Antiretroviral Regimens Research Articles

Advances in the transdermal delivery of antiretroviral drugs.

Antiretroviral therapy regimens are successful in stopping the advancement of human immunodeficiency virus infection to acquired immunodeficiency syndrome, and other opportunistic infections. However, they do have significant disadvantages, including long-term treatment, limited oral bioavailability, inaccessibility to organs, non-adherence by patients, and the development of medication resistance. Because of the listed drawbacks of available routes and the availability of curative medicines for human immunodeficiency virus/acquired immunodeficiency syndrome, advanced solutions are required. Antiretroviral therapy transdermal delivery is one of the current strategies that have attracted much attention from many researchers. In this narrative review, various in vitro, in vivo, and ex vivo transdermal antiretroviral therapy delivery strategies were reviewed, such as transdermal patches and films, lipid-based nano-delivery systems, microneedles, chemical penetration enhancers, and iontophoresis, which showed promising results. Although the majority of studies on Antiretroviral transdermal delivery have produced hopeful findings, additional in-depth research on passive and physical enhancement techniques, both existing and new, is necessary to fully understand the potential of this route and to make it accessible to human immunodeficiency virus patients.

Immunovirological response and adverse effects of dolutegravir-based regimen in people living with HIV/AIDS

Background: After the WHO and NACO recommendation and implementation of dolutegravir (DTG)-based regimen as the preferred first-line regimen for adults living with HIV and as a preferred second-line regimen for adult people living with HIV (PLHIV) for whom non-DTG-based regimens are failing, only a few studies are present on its efficacy and adverse effects as first line and as a switch option in this part of the world. Objectives: The primary and secondary objectives were to evaluate the immunovirological response and to assess the adverse effects of DTG-based regimens in PLHIV/AIDS respectively. Materials and Methods: This prospective longitudinal study was conducted in the Regional Institute of Medical Sciences, Imphal for a period of 22 months, to study the immunovirological response and adverse effects of DTG-based regimen in PLHIV/AIDS. Results: Mean CD4 cells count ± standard deviation (cells/µL) was 495.42 ± 215.13 at enrollment, 529.53 ± 202.86 at 6 months, and 578.84 ± 204.84 at 1 year on DTG-based regimen. Increase in mean CD4 cells count was 34.11 cells/µL after 6 months (95% confidence interval [CI]: 22.76–45.46, P<0.000) and 83.42 cells/µL (95% CI: 68.57–98.26, P <0.000) after 1 year of starting DTG regimen. At enrollment, 92% (n = 92) were virologically suppressed, whereas 8% (n = 8) were not. After DTG, 98/100 (98%) of patients were virologically suppressed at 6 months and 12 months. An increase in mean weight by 1.24 kg after 6 months (95% CI: 0.93–1.54, P <0.000) and 2.2 kg (95% CI: 1.67–2.72, P <0.000) after 1 year from baseline was noted. The increase in mean random blood sugar (RBS) was 6.22 mg% (95% CI: 2.51–9.92, P <0.000) at 6 months and 12.15 mg% (95% CI: 6.19–8.10, P<0.000) at 1 year of initiation of DTG. There were two cases where RBS >300 mg% after 1 year of DTG. Conclusions: Treatment with a DTG-based regimen in treatment-naïve PLHIV and/or switching from the previous antiretroviral therapy regimen to DTG based has good immunological response and high rates of viral suppression without major clinical adverse effects. Weight gain and hyperglycemia should be monitored in patients on DTG.

Evaluation of Adverse Drug Events in Patients on Anti-Retroviral Therapy Regimen at Omdurman Voluntary Counselling and Testing and Anti-Retroviral Therapy Center in Sudan - A Cross-Sectional Study.

Anti-retroviral therapy-related adverse drug events are accounted as a main cause of anti-retroviral therapy non-adherence. In Sudan, pharmacovigilance studies are relatively rare and obstructed by the problem of under-reporting. It is a well-defined issue worldwide and is highly reported in developing countries. This study aimed to evaluate the prevalence of adverse events associated with anti-retroviral therapy among adult patients with immunodeficiency virus at Omdurman Voluntary Counselling and Testing and Anti-retroviral Therapy Center. The study was a descriptive cross-sectional study conducted through direct interviews with 429 patients at the selected center using the Adverse Drug Events (ADEs) reporting form. The collected data were analyzed by The Statistical Package for Social Sciences. More than half (55.5%) of the participants experienced adverse events, with 48.7% having experienced them at the beginning of treatment. Central nervous system manifestations were the most common adverse events. By using the Naranjo scale, most adverse events showed a "probable" relationship to anti-retroviral medicines. Based on the chi-square test, medication regimen was significantly associated with the presence of ADEs (namely abdominal pain and jaundice) (p values = 0.03 and 0.001), respectively. This study clearly stated that ART-related ADEs are common among Sudanese PLHIV and with central nervous system being the main adverse events. More pharmacovigilance studies and efforts by healthcare providers should be applied targeting ART-related ADEs under-reporting in Sudanese healthcare facilities.

