Cohort profile: PRESTIGIO, an Italian prospective registry-based cohort of people with HIV-1 resistant to reverse transcriptase, protease and integrase inhibitors.

PURPOSE: The PRESTIGIO Registry was established in 2017 to collect clinical, virological and immunological monitoring data from people living with HIV (PLWH) with documented four-class drug resistance (4DR). Key research purposes include the evaluation of residual susceptibility to specific antiretrovirals and the validation of treatment and monitoring strategies in this population. PARTICIPANTS: The PRESTIGIO Registry collects annual plasma and peripheral blood mononuclear cell samples and demographic, clinical, virological, treatment and laboratory data from PLWH followed at 39 Italian clinical centres and characterised by intermediate-to-high genotypic resistance to ≥1 nucleoside reverse transcriptase inhibitors, ≥1 non-nucleoside reverse transcriptase inhibitors, ≥1 protease inhibitors, plus either intermediate-to-high genotypic resistance to ≥1 integrase strand transfer inhibitors (INSTIs) or history of virological failure to an INSTI-containing regimen. To date, 229 people have been recorded in the cohort. Most of the data are collected from the date of the first evidence of 4DR (baseline), with some prebaseline information obtained retrospectively. Samples are collected from the date of enrollment in the registry. FINDINGS TO DATE: The open-ended cohort has been used to assess (1) prognosis in terms of survival or development of AIDS-related or non-AIDS-related clinical events; (2) long-term efficacy and safety of different antiretroviral regimens and (3) virological and immunological factors predictive of clinical outcome and treatment efficacy, especially through analysis of plasma and cell samples. FUTURE PLANS: The registry can provide new knowledge on how to implement an integrated approach to study PLWH with documented resistance to the four main antiretroviral classes, a population with a limited number of individuals characterised by a high degree of frailty and complexity in therapeutic management. Given the scheduled annual updates of PLWH data, the researchers who collaborate in the registry can send study proposals at any time to the steering committee of the registry, which evaluates every 3 months whether the research studies can be conducted on data and biosamples from the registry and whether they are aimed at a better understanding of a specific health condition, the emergence of comorbidities or the effect of potential treatments or experimental drugs that may have an impact on disease progression and quality of life. Finally, the research studies should aim to be inclusive, innovative and in touch with the communities and society as a whole. TRIAL REGISTRATION NUMBER: NCT04098315.

Prevalence, treatment, and factors associated with cryptococcal meningitis post introduction of integrase inhibitors antiretroviral based regimens among People Living with HIV in Tanzania.

OBJECTIVE: This study aimed to assess the prevalence of Cryptococcal Meningitis (CM), treatment practice, and the associated factors post-introduction of Tenofovir Lamivudine and Dolutegravir (TLD) regimen among People Living with HIV (PLHIV) in Tanzania. METHODS: This was an analytical cross-sectional study, and the data was collected retrospectively in three public regional referral hospitals (RRHs) in Dar es Salaam, Tanzania. A total of 405 files of the PLHIV admitted in the medical wards on the TLD regimen from January 2019 to December 2022 were reviewed. The collected information includes the patient's demographic characteristics, Cryptococcal status, CD4 level at the time of CM diagnosis, status of using ART, CM treatment approach, and outcome. Data was analyzed using SPSS software version 23. RESULTS: Out of 405 patients, the majority 267(65.9%) were female, 224(55.3%) were aged between 36-55 years, and 293(72.3%) were married. ART defaulters were found to be 37(9.1%). The prevalence of CM was found to be 48(11.9%), out of which 42(87.5%) received fluconazole alone. ART defaulter and marital status significantly (p-value < 0.05) were associated with those who tested CM positive. CONCLUSION: The study found the prevalence of CM among PLHIV to be significantly high and the majority were treated with fluconazole alone. ART defaulters and marital status were significantly associated with one being CM positive. Responsible authorities and stakeholders should enforce guideline adherence and PLHIV should be encouraged on medication adherence.

