Previous Antiretroviral Therapy Research Articles

Stated preferences for long-acting injectable ART among mobile men living with HIV in Malawi: a qualitative study

Background: Long-acting injectable (LAI) antiretroviral medications are as effective as daily oral antiretroviral therapy (ART) and offer discreet, less frequent dosing. LAIs may be ideal treatment options for people who experience challenges with adherence to daily oral ART, including mobile men living with HIV (MLHIV). Methods: We conducted a qualitative sub-study within two trials (ENGAGE and IDEaL) in 24 health facilities in Malawi that enrolled MLHIV >15 years not on ART. We conducted in-depth interviews with a stratified random sample of participants who had taken oral ART and self-reported mobility (travel) during the 6-month study (>1 trip of >3 nights). Interviews described cabotegravir/rilpivirine and asked about clients’ stated preferences for LAI vs. oral ART and their reasoning. Interviews were translated, transcribed, coded in Atlas.ti, and analyzed using framework analysis. Results: We interviewed 29 mobile MLHIV from 1 July to 30 August 2022, median age 36 (IQR:31-41), mean 28 nights away in last six months (SD: 40). Nearly all participants (26/29) expressed a preference for LAI over daily oral ART because LAI would reduce the risks of forgetting to take pills and unwanted disclosure. Three men preferred oral ART primarily due to fear of side effects from a new medication. A few men reported they would change their preference if injection site reactions prevented them from working. Conclusion: Mobile MLHIV in Malawi with previous ART adherence challenges expressed strong stated preferences for LAI over daily oral ART. Further research is needed to understand implementation challenges and potential effectiveness of LAI among harder-to-reach populations.

Analysis of ART effects and drug resistance in adult HIV/AIDS patients in Meigu County, Liangshan Prefecture, China

Background objectiveThis study aimed to understand the basic situation of adults with human immunodeficiency virus (HIV) receiving antiretroviral therapy (ART) in Meigu County, Liangshan Yi Autonomous Prefecture. The information of patients who had been on ART for more than 6 months, the effect of ART, the possible reasons for ART failure, knowledge of drug resistance among patients with ART failure and the possible reasons for the emergence of drug resistance were analyzed.MethodsA total of 2753 people living with HIV (PLWH) were collected for HIV-1 RNA virus nucleic acid testing. Plasma specimens with HIV-1 RNA ≥ 1000 copies/mL were sent to the laboratory for nucleic acid extraction, PCR, electrophoresis and sequencing, and the sequencing results were submitted to the HIV drug resistance database of Stanford University for subtyping to determine the drug resistance mutation sites and drug sensitivity levels.ResultsA total of 2753 patients were enrolled in this study. Antiviral therapy failed in 288 patients and was successfully amplified in 245, of which 111 had resistance genes. The resistance rate to failure of viral suppression was 45.3% (111/245). The highest rates of resistance to NNRTIs were found for efavirenz (EFV) and nevirapine (NVP) (42.9%), and the highest rates of resistance to NRTIs were found for 3TC and emtricitabine (FTC) (15.9%). The most common NNRTI resistance mutation site was K103N (20.8%), followed by V179D (9.4%) and V106M (7.8%); the most common NRTI resistance mutation site was M184V/I/MV (14.3%), followed by K65R (6.9%); three PI-associated resistance mutation sites were identified. The subtype of the resistant strain was CRF07-BC in almost all patients (98.9%).ConclusionsCompared with the previous low ART efficacy in the county, this study showed that the overall virological failure (VF) resistance rate in the county is still low, dominated by resistance to EFV, NVP, 3TC, FTC, and didanosine (DDI). Due to economic constraints, the core regimen is still 3TC + TDF, but before initiating ART, testing for HIV-1 subtypes and resistance should be conducted to avoid resistance that can lead to VF, especially for patients with high risk factors for resistance as shown by epidemiologic investigations.

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.

Consistency of drug-resistant mutations in plasma and peripheral blood mononuclear cells of patients with treatment-naïve and treatment-experienced HIV-1 infection.