A Phase-IV Non-interventional Study to Assess Virological Effectiveness, Safety, and Tolerability of DTG-based Antiretroviral Therapy in HIV-1 Infected Indian Persons Living with HIV.

Dolutegravir (DTG) is a novel yet preferential first- and -second-line treatment for persons living with HIV (PLH). Owing to its recent introduction, DTG-based regimens have not undergone a comprehensive, systematic evaluation regarding their real-world utilization and safety profile among a sizeable Indian population. This study aimed to assess the 24 week immunovirological outcomes, anthropometric and metabolic changes, tolerability, and adverse events (AEs) of DTG-based antiretroviral (ART) regimens. A single-centre phase-IV non-interventional observational study involving 322 ART naïve and treatment-experienced PLH initiating DTG-based-regimens until October 2022 were followed up for outcomes at 24 weeks. At 24 weeks, all PLH (n = 113) in the naïve group, all PLH (n = 67) in the first-line substitution group, 93.9% PLH (n = 46) in the first-line failure group, and 95.7% PLH (n = 89) in the second-line substitution group were virologically suppressed to plasma HIV-RNA <1000 copies/mL. Virological suppression rates to plasma HIV-RNA <200 copies/mL and <50 copies/mL were consistent among PLH who received DTG as first- or second-line ART. The mean-unadjusted weight gain observed was 3.5 kg (SE: 0.330), and it was significantly higher in PLH with poorer health at baseline (either HIV-RNA ≥ 1000 copies/ml or CD4 cell count <350 cells/μL). Overall, 27.3% PLH (n = 88) gained ≥10% of their baseline body weight, corresponding to 3.7% incidence (n = 12) of treatment-emergent clinical obesity. DTG had an overall lipid-neutral effect, with an advantageous effect being observed in PLH switching from non-nucleoside analogue reverse-transcriptase inhibitors (NNRTI) or ritonavir-boosted protease inhibitors (b/PI), especially in dyslipidemic pre-treated PLH (median change in total cholesterol: 28.5 mg/dL and triglycerides: 51 mg/dL), possibly emanating from the withdrawal of the offending ART. The incidence of DTG-specific AEs, including CNS AEs, was low. Two PLH developed proximal myopathy and one developed transaminitis, warranting DTG discontinuation. Asymptomatic serum-CPK elevation and drug-induced transaminitis were seen in 25.2% (n = 27) and 3.2% (n = 10) PLH, respectively. No apparent negative effects on renal function were detected. Our results from a large Indian cohort indicate a favourable virological and metabolic response, with good tolerance of DTG-based ART at 24 weeks.

Cost-effectiveness of antiretroviral regimens used in post-exposure prophylaxis program at United States’ PEPFAR-APIN clinics in a developing country: a retrospective pharmaco-economic analysis

Cost-effectiveness of antiretroviral regimens used in post-exposure prophylaxis program at United States’ PEPFAR-APIN clinics in a developing country: a retrospective pharmaco-economic analysis

Demographic, Clinical, and Antiretroviral Regiment Treatment Characteristics of HIV/AIDS Patients at the Regional General Hospital of Central Papua

The incidence of HIV infections in Papua is currently on the rise, primarily due to restricted access to antiretroviral treatment and insufficient support and care. Additionally, there is a lack of awareness among residents in rural or mountainous areas about HIV/AIDS infection, as provided by healthcare professionals. Until now, research data have been scarce on the demographic characteristics, clinical features, and treatment approaches for HIV/AIDS patients in the interior regions of Papua. This data is crucial for devising strategies aimed at enhancing healthcare services for individuals affected by HIV/AIDS.Consequently, this study endeavors to gain insights into the demographic characteristics, clinical features, and treatment modalities for HIV/AIDS patients at the Regional General Hospital of the Central Papua Region. It employs an observational descriptive approach, utilizing medical records of HIV/AIDS patients who visited the Central Papua Regional Government Hospital in June 2023. The findings indicate that, based on demographic data, the majority of patients were, on average, ≤25 years old (60.8%), male (52.5%), married (56.7%), and the highest number of HIV/AIDS cases were among secondary education graduates (40.8%). The majority were employed (67.5%) with incomes below the minimum wage threshold (69.2%). All heterosexual patients exhibited behavioral risk factors, and 4.2% had comorbidities such as hypertension. Tuberculosis was the most common opportunistic infection (17.5%). The highest proportion of individuals with HIV/AIDS were in stage II (66.7%). The predominant antiretroviral treatment regimen was a fixed-dose combination (FDC) containing Tenofovir 300mg, Lamivudine 300mg, and Efavirenz 600mg. The duration of use of ARV therapy in people with HIV / AIDS is at most 1 month.

