HIV VL Research Articles

The impact of analytical treatment interruptions and trial interventions on time to viral re-suppression in people living with HIV restarting ART in cure-related clinical studies: a systematic review and meta-analysis.

To assess the effectiveness of novel HIV curative strategies, "cure" trials require periods of closely monitored antiretroviral therapy (ART) analytical treatment interruptions (ATIs). We performed a systematic review and meta-analysis to identify the impact of ATI with or without novel therapeutics in cure-related studies on the time to viral re-suppression following ART restart. Medline, Embase and Web of Science databases were searched for human studies involving ATIs from 1 January 2015 till 22 April 2024. The primary outcome was time to first viral re-suppression (plasma HIV viral load [VL] <50 copies/ml) stratified by receipt of interventional drug with ATI (IA) or ATI-only groups. Random-effects proportional meta-analysis and multivariable Cox proportional hazards analysis were performed using R. Of 1073 studies screened, 13 were included that met the inclusion criteria with VL data available after restarting ART (n = 213 participants). There was no difference between time to viral suppression in IA or ATI-only cohorts (p = 0.22). For 87% of participants, viral suppression within 12 weeks of ART restart was achieved, and all eventually had at least one VL <50 copies/ml during follow-up. After adjusting for covariables, while participants in the IA cohort were associated with less rapid suppression (adjusted hazard ratio [aHR] 0.61, 95% CI 0.40-0.94, p = 0.026), other factors include greater log VL at ART restart (aHR 0.56, 95% CI 0.46-0.68, p<0.001), duration since HIV diagnosis (aHR 0.93, 95% CI 0.89-0.96) and longer intervals between HIV VL monitoring (aHR 0.66, 95% CI 0.59-0.74, p<0.001). However, the use of integrase inhibitors was associated with more rapid viral suppression (aHR 1.74, 95% CI 1.16-2.59). When designing studies involving ATIs, information on time to viral re-suppression after restarting ART is important to share with participants, and should be regularly monitored and reported, to assess the impact and safety of specific trial interventions in ATI studies. The majority of participants achieved viral suppression after restarting ART in ATI studies. ART regimens containing integrase inhibitors and frequent VL monitoring should be offered for people restarting ART after ATI studies to ensure rapid re-suppression.

Mpox across countries from Central and Eastern Europe - 2022 outbreak

BackgroundThe aim of the study was to assess socio-demographical characteristics, clinical presentation, and outcomes in patients diagnosed with mpox. MethodsA survey on patients diagnosed with mpox was performed in 14 countries from Central and Eastern Europe. Data was compared according to HIV status and country of origin (EU vs. non-EU). Mpox diagnosis was confirmed by RT-PCR from oropharyngeal swabs, skin lesions, and other body fluids. ResultsOut of 154 patients confirmed with mpox in 2022, 99.3% were males, with a median age (years) of 35 (IQR 30–39), 90.2% MSM and 48.7% PLWH. Compared to HIV-negative subjects, PLWH had more frequent high-risk behaviours:chemsex (p = 0.015), group sex (p = 0.027), and a history of sexually transmitted infections (STIs) (p = 0.004). Persons from EU were more often PLWH (p = 0.042), MSM (p < 0.0001), had multiple sexual partners (p = 0.025), practiced chemsex (p = 0.008) or group-sex (p = 0.005) and had more often history of STIs (p < 0.0001). The median CD4 cell count/mL at mpox diagnosis was 713 (IQR 486–996) and 73.5% had undetectable HIV VL. The commonest clinical features were fever (108 cases), lymphadenopathy (78), and vesiculo-pustular rash: penile (76), perianal (48), limbs (67). Fifty-one (31%) persons were hospitalized due to complications or epidemiological reasons. Three patients received tecovirimat or cidofovir. The outcome was favorable for all patients, including 4 with severe forms. ConclusionsMpox was diagnosed predominantly in young MSM, with high-risk behaviors and history of STIs. Effective contact tracing and vaccination are important strategic pillars to control mpox outbreaks.

A Characterization of Women Living with HIV in Belgium.

