Plasma Viral Load Research Articles

The incidence of symptomatic CSF viral escape in patients on antiretroviral therapy in western India: a retrospective cohort study.

Antiretroviral treatment (ART) effectively suppresses viral loads in both plasma and cerebrospinal fluid (CSF). Patients with discordant plasma and CSF viral loads may experience chronic-progressive or fluctuating neurocognitive dysfunctions. This study examined the incidence of symptomatic CSF viral escape (CSFVE) in patients receiving ART. This retrospective cohort study was conducted between 2000 and 2023. The primary outcome measure was the incidence of symptomatic CSFVE. Nonparametric Mann-Whitney U and Fisher exact/χ 2 tests were applied for continuous and categorical variables, respectively. The cumulative incidence function with Gray's test was used to compare the incidence of CSFVE across the treatment regimens. During the study period, 52 of the 8415 patients were diagnosed with CSFVE. The median duration of HIV diagnosis in patients with CSF VE was 150 (12-288) months, with a median nadir CD4 + T-cell count 96.5 (13-601 cells/L)], and 75% of the patients were on a ritonavir-boosted protease inhibitor (PI/r) regimen. The cumulative incidence of symptomatic CSFVE at a follow-up of 14 years was 1% (95% CI, 0-1%). PI/r (HR 34.73; 95% CI 13.5 to 89.4; p < 0.001) and integrase strand transfer inhibitor (INSTI) (HR 3.42; 95% CI 1.94 to 6.02; p < 0.001) regimens were significantly more likely to be associated with CSFVE than the Non-nucleoside reverse transcriptase inhibitors (NNRTIs) regimens. NNRTIs had the lowest risk of CSFVE compared to the PI/r and INSTI regimens. A rapid and complete recovery is possible with symptomatic CSFVE if it is diagnosed and treated early.

Efficacy and safety of DTG plus 3TC for prophylaxis of perinatal transmission of HIV infection in pregnant women who have detectable viral load after 14 weeks of gestation: A pilot study (PREGNANCY)

Abstract Background The prevention of perinatal HIV transmission depends on the safe and effective use of antiretroviral therapy (ART). Simplifying treatment reduces drug exposure for both mother and child. We evaluated the safety and efficacy of DTG/3TC for antiretroviral-naïve pregnant women living with HIV (PWLHIV). Methods This proof-of-concept trial enrolled ART-naïve pregnant women over 15 years old with HIV infection and a gestational age between 14 and 28 weeks. Participants received a fixed-dose combination of DTG/3TC. Baseline HIV genotyping was performed. Participants were monitored at baseline, every 4 weeks, and at delivery. Infants were assessed at birth, 4 weeks, and 6 weeks of age. Outcomes included the proportion of women achieving an undetectable HIV-1 plasma viral load (&amp;lt;50 copies/mL) at delivery, therapy modification frequency, perinatal HIV transmission rate, and adverse events. Results Between January 2019 and March 2021, 20 women were enrolled. At baseline, the median CD4 cell count was 401.6 ± 113.6 cells/μL, increasing to 690.2 ± 266 cells/μL at delivery. Median viral load was 9,514 copies/mL. All women achieved an undetectable viral load after an average of 40 days. No cases of perinatal HIV transmission were detected. No therapy modifications were necessary during the study, and no adverse events were related to the ART. Conclusion In this pilot trial, DTG/3TC demonstrated safety and efficacy, with all participants achieving viral suppression before delivery. There were no cases of perinatal HIV transmission and no drug-related adverse events. DTG/3TC can be an option for initial treatment of drug-naïve PWLHIV.

Asymptomatic Cerebrospinal Fluid HIV-1 Escape: Incidence and Consequences.