HIV-1-specific T-cell responses and exhaustion profiles in people with HIV after switching to dual therapy vs. maintaining triple therapy based on integrase inhibitors.

BACKGROUND: Dual therapy (DT) has shown comparable results to triple therapy (TT) in efficacy and other immunological aspects. However, there are still some concerns about DT, including several immunological features. Therefore, we evaluated whether HIV-1-specific memory T-cell responses and exhaustion phenotypes are adversely influenced after simplification to DT. METHODS: HIV-1-specific CD4+ and CD8+ T-cell responses were assessed by intracellular cytokine and degranulation marker staining, and polyfunctionality indexes after stimulation with a Gag peptide pool. Exhaustion phenotypes were evaluated by PD-1, TIM-3, and LAG-3 expression in CD4+ and CD8+ T cells. RESULTS: Forty participants in the TRIDUAL trial (ClinicalTrials.gov: NCT03447873) who were randomized to continue integrase inhibitor-based TT (n = 20) or to switch to DT (dolutegravir or darunavir/cobicistat plus lamivudine) (n = 20). After 96 weeks, the magnitude of CD4+ and CD8+ T-cell responses was similar in both treatment arms (p = 0.221 and p = 0.602, respectively). The CD4+ polyfunctionality index decreased in the TT arm (p = 0.013) and remained stable in the DT arm, while the polyfunctionality of CD8+ T cells was unchanged in both arms. There was a significant decrease in the expression of PD-1, TIM-3, and the co-expression of PD-1+TIM-3+LAG-3+, and PD-1 +TIM-3 + in both CD4+ and CD8+ T cells. However, the decrease in the expression of exhaustion markers did not improve HIV-1-specific T-cell responses. CONCLUSIONS: Our results suggest that simplification to DT does not negatively influence the HIV-1-specific T-cell response or the exhaustion phenotype after 96 weeks of follow-up.

Integrase inhibitors: current protagonists in antiretroviral therapy.

Since HIV was identified as the etiological agent of AIDS, there have been significant advances in antiretroviral therapy (ART) that has reduced morbidity/mortality. Still, the viral genome's high mutation rate, suboptimal ART regimens, incomplete adherence to therapy and poor control of the viral load generate variants resistant to multiple drugs. Licensing over 30 anti-HIV drugs worldwide, including integrase inhibitors, has marked a milestone since they are potent and well-tolerated drugs. In addition, they favor a faster recovery of CD4+ T cells. They also increase the diversity profile of the gut microbiota and reduce inflammatory markers. All of these highlight the importance of including them in different ART regimens.

Research on HIV/AIDS has been focused on finding ways to prevent or cure the disease. One important class of drugs called integrase inhibitors has gained attention. These drugs are effective and have been widely used in the past decade to treat HIV. Integrase inhibitors help in the recovery of immune cells and improve the diversity of gut bacteria while reducing inflammation. It is important to include these drugs in treatment regimens for people living with HIV.

Use of integrase inhibitors vs protease inhibitors is associated with improved HIV viral suppression.

