Human Immunodeficiency Virus Ribonucleic Acid Research Articles

Human Immunodeficiency Virus Viral Load Monitoring and Rate of Virologic Suppression Among Patients Receiving Antiretroviral Therapy in Democratic Republic of the Congo, 2013-2020.

Antiretroviral therapy (ART) expansion and viral load as a treatment monitoring approach have increased the demand for viral load testing. Many hurdles affect the coverage, quality, and use of viral load results. Estimates of viral load monitoring and viral suppression rates are needed to assess the performance of ART programs and improve human immunodeficiency virus (HIV) management outcomes. People with HIV (PWH) viral load monitoring data were routinely collected in 84 health facilities in Kinshasa, Democratic Republic of the Congo (DRC), between 2013 and 2020. The number of PWH under ART, the number of participants with at least 1 viral load test result, the rate of viral suppression (defined as ≤1000 HIV ribonucleic acid copies per mL), and the mean turnaround time from sample collection to release of viral load test results were collected together with clinical data. A total of 14 057 PWH were included in the analysis. People with HIV were mainly enrolled after the "test and treat" implementation. The patients were followed for a median period of 27 months. The proportion of PWH with at least 1 available viral load largely increased in recent years. The delay from sample collection to release of viral load test results decreased overtime, from 35 days in 2018 to 16 days in 2020. Pregnancy and advanced HIV disease were associated with a lower chance of viral suppression. There has been considerable success in increasing viral load access for all PWH under therapy in DRC. Nevertheless, viral load testing should be intensified with a particular effort to be made in groups at higher risk of viral failure.

Characterization of Rare Spontaneous Human Immunodeficiency Virus Viral Controllers Attending a National United Kingdom Clinical Service Using a Combination of Serology and Molecular Diagnostic Assays.

We report outcomes and novel characterization of a unique cohort of 42 individuals with persistently indeterminate human immunodeficiency virus (HIV) status, the majority of whom are HIV viral controllers. Eligible individuals had indeterminate or positive HIV serology, but persistently undetectable HIV ribonucleic acid (RNA) by commercial assays and were not taking antiretroviral therapy (ART). Routine investigations included HIV Western blot, HIV viral load, qualitative HIV-1 deoxyribonucleic acid (DNA), coinfection screen, and T-cell quantification. Research assays included T-cell activation, ART measurement, single-copy assays detecting HIV-1 RNA and DNA, and plasma cytokine quantification. Human immunodeficiency virus seropositivity was defined as ≥3 bands on Western blot; molecular positivity was defined as detection of HIV RNA or DNA. Human immunodeficiency virus infection was excluded in 10 of 42 referrals, remained unconfirmed in 2 of 42, and was confirmed in 30 of 42, who were identified as HIV elite controllers (ECs), normal CD4 T-cell counts (median 820/mL, range 805-1336), and normal CD4/CD8 ratio (median 1.8, range 1.2-1.9). Elite controllers had a median duration of elite control of 6 years (interquartile range = 4-14). Antiretroviral therapy was undetected in all 23 subjects tested. Two distinct categories of ECs were identified: molecular positive (n = 20) and molecular negative (n = 10). Human immunodeficiency virus status was resolved for 95% of referrals with the majority diagnosed as EC. The clinical significance of the 2 molecular categories among ECs requires further investigation.

Long-Term Virological Treatment Outcomes in Adolescents and Young Adults With Perinatally and Non-Perinatally Acquired Human Immunodeficiency Virus

Long-term viral suppression on antiretroviral therapy (ART) is not established among all people with human immunodeficiency virus (PWH). Young adults (18-24 years) are recognized as a group vulnerable for suboptimal virological treatment outcomes. The aim of this study is to evaluate longitudinal virological treatment outcomes and to identify risk factors for virological failure (VF) among young adults with non-perinatally and perinatally acquired human immunodeficiency virus (HIV) in the Netherlands. We included individuals registered in the national ATHENA observational cohort from 2000 until 2020 who had entered care before the age of 25 years, who had received ART for at least 6 months with at least 2 available HIV ribonucleic acid measurements between the age of 18 and 24 years. We compared VF between age groups 12-17, 18-24, and 25-30 years. A multivariable generalized linear mixed model was used to evaluate risk factors for VF. Analyses were stratified by HIV acquisition mode. In total, 1174 non-perinatally PWH and 157 perinatally PWH were included. In 2020, VF rate was 7% in non-perinatally PWH young adults and 19% in perinatally PWH young adults. The adjusted risk for VF was significantly higher in those aged 18-24 compared to 25-30 years in both non-perinatally PWH (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.07-1.50) and perinatally PWH (OR, 2.34; 95% CI, 1.48-3.71). Young adulthood is a vulnerable period, with increased risk for VF, especially for perinatally PWH. The probability of VF decreased over time, but less for perinatally PWH compared to non-perinatally PWH.