Genotypic drug resistance testing is cursrently recommended by the World Health Organization for all patients infected with human immunodeficiency virus type 1 (HIV-1) undergoing care or switching regimes due to failure with previous antiretroviral therapy (ART). Patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) who meet the criteria for free testing for genotypic drug resistance due to poor adherence in Henan Province may resume their previous regimens before resampling. Therefore, resistance testing based on plasma RNA can fail in a proportion of patients. Resistance testing based on peripheral blood mononuclear cells (PBMCs) is an alternative option. In this study, we investigated the differences in drug-resistant mutations (DRMs) between plasma HIV RNA and proviral DNA in treatment-experienced and treatment-naïve patients. Matched plasma RNA and proviral DNA samples of 66 HIV-1 infected treatment-naïve and 78 treatment-experienced patients were selected for DRM analysis and comparison. DRMs were detected in 27.3% (18/66) of treatment-naïve and 80.8% (63/78) of treatment-experienced samples. Resistance to at least one drug was detected based on analysis of plasma RNA and proviral DNA in 7.6% (5/66) and 9.1% (6/66) of treatment-naïve patients and in 79.5% (62/78) and 78.2% (61/78) of treatment-experienced patients, respectively. Furthermore, 61/66 (92.4%) of treatment-naïve patients showed concordant RNA and DNA drug resistance. When drug resistance was defined as intermediate and high, the concordance of drug resistance profiles of paired RNA and proviral DNA samples derived from treatment-naïve patients were up to 97.0% compared with only 80.8% (63/78) in treatment-experienced patients. Our data indicate that drug resistance testing based on plasma RNA or proviral DNA might be interchangeable in treatment-naïve patients, whereas plasma RNA-based testing remains the best choice for drug resistance analysis in patients with ART failure in clinical practice.

Bictegravir/Tenofovir Alafenamide/Emtricitabine: A Real-Life Experience in People Living with HIV (PLWH).

Bictegravir (BIC), a recently introduced integrase inhibitor, is available in a single tablet regimen with tenofovir alafenamide (TAF) and emtricitabine (FTC) (BIC-STR). This study aimed to describe a real-life experience with BIC-STR. We retrospectively analyzed the data of people living with HIV (PLWH) on antiretroviral therapy (ART) with BIC-STR followed by the Clinic of Infectious Diseases of Perugia (Perugia, Italy) from September 2019 to February 2023. 270 PLWH were enrolled with a median follow-up time on BIC-STR of 2.2 years (IQR 1.2-2.7). In the overall population, in treatment-experienced (N = 242), in treatment-naïve (N = 28), and in population with age > 60 years old (N = 86), we observed that CD4 cell count improved in absolute number, percentage and CD4/CD8 ratio, under BIC-STR. Patients with viremia < 50 cp/mL increased in all groups. In the overall population, previous ART with TAF and nadir CD4 cell count favored immunological recovery. In the ART-experienced group, time in therapy with BIC-STR was associated with HIV-RNA undetectability. In the older group, previous opportunistic infection and advanced age were associated with lower CD4 count. BIC-STR was demonstrated, in real-life, to be a valid option for a switch, such as initial ART.

Prior exposure to antiretroviral therapy among adult patients presenting for HIV treatment initiation or reinitiation in sub-Saharan Africa: a systematic review

ObjectivesAs countries have scaled up access to antiretroviral therapy (ART) for HIV, attrition rates of up to 30% annually have created a large pool of individuals who initiate treatment with...

Interventional study on Dolutegravir and other antiretrovirals in patients with subclinical atherosclerosis in the Kinshasa Hospital

After 2016, the World Health Organization (WHO) proposed Dolutegravir (DTG) as an alternative first-line treatment for adults. Thus, the purpose of this study was to identify biomarkers of cardiometabolic risk capable of demonstrating the beneficial effect of Dolutegravir (DTG) compared to other antiretrovirals in predicting atherosclerosis in people living with HIV (PLHIV) and hospitalized in Kinshasa Hospital. we conducted an interventional study of people living with HIV who had received antiretroviral therapy (ART) for at least 6 months and were treated in the structures of the network coordinated by the Catholic Church (BDOM-Bureau Diocésain des Oeuvres Médicales) and of the University Clinics of Kinshasa (CUK) between January 2017 and December 2021. Subclinical atherosclerosis was defined as Pulsed Pressure (PP) ≥60 mm Hg; Carotid Intima-Media Thickness (CIMT) > 0.8 mm; and Systolic Pressure Index (SPI) < 0.9. Logistic regression was used in the statistical analysis of associations. a total of 334 PLHIV were recruited, of whom 96.1% (n=321) were on ART and 13.9% (n=13) were ART naïve patients. The mean age of PLHIV was 51±12 years with a female predominance (70.4%; n=235); the independent determinants of subclinical atherosclerosis were marital status (aOR: 4. 95% CI 1.5-10.5; p<0.006), low socioeconomic level (aOR: 10.7, 95% CI 2.3-48.7 p<0.002), duration of HIV infection (aOR: 6.6, 95% CI 2.8-16; p<0.0001), duration of antiretroviral therapy ≥9 years (aOR: 0.3, 95% CI 0.2-0.7; p<0.005) and total cholesterol ratio/high-density lipoprotein-cholesterol (CT/HDL-c)(aOR: 2, 95% CI 1.1-3.6; p= 0.034). The mean values of traditional and emergent variables were significantly higher in the previous ART regimen without DTG than in the new regimen with DTG. However, dyslipidemia was detected during the new DTG-based regimen. dyslipidemia was common during the DTG-based regimen. Marital status, low socioeconomic level, duration of HIV infection, duration of antiretroviral treatment beyond 9 years and the TC/HDL-c ratio were identified as determinants of subclinical atherosclerosis in PLHIV on ART hospitalized in the Kinshasa hospital.