BACKGROUND: Current guidelines for antiretroviral therapy in pregnancy include the use of a dual-nucleoside reverse transcriptase inhibitor with either an integrase strand transfer inhibitor or a ritonavir-boosted protease inhibitor, although there is no designation of which is the preferred option. OBJECTIVE: This study aimed to compare viral suppression at delivery among patients on dual-nucleoside reverse transcriptase inhibitors combined with either an integrase strand transfer inhibitor or a protease inhibitor. A hypothesis was made that the incidence of viral suppression is higher with the use of a dual-nucleoside reverse transcriptase inhibitor backbone combined with an integrase strand transfer inhibitor than with the use of a dual-nucleoside reverse transcriptase inhibitor backbone combined with a protease inhibitor. STUDY DESIGN: This study was an observational study of pregnant patients living with HIV who received prenatal care and delivered after 20 weeks of gestation at an urban safety net hospital. All pregnant patients with HIV were referred to a centralized clinic for HIV counseling, medication management, and prenatal care. Antiretroviral therapy was continued or initiated according to protocols based on national guidance. Among patients on a dual-nucleoside reverse transcriptase inhibitor backbone combined with integrase strand transfer inhibitor vs protease inhibitor at delivery, we compared the demographics and HIV disease characteristics, including year of diagnosis, viral load, and antiretroviral therapy class. The outcome of interest was viral suppression at delivery, defined as a viral load of <50 copies/mL. RESULTS: From January 2011 to December 2021, 604 patients on dual-nucleoside reverse transcriptase inhibitor met the inclusion criteria, including 411 patients (68%) on protease inhibitor and 193 patients (32%) on integrase strand transfer inhibitor at delivery. Demographic distribution was similar, and prenatal care was initiated at 12 weeks of gestation. Among the integrase strand transfer inhibitor group, 101 (17%) were on antiretroviral therapy at initiation of prenatal care compared with 169 (28%) in the protease inhibitor group. At delivery, the frequency of viral load suppression was higher among those on an integrase strand transfer inhibitor (147/193 [76%]) than among those on a protease inhibitor (275/411 [67%]) (odds ratio, 1.59; 95% confidence interval, 1.08-2.33). Among those with a detectable virus, quantitative viral load was not different. During the study period, the use of a protease inhibitor decreased, whereas the use of an integrase strand transfer inhibitor increased. CONCLUSION: Among pregnant patients living with HIV, viral suppression was more common among those on a dual-nucleoside reverse transcriptase inhibitor backbone combined with integrase strand transfer inhibitor than among those on a dual-nucleoside reverse transcriptase inhibitor backbone protease inhibitor at delivery. Our results support the use of dual-nucleoside reverse transcriptase inhibitor with integrase strand transfer inhibitor as a first-line antiretroviral therapy regimen in pregnancy.

Weight gain following switch to integrase inhibitors from non-nucleoside reverse transcriptase or protease inhibitors in people living with HIV in the United States: analyses of electronic medical records and prescription claims.

OBJECTIVES: Real-world data evaluating weight changes in people living with HIV (PLWH) following switch to integrase strand transfer inhibitor (INSTI), specifically bictegravir (BIC), are limited. This retrospective cohort study analyzed weight changes upon switching to INSTI from non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) in treatment-experienced PLWH. METHODS: Adult PLWH (≥18 years) treated with NNRTI or PI (non-switch cohorts) and those switching to INSTI (switch cohorts) between January 1, 2014 and August 31, 2019 were identified using IQVIA's Ambulatory Electronic Medical Records linked to a prescription drug claims database. The associations of switching to INSTI and individual INSTI agents with having ≥5% weight gain at 12 months of follow-up were evaluated, adjusting for demographics and baseline clinical characteristics. RESULTS: At 12 months of follow-up, PLWH in the NNRTI-INSTI switch cohort (n = 508) were more likely to have ≥5% weight gain over 12 months compared to the NNRTI non-switch cohort (n = 614; odds ratio, OR [95% CI], 1.7 [1.2-2.4]). Switching from NNRTI to dolutegravir (DTG: OR [95% CI], 2.1 [1.4-3.0]) or BIC (2.0 [1.0-4.2]) resulted in significantly higher odds of ≥5% weight gain. PI-INSTI switch (n = 295) and non-switch (n = 228) cohorts had similar proportions of PLWH with ≥5% (21.1-23.4%) or ≥10% (7.8-7.9%) weight gain, and no significant association was found between switching from PI to INSTI and weight gain. CONCLUSION: Weight gain and related metabolic health of PLWH switching from NNRTI to DTG or BIC should be closely monitored by clinicians. Further research is needed to assess other metabolic outcomes in PLWH remaining on PI and those who switch from PI to INSTI.

Identification of integrase inhibitor-related drug resistance mutations in newly diagnosed ART-naïve HIV patients.