Dolutegravir Monotherapy as Maintenance Strategy: A Meta-Analysis of Individual Participant Data From Randomized Controlled Trials.

BackgroundDolutegravir monotherapy (DTG-m) results in virological failure (VF) in some people with human immunodeficiency virus (PWH). We sought to identify the independent factors associated with the risk of VF and to explore the effect size heterogeneity between subgroups of PWH enrolled in DTG-m trials.MethodsWe searched for randomized clinical trials (RCTs) evaluating DTG-m versus combined antiretroviral therapy (cART) among PWH virologically controlled for at least 6 months on cART. We performed an individual participant data meta-analysis of VF risk factors and quantified their explained heterogeneity in random-effect models. Definition of VF was a confirmed plasma human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) >50 copies/mL by week 48.ResultsAmong 416 PWH from 4 RCTs, DTG-m significantly increased the risk of VF (16 of 227 [7%] versus 0 of 189 for cART; risk difference 7%; 95% confidence interval [CI], 1%–2%; P = .02; I2 = 51%). Among 272 participants exposed to DTG-m, VF were more likely in participants with the following: first cART initiated ≥90 days from HIV acute infection (adjusted hazard ratio [aHR], 5.16; 95% 95% CI, 1.60–16.65), CD4 T cells nadir <350/mm3 (aHR, 12.10; 95% CI, 3.92–37.40), HIV RNA signal at baseline (aHR, 4.84; 95% CI, 3.68–6.38), and HIV-deoxyribonucleic acid (DNA) copy number at baseline ≥2.7 log/106 peripheral blood mononuclear cells (aHR, 3.81; 95% CI, 1.99–7.30). Among these independent risk factors, the largest effect size heterogeneity was found between HIV DNA subgroups (I2 = 80.2%; P for interaction = .02).ConclusionsOur study supports the importance of a large viral reservoir size for explaining DTG-m simplification strategy failure. Further studies are needed to link size and genetic diversity of the HIV-1 reservoir.

A group-based mental health intervention for Tanzanian youth living with HIV: Secondary analysis of a pilot trial.

Background:Youth living with human immunodeficiency virus (YLWH) are vulnerable to incomplete adherence to antiretroviral therapy in the context of stigma, decreased hope for future, and mental health challenges. Despite these challenges, few mental health interventions have been developed to support YLWH. Previous randomized results from the Sauti ya Vijana (SYV; “The Voice of Youth”) mental health intervention were indicative of the intervention's benefits in promoting virologic suppression.Methods:SYV is a group-based mental health and life skills intervention (pilot, individually randomized group treatment trial) developed alongside YLWH. SYV was comprised of 10, 90-minute sessions based on evidence-based treatment models designed to improve coping, social support, and hope for future as a pathway to improved adherence and virologic suppression. At baseline, YLWH 12 to 24 years of age were randomized to SYV or standard of care. Participants included in this secondary analysis were enrolled in SYV's crossover waves due to either being randomized to standard of care or inability to attend an earlier group, and therefore delayed intervention exposure. Measured outcomes included self-reported mental health measures, self-reported human immunodeficiency virus measures (stigma and adherence), and human immunodeficiency virus ribonucleic acid. Data was collected at baseline, preintervention, and postintervention timepoints. Participants were included if they attended a crossover wave and had data at all 3 timepoints.Results:Twenty-one crossover participants met inclusion criteria. Mean scores of self-reported mental health questionnaires were in an asymptomatic range both pre- and postintervention. Viral suppression was N = 15 (71%) preintervention compared to N = 17 (81%) postintervention. The participants who became virologically suppressed had no change in antiretroviral therapy.Conclusions:Despite the small sample size, findings from this study demonstrate that mental wellbeing may be an important pathway to improved HIV outcomes for YLWH. The same trend toward virologic suppression pre- to postintervention was demonstrated in the randomized pilot trial and suggests that SYV holds promise to improve HIV outcomes. Data from this analysis support the fully powered trial that is now underway.