The incidence and clinical relevance of asymptomatic cerebrospinal fluid escape (CSF-E) during antiretroviral therapy (ART) is uncertain. We examined the impact and incidence of asymptomatic CSF-E in a Swedish HIV cohort. Neuroasymptomatic people living with HIV (PLWH) who have been on ART for at least six months with suppressed plasma viral load were followed longitudinally. CSF-E was defined as either increased CSF HIV-1 RNA with concurrent plasma suppression or as CSF HIV-1 RNA exceeding that in plasma when both were quantifiable. Paired CSF and plasma were analyzed for HIV-1 RNA, neopterin, neurofilament light protein (NfL), white blood cell (WBC) count, and albumin ratio. Asymptomatic CSF-E (cut-off 50 copies/mL) was found in 4/173 PLWH (2%) and 5/449 samples (1%). The corresponding proportions were 8% of PLWH and 4% for samples using a 20 copies/mL cut-off for CSF HIV-1 RNA. CSF-E samples (cut-off 20 copies/mL) had a 25% higher geometric mean of CSF neopterin (P = .01) and 8% higher albumin ratio (P = .04) compared to samples without CSF-E. No differences were observed in CSF NfL levels (P = .8). The odds ratio for increased CSF WBC (≥ 3 cells/μL) in samples with CSF-E was 3.9 (P = .004), compared to samples without elevated CSF viral load. Asymptomatic CSF-E was identified in only four (2%) PLWH, with no cases of continuous CSF-E observed. Increased CSF HIV-1 RNA was associated with biomarkers of CNS immune activation and blood-brain-barrier impairment, but not with biomarkers of neuronal injury.

Impact of Dolutegravir plus Lamivudine as First-Line Antiretroviral Treatment on HIV-1 Reservoir and Inflammatory Markers in Peripheral Blood.

To compare the effects of first-line antiretroviral treatment (ART) with dolutegravir plus lamivudine (DTG+3TC) versus DTG plus emtricitabine/tenofovir alafenamide (FTC/TAF) on the evolution of the HIV-1 reservoir and immune activation biomarkers in people with HIV (PWH). DUALITY was a 48-week, single-center, randomized, open-label clinical trial in ART-naïve PWH. Participants were randomized (1:1) to receive ART with DTG+3TC (2DR group) or DTG+FTC/TAF (3DR group). Total and intact proviral HIV-1 DNA, cell-associated RNA in CD4+ T cells, the frequency of HIV-infected CD4+ T cells able to produce p24, plasma soluble inflammatory markers (IL-6, sCD14, TRAIL, IP-10, FABP2, CRP and D-dimer), and activation and exhaustion markers in CD4+ and CD8+ T cells were longitudinally determined. Forty-four participants (22 per study arm) were enrolled. Baseline mean (SD) log10 plasma viral load (pVL) and CD4+ T cell counts were 4.4 (0.7) copies/mL and 493 (221) cells/mm3, respectively. All participants completing the study (2DR n=20; 3DR n=21) had pVL <50 copies/mL at week 48, except for one in the 2DR group who was resuppressed after treating syphilis. Changes from baseline to week 48 in all reservoir parameters or in levels of soluble inflammatory biomarkers and activated or exhausted CD4+ and CD8+ T cells were similar between 2DR and 3DR groups. First-line ART with DTG+3TC resulted in a similar reduction of HIV-1 persistence parameters in peripheral blood, and comparable changes in immune-associated soluble and T-cell markers compared with DTG+FTC/TAF. These findings support recommendation of DTG/3TC among preferred options for first-line ART in PWH.

Comparison of the Performance of Commercially Available Quantitative Viral Load Assays Using Clinical Samples from Patients from Regions Where Distinct HIV-1 Subtypes Co-Circulate: Potential Implications for Patient Management.