BACKGROUND: In China, the recommended treatment regimens for HIV-infected individuals were tenofovir in combination with lamivudine or emtricitabine as NRTIs, efavirenz or rilpivirine as NNRTIs, lopinavir/ritonavir as protease inhibitors, and raltegravir or dolutegravir as INSTIs. The development of drug resistance increases the risk of viral rebound, opportunistic infections, and ultimately treatment failure such that the early detection of resistance is ideal. This study was developed to explore primary drug resistance characteristics and genotypic distributions in newly diagnosed antiretroviral therapy (ART)-naïve HIV-1 patients in Nanjing with the goal of establishing a basis for their individualized treatment in the clinic. METHODS: Samples of serum were collected from newly diagnosed ART-naïve HIV patients from the Second Hospital of Nanjing between May 2021 and May 2022. The HIV-1 integrase (IN), protease (PR), and reverse transcriptase (RT) gene coding sequences were amplified from these samples, sequenced, and assessed for drug resistance-related mutations. RESULTS: Major integrase resistance-related mutations were detected in 4/360 amplified samples, with 5 other patient samples exhibiting accessory resistance mutations. The overall prevalence of PR and RT inhibitor-related transmitted drug resistance mutations (TDRMs) in this patient population was 16.99% (61/359). The most common mutations were non-nucleoside reverse transcriptase inhibitor-related mutations (51/359; 14.21%), followed by those associated with nucleoside reverse transcriptase inhibitors (7/359; 1.95%) and protease inhibitors (7/359; 1.95%). Dual-resistant strains were also observed in a subset of patients. CONCLUSIONS: In summary, this study is the first to have surveyed the prevalence of integrase inhibitor resistance-related mutations and other drug resistance-related mutations among newly diagnosed ART-naïve HIV-positive patients in Nanjing, China. These results highlight the need for further molecular surveillance-based monitoring of the HIV epidemic in Nanjing.

Real-world discontinuations due to neuropsychiatric symptoms in people living with HIV treated with second-generation integrase inhibitors: a systematic review.

INTRODUCTION: Second-generation integrase strand transfer inhibitors such as bictegravir (BIC) and dolutegravir (DTG) are the standard of care for starting therapy in people living with HIV (PLHIV). However, their use has been associated with neuropsychiatric symptoms (NPSs) that may lead to treatment discontinuation. We aim to describe and synthesize information on safety and discontinuation rates and to summarize potential risk factors associated with the development of NPSs in PLHIV treated with these regimens. AREAS COVERED: A systematic review of the literature was carried out in the international databases PubMed/Medline, Web of Science (WoS), Scopus, Embase, and Cochrane Library from 2013 to June 2022. Ninety observational studies reporting data on treatment discontinuation due to drug-related adverse events and NPSs were identified. EXPERT OPINION: Discontinuation rates due to NPSs increase with treatment time and, in light of the reviewed studies, are higher in PLHIV treated with DTG-based regimens compared with those treated with BIC/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF). This information could be useful for clinicians during treatment decision-making, reducing discontinuation rates and thereby promoting treatment success and durability. Additionally, the identification of potential risk factors in PLHIV prior to starting therapy could also help make the best therapy choices based on the characteristics of each individual.

The Burden of Neuropsychiatric Disorders in Medicaid Patients Living With HIV-1 Treated With Integrase Inhibitor or Protease Inhibitor Antiretroviral Therapies.