Cell-Associated Human Immunodeficiency Virus (HIV) Ribonucleic Acid Has a Circadian Cycle in Males With HIV on Antiretroviral Therapy.

Circadian transcription factors that regulate cell-autonomous circadian clocks can also increase human immunodeficiency virus (HIV) transcription in vitro. We aimed to determine whether circadian variation in HIV transcription exists in people with HIV (PWH) on antiretroviral therapy (ART). We performed a prospective observational study of male PWH on ART, sampling blood every 4 hours for 24 hours. Using quantitative polymerase chain reaction, we quantified expression of circadian-associated genes, HIV deoxyribonucleic acid (DNA), and cell-associated unspliced (CA-US) ribonucleic acid (RNA) in peripheral blood CD4+ T cells. Plasma sex hormones were quantified alongside plasma and salivary cortisol. The primary outcome was to identify temporal variations in CA-US HIV RNA using a linear mixed-effect regression framework and maximum likelihood estimation. Salivary and plasma cortisol, and circadian genes including Clock, Bmal1, and Per3, varied with a circadian rhythm. Cell-associated unspliced HIV RNA and the ratio of CA-US HIV RNA/DNA in CD4+ T cells also demonstrated circadian variations, with no variation in HIV DNA. Circulating estradiol was highly predictive of CA-US HIV RNA variation in vivo. Cell-associated unspliced HIV RNA in PWH on ART varies temporally with a circadian rhythm. These findings have implications for the design of clinical trials and biomarkers to assess HIV cure interventions.

Association between human immunodeficiency virus serostatus and the prevalence of atrial fibrillation.

Atrial fibrillation (AF) leads to increased risk for stroke. Human immunodeficiency virus (HIV) is associated with cardiovascular disease (CVD), although it is unclear if HIV is associated with AF. The purpose of this study was to evaluate the association between HIV serostatus and the prevalence of AF in the Multicenter AIDS Cohort Study.A cross sectional study was conducted among 1674 HIV-infected (HIV+) and uninfected (HIV–) men who completed resting 12-lead electrocardiograms, and/or ambulatory electrocardiogram monitoring. Multivariable logistic regression was used to evaluate the association between AF, defined as the presence of either AF or atrial flutter, and HIV+ serostatus. Associations were adjusted for demographic variables, and then also for CVD risk factors.HIV+ men were younger than HIV– men (median 55.5 vs 61.7 years, P < .001) and were more frequently African-American (30.5% vs 17.8%, P < .001). Most HIV+ men (81%) had undetectable viral load. The age and race adjusted prevalence of AF was 3.0% in HIV+ and 3.3% in HIV– men. There was only 1 case of AF among African-American men. There were no associations between AF and HIV serostatus after adjusting for demographic factors (odds ratio 0.76; 95% CI 0.37 to –1.58; P = .47) or after further adjustment for CVD risk factors (odds ratio 0.84; 95% CI 0.39 to –1.81; P = .66).We found no association between HIV and AF in this cohort in which viral replication among the HIV+ men is generally suppressed. The overall prevalence of AF was low and was rare in African-American men.

Associations Between Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid Levels and Incidence of Invasive Cancer in People With HIV After Initiation of Combination Antiretroviral Therapy.