The primary objective of this study was to characterize women living with HIV (WLWH) in Belgium. The secondary objective was an exploratory analysis comparing women and men living with HIV (MLWH). This was a cross-sectional, observational, multicenter study. Inclusion criteria for the primary objective were all adult treatment-naïve and experienced WLWH actively being treated at one of the participating centers. For the secondary objective, inclusion criteria were all adult naïve and experienced women and MLWH, actively being treated at a single participating center. Data were collected between December 2022 and March 2023. A multivariable analysis was performed on all women included to evaluate for associations with having hypertension (HTN) or being virologically nonsuppressed (HIV-1 VL ≥200 copies/mL). In the exploratory analysis of women and MLWH, a multivariable analysis was carried out to evaluate whether female gender was associated with having HTN or being virologically nonsuppressed. Overall, 2797 WLWH were included. The majority were Black (73.5%) and 48.5% were aged ≥50 years. The most common comorbidity was HTN (17.3%) and most individuals were virologically suppressed (HIV-1 VL <50 copies/mL; 85.6%). Black race was associated with having HTN (p < 0.0001). Prior AIDS-defining illness (p = 0.02) and a CD4+ T-cell count <500 cells/µL (p < 0.0001) were associated with being nonsuppressed. A total of 1094 WLWH and 1878 MLWH were included in the exploratory analysis. HTN was higher among WLWH (20.2% vs. 12% MLWH). Female gender was not found to be associated with having HTN (p = 0.86) or being nonsuppressed (p = 0.14). In this analysis of WLWH in Belgium, the results depict an ageing population that is predominantly Black. The most common comorbidity observed was HTN. Women had a low rate of virologic nonsuppression, and female gender was not associated with being nonsuppressed.

Impact of very early antiretroviral therapy during acute HIV infection on long-term immunovirological outcomes

ObjectivesWe aimed to determine if starting antiretroviral therapy (ART) in the first 30 days after acquiring HIV infection has an impact on immunovirological response. MethodsObservational, ambispective study including 147 patients with confirmed acute HIV infection (January/1995-August/2022). ART was defined as very early (≤30 days after the estimated date of infection), early (31-180 days), and late (>180 days). We compared time to viral suppression (viral load [VL] <50 copies/ml) and immune recovery (IR) (CD4+/CD8+ ratio ≥1) according to the timing and type of ART using survival analysis. ResultsART was started in 140 (95.2%) patients. ART was very early in 24 (17.1%), early in 77 (55.0%), and late in 39 (27.9%) cases. Integrase strand transfer inhibitor (INSTI)-based regimens were the most used in both the overall population (65%) and the very early ART group (23/24, 95.8%). Median HIV VL and CD4+/CD8+ ratio pre-ART were higher in the very early ART group (P <0.05). Patients in the very early and early ART groups and treated with INSTI-based regimens achieved IR earlier (P <0.05). Factors associated with faster IR were the CD4+/CD8+ ratio pre-ART (hazard ratio: 9.3, 95% CI: 3.1-27.8, P <0.001) and INSTI-based regimens (hazard ratio: 2.4, 95% CI: 1.3-4.2, P = 0.003). ConclusionsThe strongest predictors of IR in patients who start ART during AHI are the CD4+/CD8+ ratio pre-ART and INSTI-based ART regimens.

A randomized control trial of a combined community health worker and re-entry intervention for people with HIV recently released from jail who use substances

IntroductionPeople with human immunodeficiency virus (HIV; PWH) who use substances are disproportionately involved in the criminal justice system. While HIV viral suppression typically improves during incarceration, these gains are frequently lost after release. We evaluated the impact of a combined intervention (formerly incarcerated community health workers [CHW] plus a re-entry organization; CHW+) on postrelease HIV- and substance use–related outcomes. MethodsWe conducted a pilot randomized controlled trial of a CHW+ for PWH who use substances, within 30 days of release from a large southern, urban jail. Between February 2019 and August 2021, participants were recruited, enrolled, and randomized to treatment as usual (TAU; passive referral to care) or CHW+. Follow up study visits occurred at 3, 6, and 12 months. The primary outcome was HIV VL at 6 months; secondary outcomes included 6-month urinary toxicology and high-risk substance use at 12 months. ResultsA total of 31 participants were enrolled who were primarily male (n = 24; 77 %), Black (n = 22; 71 %), unemployed (n = 23; 74.2 %), had unstable housing (n = 18; 58 %), had food insecurity (n = 14; 45 %), and reported their drug of choice was stimulants (n = 24; 77 %). The study identified no significant difference in HIV VL suppression at 6 months (20 % v. 37 %; [CHW+ v. TAU], p = 0.61). We observed improved substance use outcomes in CHW+ v. TAU, including fewer positive urinary toxicology screens for stimulants (40 % v. 100 %; p = 0.01) and a trend toward less high-risk substance use (30 % v. 43 %). The CHW+ group met more basic needs, such as food security [+32 % v. +11 %], housing security [+52 % v. −7 %] and full-time employment [+20 % v. +5 %] compared to TAU. ConclusionsPWH who use substances assigned to a combined intervention of CHW+ after jail release did not achieve higher rates of HIV VL suppression than TAU; however, they had improved substance use outcomes and met more basic subsistence needs. Results highlight the potential of culturally informed interventions to address the competing needs of PWH who use substances after release from jail and call for further development of innovative solutions to successfully bridge to HIV care in the community.