Objective: Data are scarce regarding the incidence of neuropsychiatric events (NPEs) in people living with human immunodeficiency virus (HIV)-1 taking integrase inhibitor (INI)- or protease inhibitor (PI)-based regimens. This study evaluated the prevalence, incidence, and economic burden of NPEs among people living with HIV-1 who were newly treated with INI- or PI-based regimens in a Medicaid population.Methods: A retrospective cohort study was conducted using administrative claims from the IBM MarketScan Multi-State Medicaid Database (January 1, 2014-December 31, 2018). Treatment-naive and treatment-experienced adults with HIV-1 newly treated with an INI- or PI-based regimen were included. Outcomes included NPE prevalence during the 12-month baseline period, prevalence of existing and incidence of new-onset NPEs during the 6-month post-index period, and total all-cause and NPE-related costs between treatment cohorts. Baseline characteristics between the 2 cohorts were balanced using inverse probability treatment weighting.Results: In the INI (n = 3,929) and PI (n = 3,916) cohorts, mean (SD) ages were 44.87 (12.81) and 44.36 (11.85) years, and 41.7% and 41.3% were female, respectively. High proportions of patients in both cohorts had NPEs during the 12-month baseline period. Among patients with no baseline NPEs, adjusted NPE incident rate ratios (95% CIs) during the post-index period were as follows: any, 1.15 (1.00-1.33); chronic, 1.18 (0.98-1.42); and acute, 1.16 (0.96-1.39). Mean all-cause and NPE-related costs were similar between cohorts.Conclusions: In this study of the Medicaid population, the prevalence and incidence of NPEs, as well as health care costs, were similar among people living with HIV-1 newly treated with an INI- or PI-based regimen.

Treatment-related early discontinuations and adverse events among newly diagnosed people living with HIV initiating integrase inhibitors in a real-world setting.

BACKGROUND: Cohort studies suggest higher discontinuation rates with integrase strand transfer inhibitors (INSTIs) than are seen in clinical trials. We assessed discontinuations and adverse events (AEs) that were considered related to the initial INSTI in the first year following initiation among treatment-naïve people living with HIV (PLWH). METHODS: Newly diagnosed PLWH initiating raltegravir, elvitegravir/cobicistat, dolutegravir or bictegravir in combination with emtricitabine/tenofovir alafenamide or emtricitabine/tenofovir disoproxil fumarate between 10/2007 and 1/2020 at the Orlando Immunology Center were included. Unadjusted incidence rates (IRs) and incidence rate ratios (IRRs) were calculated for treatment-related discontinuations and AEs associated with the initial INSTI in the first year following initiation. RESULTS: Of 331 enrolled, 26 (8%) initiated raltegravir, 151 (46%) initiated elvitegravir/cobicistat, 74 (22%) initiated dolutegravir and 80 (24%) initiated bictegravir. Within the first year, treatment-related discontinuations occurred in 3 on elvitegravir/cobicistat (IR 0.02 per person-years (PPY)) and 5 on dolutegravir (IR 0.08 PPY); no treatment-related discontinuations occurred among those initiating raltegravir or bictegravir. Eleven treatment-related AEs occurred in 7 on raltegravir (IR 0.46 PPY), 100 treatment-related AEs occurred in 63 on elvitegravir/cobicistat (IR 0.72 PPY), 66 treatment-related AEs occurred in 37 on dolutegravir (IR 0.97 PPY) and 65 treatment-related AEs occurred in 34 on bictegravir (IR 0.88 PPY). Unadjusted IRRs did not reveal any significant difference between INSTIs in terms of early treatment-related discontinuations or AEs. CONCLUSIONS: In our cohort, treatment-related AEs occurred in 43% initiating INSTIs but were responsible for early discontinuation in only 2% with no treatment-related discontinuations observed among those initiating RAL or BIC.

Safety and efficacy of switching to elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate in treatment-experienced people with HIV: a multicenter cohort study.

OBJECTIVES: We assessed the virologic efficacy of switching to co-formulated elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate (E/C/F/TDF) in patients with controlled HIV infection. METHODS: We conducted a retrospective multicenter observational cohort study including adult patients with controlled HIV-1 infection on any stable antiretroviral (ART) regimen, who switched to E/C/F/TDF. Success was measured by the proportion of patients with plasma viral load < 50 copies/ml at W48 using the FDA snapshot algorithm. We also assessed risk factors associated with virological failure (VF). RESULTS: 382 patients with HIV RNA < 50 copies/mL who switched to E/C/F/TDF were included in the study. Most patients (69.9%) were male, with median age 44 years (IQR 38-51), who had been on ART for a median of 7 years (IQR 4-13). Median CD4 count was 614/mm3 and 24.6% of the patients had a history of previous virological failure. The reasons for switching were simplification (67.0%) and tolerance issues (22.0%). At week 48, 314 (82.0% [95% CI 78.4-86.0]) patients had HIV RNA < 50 copies/mL, 13 (3.5% [95% CI 3.64-8.41]) experienced virological failure. Genotype at failure was available in 6/13 patients with detection of resistance-associated mutations to integrase inhibitors and NRTIs in 5/6 (83.3%) patients. We found no predictive factor associated with virological failure except for a borderline significance with the duration of viral suppression before the switch. Tolerability of E/C/F/TDF was good with 23/382 (6.0%) patients experiencing mild adverse reactions. CONCLUSION: In our cohort, switching well-suppressed patients to E/C/F/TDF resulted in few virologic failures and was well tolerated. However, resistance to integrase inhibitors emerged in patients with virological failure.