BackgroundHuman immunodeficiency virus (HIV) viremia could be involved in the increased risk of cancer in people with HIV (PWH) receiving combination antiretroviral therapy (cART). We analyzed the association between plasma HIV ribonucleic acid levels in PWH starting cART and incident invasive cancer using the Swedish cohort InfCare HIV linked with national registers.MethodsAdults starting cART in 1996–2017 were included if they had ≥1 viral load (VL) measurement before receiving any antiretroviral agent (pre-ART VL) and ≥2 VLs ≥6 months after start of cART. Viremia during cART was analyzed both as viremia-copy-years and categorized as suppression (<50 copies/mL), low-level viremia ([LLV] 50–999 copies/mL), and nonsuppression (≥1000 copies/mL). The main outcome was a composite of invasive malignancies with increased incidence among PWH. We fitted proportional subhazard models (including sex, age, pre-ART CD4 count, and injection drug use) for both pre-ART VL and viremia during cART.ResultsAfter 32 105 person-years, 3254 of 4931 participants (66%) were classified as suppressed, 438 (9%) were classified as LLV, and 1221 (25%) were classified as nonsuppressed. Neither viremia category nor cumulative viremia during cART had a statistically significant association with cancer. Higher pre-ART VL was associated with cancer (adjusted subhazard ratio, 1.4; 95% confidence interval, 1.0–1.8); this remained statistically significant with viremia during cART in the model. In subanalysis, the association with pre-ART VL was statistically significant for acquired immune deficiency syndrome (AIDS)-defining and infection-related non-AIDS-defining cancer, but not for other malignancies.ConclusionsIn this nationwide cohort, pre-ART VL was an independent predictor of invasive cancer, whereas viremia profile during cART was not associated with cancer incidence.

Evaluation of virologic suppression rates during the COVID-19 pandemic with outpatient interdisciplinary HIV care.

IntroductionThe Coronavirus Disease 2019 (COVID‐19) pandemic has presented social distancing challenges leading healthcare systems to adapt and utilize telemedicine platforms more than ever before. Reducing patient exposure to COVID‐19 became a primary concern, especially for populations at an increased risk for severe illness, such as human immunodeficiency virus (HIV) positive patients.ObjectivesThe primary objective of this study was to measure the impact of pharmacy services including telehealth through the percentage of virologically suppressed patients (HIV ribonucleic acid [RNA] < 200 copies/mL) during the pre‐COVID and post‐COVID time periods. Secondary objectives included the percentage of patients with undetectable viral loads (HIV RNA < 20 copies/mL), percentage of patients with cluster of differentiation 4 (CD4) cell counts greater than 200 cells/mm3, and changes in CD4 cell counts and percentages pre‐COVID and post‐COVID.MethodsThis was a retrospective chart review at a single center HIV primary care clinic in Brooklyn, NY evaluating electronic medical records (EMRs) of 211 HIV‐positive patients. Pre‐COVID was defined as 1 year prior to March 13, 2020, and post‐COVID was defined as March 13 to July 20, 2020.ResultsViral load suppression rates for pre and post‐COVID were 88.6% and 85.3%, respectively (P = .28). Undetectable viral load rates for pre and post‐COVID were approximately 81.5% and 74.4% (P = .096). Mean CD4 cell counts and percentages were 617 cells/mm3 and 29% for pre‐COVID, and 460 cells/mm3 and 22% for post‐COVID. CD4 cell counts greater than 200 cells/mm3 pre‐COVID and post‐COVID was 92.6% and 78.3%, respectively (P = .001).ConclusionUtilization of pharmacy services including telehealth, may allow clinical pharmacists to collaboratively provide remote services without jeopardizing patient outcomes. Larger studies are needed to confirm these findings, and display the long‐term impact and satisfaction of these services.

Evaluation of Tp-e interval and Tp-e: QT and Tp-e: QTc ratios in patients infected with HIV and using antiretroviral therapy

Sudden cardiac death (SCD) is one of the causes of death among patients infected with human immunodeficiency virus (HIV). The T peak to T end interval (Tp-e interval) is a parameter that is used in the prediction of SCD. The aim of this study was to investigate the difference in Tp-e interval and Tp: QT and Tp: corrected QT interval (QTc) ratios between patients infected with HIV and healthy individuals as well as in other factors affecting patients infected with HIV.A total of 83 patients infected with HIV with negative HIV ribonucleic acid (RNA) levels who were receiving antiretroviral therapy (ART) and 83 healthy individuals were included in this study. All the participants underwent electrocardiography, their Tp-e and QT intervals were measured, and QTc intervals and Tp-e: QT and Tp-e: QTc ratios were calculated. In addition, in the patients infected with HIV, CD4 and CD8 T-cell count and HIV RNA levels were measured.The Tp-e interval was found to be longer and the Tp-e: QT and Tp-e: QTc ratios were found to be higher in patients infected with HIV. Nadir CD4 was observed to be an independent predictor of Tp-e interval (p=0.014, β=‒0.28). Furthermore, correlation analysis revealed a negative correlation of the nadir CD4 level and CD4: CD8 ratio with Tp-e interval and Tp-e: QT ratio.Low nadir CD4 and a reversed CD4: CD8 ratio in patients infected with HIV receiving ART were found to be associated with a prolonged Tp-e interval and increased Tp-e: QT and Tp-e: QTc ratios. Thus, more attention should be taken in terms of SCD in patients infected with HIV, especially in those with low nadir CD4 and reversed CD4: CD8 ratio.