Human-centered design of a smartphone-based self-test for HIV viral load monitoring.

HIV viral load self-testing could enable people living with HIV (PLHIV) to monitor their viral suppression status more easily, potentially facilitating medication adherence and safe behavior decision-making. Smartphone-based viral load testing innovations have the potential to reach resource-limited and vulnerable communities to address inequities in access to HIV care. However, successful development and translation of these tests requires meaningful investigation of end-user contexts and incorporation of those context-specific needs early in the design process. The objective of this study is to engage PLHIV and HIV healthcare providers in human-centered design research to inform key design and implementation considerations for a smartphone-based HIV viral load self-testing device prototype in development. Semi-structured in-depth interviews were conducted with PLHIV (n = 10) and HIV providers (n = 4) in Indiana, a state with suboptimal viral suppression rates and marked disparities in access to HIV care. Interview guides were developed based on contextual investigation and human-centered design frameworks and included a demonstration of the device prototype with feedback-gathering questions. Thematic analysis of interview transcripts revealed important benefits, concerns, and user requirements for smartphone-based HIV VL self-testing within the context of PLHIV lived experience, knowledge, and barriers to care in Indiana. End-user needs and preferences were identified as key design specifications and implementation considerations to facilitate the acceptability and inform ongoing development and ultimately real-world translation of the HIV VL monitoring device prototype.

2061. High Rates of Viremic HIV, Risky Sexual Behaviors, and Interest in Gender Affirming Hormone Therapy among Transgender Individuals Who Engage in Transactional Sex

Abstract Background In the U.S., HIV transmission persists largely through sexual transmission in gender and sexual minorities. Transactional sex (TS) is a known risk factor for HIV transmission, yet risk behaviors and engagement in HIV treatment and other medical services among transgender (TG) individuals who have TS are poorly understood. Methods PATCH is a natural history study of TG individuals in Washington, DC. Participants complete laboratory testing and surveys, including assessment of TS – defined as previous year sex in exchange for drugs, money or shelter. Fisher’s exact test was used for statistical analysis. Results Of 54 participants assigned male at birth (AMAB), 21(39%) endorsed TS, the majority of whom were female (81%), Black (95%), median age 35, and HIV+ (76%; Table 1). Of those with HIV, 12 (75%) were prescribed ART, though only 8 (50%) had HIV VL &amp;lt; 200. The majority of TG people with TS had sex weekly or more (75%), with &amp;gt; 5 partners/year (62%) and used their penis (80%) and anus (90%) during TS. A minority consistently used condoms in receptive anal sex (29%), penetrative anal sex (25%), penetrative vaginal sex (17%), and chem sex (8%). While 95% had ever taken gender affirming hormone therapy (GAHT), 62% were not prescribed GAHT at screening, of whom, 54% were interested in seeing a provider for GAHT. When compared to non-TS participants, TG individuals with TS were more likely to have chem sex (p&amp;lt; 0.01), use drugs daily or more (p=0.04), use amphetamines (p&amp;lt; 0.01) and cocaine (p&amp;lt; 0.01), and less likely to have GAHT prescribed by a provider (p=0.03). HIV+ patients with TS were less likely to have HIV VL&amp;lt; 200 (p=0.02). Table 1:Participant Characteristics and Associations with Transactional Sex Conclusion This cohort of AMAB TG individuals with TS had high rates of viremic HIV, and multiple risk factors for HIV transmission, including frequent condomless sex with multiple partners. Additionally, those with TS were more likely to have high risk drug use, indicating that novel strategies to decrease risk associated with chem sex, particularly stimulant use, should be prioritized. Further, nearly all TG participants with TS had taken GAHT, yet were less likely to get GAHT from a provider. As many had interest in seeing a provider for GAHT, co-locating GAHT with HIV treatment and prevention services could help providers engage this population and address HIV-related risks. Disclosures Shyam Kottilil, MD, PhD, Arbutus Pharmaceuticals: Grant/Research Support|Gilead: Grant/Research Support|Merck: Grant/Research Support|Regeneron Pharmaceuticals: Advisor/Consultant|Silverback Therapeutics: Advisor/Consultant|The Liver Company: Advisor/Consultant|Yufan Biotechnologies: Advisor/Consultant Sarah Kattakuzhy, MD, Gilead: Grant/Research Support Elana S. Rosenthal, MD, Gilead: Grant/Research Support|Merck: Grant/Research Support.