[Genetic Subtypes and Status of Transmitted Drug Resistance of HIV/AIDS Patients in Sichuan].

Objective: To investigate the distribution characteristics of the HIV genetic subtypes and the status quo of transmitted drug resistance among HIV/AIDS patients in Sichuan with no previous history of receiving antiretroviral therapy (ART). Methods: Adult HIV/AIDS patients who were hospitalized in Sichuan and who had no previous history of exposure to ART drugs exposure were enrolled. In-house sequencing of the HIV gene was done and phylogenetic tree was constructed to analyze the HIV genetic subtypes. The Stanford HIV drug resistance database was used to make online comparison of the drug resistance mutation sites and to determine the presence or absence of drug resistance, and the type and level of drug resistance. Results: A total of 120 patients were enrolled for the study, and 120 blood samples were collected. The genetic subtypes of 87.5% (105/120) of the samples were successfully amplified. The distribution characteristics of HIV genotype were as follows, CRF01_AE accounted for 46.67% (49/105), CRF07_BC accounted for 39.05% (41/105), and the others genetic subtypes, 14.28% (15/105). There were no significant differences between the different genetic subtypes in sex, age, ethnicity, HIV transmission route, drug resistance, baseline HIV RNA and baseline CD4 ( P>0.05). Drug-resistant mutation sites were detected in 25 samples, accounting for 20.83% (25/120) of all samples, with 16.67% (20/120) being potential drug resistance and 4.17% (5/120) being transmitted drug resistance. For the 24 samples found to be resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs), the mutation frequency of V179D/E was the highest. One patient showed resistance to protease inhibitors (PI) and the mutation site was M46I. No nucleoside reverse transcriptase inhibitor (NRTI) or integrase inhibitors (INTI) resistance were found. Conclusions: The main genetic subtypes of HIV/AIDS patients in Sichuan with no previous history of receiving ART were CRF01_AE and CRF07_BC. The incidence of transmitted drug resistance was low. The drug resistance detected in the study was predominantly resistance to NNRTIs. Baseline HIV drug resistance testing is of great significance for formulating effective ART regimens.

Safety and efficacy of pharmacotherapy containing INSTIs and chemotherapy drugs in people living with HIV and concomitant colorectal cancer.

BACKGROUND: Previous clinical data have shown that raltegravir-based antiretroviral therapy (ART) with fewer drug-drug interactions (DDIs) and adverse events (AEs) is a good regimen in patients with HIV infection who need cancer chemotherapy. There are currently few data on ART regimens that include Integrase inhibitors (INSTIs) other than RAL among this patient subgroup. METHODS: We evaluated the safety and efficacy of different kinds of INSTI-based regimens among patients with HIV and concomitant colorectal cancer (CRC) who received antineoplastic agents. RESULTS: From January 2020 to November 2021, 66 patients were enrolled. The patients were divided into three groups: 20 patients treated with dolutegravir (DTG)/lamivudine (3TC)/tenofovir (TDF) (group I), 24 patients treated with DTG/albuvirtide (ABT) (group II), and 22 patients treated with bictegravir (BIC)/tenofovir alafenamide (TAF)/emtricitabine (FTC) (group III). The majority of AEs during treatment were of grade 1-2. Treatment-related AEs of grade 3-4 occurred in 6 patients (9.09%), and no grade 5 AEs occurred. The most common AEs were nausea (100%) and neutrophils (84.85%) attributed to anticancer agents, and there was no significant difference in the incidence of these AEs among the three groups (P > 0.05). Viral load rebound was not observed among pretreated patients during chemotherapy. The viral load of untreated patients who started their ART concomitant with chemotherapy almost decreased to the lower limit of detection 6 months after ART initiation (only one patient in group III had a viral load of 102 copies/ml). At the 6th month, the CD4 count in group I decreased significantly from baseline (P < 0.05). However, the change in CD4 count was not significant in group II (P = 0.457) or group III (P = 0.748). CONCLUSIONS: DTG- or BIC-containing regimens are good options for patients with HIV and concomitant CRC.