Proximal tubular dysfunction related to tenofovir in people living with HIV/AIDS: a pharmacogenetic study.

The purpose of this case-control study was to verify the association between single nucleotide polymorphisms (SNPs) in genes encoding drug transporters related to tenofovir disoproxil fumarate (TDF) and proximal renal tubular dysfunction (PRTD), and the association between PRTD and clinical characteristics. The 'cases' met the diagnostic criteria for PRTD, determined by the presence of two or more of the following abnormalities: non-diabetic glycosuria, metabolic acidosis, increased uric acid and phosphorus excretion, decreased tubular phosphorus reabsorption and β2-microglobulinuria. We analyzed eight SNPs in ABCC2, ABCC4, ABCC10 and SLC28A2 genes. Genotyping was performed using real-time PCR. Of the 204 people living with HIV, 38 (18.6%) met the criteria for diagnosis of PRTD and 131 were male (64.2%), with a mean age of 49 years and a history of previous antiretroviral therapy for an average of 5 years. In the multivariate analysis, older individuals, TDF use, protease inhibitor, antihypertensives and anticonvulsants were associated with a risk of developing PRTD. Increased excretion of β2microglobulin was associated with the A/G genotype of rsCC8187710 from ABCC2 ( P = 0.003) and the following genotypes of ABCC4 SNPs: A/G from rs1059751 ( P = 0.023), G/G from rs1059751 ( P = 0.030) and C/C of rs3742106 ( P = 0.041). The increase in the fraction of excreted phosphorus was associated with the C/T genotype of SNCC rsP40037 from ABCC2 ( P = 0.0041). The results indicate an important relationship between SNPs associated with these markers and changes in proximal renal tubule function, and thus support their use as biomarkers for the early detection of PRTD risk.

Observed CD4 counts at entry into HIV care and at antiretroviral therapy prescription by age in the USA, 2004-18: a cohort study.

Adults aged 50 years or older comprise a majority of people with HIV in the USA. Our objective was to describe observed differences by age in CD4 count at entry into HIV care, timing of antiretroviral therapy (ART) prescription, and CD4 count at time of ART prescription before (2004-11) and during (2012-18) the current era of universal treatment. For this descriptive study, we calculated median (IQR) CD4 count at entry into care, days from entry into care to ART prescription, and CD4 count at time of ART prescription among patients enrolled in US-based clinical cohorts of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD; see appendix). We excluded participants with no CD4 count recorded at entry into care, medical records that suggested previous ART use, or previous AIDS diagnosis. All calculations were stratified by age (≥50 and 18-50 years) and calendar year. Of 35 293 ART-naive adult participants entering care between Jan 1, 2004 and Dec 31, 2018, 5794 (16%) were women and 29 499 (84%) were men; 15817 (45%) were Black, 11566 (33%) were White, 5538 (16%) were Hispanic (any race), 737 (2%) were Asian or Pacific Islander, 152 (0.4%) were Indigenous, and 98 (0.3%) were multiracial. Median age at entry into care was 39 years (IQR 29-49); 8004 (23%) were aged 50 years or older. Of 29 141 participants initially prescribed ART, 7274 (25%) were aged 50 years or older. From 2004 to 2018, median CD4 count at entry into care increased from 228 cells per µL (IQR 80-422) to 295 cells per µL (134-489) among adults aged 50 years and older, and from 297 cells per µL (119-480) to 378 cells per µL (202-564) among adults younger than 50 years. Median days from entry into care to ART prescription declined from 56 (IQR 17-658) to 6 (0-15) among adults older than 50 years, and from 61 (17-509) to 6 (0-16) among adults younger than 50 years. Median CD4 count at time of ART prescription increased from 139 cells per µL (IQR 59-257) to 311 cells per µL (137-504) among adults aged 50 years or older, and from 166 cells per µL (49-287) to 377 cells per µL (198-564) among adults younger than 50 years. Before the release of universal treatment guidelines by the US Department of Health and Human Services in 2012, median time to ART prescription was already falling, leading to increases in median CD4 count at ART prescription for both age groups; both measures continued to improve in the treat-all era. However, median CD4 counts, both at entry into care and at ART prescription, among adults aged 50 years and older were lower than those of adults younger than 50 years throughout the study period. Furthermore, even into the treat-all era, over half of adults aged 50 years and older entered care with CD4 counts of less than 350 cells per µL, potentially because of factors including immunosenescence, delayed HIV diagnosis, and late presentation to care. Given that age-related immunological changes might not be fully avoidable, targeted strategies for increasing HIV risk awareness, routine testing, and immediate linkage to HIV care at diagnosis are particularly essential for this population. US National Institutes of Health grant U01AI069918.