1091. HIV Does Not Increase Risk of Disease Severity in Patients with COVID-19 Infection

Abstract Background Limited literature on the impact of COVID-19 infection in persons living with HIV infection (PLWHIV) has shown conflicting results, especially on the degree of disease severity and morbidity/mortality risk impact. The advent of vaccinations against COVID-19 infection helped combat this horrific pandemic. However, their efficacy in immunocompromised hosts is understudied. The measurement of anti-spike antibody levels makes them an ideal surrogate to study the efficacy of the immune response conferred after vaccination. Methods A quality improvement project was conducted between 03/2020 and 03/2022 at Positive Health Clinic (PHC), a Pittsburgh urban Ryan White-funded HIV clinic, where approximately 930 PLWHIV receive care. PHC patients who tested positive for COVID-19 were followed up for their clinical presentations and outcomes. Goals were to observe longitudinal clinical impact with or without vaccinations; the COVID-19 vaccination acceptance and its serum anti-spike antibody response (AS-Ab); and COVID-19 variants impact on protection by vaccination. Results By 02/21, a 70% vaccination rate was achieved for PHC PLWHIV. 136 serum AS-Ab tests were collected at least 28 days after completing the primary vaccination series. Five non-responders were noted (2 renal transplant recipients, 2 with advanced AIDS with uncontrolled HIV, and 1 with liver cirrhosis). Low AS-Ab titers were observed in patients with CD4 &amp;lt; 200 or HIV VL &amp;gt; 200. A total of 109 COVID-19 infections in 105 patients were seen. From 03/20 – 11/21, there were 53 infections noted (45 unvaccinated: 5 with severe disease; 8 vaccinated: 0 severe disease). 58 infections (8 unvaccinated, 2 severe, 50 vaccinated (including four 2nd infections: 0 severe) were observed during 11/221 – 03/22. No mortality was noted. Figure 1.Figure 2.Figure 3Demographics of PHC Conclusion This report did not show mortality directly associated with COVID-19 infection in PLWHIV. Moreover, COVID-19 vaccination is known to reduce the risk and severity of COVID-19 infection in the general population, which was consistent across our study. Interestingly, there were very few COVID-19 infections diagnosed in PLWHIV who had low CD4 count and uncontrolled HIV (CD4 &amp;lt; 200 &amp; HIV VL &amp;gt; 500 copies) even after the surge of the Omicron variant. Disclosures All Authors: No reported disclosures.

Viral load testing among pregnant women living with HIV in Mutare district of Manicaland province, Zimbabwe

BackgroundViral load (VL) monitoring of pregnant women living with HIV (PWLHIV) and antiretroviral therapy (ART) may contribute to lowering the risk of vertical transmission of HIV. The aims of this study were to assess the uptake of HIV VL testing among PWLHIV at entry to the prevention-of-mother-to-child transmission (PMTCT) services and identify facilitatory factors and barriers to HIV VL access.MethodsA retrospective, cross-sectional study was conducted at 15 health facilities in Mutare district, Manicaland Province, Zimbabwe from January to December 2018. This analysis was complemented by prospective interviews with PWLHIV and health care providers between October 2019 and March 2020. Quantitative data were analysed using descriptive and inferential statistical methods. Risk factors were evaluated using multivariate logistic regression. Open-ended questions were analysed and recurring and shared experiences and perceptions of PWLHIV and health care providers identified.ResultsAmong 383 PWLHIV, enrolled in antenatal care (ANC) and receiving ART, only 121 (31.6%) had a VL sample collected and 106 (88%) received their results. Among these 106 women, 93 (87.7%) had a VL < 1000 copies/mL and 77 (73%) a VL < 50 copies/mL. The overall median duration from ANC booking to VL sample collection was 87 (IQR, 7–215) days. The median time interval for the return of VL results from date of sample collection was 14 days (IQR, 7–30). There was no significant difference when this variable was stratified by time of ART initiation. VL samples were significantly less likely to be collected at local authority compared to government facilities (aOR = 0.28; 95% CI 0.16–0.48). Barriers to VL testing included staff shortages, non-availability of consumables and sub-optimal sample transportation. Turnaround time was prolonged by the manual results feedback system.Conclusions and recommendationThe low rate of HIV VL testing among PWLHIV in Mutare district is a cause for concern. To reverse this situation, the Ministry of Health should consider interventions such as disseminating antiretroviral guidelines and policies electronically, conducting regular PMTCT mentorship for clinical staff members, and utilising point of care testing and telecommunication devices like mHealth to increase uptake of VL testing and improve results turnaround time.