Real-life use of Doravirine in treatment-experienced people living with HIV: A multicenter Italian study.

Use of doravirine (DOR), a new nonnucleoside reverse-transcriptase inhibitors recently approved for HIV treatment, is still unclear in clinical practice and real-life data are scarce. We retrospectively investigated the rationale for switching people with HIV to DOR-containing/-based regimens in a real-life cohort. Among 132 patients (68.9% males, median age 56 years), the main reasons to start DOR were prevention of toxicities (39.4%) and dyslipidemia (18.2%). DOR was combined with integrase inhibitors in 40.9% cases, and in 25.7% of patients, DOR was prescribed without availability of a genotypic resistance test. Twenty-four weeks after the switch to DOR-containing/-based regimens, no significant changes in CD4+ T-cell count, CD4/CD8 ratio, detectable HIV-RNA, serum creatinine levels, and body weight were detected. By contrast, a significant reduction in lipids (both cholesterol and triglycerides) was observed in 52 patients for whom a follow-up assessment was available (P = .008 and .01, respectively). Our data confirmed that switching to DOR-containing/-based regimens may have a favorable impact on lipid profile and a neutral impact on weight gain. However, more data are needed to support its use in patients who do not have a genotypic test available or have an extensive nonnucleoside reverse-transcriptase inhibitors-associated resistance, as well as its use in a dual regimen, especially in combination with second-generation integrase inhibitors.

Rapid Antiretroviral Therapy Program: Development and Evaluation at a Veterans Affairs Medical Center in the Southern United States.

Early HIV viral suppression (VS) improves individual health outcomes and decreases onward transmission. We designed an outpatient clinic protocol to rapidly initiate antiretroviral therapy (ART) in a large Veterans Health Administration (VA) HIV clinic. A pre-post evaluation was performed using a retrospective cohort study design for new diagnoses of HIV infection from January 2012 to February 2020. Time-to-event analyses were performed using the Cox proportional hazards model with the intervention group as the main exposure adjusted for integrase inhibitor usage, baseline viral load, age, gender, and race. Most of the patients were men (historical control: 94.8%, n = 55; Rapid Start: 94.8%, n = 55) and Black or African American persons (historical control: 87.9%, n = 51; Rapid Start: 82.8%, n = 48). More patients initiated treatment with an integrase inhibitor-based regimen in the Rapid Start group (98.3%, n = 57) compared with the historical control group (39.7%, n = 23). Compared with controls, the Rapid Start patients were significantly more likely to achieve VS at any given time during the study period (hazard ratio 2.65; p < 0.001). Median days (interquartile range) from diagnosis to VS decreased from 180.5 (102.5-338.5) to 62 (40-105) (p < 0.001), first appointment to VS decreased from 123 (68.5-237.5) to 45 (28-82) (p < 0.001), referral to first visit decreased from 20 (10-43) to 1 (0-3) (p < 0.001), and from first visit to ART dispense date decreased from 27.5 (3-50) to 0 (0-0) (p = 0.01). Prioritizing immediate ART initiation can compress the HIV care continuum from diagnosis to linkage to VS. Implementation of the Rapid Start Protocol should be considered at all VA facilities providing HIV care.