THE IMPACT OF AGING ON ATTITUDES TOWARD WEIGHT CHANGE AND BODY IMAGE AMONG ADULTS LIVING WITH HIV

Abstract Some newer HIV antiretroviral therapy regimens have been associated with weight gain in populations at risk for obesity. This study examined perspectives on weight change and body image among people living with HIV and the extent to which age and gender have an impact on those attitudes. We conducted interviews with 61 individuals in a Medicaid managed care plan. The age range was 23 to 65 years; 49% were aged 50 or older. The sample was 56% non-Hispanic Black and 31% Hispanic. About half were cisgender men, 36% were cisgender women, and 13% were transgender/nonbinary individuals. Many participants had weight gain they associated with HIV medications. While experiences varied widely, we found that older and younger participants offered some different perspectives. Younger people, including transgender individuals, more often welcomed weight gain, associating it with better health. Participants aged 50 and older sometimes saw weight gain as a natural part of aging, and spoke of acceptance, whereas younger participants tended to focus on their appearance. Among those with unwanted weight gain, older participants expressed concerns about its negative effect on mobility and comorbid health conditions. Some older women in particular struggled with improving their diets. Healthcare providers should consider these different perspectives and the various challenges individuals face associated with age when advising patients with HIV about weight management. For providers working with older patients with HIV, specific considerations of how increased weight affects mobility and risk for comorbid conditions are warranted.

FEATURES OF HIV-INFECTION IN PATIENTS WITH LATE PRESENTATION WHO RECEIVE DTG-BASED ANTIRETROVIRAL THERAPY REGIMENS

Late presentation of HIV-infection is one of the most serious challenges in providing medical care to HIV-infected patients, because delay in detection and treatment of HIV-infection leads to a gradual decrease in the number of CD4+lymphocytes and the threat of infectious complications and tumor processes.&#x0D; Objective of this study is to find out the features of HIV-infection in people with late presentation of the disease, to evaluate the effectiveness of treatment and factors influencing the emergence of severe opportunistic infections on the background of dolutegravir-based antiretroviral therapy regimens. To achieve this goal, a cohort retrospective study was conducted, during which data from 210 outpatient records were analyzed.&#x0D; Analysis of opportunistic infections depending on the level of lymphocytes at the time of registration showed that in 123 (58.6%) of 210 late presenters, opportunistic infections were diagnosed at lymphocytes level below 200 cells/mL, in 22 people, while severe opportunistic infections were registered at a lymphocytes level above 500 cells/mL.&#x0D; Analysis of the clinical effectiveness of antiretroviral therapy showed that while taking the drugs, some patients continued to develop severe opportunistic infections such as tuberculosis, oropharyngeal candidiasis and severe bacterial diseases. An analysis of the Kaplan-Meier survival curve showed that there is a significant relationship between low baseline lymphocytes counts and the development of late opportunistic infections during treatment.&#x0D; Thus, the majority of HIV-infected patients were diagnosed with wasting syndrome, profound immunosuppression, severe opportunistic infections, and their combination at the time of registration. In some patients, severe late opportunistic infections were diagnosed with a satisfactory lymphocytes count above 500 cells/mL and subsequently on antiretroviral treatment. A low baseline lymphocytes count was identified as a risk factor for the development of severe opportunistic infections on antiretroviral therapy.

Simultaneous pharmacokinetic modeling of unbound and total darunavir with ritonavir in adolescents: a substudy of the SMILE trial.

Darunavir (DRV) is an HIV protease inhibitor commonly used as part of antiretroviral treatment regimens globally for children and adolescents. It requires a pharmacological booster, such as ritonavir (RTV) or cobicistat. To better understand the pharmacokinetics (PK) of DRV in this younger population and the importance of the RTV boosting effect, a population PK substudy was conducted within SMILE trial, where the maintenance of HIV suppression with once daily integrate inhibitor + darunavir/ritonavir in children and adolescents is evaluated. A joint population PK model that simultaneously used total DRV, unbound DRV, and total RTV concentrations was developed. Competitive and non-competitive models were examined to define RTV's influence on DRV pharmacokinetics. Linear and non-linear equations were tested to assess DRV protein binding. A total of 443 plasma samples from 152 adolescents were included in this analysis. Darunavir PK was best described by a one-compartment model first-order absorption and elimination. The influence of RTV on DRV pharmacokinetics was best characterized by ritonavir area under the curve on DRV clearance using a power function. The association of non-linear and linear equations was used to describe DRV protein binding to alpha-1 glycoprotein and albumin, respectively. In our population, simulations indicate that 86.8% of total and unbound DRV trough concentrations were above 0.55 mg/L [10 times protein binding-adjusted EC50 for wild-type (WT) HIV-1] and 0.0243 mg/L (10 times EC90 for WT HIV-1) targets, respectively. Predictions were also in agreement with observed outcomes from adults receiving 800/100 mg DRV/r once a day. Administration of 800/100 mg of DRV/r once daily provides satisfactory concentrations and exposures for adolescents aged 12 years and older.