Prolonged Posttreatment Virologic Control and Complete Seroreversion After Advanced Human Immunodeficiency Virus-1 Infection

Possible human immunodeficiency virus (HIV)-1 clearance has rarely been reported. In this study, we describe a unique case of an HIV-positive, combination antiretroviral therapy (cART)-experienced woman with prior acquired immunodeficiency syndrome (AIDS) who has not experienced viral rebound for over 12 years since discontinuing cART. Leukapheresis, colonoscopy, and lymph node excision were performed for detailed examination of virologic (including HIV reservoir) and immunologic features. Comparisons were made with chronically infected patients and healthy controls. No HIV-specific antibodies were detected in serum. Plasma HIV ribonucleic acid (RNA) levels were <0.2 copies/mL, and, except for low-frequency HIV deoxyribonucleic acid (DNA)+ cells in lymph node tissue (1 copy/3 × 106 cells), HIV antigen could not be detected by quantitative virus outgrowth (<0.0025 infectious units/106 CD4+ T cells) or by most measurements of HIV RNA or DNA in blood, lymph node, or gut-associated mononuclear cells. Human immunodeficiency virus-specific T-cell responses were detectable but low. Brain imaging revealed a prior biopsy site and persistent white matter disease since 1996. Human immunodeficiency virus DNA+ cells in the 1996 brain biopsy specimen confirmed her identity and initial HIV diagnosis. This represents the first report of complete seroreversion, prolonged posttreatment virus suppression, a profoundly small HIV reservoir, and persistent HIV-specific T cells in an adult with prior AIDS.

Hepatitis C Virus (HCV) Clearance After Treatment With Direct-Acting Antivirals in Human Immunodeficiency Virus (HIV)-HCV Coinfection Modulates Systemic Immune Activation and HIV Transcription on Antiretroviral Therapy.

BackgroundHepatitis C virus (HCV) coinfection among people with human immunodeficiency virus (HIV) might perturb immune function and HIV persistence. We aimed to evaluate the impact of HCV clearance with direct-acting antivirals (DAAs) on immune activation and HIV persistence in HIV/HCV-coinfected individuals on antiretroviral therapy (ART).MethodsIn a prospective observational study, ART-treated participants with HIV/HCV coinfection received sofosbuvir/daclatasvir ± ribavirin (n = 19). Blood samples were collected before DAA therapy, at the end of treatment, and 12 months after DAA termination (12MPT). T- and natural killer (NK)-cell phenotype, soluble plasma factors, cell-associated (CA)-HIV deoxyribonucleic acid (DNA) forms (total, integrated, 2LTR), CA-unspliced (US) and multiple-spliced ribonucleic acid (RNA), and plasma HIV RNA were evaluated.ResultsHepatitis C virus clearance was associated with (1) a downmodulation of activation and exhaustion markers in CD4+, CD8+ T, and NK cells together with (2) decreased plasma levels of Interferon gamma-induced protein 10 (IP10), interleukin-8 (IL-8), soluble (s)CD163 and soluble intercellular adhesion molecule (sICAM). Cell-associated US HIV RNA was significantly higher at 12MPT compared to baseline, with no change in HIV DNA or plasma RNA.ConclusionsElimination of HCV in HIV/HCV-coinfected individuals alters immune function and the transcriptional activity of latently infected cells. This report provides insights into the effects of HCV coinfection in HIV persistence and regards coinfected subjects as a population in which HIV remission might prove to be more challenging.

Circulating CD30+CD4+ T Cells Increase Before Human Immunodeficiency Virus Rebound After Analytical Antiretroviral Treatment Interruption.