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).

Prevalence of undetectable and suppressed viral load in HIV-infected pregnant women initiating Option B+\u2009in Uganda: an observational study nested within a randomized controlled trial

BackgroundViral load (VL) testing is key in monitoring adherence to antiretroviral therapy (ART) and documenting HIV treatment response. As per HIV treatment guidelines in Uganda, the first VL test is recommended 6 months after initiation of ART. Undetectable VL (uVL) at ART initiation may be helpful in detecting elite controllers in the absence of previous ART use. We investigated viral suppression at ART initiation among a cohort of HIV-positive pregnant women enrolled in the Friends for Life Circles (FLC) for Option B+ randomized controlled trial (RCT).MethodsPregnant women ≥ 18 years of age testing positive for HIV at their first antenatal care visit and starting on ART Option B+ as per the National PMTCT Program guidelines were enrolled into the FLC for Option B+ RCT in urban Kampala and rural Mityana districts of Uganda. Each participant had whole blood samples collected at enrolment to assess baseline VL. Plasma HIV-1 RNA was quantified using COBAS Ampliprep /COBAS Taqman. Baseline VL below 400 RNA copies/ml was considered as viral suppression while baseline VL below 20 RNA copies/ml was considered uVL.ResultsThe mean duration from the date of ART initiation to time of sample collection for baseline VL assessment was 4.4 days (SD 3.6). Of the 532 HIV-positive pregnant women enrolled in the FLC for Option B+ study and newly starting Option B+ without a self-reported history of prior ART use, 29 (5.5%) had uVL and 113 (21.4%) had suppressed VL at baseline. There was no association between participants’ age, gravidity, marital status, mean monthly income, educational level, disclosure of HIV status to partner, and uVL or viral suppression at baseline. However, non-disclosure of HIV status to any other person was associated with decreased odds of viral suppression at baseline (OR 0.640; 0.416–0.982).ConclusionTwenty-one percent of HIV-positive Ugandan pregnant women initiating ART (Option B+) showed virological suppression at baseline and were presumed to be “elite controllers” or to have misreported being ART-naive. Further studies are needed to better understand the biologic mechanisms of elite controllers among pregnant women as well as to differentiate elite controllers from concealed ART use.Trial Registration The trial was registered as NCT02515370 (04/08/2015) on Clinicaltrials.gov.

Physiologically Relevant Concentrations of Dolutegravir, Emtricitabine, and Efavirenz Induce Distinct Metabolic Alterations in HeLa Epithelial and BV2 Microglial Cells.