DETERMINATION OF INTRACELLULAR REACTIVE OXYGEN SPECIES IN T-CELL SUBSETS OF HIV+ PATIENTS ON CONTINUOUS cART

Background: Reactive oxygen species (ROS) are generated at physiological levels as a result of cellular metabolism and contribute to cellular interaction and immune response. Elevated ROS may cause cell stress, damage, and apoptosis, and have been detected in different pathological states of infectious and non-infectious etiology. Aim: To evaluate the association between intracellular ROS in T-cell subsets and HIV VL in chronic HIV infection. Material and methods: Whole blood samples (Li-heparin, n=33) were analyzed during routine immune monitoring in two groups of HIV+ patients: A (n=21), on continuous cART for at least 2y, with sustained viral suppression (HIV VL&lt;40 copies/ml) and group B (n=12) on cART for less than 2y, average HIV VL 92330 c/ml. Percentage and absolute counts (AC) of CD4+ and CD8+T cells were determined by flow cytometry (Multitest, BD Trucount™ tubes, FACS Canto II). Fluorometric ROS assay kit (Sigma-Aldrich) was adapted for flow cytometry analysis to detect intracellular ROS in CD4+ and CD8+ T-cells (FACSDiva 6.1.2). Results: The average CD4AC did not differ significantly between group A and B (714 vs. 568, p&gt;0.05), unlike the CD4/CD8 ratio (1.2 vs. 0.6, p&lt;0.01). The mean fluorescence intensity (MFI) of CD4+T intracellular ROS was significantly lower in group A (mean MFI 1744 vs. 2492, p&lt;0.05), unlike the CD8+T cell ROS content (1753 vs. 2129, p&gt;0.05). Noteworthy, CD4+T intracellular ROS correlated positively with HIV VL (R=0.5, p&lt;0.05), unlike CD8+T ROS. On the other hand, positive correlations between CD8+T ROS and cART duration, as well as age (R=0.5, p&lt;0.05 for both) were observed in group A. Conclusions: CD4+T ROS production may be an indicator of residual HIV activity in the settings of undetectable HIV VL. The combined effects of ageing and long-term cART affect mostly the CD8+T cell compartment.

Asymptomatic SARS-CoV-2 Infection Is Common Among ART-Treated People With HIV.

Limited data are available regarding asymptomatic COVID-19 among people with HIV (PWH). Data on a representative subset of PWH enrolled in Randomized Trial to Prevent Vascular Events in HIV, a global clinical trial, are presented here. Randomized Trial to Prevent Vascular Events in HIV is an atherosclerotic cardiovascular disease prevention trial among 7770 PWH on antiretroviral therapy. Beginning April 2020, targeted data on coronavirus disease 2019 (COVID-19) diagnosis and symptoms were collected during routine trial visits. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was defined as either COVID-19 clinical diagnosis or presence of SARS-CoV-2 Immunoglobulin G (IgG) or Immunoglobulin A (IgA) receptor binding domain protein (antispike) antibodies in the absence of prior COVID-19 vaccine. The group (N = 2464) had a median age 53 years, 35% female sex, 47% Black or African American race, median CD4 count 649 c/mm 3 , and 97% with HIV VL <400 cp/m. SARS-CoV-2 infection occurred in 318 persons (13%): 58 with clinical diagnosis and 260 with detectable antibodies. Of these PWH, 304 completed symptom questionnaires: 121 (40%) reported symptoms, but 183 (60%) were asymptomatic. PWH with asymptomatic SARS-CoV-2 infection were more likely to be from low-income or middle-income regions, of Black or African American race, older in age, and with higher atherosclerotic cardiovascular disease risk score. Symptomatic COVID was more common with obesity, metabolic syndrome, and low HDL levels. CD4 counts and HIV viral suppression rates were similar among PWH with symptomatic vs. asymptomatic COVID. Asymptomatic SARS-CoV-2 infection is common among antiretroviral therapy-treated PWH globally. We determined that 60% of infections in PWH were asymptomatic. HIV clinicians must remain vigilant about COVID-19 testing among PWH to identify asymptomatic cases.