Identification of nonviral markers of human immunodeficiency virus (HIV) infection that increase before viral rebound during analytical treatment interruption (ATI) may affect HIV persistence research. We previously showed that HIV ribonucleic acid (RNA) is enriched in CD30+CD4+ T cells in many individuals. Here, we studied CD30+CD4+ T-cell dynamics before ATI, during ATI (before detectable plasma RNA), and after HIV rebound. Peripheral blood mononuclear cells from 23 participants collected longitudinally from 5 Adult AIDS Clinical Trials Group studies incorporating ATI were included in this study. Flow cytometric characterization of expression of CD30 and markers of T-cell activation and exhaustion were performed along with HIV-1 RNA and deoxyribonucleic acid quantification and measurement of soluble plasma CD30 and CD30 ligand. The percentage of CD4+ T cells expressing CD30 significantly increased from pre-ATI to postinterruption time points before detectible viremia (1.65 mean relative increase, P = .005). Seventy-seven percent of participants experienced an increase in CD30+ cells before viral rebound. In contrast, there were no significant differences between pre-ATI and postinterruption pre-rebound time points in percentages of lymphocytes expressing CD69, CD38/HLA-DR, or PD-1 until after HIV recrudescence. CD30 may be a surrogate marker of early replication or viral transcriptional activity before detection by routine peripheral blood sampling.

Plasma Profiles of Inflammatory Markers Associated With Active Tuberculosis in Antiretroviral Therapy-Naive Human Immunodeficiency Virus-Positive Individuals

BackgroundDiagnosis of tuberculosis (TB) in human immunodeficiency virus (HIV)-coinfected individuals is challenging. We hypothesized that combinations of inflammatory markers could facilitate identification of active TB in HIV-positive individuals.MethodsParticipants were HIV-positive, treatment-naive adults systematically investigated for TB at Ethiopian health centers. Plasma samples from 130 subjects with TB (HIV+/TB+) and 130 subjects without TB (HIV+/TB−) were tested for concentration of the following markers: CCL5, C-reactive protein (CRP), interleukin (IL)-6, IL12-p70, IL-18, IL-27, interferon-γ-induced protein-10 (IP-10), procalcitonin (PCT), and soluble urokinase-type plasminogen activator receptor (suPAR). Analyzed markers were then assessed, either individually or in combination, with regard to infection status, CD4 cell count, and HIV ribonucleic acid (RNA) levels.ResultsThe HIV+/TB+ subjects had higher levels of all markers, except IL12p70, compared with HIV+/TB− subjects. The CRP showed the best performance for TB identification (median 27.9 vs 1.8 mg/L for HIV+/TB+ and HIV+/TB−, respectively; area under the curve [AUC]: 0.80). Performance was increased when CRP was combined with suPAR analysis (AUC, 0.83 [0.93 for subjects with CD4 cell count <200 cells/mm3]). Irrespective of TB status, IP-10 concentrations correlated with HIV RNA levels, and both IP-10 and IL-18 were inversely correlated to CD4 cell counts.ConclusionsAlthough CRP showed the best single marker discriminatory potential, combining CRP and suPAR analyses increased performance for TB identification.

Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens.

BackgroundEfavirenz (EFV)-based regimens select broad drug resistance to nonnucleoside reverse-transcriptase inhibitors (NNRTIs), limiting the effectiveness of EFV and other NNRTIs. The duration, persistence, and decay of drug resistance mutations (DRMs) in the proviral reservoir is not well defined.MethodsParticipants with virologic failure of EFV-based regimens and drug-resistant viremia with the K103N mutation in plasma ribonucleic acid (RNA) were identified from AIDS Clinical Trials Group (ACTG) studies A364 and A5095. These individuals received a second-line, boosted protease inhibitor-based regimen with suppression of viremia for up to10 years during long-term follow-up (median = 3.6 years; interquartile range, 2.1–6.9 years). Proviral deoxyribonucleic acid (DNA) from cryopreserved peripheral blood mononuclear cells was sequenced to identify the persistence of DRM.ResultsTwenty-eight participants from ACTG 364 and ACTG 5095 were evaluated. Sanger sequencing of proviral DNA detected K103N as well as additional reverse-transcriptase inhibitor (RTI) mutations. Ultradeep sequencing confirmed persistence of K103N in 71% of participants with minimal decay over time. In an adjusted model including years since suppression, persistent proviral K103N was 2.6 times more likely (95% confidence interval, 1.0–6.4) per log10 higher human immunodeficiency virus RNA at EFV failure.ConclusionsPersistence of RTI mutations in proviral DNA after virologic failure has implications for the effectiveness of future drug regimens and the recycling of RTI drugs.