Incidence of hypertension in people with HIV who are treated with integrase inhibitors versus other antiretroviral regimens in the RESPOND cohort consortium.

OBJECTIVE: To compare the incidence of hypertension in people living with HIV receiving integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) versus non-nucleoside reverse transcriptase inhibitors (NNRTIs) or boosted protease inhibitors (PIs) in the RESPOND consortium of HIV cohorts. METHODS: Eligible people with HIV were aged ≥18 years who initiated a new three-drug ART regimen for the first time (baseline), did not have hypertension, and had at least two follow-up blood pressure (BP) measurements. Hypertension was defined as two consecutive systolic BP measurements ≥140 mmHg and/or diastolic BP ≥90 mmHg or initiation of antihypertensives. Multivariable Poisson regression was used to determine adjusted incidence rate ratios (aIRRs) of hypertension, overall and in those who were ART naïve or experienced at baseline. RESULTS: Overall, 4606 people living with HIV were eligible (INSTIs 3164, NNRTIs 807, PIs 635). The median baseline systolic BP, diastolic BP, and age were 120 (interquartile range [IQR] 113-130) mmHg, 78 (70-82) mmHg, and 43 (34-50) years, respectively. Over 8380.4 person-years (median follow-up 1.5 [IQR 1.0-2.7] years), 1058 (23.0%) participants developed hypertension (incidence rate 126.2/1000 person-years, 95% confidence interval [CI] 118.9-134.1). Participants receiving INSTIs had a higher incidence of hypertension than those receiving NNRTIs (aIRR 1.76; 95% CI 1.47-2.11), whereas the incidence was no different in those receiving PIs (aIRR 1.07; 95% CI 0.89-1.29). The results were similar when the analysis was stratified by ART status at baseline. CONCLUSION: Although unmeasured confounding and channelling bias cannot be excluded, INSTIs were associated with a higher incidence of hypertension than were NNRTIs, but rates were similar to those of PIs overall, in ART-naïve and ART-experienced participants within RESPOND.

Predictors of low-level HIV viraemia and virological failure in the era of integrase inhibitors: A Spanish nationwide cohort.

OBJECTIVES: To pinpoint factors associated with low-level viraemia (LLV) and virological failure (VF) in people living with HIV in the era of high-efficacy antiretroviral treatment (ART) and widespread use of integrase strand transfer inhibitor (INSTIs)-based ART. METHODS: We included adults aged > 18 years starting their first ART between 2015 and 2018 in the Spanish HIV/AIDS Research Network National Cohort (CoRIS). Low-level viraemia was defined as plasma viral load (pVL) of 50-199 copies/mL at weeks 48 and 72 and VF was defined as pVL ≥ 50 copies/mL at week 48 and pVL ≥ 200 copies/mL at week 72. Multivariable logistic regression models assessed the impact on LLV and VF of baseline CD4 T-cell count, CD4/CD8 T-cell ratio and pVL, initial ART classes, age at ART initiation, time between HIV diagnosis and ART initiation, gender and transmission route. RESULTS: Out of 4186 participants, 3120 (76.0%) started INSTIs, 455 (11.1%) started boosted protease inhibitors (bPIs) and 443 (10.8%) started nonnucleoside reverse transcriptase inhibitors (NNRTIs), either of them with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs). Low-level viraemia was met in 2.5% of participants and VF in 4.3%. There were no significant differences throughout the years for both virological outcomes. Baseline HIV-1 RNA > 5 log10 copies/mL was the only consistent predictor of higher risk of LLV [adjusted odds ratio (aOR) = 9.8, 95% confidence interval (CI): 2.0-48.3] and VF (aOR = 5.4, 95% CI: 1.9-15.1), even in participants treated with INSTIs. CONCLUSIONS: The rates of LLV and VF were low but remained steady throughout the years. Baseline HIV-1 RNA > 5 log10 copies/mL showed a persistent association with LLV and VF even in participants receiving INSTIs.