Mindfulness instruction for medication adherence among adolescents and young adults living with HIV: a randomized controlled trial

ABSTRACT Adolescents and young adults (AYA) 13–24 years old make up a disproportionate 21% of new HIV diagnoses. Unfortunately, they are less likely to treat HIV effectively, with only 30% achieving viral suppression, limiting efforts to interrupt HIV transmission. Previous work with mindfulness-based stress reduction (MBSR) has shown promise for improving treatment in AYA living with HIV (AYALH). This randomized controlled trial compared MBSR with general health education (HT). Seventy-four 13–24-year-old AYALH conducted baseline data collection and were randomized to nine sessions of MBSR or HT. Data were collected at baseline, post-program (3 months), 6 and 12 months on mindfulness and HIV management [medication adherence (MA), HIV viral load (HIV VL), and CD4]. Longitudinal analyses were conducted. The MBSR arm reported higher mindfulness at baseline. Participants were average 20.5 years old, 92% non-Hispanic Black, 51% male, 46% female, and 3% transgender. Post-program, MBSR participants had greater increases than HT in MA (p = 0.001) and decreased HIV VL (p = 0.052). MBSR participants showed decreased mindfulness at follow-up. Given the significant challenges related to HIV treatment in AYALH, these findings suggest that MBSR may play a role in improving HIV MA and decreasing HIV VL. Additional research is merited to investigate MBSR further for this important population.

Factors associated with HIV viral suppression among children and adults receiving antiretroviral therapy in Malawi in 2021: Evidence from the Laboratory Management Information System.

To describe the prevalence of HIV viral suppression and assess the factors associated with HIV viral suppression among persons receiving antiretroviral therapy (ART) in Malawi in 2021. Implementation study using routinely collected patient-level HIV RNA-PCR test result data extracted from the national Laboratory Management Information System (LIMS) database managed by the Department of HIV/AIDS in 2021. We calculated frequencies, proportions and odds ratios (OR) of HIV viral suppression with their associated 95% confidence intervals (95%CIs). We performed a random-effects logistic regression to determine the risk factors associated with HIV viral suppression among ART patients, controlling for the spatial autocorrelation between districts and adjusting for other variables. We evaluated 515,797 adults and children receiving ART and having a viral load test in 2021. Of these, 92.8% had HIV viral suppression. ART patients living in urban areas had lower likelihood of HIV viral suppression than those living in rural areas (adjusted OR [aOR]=0.95, 95%CI: 0.92-0.99, p= 0.01). There was an increasing trend in HIV viral suppression with increasing ART duration. Routine VL monitoring samples were 39% more likely to have suppressed VL values than confirmatory HIV VL monitoring samples (aOR=1.39; 95%CI: 1.34-1.43, p< 0.001). This is the first national analysis of Malawi HIV VL data from LIMS. Our findings show the need to particularly consider the urban residents, those below 20 years, males, those on ART for less than a year as well as those on specific ARV regimens in order to persistently suppress HIV VL and consequently achieve the goal of achieving HIV VL suppression by 2030.

Diagnostic Accuracy of the Rapid Xpert HIV-1 Viral Load XC, Xpert HIV-1 Viral Load, & m-PIMA HIV-1/2 Viral Load in South African Clinics.

BackgroundWe aimed to evaluate the analytic performance of three rapid HIV viral load assays: the novel Xpert HIV-1 VL XC (Xpert XC), the Xpert HIV-1 VL (Xpert VL), and the m-PIMA HIV-1/2 VL (m-PIMA).SettingTwo South African clinics.MethodsWe conducted a prospective diagnostic accuracy study. Site-laboratory technicians and nurses used the Xpert XC, Xpert VL and m-PIMA to test plasma samples from people with HIV receiving antiretroviral therapy. We compared results with the Roche Cobas HIV-1 reference assay. We determined accuracy to detect viraemia at the World Health Organization (WHO) failure threshold of 1000 copies/mL on all three assays, and 50 and 200 copies/mL on the Xpert assays. We assessed agreement using Bland-Altman plots.ResultsWe enrolled 140 participants (98 [70%] women, median age 37 years), who provided 189 paired samples at one or more timepoints. We tested 174 samples with the Xpert XC, 188 with the Xpert VL, and 128 with the m-PIMA. At 1000 copies/mL, sensitivity and specificity (95% confidence intervals) were 97% (82-100) and 98% (93-99) (Xpert XC), 100% (87-100) and 96% (91-98) (Xpert VL), and 92% (72-99) and 99% (93-100) (m-PIMA) respectively. At 50 copies/mL, sensitivity and specificity were 93% (81-98) and 96% (91-99) (Xpert XC), and 95% (84-99) and 95% (90-98) (Xpert VL) respectively. Mean bias was -0.10 (-0.54 to 0.34) log10 copies/mL (Xpert XC), 0.07 (-0.37 to 0.52) log10 copies/mL (Xpert VL) and -0.26 (-0.83 to 0.31) log10 copies/mL (m-PIMA).ConclusionsIn these South African clinics, the accuracy of all three assays was clinically acceptable to detect viraemia at the WHO failure threshold, while both Xpert assays were also accurate at detecting low level viraemia.