The consensus guideline of perioperative antiviral therapy for AIDS patients in China based on clinical practice.

The prevalence of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) has emerged as a major public health concern in China. When patients with HIV infection undergo surgical treatment, there are two main challenges. Firstly, medical staff face a high risk of HIV infection due to occupational exposure. Secondly, the patient's immune function is impaired, increasing the risk of opportunistic infections and postoperative complications. The surgical treatment of such patients is unique, and the risk of occupational exposure during the operation primarily depends upon the viral load of HIV/AIDS patients. Therefore, perioperative antiretroviral therapy is of paramount importance in order to standardize the perioperative antiretroviral therapy (ART) for HIV/AIDS patients. The Surgery Group of the Chinese Association of STD and AIDS Prevention and Control, in collaboration with the Treatment Association, and Surgery Group of the Chinese Medical Association of Tropical Diseases and Parasitology, has developed an expert consensus on perioperative antiretroviral therapy for HIV/AIDS patients. This consensus encompasses various aspects, including surgical risk assessment, selection of perioperative antiretroviral therapy regimens, prevention of opportunistic infections, and the crucial focus on rapid preoperative viral load reduction and immune function reconstruction for HIV/AIDS patients.

Treatment Responses to Integrase Strand-transfer Inhibitor-containing Antiretroviral Regimens in Combination With Short-course Rifapentine-based Regimens for Latent Tuberculosis Infection Among People With HIV.

Real-world experience with combinations of short-course rifapentine-based regimens and integrase strand-transfer inhibitor-containing antiretroviral therapy (ART) in management of latent tuberculous infection (LTBI) is limited among people with human immunodeficiency virus (PWH). From August 2019 to October 2022, PWH receiving 3 months of weekly rifapentine plus isoniazid (3HP) or 1 month of daily rifapentine plus isoniazid (1HP) in combination with ART were included. The primary outcome was virologic response within 12 months after LTBI treatment; secondary outcomes included treatment completion rate and safety of LTBI regimens. During the study period, 479 PWH (94.6% male; median age, 43 years) were included: 142 received 1HP and bictegravir (BIC)-containing regimens (1HP/BIC group), 46 1HP and dolutegravir (DTG)-containing regimens (1HP/DTG group), 38 3HP and BIC-containing regimens (3HP/BIC group), 214 3HP and DTG-containing regimens (3HP/DTG group), 17 1HP and other ART regimens (1HP/others group), and 22 3HP/other ART regimens (3HP/others group). In the intention-to-treat analysis, the proportions of PWH maintaining plasma HIV-1 RNA <200 copies/mL within 12 months after LTBI treatment completion were 96.5% (1HP/BIC), 100% (1HP/DTG), 100% (3HP/BIC), 95.8% (3HP/DTG), 100% (1HP/others), and 100% (3HP/others). The overall completion rates were >80% for all treatment groups, whereas >50% of the included PWH experienced any adverse event. LTBI regimens and ART combinations were not associated with virologic response and completion rate. Combinations of short-course rifapentine-based regimens and integrase strand-transfer inhibitor-containing ART maintained viral suppression for most PWH within 12 months of LTBI treatment completion with low rates of grade 3 or higher adverse events.

First 15 Years of Assisted Reproductive Technology Using Washed Sperm in HIV-Positive Individuals Under Antiretroviral Therapy: Sweden's Nationwide Outcomes.