Antiviral activity of Acanthaster planci phospholipase A2 against human immunodeficiency virus.

Aim:Investigation of antiviral activity of Acanthaster planci phospholipase A2 (AP-PLA2) from moluccas to human immunodeficiency virus (HIV).Materials and Methods:Crude venom (CV) and F20 (PLA2 with 20% fractioned by ammonium sulfate) as a sample of PLA 2 obtained from A. planci’s extract were used. Enzymatic activity of PLA2 was determined using the degradation of phosphatidylcholine (PC). Activity test was performed using in vitro method using coculture of phytohemagglutinin-stimulated peripheral blood mononuclear cell (PBMC) from a blood donor and PBMC from HIV patient. Toxicity test of AP-PLA2 was done using lethal concentration required to kill 50% of the population (LC50).Results:AP-PLA2 F20 had activity and purity by 15.66 times bigger than CV. The test showed that the LC50 of AP-PLA2 is 1.638 mg/ml. Antiviral analysis of AP-PLA2 in vitro showed the inhibition of HIV infection to PBMC. HIV culture with AP-PLA2 and without AP-PLA2 has shown the number of infected PBMC (0.299±0.212% and 9.718±0.802%). Subsequently, RNA amplification of HIV using reverse transcriptase-polymerase chain reaction resulted in the decrease of band intensity in gag gene of HIV.Conclusion:This research suggests that AP-PLA2 has the potential to develop as an antiviral agent because in vitro experiment showed its ability to decrease HIV infection in PBMC and the number of HIV ribonucleic acid in culture.

Distribution of Human Immunodeficiency Virus (HIV) Ribonucleic Acid in Cerebrospinal Fluid and Blood Is Linked to CD4/CD8 Ratio During Acute HIV.

Human immunodeficiency virus (HIV) ribonucleic acid (RNA) levels in the plasma and cerebrospinal fluid (CSF) are correlated in chronic HIV infection, but their dynamics have not been characterized during acute infection. This study analyzed predictors of CSF HIV RNA and relative degree of CNS viral transmigration expressed as plasma minus CSF HIV log10 RNA (PCratio) during untreated acute HIV infection. Cerebrospinal fluid immune markers were compared between groups with different PCratio. One hundred seventeen mostly male (97%) participants in the RV254 cohort in Bangkok, Thailand, had a median age of 28 years and an estimated median 18 days duration of infection; 43 (37%) were Fiebig stages I/II. Twenty-seven (23%) had CSF HIV RNA <80 copies/mL. Those with quantifiable levels (n = 90) had median CSF HIV RNA and PCratio of 3.76 and 2.36 log10 copies/mL, respectively. Human immunodeficiency virus RNA peaked at Fiebig III in plasma and Fiebig IV in CSF. In multivariable analyses, plasma HIV RNA and CD4/CD8 ratio independently correlated with CSF HIV RNA (P < .001), whereas CD4/CD8 ratio predicted PCratio (P = .018). Participants with PCratio <1 had higher CSF neopterin, soluble (s)CD163, interleukin-6, and sCD14 levels (all P < .05). CD4/CD8 ratio independently correlated with CSF HIV RNA and PCratio, suggesting that immune responses modulate central nervous system viral entry at early infection.

Pembrolizumab combined with stereotactic body radiotherapy in a patient with human immunodeficiency virus and advanced non-small cell lung cancer: a case report