Microglia, the resident brain phagocytes, likely play a key role in human immunodeficiency virus (HIV) infection of the central nervous system (CNS) and subsequent neuropathogenesis; however, the nature of the infection-induced changes that yield damaging CNS effects and the stimuli that provoke microglial activation remains elusive, especially in the current era of using antiretroviral (ARV) drugs for ARV therapy (ART). Altered microglial metabolism can modulate cellular functionality and pathogenicity in neurological disease. While HIV infection itself alters brain energy metabolism, the effect of ARV drugs, particularly those currently used in treatment, on metabolism is understudied. Dolutegravir (DTG) and emtricitabine (FTC) combination, together with tenofovir (TAF or TDF), is one of the recommended first line treatments for HIV. Despite the relatively good tolerability and safety profile of FTC, a nucleoside reverse transcriptase inhibitor, and DTG, an integrase inhibitor, adverse side effects have been reported and highlight a need to understand off-target effects of these medications. We hypothesized that similar to previous ART regimen drugs, DTG and FTC side effects involve mitochondrial dysfunction. To increase detection of ARV-induced mitochondrial effects, highly glycolytic HeLa epithelial cells were forced to rely on oxidative phosphorylation by substituting galactose for glucose in the growth media. We assessed ATP levels, resazurin oxidation-reduction (REDOX), and mitochondrial membrane potential following 24-hour exposure (to approximate effects of one dose equivalent) to DTG, FTC, and efavirenz (EFV, a known mitotoxic ARV drug). Further, since microglia support productive HIV infection, act as latent HIV cellular reservoirs, and when dysfunctional likely contribute to HIV-associated neurocognitive disorders, the experiments were repeated using BV2 microglial cells. In HeLa cells, FTC decreased mitochondrial REDOX activity, while DTG, similar to EFV, impaired both mitochondrial ATP generation and REDOX activity. In contrast to HeLa cells, DTG increased cellular ATP generation and mitochondrial REDOX activity in BV2 cells. Bioenergetic analysis revealed that DTG, FTC, and EFV elevated BV2 cell mitochondrial respiration. DTG and FTC exposure induced distinct mitochondrial functional changes in HeLa and BV2 cells. These findings suggest cell type-specific metabolic changes may contribute to the toxic side effects of these ARV drugs.

Durability of non-nucleotide reverse transcriptase inhibitor-based first-line ART regimens after 7 years of treatment in rural Uganda: A prospective cohort study.

Most antiretroviral therapy (ART) programs in resource-limited settings have historically used non-nucleotide reverse transcriptase inhibitor (NNRTI)-based regimens with limited access to routine viral load (VL) testing. We examined the long-term success of these regimens in rural Uganda among participants with 1 measured suppressed VL.We conducted a prospective cohort study of participants who had been on NNRTI-based first-line regimens for ≥4 years and had a VL <1000 copies/mL at enrollment in Jinja, Uganda. We collected clinical and behavioral data every 6 months and measured VL again after 3 years. We quantified factors associated with virologic failure (VF) (VL ≥ 1000 copies/mL) using Wilcoxon Rank Sum, chi-square, and Fisher's Exact Tests.We enrolled 503 participants; 75.9% were female, the median age was 45 years, and the median duration of time on ART was 6.8 years (IQR = 6.0–7.6 years). Sixty-nine percent of participants were receiving nevirapine, lamivudine, and zidovudine regimens; 22.5% were receiving efavirenz, lamivudine, and zidovudine; and 8.6% were receiving other regimens. Of the 479 with complete follow-up data, 12 (2.5%) had VL ≥ 1000 copies/mL. VF was inversely associated with reporting never missing pills (41.7% of VFs vs 72.8% non-VFs, P = .034). There were differences in distribution of the previous ART regimens (P = .005), but no clear associations with specific regimens. There was no association between having a VL of 50 to 999 copies/mL at enrollment and later VF (P = .160).Incidence of VF among individuals receiving ART for nearly 7 years was very low in the subsequent 3 years. NNRTI-based regimens appear to be very durable among those with good initial adherence.

Emergency immune reconstitution inflammatory syndrome (IRIS) in HIV drug discontinued with tuberculous meningoencephalitis: a case report

Background: Immune reconstitution inflammatory syndrome (IRIS) is a paradoxical condition in which the administration of ART (antiretroviral therapy) to human immune virus (HIV) patients causes a deterioration in clinical situations. This article describes IRIS in an HIV patient who discontinued the drugs and was accompanied by opportunistic infection with tuberculous meningoencephalitis.Case Presentation: A 40-year-old male complained of high fever and severe headache for 1 week, then the patient had general tonic-clonic seizures twice and less than 5 minutes. After seizure, patient experiences a loss of consciousness with the only response to pain stimuli. He was diagnosed with HIV since 3 years ago and only taking ART 2 months after being diagnosed. The physical examination revealed neck stiffness with a positive Brudzinski I and Kernig Sign, as well as lateralization to the right side. Oral candidiasis was found. HIV screening tests were reactive with CD4 65 cells/mm3. Cerebrospinal fluid (CSF) examination showed 172.8 mg/dL protein, 23 mg/dL glucose, MN 13/mm3 dominant cells, clear CSF fluid and colorless, supporting tuberculous meningoencephalitis (METB). Multi sliced CT-Scan (MSCT) head contrast shows enhancement of the basal cistern. The patient received the ART tenofovir-lamivudine-efavirenz. Then he has experienced a deterioration in clinical condition. He had ARDS, respiratory failure and was intubated, but failed resuscitation attempts.Conclusion: The patient was diagnosed with HIV 3 years ago but discontinued the treatment. HIV causes diffuse inflammation throughout the body including the cardiac, where myocarditis cannot be ruled out as a cause of death. IRIS may occur when the patient has risk factors for not getting previous ART (withdrawal of drugs) and has a low CD4 count. According to the criteria proposed by Robertson, there were worsening clinical symptoms, associated with initiation of ART administration, not explained by the presence of previously acquired infection, we suggest IRIS as causes of death in this patient.Â