Antiretroviral therapy has made HIV a chronic infectious disease. In Sweden, assisted reproductive technologies using sperm washing were implemented in 2004 for treatment of all HIV-positive males in serodiscordant couples at Karolinska Hospital in Stockholm. This study aimed to assess efficacy and safety of this approach and to investigate the effect of antiretroviral regimens on sperm quality of men treated for HIV. The study included all HIV-positive men (n = 53) adherent to antiretroviral treatment, including nucleoside/nucleotide analog reverse-transcriptase inhibitors (NRTIs) combined with non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in 22 cases, or with other medication in 31 cases wishing fertility treatment. Sperm was washed using gradient centrifugation with a double tube system, frozen and thawed. Thereafter, single spermatozoa were injected in oocytes by intracytoplasmic sperm injection (ICSI). Treatment outcomes were compared to those of hepatitis B virus (HBV)-seropositive men in serodiscordant couples (n = 56), undergoing similar sperm washing protocols and ICSI at the center. In total, 82 fresh and 39 frozen/thawed embryo transfer (FET) cycles were performed in discordant HIV couples and 92 fresh and 36 FET cycles in HBV. Fertilization rates (69.2% vs. 64.6%, p = 0.310), clinical pregnancy rates (39.2% vs. 32.6%, p = 0.378), and live birth rates (35.8% vs. 31.5%, p = 0.565) were similar between the groups and the cumulative results yielded similar outcomes with a live birth rate of 52.8% and 51.8% (p = 0.913), respectively. No post-wash sperm sample was found positive for HIV viral particles. No partner seroconversion or offspring infection was reported. NNRTI-treated men had significantly lower motile sperm concentration than non-NNRTI-treated patients (54.48% vs. 36.41%, p < 0001). This study showed that in vitro fertilization/ICSI treatment with sperm washing was safe in individuals compliant to antiretroviral treatment and the reproductive outcome was similar to that of HBV-positive men. The observed moderate negative impact on sperm motility of NNRTI regimens may be overcome by using ICSI.

Fostemsavir: A Novel CD4 Attachment Inhibitor for Heavily Treated HIV-1 Patient

Abstract: Despite the evident success of antiretroviral therapy in recent years, many patients undergoing intense treatment still struggle to find a cure for their disease due to drug resistance or treatment failure. To solve this problem, new antiretroviral drug alternatives are required. The HIV-1 antiretroviral drug fostemsavir (GSK3684394, previously BMS-663068) is a first-in-class HIV-1 attachment inhibitor with a novel mechanism. After oral administration, fostemsavir gets converted into temsavir in the gastrointestinal lumen, which then attaches to the glycoprotein 120 surface subunit on HIV-1 and produces a conformational change that prevents it from adhering to CD4+ T cells of the host immune system, thereby preventing the virus from infecting other cells. Fostemsavir is indicated in heavily treated (HTE) patients with an ideal antiretroviral (ARV) regimen. The drug has shown significant tolerability, and no hepatic or renal dose adjustments were required. Fostemsavir can be used as an effective alternative in salvage therapy because of its favourable adverse effect profile and few drug interactions.

1568. Evaluating the Appropriateness of Antiretroviral Therapy in the Critical Care Setting

Abstract Background The care of patients with HIV in the intensive care unit (ICU) can be complex as they may develop acute kidney injury and therefore necessitating continuous renal replacement therapy, need feeding tubes, and are prescribed new medications. Issues regarding drug-drug interactions, fluctuating renal &amp; hepatic function, adverse effects, oral administration issues including crushing of tablets are challenges that may arise. The purpose of this study was to evaluate the appropriateness of antiretroviral (ARV) therapy in the ICU. Background - HIV and ICUs In 2018, almost half of Americans living with HIV were aged 50 and older. Co-morbidities associated with ICU admissions include cardiovascular, renal, hepatic, and pulmonary disease. Medication errors are defined as: incorrect/incomplete regimen, incorrect dose, incorrect renal adjustment, incorrect administration, and major drug-drug interaction. Methods This was a retrospective, observational, quality improvement project that reviewed charts from January 2018 to August 2022. Adult patients that were admitted to the the ICU at Long Island Jewish Medical Center and receiving ART for HIV were included. Patients receiving ARV for indications other than HIV were excluded. Using the medical record system, data was collected: demographics, renal and hepatic dysfunction, ARV ordered (e.g., tablet formulation, combination/single tablet), completeness of treatment regimen, drug-drug interactions, feeding placement, and concomitant medications. Descriptive statistics were utilized. Results Of the 68 patients screened, 43 were included in the study. The mean age was 57 ± 13 years, 60.5% males, and majority of patients were admitted to the medical ICU (55.8%). The median CD4 count was 250 cells/μL and 37.2% of the patients had undetectable viral loads. A total of 18 patients (41.9%) required a gastric tube during their ICU stay. ID was consulted in 41.9% of the cases. Inappropriate ART was found in 46.5% of patients with drug-drug interactions, inappropriate tablet crushing, and renal dose adjustment needed being the most prevalent reasons for inappropriateness. 27 patients (62.8%) had opportunities for interventions. which included failure to re-initiate ARV sooner (n = 8), inappropriate ARV crushing (n = 8), ARV use contraindicated at time prescribed (n = 6), ARV not reconciled once stable (n = 5), and drug-drug interactions (n = 4). An intervention could have been made 5 days sooner on average. 20 patients identified with an inappropriate ART regimen and patients could have had more than one reason for inappropriateness so total 26 identified reasons for inappropriate ART Most reasons for inappropriateness were related to patient’s renal function, ART administration, and drug-drug interactions followed by incomplete regimen. The other reason for inappropriateness was that patient was not re-initiated on ART during ICU stay when it was appropriate to do so. 27 patients identified with one or more areas for improvement– these were interventions that could have been made. Most areas for improvement included earlier ARV re-initiation either to the same regimen from home PTA or a more appropriate regimen (such as a kidney or liver-sparring regimen) Other areas identified included inappropriate formulation/administration of ART, contraindications such as AKI were present at the time ART was ordered, addressing drug-drug interactions, Other = address drug-drug interactions (4), earlier initiation of new ARV regimen (patient was tx-naïve) (1), earlier initiation of adjusted ARV regimen (1), incomplete regimen (1) Conclusion The study demonstrates that there are opportunities for improvement in the care of HIV in the ICU setting. Daily assessments of ART for re-initiation, dose adjustment, appropriate administration is crucial. Disclosures All Authors: No reported disclosures