The Effect of cART on Platelets/Lymphocytes Ratio and Viral Load Indices in HIV+ Subjects Initiating Therapy in a Tertiary Hospital in Port Harcourt, Nigeria

<i>Background:</i> In other to enhance immune response and remove completely the danger of disease associated with AIDS, commencement of combination Antiretroviral Therapy (cART) is advocated. Common among HIV positive subjects are diseases such as cardiovascular conditions among others which happen when there is distortion in the gut mucosa, existence of co-infections, and long-term cART effect which gives room to vicious cycle that impairs on immune activities and inflammation. Inflammatory predictors which reveal the danger of morbidity and mortality are raised in HIV disease. A novel marker for inflammation – Platelet/Lymphocyte ratio (PLR), is a prognostic tool for assessing inflammation, atherosclerosis and platelet activation. <i>Aim:</i> This study was aimed at assessing prospectively, cART effect on the PLR and coagulation indices in HIV positive subjects presenting to commence cART in Rivers State University Teaching Hospital. <i>Methods</i>: Six milliliters of venous blood was collected from each participants into EDTA bottles at entry into the study, after 3 months and 6 months on cART respectively for Full Blood Count using a 3-part Sysmex XP300 and HIV Viral Load using RT-PCR Cobas TaqMan version 1.5 <i>Results</i>: A total of 40 subjects were recruited, with a mean age of 36.20 years, 14 (35%) of them were males. Mean PCV, Platelet: Lymphocyte ratio and HIV VL at Month 0 were 31.65±7.30%, 7.82±2.90 and 215767.85 ± 360338.04cp/ml respectively. There was a statistically significant increase (p <0.001) in the haematocrit by the 6^th month on cART, the reduction in Platelet: Lymphocyte count and of HIV VL by the 6^th month was also significant (P<0.001). Interestingly, PLR positively correlated with the VL at baseline (0.3676), however, there was a negative correlation at 3 months (-0125) and 6 months (-0.028). <i>Conclusion</i>: From this work it is clear that all the cases in this regard, confirm the fact that cART remarkably drops the viral load and inflammation in HIV positive subjects; nevertheless, it also shows that a low-level inflammation continues which probably leads to chronic inflammatory state, morbidity and mortality in this group of subjects.

Low-Level Viremia Is Associated With Cumulative Adherence to Antiretroviral Therapy in Persons With HIV.

The drivers of low-level viremia (LLV) between 20 and 200 copies/mL remain unclear. In 1042 person-visits from 497 persons with HIV on tenofovir disoproxil fumarate–containing antiretroviral therapy (ART), the association between LLV and cumulative antiretroviral adherence (quantified using tenofovir diphosphate [TFV-DP] in dried blood spots) was assessed. Lower TFV-DP levels were associated with higher odds of LLV. As TFV-DP (fmol/punch) categories decreased from >1650 to 800–1650; 800–1650 to <800; and >1650 to <800, the adjusted odds ratios for LLV vs HIV VL <20 copies/mL were 2.0 (95% CI, 1.2–3.1), 2.4 (95% CI, 1.1–5.0), and 4.6 (95% CI, 2.2–9.9), respectively. This suggests that adherence could impact LLV.

BK polyomavirus associated progressive multifocal leukoencephalopathy in a person living with HIV

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the white matter central nervous system occurring in immunocompromised patients particularly those with T cell deficiency such as in HIV, haematological and solid organ malignancies and those taking immunomodulatory medications. PML is caused by JC virus however in rare cases BK virus has been isolated in the cerebral spinal fluid of patients presenting with PML.In this case we describe a 49 year old man who presented to the emergency department with a 2 week history of progressive right sided weakness and dysarthria. His background history included HIV diagnosed in 2005, he had not engaged with care in the past 2 years and had not been taking anti-retroviral therapy (ART). Other past medical history included untreated hepatitis C. His CD4 count was 90 (11%) cells/mm3 on admission and his HIV viral load VL) was 141,000 copies/ml. Magnetic resonance imaging(MRI) showed a hypointense lesion on T1, hyperintense on T2 and FLAIR without diffusion restriction and without mass effect. A lumbar puncture was performed which confirmed JC virus was positive (PCR <50 copies/ml) and also revealed BK virus was positive (PCR 46,511 copies/ml). The patient was commenced on tenofovir alafenamide fumarate/emtricitabine/darunavir/cobicistat in combination with dolutegravir 50mg twice daily. On day 40 post commencement of ART the patient was readmitted with worsening of his right arm weakness and dysarthria. A repeat MRI was performed which showed the hyperdense lesion on T2 and FLAIR appeared slightly larger with some slight enhancement with gadolinium contrast but no other features suggesting PML immune reconstitution inflammatory syndrome (IRIS). The CD4 count had increased to 141(17%) and HIV VL had decreased to 85 copies/ml. A clinical diagnosis of PML IRIS was made and the patient was commenced on prednisolone 30mg BD which lead to an initial improvement in symptoms.Interestingly in this case, both JC virus and BK virus were detected in the CSF of this patient with the level of JC virus being too low to quantify. BK virus was not detectable on peripheral serum sampling suggesting that BK virus is replicating in the CNS independent of other body sites. There have been 5 case reports in the literature of BK virus as the cause of PML.Testing for BK virus should be considered in patients presenting with signs and symptoms of PML and encephalitis particularly when no other cause is found.