Pretreatment HIV Drug Resistance Among Adults Initiating or Re-Initiating First-Line Antiretroviral Therapy in Zimbabwe: Fast-Tracking the Transition to Dolutegravir-Based First-Line Regimens?

Pretreatment drug resistance (PDR) can compromise antiretroviral therapy (ART) efficacy and undermine the WHO targets to end the AIDS epidemic as a public health threat by 2030. Thus, we examined the level of PDR in Harare, Zimbabwe. Eligible study participants were adults who were ART naive or individuals with previous ART exposure reinitiating treatment, recruited between October 2018 and February 2020 in a HIV ART treatment clinic, in Harare. HIV drug resistance tests were performed for all specimens with viral load ≥400 copies/mL and interpreted using the Stanford HIVDB Algorithm. Chi-square test or Fisher's exact test was used for comparison of proportions of PDR across ART-naive or prior ART-exposed participants. All statistical analyses were performed using Stata version 14. Overall, 120 samples were genotyped of whom 104 were ART naive and 16 reported previous ART exposure. The overall PDR frequency among all participants was 31% [95% confidence interval (CI): 22.5-39.6]. PDR to any non-nucleotide reverse transcriptase inhibitor (NNRTI) was reported in 29% (95% CI: 21.0-37.9). PDR to nucleotide reverse transcriptase inhibitors (NRTIs) and protease inhibitors were low, found in 3% (95% CI: 0.9-8.2) and 1% (95% CI: 0.02-4.52), respectively. PDR to NNRTIs [efavirenz/nevirapine (EFV/NVP)] was found in 17% (95% CI: 10.5-24.6) and was more than six times higher among people with previous ART exposure than ART-naive people: 63% versus 10%, p < .001. Our study shows that PDR to NNRTIs in Zimbabwe has remarkably increased from the 10.9% prevalence reported in the 2016 WHO survey. Addressing PDR at a national level is a critical need and will be facilitated by fast-tracking the transition to dolutegravir in first-line ART regimens.

Is age and not antiretroviral therapy the strongest risk factor for chronic pain in HIV-infected population?

BackgroundChronic pain in HIV-infected patients on effective antiretroviral therapy (ART) limits patients’ normal functioning both somatically and psychologically. The current state of knowledge on the topic is insufficient, with the underlying causes of this pain unexplained. Therefore we analyzed the frequency and factors associated with chronic pain in HIV-infected patients on ART.MethodsWe conducted a prospective, survey study, including consecutive HIV-infected patients under specialist care at the HIV Outpatient Clinic of the Hospital for Infectious Disease in Warsaw between February 2014 and December 2016. During their routine visit all patients who agreed to participate in the study were surveyed using a study questionnaire. For all patients reporting any pain the Brief Pain Inventory (BPI) form and Douleur Neuropathique 4 Questions form (DN4) were completed. Data on history and current ART and laboratory measurements were obtained from electronical database. Chi-squared and Kruskal-Wallis tests were used for group comparison. The potential factors associated with chronic pain were identified via logistic regression models.ResultsIn total 196 HIV-infected patients were included in the study, 57 (29,1%) of them reported chronic pain. The reported pain was mostly (75%) limited to a single area of the body. In univariable logistic regression model the odds of chronic pain were significantly higher with increasing age (OR 1.36 [95%CI:1.17–1.58]), time under specialist care (OR 2.25 [95%CI:1.42–35.7]), time on ART (OR2.96 [95%CI:1.60–5.49]), previous ART with zidovudine (OR 2.00[95%CI:1.06–1.55]) and previous treatment with ddI, ddC or d4T (OR4.13 [95%CI:1.92–8.91]). Homosexual route of HIV infection as compared to injecting drug use was decreasing the odds of chronic pain (OR0.33 [95%CI: 014–0.75]). In multivariable analyses, adjusting for all above the only factor associated with chronic pain was age (OR1.28 [95%CI:1.06–1.55]).ConclusionsThe prevalence of chronic pain in the studied population of HIV-infected Polish patients was high. The only risk factor for chronic pain identified was age. With ageing HIV population it is therefore imperative to develop cooperation protocols for specialist HIV treatment clinics, pain treatment clinics, and rehabilitation units.

