total of 146 patients were included (80% male, 40% MSM). Mean age was 44 years, HIV-1 RNA was 4.98 log10 copies/mL, and CD4 count was 254 cells/μL. The most common initial antiretroviral combination included non-nucleoside reverse transcription inhibitor (NNRTI) drugs followed by protease inhibitor (PI) and integrase strand transfer inhibitor (INSTI)-based regimens. At month 36, an increase was seen in the body mass index (BMI), total fat, trunk fat, and limb fat. The fat mass ratio (FMR) also showed a significant increase in both men and women (P = 0.001). In patients receiving NNRTI- or INSTI-based regimens (but not PIs), there was a marginal but statistically significant increase in the FMR (0.10 and 0.07, respectively; P = 0.01). Sixty-two subjects completed 60 months of follow-up. FMR showed a significant increase even in the PI group at this time point (P < 0.03). We observed a significant increase in the fat and lean body mass in all compartments and treatment groups over 36 and 60 months. Clinically irrelevant differences were found in fat distribution regardless of the treatment group and baseline characteristics. The data suggest that current antiretroviral regimens have little impact on BFD during the first years of treatment.

Practice Paper of the Academy of Nutrition and Dietetics: Nutrition Intervention and Human Immunodeficiency Virus Infection

Nutrition is an integral component of medical care for people living with human immunodeficiency virus (HIV)/autoimmune deficiency syndrome (AIDS) (PLWHA). The Academy of Nutrition and Dietetics supports integration of medical nutrition therapy into routine care for this population. Fewer PLWHA experience wasting and undernutrition, while the prevalence of obesity and other chronic diseases has increased significantly. Improved understanding of HIV infection’s impact on metabolism and chronic inflammation has only increased the complexity of managing chronic HIV infection. Nutrition assessment should encompass food insecurity risk, changes in body composition, biochemical indices, and clinical indicators of comorbid disease. Side effects from current antiretroviral therapy regimens are less prevalent than with previous generations of therapy. However, micronutrient deficiencies and chronic anemia also remain significant nutritional risks for PLWHA, making vitamin and mineral supplementation necessary in cases of acute deficiency or food insecurity. Additional factors can impact HIV-related nutrition care among the pediatric population, older adults, minority groups, those co-infected with tuberculosis or hepatitis, and PLWHA in rural or underserved areas. Registered dietitian nutritionists and nutrition and dietetic technicians, registered should participate in multidisciplinary care to incorporate nutrition into the medical management of PLWHA.