2541. Steady-state PK of Fixed Dose Dolutegravir+Rilpivirine in Hemodialysis

Abstract Background Fixed dose combination (FDC) dolutegravir (DTG) plus rilpivirine (RPV) is an approved antiretroviral treatment regimen for people with HIV. The steady-state PK of FDC DTG+RPV in those requiring hemodialysis (HD) has not been previously studied. Methods We performed a single-center, prospective evaluation of the steady-state PK of FDC DTG (50mg)+RPV(25mg) in HIV-negative adults either requiring HD (n=4; 2 men, 2 women) or with normal renal function, defined as CrCl ≥ 75mL/min (n=2; 1 man, 1 woman). All participants received DTG+RPV daily for 10-14 days with food before undergoing an intensive 24-hour PK evaluation (performed between dialysis days for those requiring HD). Plasma drug and metabolite concentrations were measured using a validated LC/MS/MS assay method (QTRAP 6500+LC-MS/MS system) with turboelectrospray source operating in both positive (confirmation) and negative (quantification) modes. We did not evaluate dialysis extraction of DTG+RPV. Descriptive PK parameters were calculated. Results No participant experienced serious or grade 3-4 adverse events; there were no study discontinuations. The 4 HD and 2 normal renal function participants were of similar ages (range, 50-60 vs 53-58 years) and BMI (range, 18.5-28.2 vs 20.3-24.0 kg/m2). The Table shows the PK parameters assessed in the study population for circulating plasma DTG, DTG-glucuronide (DTG’s primary metabolite), and RPV. Conclusion In this study, HD did not lead to clinically appreciable differential exposures to DTG and RPV; the markedly increased exposure to DTG-glucoranide (which is considered inert) in HD suggests increased UGT1A1 activation. All participants maintained exposures throughout the dosing interval greater than the reported IC90 efficacy values for DTG (64ng/mL) and RPV (12ng/mL). These data suggest no dosing modifications are needed for the FDC DTG+RPV regimen in HD. Disclosures Samir K. Gupta, MD, Gilead Sciences: Advisor/Consultant|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support Allon Friedman, MD, Eli Lilly: Advisor/Consultant|Eli Lilly: Stocks/Bonds|GI Dynamics: Advisor/Consultant|Gila Therapeutics: Advisor/Consultant

1716. Outcomes and adverse effects of risk-based perinatal antiretroviral regimens to prevent HIV transmission: A real-world experience