BackgroundPembrolizumab has significantly improved outcomes in patients with advanced non-small cell lung cancer. Combining programmed death-1 inhibitor with stereotactic body radiotherapy showed a slight toxicity and good benefits in recent clinical trials. However, patients infected with human immunodeficiency virus were excluded from most trials because it was assumed that their anti-tumor immunity was compromised compared with immunocompetent patients.Case presentationIn June 2016, a 52-year-old Chinese man presented with human immunodeficiency virus and lung adenocarcinoma (T1bN3M1b). From November 2016 to December 2016, systemic chemotherapy and palliative radiotherapy for bone metastasis of femoral neck were carried out, but the tumor progressed. In January 2017, after immunochemistry detection of programmed death-1 and programmed death-ligand 1 expression (both > 50%), pembrolizumab was started. Three weeks after pembrolizumab, we combined stereotactic body radiotherapy for the primary lung tumor. He received no comfort and his CD4 lymphocyte count was stable. Human immunodeficiency virus-ribonucleic acid remained below the limits of detection. In March 2017, after three cycles of pembrolizumab and 5 weeks of stereotactic body radiotherapy therapy, he suddenly presented with palpitations. Emergency computed tomography scanning showed massive pericardial effusion and interstitial pneumonia. So we interrupted the pembrolizumab use and initiated treatment with prednisolone 1 mg/kg; however, the tumor progressed. Then, his CD4 lymphocyte count declined. Finally he died in June 2017 due to dyscrasia.ConclusionsPembrolizumab combined with SBRT therapy for patients with human immunodeficiency virus infection and non-small cell lung cancer may lead to serious immune-related adverse events and more clinical trials are needed.

Highly Successful Hepatitis C Virus (HCV) Treatment Outcomes in Human Immunodeficiency Virus/HCV-Coinfected Patients at a Large, Urban, Ryan White Clinic.

BackgroundThe introduction of direct-acting antivirals (DAAs) created a major paradigm shift in the treatment of chronic hepatitis C. Currently, there is little “real-world” data regarding hepatitis C virus (HCV) treatment outcomes in the human immunodeficiency virus (HIV)/HCV-coinfected population.MethodsThis retrospective cohort study examined HCV treatment outcomes of HIV/HCV-coinfected patients at a large, urban, Ryan White-funded clinic caring for an underserved population. All HIV patients initiating HCV treatment from January 1, 2013 to November 30, 2015 were included in the analysis. The primary end point was sustained virologic response 12 weeks after the end of therapy (SVR12).ResultsA total of 172 patients initiated HCV treatment within the study period: 79% were male, 83% were black, 95% were HCV genotype 1, 79% were HCV treatment naive, and 16% had cirrhosis. At baseline, median CD4 was 494 cells/μL (interquartile range, 316–722) and 92% had HIV ribonucleic acid less than 40 copies/mL. The most common DAA initiated was ledipasvir/sofosbuvir (LDV/SOF) (85%), with 92% receiving 12 weeks of treatment. Overall, SVR12 was 93% by intention-to-treat analysis and 98% by per-protocol analysis. The majority of patients on LDV/SOF did not report any adverse effect. One patient in the ribavirin plus SOF group discontinued treatment due to adverse effect.ConclusionsIn a cohort of mainly black, male, HIV/HCV-coinfected patients at a large, urban, Ryan White clinic, HCV treatment with DAAs resulted in high SVR12 rates and was well tolerated despite real-world challenges including medication access barriers and drug interaction concerns.

Clinical and Mucosal Immune Correlates of HIV-1 Semen Levels in Antiretroviral-Naive Men.

BackgroundThis study was done to characterize parameters associated with semen human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) viral load (VL) variability in HIV-infected, therapy-naive men.MethodsPaired blood and semen samples were collected from 30 HIV-infected, therapy-naive men who have sex with men, and 13 participants were observed longitudinally for up to 1 year. Human immunodeficiency virus RNA, bacterial load by 16S RNA, herpesvirus (Epstein-Barr virus and cytomegalovirus [CMV]) shedding, and semen cytokines/chemokines were quantified, and semen T-cell subsets were assessed by multiparameter flow cytometry.ResultsSemen HIV RNA was detected at 93% of visits, with >50% of men shedding high levels of virus (defined as >5000 copies/mL). In the baseline cross-sectional analysis, an increased semen HIV VL correlated with local CMV reactivation, the semen bacterial load, and semen inflammatory cytokines, particularly interleukin (IL)-8. T cells in semen were more activated than blood, and there was an increased frequency of Th17 cells and γδ-T-cells. Subsequent prospective analysis demonstrated striking interindividual variability in HIV and CMV shedding patterns, and only semen IL-8 levels and the blood VL were independently associated with semen HIV levels.ConclusionsSeveral clinical and immune parameters were associated with increased HIV semen levels in antiretroviral therapy-naive men, with induction of local proinflammatory cytokines potentially acting as a common pathway.