Treatment Patterns and Predictors of Adherence in HIV Patients Receiving Single- or Multiple-Tablet Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide.

PurposeDarunavir, cobicistat, emtricitabine, and tenofovir alafenamide can be used as a single-tablet regimen (STR, DRV/c/FTC/TAF) or multiple-tablet regimen (MTR, DRV/c+FTC/TAF) to treat patients with human immunodeficiency virus (HIV). This study described treatment patterns and predictors of adherence among patients with HIV initiated on DRV/c/FTC/TAF or DRV/c+FTC/TAF.Patients and MethodsA retrospective longitudinal study was conducted using linked claims and electronic medical records from Decision Resources Group’s Real World Data Repository (7/17/2017–6/1/2019). Treatment-naïve and treatment-experienced virologically suppressed adults with HIV-1 prescribed DRV/c/FTC/TAF or DRV/c+FTC/TAF (index date) were included. Six-month persistence (no treatment gaps >60 and >90 days) and adherence (proportion of days covered [PDC]) to the index regimen were evaluated among patients with ≥6 months of observation post-index. Predictors of low adherence (PDC<80%) were evaluated using a logistic regression model.ResultsAmong 2633 eligible patients (49.5 years old, 29% female, 37% African American/Black), 12% were treatment-naïve pre-index and 88% switched from a previous antiretroviral therapy; 84% initiated DRV/c/FTC/TAF and 16% initiated DRV/c+FTC/TAF. Among 822 DRV/c/FTC/TAF patients with ≥6 months of observation post-index, 80% and 86% had no >60- and >90-day gaps in DRV/c/FTC/TAF coverage, respectively, while among 204 DRV/c+FTC/TAF patients with ≥6 months of observation post-index, 69% and 75% had no >60- and >90-day gaps in DRV/c+FTC/TAF coverage, respectively. Mean (median) PDC for the index regimen was 81% (93%) for patients treated with DRV/c/FTC/TAF and 73% (83%) for patients treated with DRV/c+FTC/TAF. Predictors of low adherence included younger age (odds ratio [OR]=2.36, p=0.017), higher Quan-Charlson comorbidity index (OR=1.32, p=0.012), use of MTR regimen at index (OR=1.69, p=0.022), and prior low adherence (OR=2.56, p<0.001).ConclusionAmong patients initiating a DRV/c-based regimen, those initiating STR had higher 6-month adherence/persistence than those initiating MTR, highlighting the potential benefits of the STR formulation, particularly among younger patients with multiple comorbidities and prior low adherence.

High Prevalence of AH in HIV Patients on ART, in Bahia, Brazil.

The prevalence of arterial hypertension (AH) in HIV-patients is highly variable and its association with antiretroviral therapy (ART) is controversial. To estimate the prevalence of AH and associated factors in HIV-patients on ART. This cross-sectional study was conducted in HIV-patients attended in a referral center in Salvador, Brazil. We evaluated clinical, socio-demographic and anthropometric data. Student's ttests or Mann-Whitney's and Pearson's chi-square tests were used to compare the groups. Values of p <0.05 were considered significant. The variables that presented a value of p <0.20 were included in a logistic regression model. We evaluated 196 patients (60.7% male) with a mean age of 46.8 ± 11.7 years and a mean body mass index of 24.9 ± 5.3 kg / m2. The median elapsed time since HIV diagnosis and ART use was 11.8 (4.4 - 18.1) and 7.2 (2.7 - 15.3) years, respectively. The prevalence of AH was 41.8%. For individuals > 50 years old, there was a significant association between the increased abdominal circumference and AH and patients ≤ 50 years old presented significant association between AH and overweight, increased abdominal circumference and number of previous ART regimens. After multivariate analysis, age [OR:1.085; 95% CI 1,039 - 1,133], overweight [OR: 4.205; 95% CI 1,841 - 9,606], family history of AH [OR: 2.938; 95% CI 1,253 - 6.885], increased abdominal circumference [OR: 2.774; 95% CI 1.116 - 6.897] and life-time number of ART regimens used [OR: 3.842; 95% CI 1.307 - 11.299] remained associated with AH. AH was highly prevalent and was associated not only with classical risk factors for arterial hypertension, but also with specific ART regimens.