Abstract Background Annually ∼5,000 women living with HIV give birth in the US. US Public Health Guidelines recommend that perinatally-exposed infants receive antiretrovirals (ARV) to reduce transmission risk. Low risk infants receive 1 ARV (zidovudine, AZT) for 4 weeks, while highest risk infants receive 3 full dose ARVs for 6 weeks. For newborns in the moderate risk category, it is unclear what the optimal ARV regimen and duration is. Methods We conducted a retrospective study of infants born to mothers living with HIV (MLWH) between July 2016-July 2022 at The Johns Hopkins Hospital and Bayview Medical Center. Patient demographic, medication administration, and clinical outcomes data were extracted from charts. Baseline characteristics and outcomes were summarized using descriptive statistics and stratified by risk category of the infant. Comparisons were made using the Fishers exact test for categorical data and the Kruskal Wallis test for continuous data. Statistical significance was defined as a p value &amp;lt; 0.05. Results 196 MLWH gave birth between July 2016 -July 2022. Mothers of high-risk infants were more likely to have lower CD4 counts, detectable viremia, illicit drug use during pregnancy, no prenatal care, and non-disclosure of their HIV status (Table 1). High-risk infants were more likely to be born at lower gestational age and have lower birth weight (Table 2). 99% of low-risk infants were prescribed AZT alone for a median of 28 days, whereas 48% of high-risk infants were prescribed 3-drug pre-emptive HIV therapy for ≥6 weeks. Amongst moderate-risk infants, 85% received 3 drug prophylaxis (nevirapine x 3 doses, lamivudine x 7 days, AZT x 6 weeks). 4 infants had a positive HIV test (Table 3), with 1 being definitively diagnosed with HIV. 3 infants had a single positive nucleic acid test that was not confirmed with additional testing. Table 1 Baseline demographics of 19 5 mothers living with HIV who gave birth to infants at The Johns Hopkins Hospital or Bayview Medical Center between 2016-2022 Table 2. Baseline demographics of 196 infants born to MLWH at The Johns Hopkins Hospital or Bayview Medical Center between 2016-2022 Table 3 Baseline demographics of 4 infants with positive HIV tests at birth Conclusion Amongst infants born to MLWH, various risk-based ARV regimens were prescribed and well tolerated; only 1 confirmed transmission occurred. 37% of infants were moderate/high risk requiring more extensive ARVS for longer duration and were more likely to have features which could be associated with non-adherence. These findings underscore the importance of the need for effective, discreet, shorter strategies to prevent perinatal transmission. Disclosures Allison Agwu, MD, ScM, Gilead: Board Member|Gilead: Site PI for multi-center study (ongoing); Investigator initiated study|Merck: Advisor/Consultant|Merck: Site PI for multi-center study (completed)|ViiV: Board Member

1590. Resistance to Etravirine, Doravine and Rilpivirine in People Living with HIV Experiencing Virologic Failure to a First-line Antiretroviral Regimen Based on a Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) in a Latin American Country.

Abstract Background To date, etravirine (ETR) is the only NNRTI indicated in people living with HIV (PLHIV) after virologic failure (VF) to first-generation NNRTIs. Data about susceptibility to ETR, doravirine (DOR) and rilpivirine (RPV) after VF in PLHIV from Latin American countries are scarce. The aim of this study is to determine the prevalence of resistance to ETR, DOR, and RPV in PLHIV who experienced VF to a first-line NNRTI-based regimen, and factors associated with high-level resistance (HLR) to ETR. Methods Retrospective cohort study. Prevalence of resistance to ETR, DOR and RPV was assessed by analyzing genotyping tests of adult PLHIV who experienced VF to a first-line NNRTI-based regimen, in Buenos Aires, Argentina (2010 to 2020). Stanford HIVdb v9.4 was used to interpret resistance profiles. We defined resistance as both intermediate resistance (IR) and HLR interpretations. A sample size of 125 subjects was calculated to allow estimation of the primary endpoint with sufficient precision (95%CI). A cross-sectional analysis was carried out to identify risk factors associated with HLR to ETR. Results N=125; 81.6% were male. Median age at VF was 39.5 years (IQR: 34.0-35.0); 82,4% received efavirenz and 17.6% nevirapine. Duration of VF: 245 days (IQR 133-413). Median HIV-1 viral load (VL): 11255 c/mL (3606-45100); median CD4+ cell count: 192 cell/uL (86-333). Seventy-seven samples (61.6%) had ETR resistance-associated mutations (RAMs); 25 (20%) had mutations associated with the highest levels of reduced susceptibility (100I, 101P, 181I/V). Most frequent ETR RAMS were: 100I (16%), 190A (16%) and 181C (12%); DOR RAMs: 100I (16%), 188L (8.8%) and 106M (4.8%), and RPV RAMs: 100I (16%), 181C (11.2%) and 138A (7.2%). Prevalence of resistance to ETR was 44.8% (IR: 32.8%, HLR: 12%), resistance to DOR: 64% (IR: 45.6%, HLR: 18.4%) and to RPV: 52% (IR: 7.2%, HLR: 44.8%). ETR maintained susceptibility to DOR resistant strains in 27.2% of the cases. We found a statistically significant association between HIV-1 VL &amp;gt;10000 c/mL and the risk of developing HLR to ETR (X2=4.5, p=0.034). Conclusion In our cohort, resistance to ETR after VF to a NNRTI-containing regimen was lower than to DOR and RPV. HLR was uncommon and associated with high HIV-1 VL. Almost one third of DOR-resistant strains remained susceptible to ETR. Disclosures Verónica Mingrone, GSK/ViiV: Educational Courses|Janssen Pharmaceutical Companies: Educational Courses Eliana Loiza, n/a, GSK/ViiV: Educational Courses|Janssen Pharmaceutical Companies: Educational Courses Norma Porteiro, n/a, GSK/ViiV: Advisor/Consultant|GSK/ViiV: Grant/Research Support|GSK/ViiV: Educational Courses|Janssen Pharmaceutical Companies: Advisor/Consultant|Janssen Pharmaceutical Companies: Grant/Research Support|Janssen Pharmaceutical Companies: Educational Courses Ezequiel Córdova, n/a, GSK/ViiV: Advisor/Consultant|GSK/ViiV: Grant/Research Support|GSK/ViiV: Educational Courses|Janssen Pharmaceutical Companies: Advisor/Consultant|Janssen Pharmaceutical Companies: Grant/Research Support|Janssen Pharmaceutical Companies: Educational Courses