Study To Evaluate the Performance of a Point-of-Care Whole-Blood HIV Viral Load Test (SAMBA II HIV-1 Semi-Q Whole Blood).

Remote areas of many low and middle income (LMI) countries have poor access to HIV viral load (HIV VL) testing. The SAMBA II (simple amplification-based assay) Semi-Q whole-blood test (Diagnostics for the Real World [DRW], Cambridge, UK) is a point-of-care assay, which uses leucodepletion technology to allow whole-blood testing in remote settings. A total of 1,540 consecutive HIV-positive clinic patients in Cameroon (250), United Kingdom (633), Ukraine (412), and Zimbabwe (245) donated venous blood (all countries) and finger prick blood (all except UK) for testing on SAMBA II. SAMBA II results were compared with simultaneous plasma results on the Abbott RealTime HIV-1 (Abbott Molecular, Des Plaines, IL) viral load assay and interpreted as either <1,000 RNA copies/ml or ≥1,000 RNA copies/ml. For 1,528 venous whole-blood samples tested on SAMBA II, overall percent agreement with the reference test at a cutoff HIV VL of ≥1,000 copies/ml was 96.9% (1,480/1,528; 95% confidence interval [CI], 95.9% to 97.7%), negative percent agreement was 97.7% (1,259/1,289; 95% CI, 96.7% to 98.4%), and positive percent agreement was 92.5% (221/239; 95% CI, 88.4% to 95.5%). For 854 finger prick samples, there was 95.0% (811/854; 95% CI, 93.3% to 96.3%) overall percent agreement, 98.0% (625/638; 95% CI, 96.5% to 98.9%) negative percent agreement, and 86.1% (186/216; 95% CI, 80.8% to 90.4%) positive percent agreement. These rose to 93.5% (82.1% to 98.6%), 97.6% (95.6% to 98.8%), and 95.6% (93.3% to 97.3%) after exclusion of aberrant results from the Ukraine center. These results show a high level of agreement between SAMBA-II and a laboratory-based assay. SAMBA-II has a performance that is suitable to use as a VL point-of-care assay in remote settings.

The Development of a Standardized Quality Assessment Material to Support Xpert® HIV-1 Viral Load Testing for ART Monitoring in South Africa.

The tiered laboratory framework for human immunodeficiency virus (HIV) viral load monitoring accommodates a range of HIV viral load testing platforms, with quality assessment critical to ensure quality patient testing. HIV plasma viral load testing is challenged by the instability of viral RNA. An approach using an RNA stabilizing buffer is described for the Xpert® HIV-1 Viral Load (Cepheid) assay and was tested in remote laboratories in South Africa. Plasma panels with known HIV viral titres were prepared in PrimeStore molecular transport medium for per-module verification and per-instrument external quality assessment. The panels were transported at ambient temperatures to 13 testing laboratories during 2017 and 2018, tested according to standard procedures and uploaded to a web portal for analysis. A total of 275 quality assessment specimens (57 verification panels and two EQA cycles) were tested. All participating laboratories met study verification criteria (n = 171 specimens) with an overall concordance correlation coefficient (ρc) of 0.997 (95% confidence interval (CI): 0.996 to 0.998) and a mean bias of −0.019 log copies per milliliter (cp/mL) (95% CI: −0.044 to 0.063). The overall EQA ρc (n = 104 specimens) was 0.999 (95% CI: 0.998 to 0.999), with a mean bias of 0.03 log cp/mL (95% CI: 0.02 to 0.05). These panels are suitable for use in quality monitoring of Xpert® HIV-1 VL and are applicable to laboratories in remote settings.

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

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