Pan-resistant HIV-1 emergence in the era of integrase strand-transfer inhibitors: a case report

In 2019, WHO reported that the prevalence of HIV-1 drug resistance to first-line regimens of non-nucleoside reverse transcriptase inhibitors is increasing in countries with a low number of therapeutic options. This increasing prevalence of drug resistance is an important threat to ending the AIDS pandemic, as it compromises individual clinical outcomes and increases the risk of transmission. In countries with a high number of therapeutic options, little global information is available regarding the prevalence of multidrug-resistant HIV-1 infections, which presents a potential challenge for the clinical management of people with HIV. Even after the approval of two new antiretroviral drug classes in 2007, which were intended to help alleviate this problem, some cases of infection with HIV-1 that show limited susceptibility to the five available antiretroviral classes have been described. We did a thorough in-vitro evaluation of the drug resistance profile of HIV-1 from an observational case to show that five-class pan-resistant clinical cases do exist. We investigated a case of a highly treatment-experienced Caucasian male with HIV-1 who had a poor virological response to previous combination antiretroviral therapy (ART) and who was not responding to a dolutegravir-based regimen. For the complete panel of approved antiretrovirals, we examined genotypic resistance using the Stanford HIV Drug Resistance Database interpretation algorithm, and we examined phenotypic resistance using the PhenoSense and Trofile assays. Using viral gp160 sequence analysis, we also explored the potential susceptibility of this virus to novel therapeutic drugs targeting viral envelope binding. The individual was diagnosed with HIV-1 on Sept 29, 1989. Since starting antiretroviral treatment in 1995, the individual had received more than 14 different antiretroviral drugs over the course of his illness. In November, 2017, a blood sample was collected from the individual and we did drug resistance analysis tests. We found that this individual was infected with a pan-resistant HIV-1 subtype B strain that showed broad genotypic and phenotypic cross-resistance to all approved antiretroviral drugs, including the newest second-generation integrase inhibitors, dolutegravir and bictegravir. With no remaining clinical options available, except for investigational drugs, this case provides evidence that new antiretroviral drugs with different mechanisms of action are needed. Our case report shows that HIV-1 multidrug cross-resistance remains an important concern, despite the extensive number of antiretroviral drugs currently available. Highly treatment-experienced patients, especially those who have been given suboptimal combination ART, can develop highly complex resistance-associated mutation patterns, conferring cross-resistance to all widely available ARTs. The identification and reporting of cases, such as the one described in this report, are needed to increase awareness of emerging trends that have the potential to affect patient management. None.

Examining psychosocial correlates of physical activity and sedentary behavior in youth with and without HIV.

The objectives of this study were to examine differences in physical activity behaviors as a function of human immunodeficiency virus (HIV) status and sex, to test differences in physical activity self-efficacy (PASE), body weight satisfaction (BWS), and enjoyment of physical activity as a function of HIV status, and to determine if PASE, BWS, and enjoyment are associated with daily physical activity (daily PA), muscle strengthening activities, and sedentary behavior of youth with and without HIV. A total of 250 HIV positive (HIV+) and HIV negative (HIV-) youth from Botswana aged 12–23 years (Mean = 17.87, SD = 2.24) participated in the study. The HIV+ group (n = 88) was recruited from a previous 12-month antiretroviral therapy (ART) and nutrition intervention study. The HIV- group (n = 162) was randomly selected from public junior and senior (secondary) high schools in and around Gaborone. Participants’ PASE, BWS, enjoyment of physical activity, daily PA, muscle strengthening, body mass index (BMI), and sedentary behavior were obtained using items from the Youth Risk Behavior Surveillance Survey. Multivariate analysis of variance (MANOVA) showed that the HIV- group (M = 1.20, SE = 0.06, CI = 1.08 to 1.32) had significantly higher daily PA than the HIV+ group (M = 0.99, SE = 0.08, CI = 0.82 to 1.15). The HIV- group (M = 0.91, SE = 0.06, CI = 0.79 to 1.03) also reported participating significantly more in muscle strengthening activities than the HIV+ group (M = 0.63, SD = 0.08, CI = 0.47 to 0.78). Multiple regression analyses showed that higher PASE (p < .001) and greater enjoyment of PA (p < .01) were predictive of higher daily PA. HIV- participants had higher PASE but lower BWS compared to HIV+ participants. Sex and age differences were observed in muscle strengthening activities and sedentary behavior. This study supports previous findings on the association of efficacy beliefs to daily PA and muscle strengthening activities. The findings have implications for PA interventions aimed at health promotion and mitigation of the effects of living with HIV/AIDS.