Mutation patterns of integrase gene affect antiretroviral resistance in various non-B subtypes of human immunodeficiency virus Type-1 and their implications for patients' therapy.

Although primary integrase strand transfer inhibitor resistance mutations are currently uncommon, the increasing use of integrase strand transfer inhibitor as a key component of the first, second and third-line antiretroviral regimens suggests that the prevalence of integrase drug resistance mutations will likely increase. The rise of several polymorphic mutations and natural polymorphisms also affects the level of susceptibility of human immunodeficiency virus (HIV) type-1 to integrase strand transfer inhibitor. The considerable variability among the various subtypes of human immunodeficiency virus type-1 may contribute to differences in integrase mutations associated with integrase strand transfer inhibitors. Notably, non-B subtypes of HIV type-1 (HIV-1) are the predominant cause of human immunodeficiency virus infection worldwide. The presence of diverse integrase drug resistance mutations can have significant implications on the administration of integrase strand transfer inhibitor-based antiretroviral therapy to patients with human immunodeficiency virus infection.

Fetal growth assessed via ultrasound in relation to maternal HIV infection status and antiretroviral regimens.

To evaluate effects of maternal HIV and antiretroviral treatment (ART) on intrauterine fetal growth. Prospective cohort studies of HIV and ZIKA infection among women living with HIV (WLHIV) and women not living with HIV (WNLHIV) conducted in Brazil and the US from 2016 to 2020. We evaluated fetal growth via repeated ultrasounds and calculated z scores for fetal growth measures using Intergrowth-21st standards among women with singleton pregnancies. Adjusted linear mixed models were fit for each fetal growth z score by HIV status. Among WLHIV, we compared fetal growth z scores by the most common maternal ART regimens, stratified by timing of ART initiation. We included 166 WLHIV and 705 WNLHIV; none had Zika infection. The z scores were similar for WLHIV and WNLHIV for femur length (latest third trimester median = 1.08) and estimated fetal weight (median ≈0.60); adjusted mean differences in fetal weight z scores by HIV status were less than 0.1 throughout gestation. Other fetal growth measurements were lower for WLHIV than WNLHIV early in gestation but increased more rapidly over gestation. Among WLHIV not on ART at conception, adjusted mean z scores were generally similar across regimens initiated during pregnancy but somewhat lower for atazanavir-based regimens for biparietal diameter compared with efavirenz-based or raltegravir-based regimens. Among WLHIV on ART at conception, mean z scores were similar across ART regimens. Within our cohorts, fetal growth was lower in WLHIV than WNLHIV early in gestation but similar by the end of gestation, which is reassuring. Among WLHIV, fetal growth measures were generally similar across ART regimens evaluated.

Exploring the HIV pre-exposure prophylaxis (PrEP) risk rituals: individualisation, uncertainty and social iatrogenesis

HIV Pre-Exposure Prophylaxis (PrEP) consists of a daily antiretroviral regimen that prevents HIV acquisition. In this article, we discuss ways in which individuals on PrEP deal with risks and uncertainties through their life experiences amid PrEP risk rituals and rational and non-rational individualisation processes. We analysed data from a web-based group of mostly gays, bisexuals and other men who have sex with men on PrEP through a thematic-content approach. We found that individuals, influenced by medical and health institutions, were involved in ‘risk rituals’ with profound effects on their subjective embodiment, emotions and feelings. These processes became amalgamated into conflicting objective consequences to themselves and their social networks, which included the acquisition of new diseases amid increasing ambivalences of being on PrEP. Our theoretical argument is that risk rituals were symptomatic of social iatrogenesis amid the contemporary risk and individualised society. By developing an analytical dialogue between our empirical data and modernisation theories of risk and individualisation, we sought to understand risk rituals through conflict, relational, group and institutional domains, as these layers of analysis help us grasp the core characterisation of social iatrogenesis. Drawing on these insights, we also pay attention to potential futures of injectable PrEP, considering the role of hope, the collective production of the unknown and medical action as a type of intensification of risk rituals and social iatrogenesis.