HIV RNA plasma viral load (VL) is the standard surrogate marker to monitor response to antiretroviral treatment (ART). We compared the linearity, repeatability, and concordance of six commercially available HIV RNA VL platforms using clinical samples from patients from Brazilian sites where different HIV-1 subtypes co-circulate. A total of 150 plasma samples from each city were collected in Curitiba, Southern Brazil (subtype C), São Paulo (subtype B), and Santos (BF recombinants), Southeast Brazil. Platforms were VERSANT® Siemens HIV RNA 1.0 (kPCR); VERSANT® Siemens HIV-1 RNA 3.0 (bDNA); Abbott Real-Time HIV-1; NucliSens EasyQ® HIV-1 v2.0 Biomerieux; COBAS® TaqMan®, Roche; and artus HIV Virus-1 RT-PCR, QIAGEN. OptiQuant HIV-1 RNA quantification panel was used to compare VL linearity, using samples containing 50, 500,5,000, 50,000, 500,000, and 5,000,000 HIV copies/mL. HIV RNA panels with subtypes A, B, C, D, F, G, H, circulating recombinant form (CRF)1, and CRF2 were utilized. A high degree of linearity and repeatability was demonstrated for all platforms. When compared with a subtype B reference sample, 17 of 54 (31.48%) samples diverged by more than 0.5 log10 copies/mL. Except for the Roche platform, all platforms underestimated subtype C VLs. A total of 743 (82.6%) valid results were obtained with samples from São Paulo, 707 (78.6%) from Santos, and 673 (74.8%) from Curitiba (São Paulo vs. Santos, p = .03; São Paulo vs. Curitiba, p = .00006; Santos vs. Curitiba, p = .06). The number of discordant samples between different methodologies when VL was undetectable in one method and detectable in the other ranged from 1.25% (Abbot vs. Siemens) to 44.8% (Abbott vs. Biomerieux). Finding samples with undetectable VL in one method and a high VL in another might have important individual and public health consequences. Standardization of VL measurements, particularly for non-B subtypes infections, especially subtype C, is necessary to maximize the individual and public health benefits of ART globally.

Emergent resistance-associated mutations at first- or second-line HIV-1 virologic failure with second-generation InSTIs in two- and three-drug regimens: the Virostar-1 study.

Second-generation integrase strand transfer inhibitors (InSTIs) have a high barrier to resistance and potent antiretroviral activity. They are recommended as first- or second-line (FL and SL) options in two- and three-drug regimens (2DR and 3DR) in international treatment guidelines. However, there are limited real-world data on emerging resistance at the time of virological failure (VF) with these regimens. The Virostar-1 study objective is to analyse the emergence of resistance-associated mutations (RAMs) over 3 years with DTG-based 2DRs and DTG- or bictegravir (BIC)-based 3DRs in people living with HIV (PLWH) experiencing a VF (FL or SL). Retrospective analysis of genotypic resistance detected at the time of a FL or SL VF with BIC/FTC/TAF, DTG/ABC/3TC, DTG/3TC and DTG/RPV between 2019 and 2022 was conducted from a French multicentre database. VF was defined as two consecutive HIV-1 plasma viral loads > 50 c/mL. Sanger assays were performed at VF within standard clinical care. Resistance mutations were reported using the ANRS algorithm. Selection biases prevent group comparisons. During the period, N = 5986 PLWH were followed either in FL or SL. The VF rate was overall low: BIC/FTC/TAF, 6.8%; DTG/ABC/3TC, 7.5%; DTG/3TC, 5.1%; and DTG/RPV, 2.1%. Some emergent InSTI or NRTI RAMs were detected with BIC/FTC/TAF 4%, DTG/ABC/3TC 8.5%, DTG/3TC 18% and 39% emergent NNRTI RAMs with DTG/RPV. However, a complete absence of dual resistance against NRTIs and InSTIs was observed. We detected rare emergent InSTI RAMs and few emergent NRTI RAMs in PLWH failing DTG- or BIC-based regimens in FL or SL. The observed rates of emergent RAMs at VF were 4% with BIC/FTC/TAF, 8.5% with DTG/ABC/3TC, 18% with DTG/3TC and 39% with DTG/RPV.

Minimally Modified HIV-1 Infection of Macaques: Development, Utility, and Limitations of Current Models.

Nonhuman primate (NHP) studies that utilize simian immunodeficiency virus (SIV) to model human immunodeficiency virus (HIV-1) infection have proven to be powerful, highly informative research tools. However, there are substantial differences between SIV and HIV-1. Accordingly, there are numerous research questions for which SIV-based models are not well suited, including studies of certain aspects of basic HIV-1 biology, and pre-clinical evaluations of many proposed HIV-1 treatment, prevention, and vaccination strategies. To overcome these limitations of NHP models of HIV-1 infection, several groups have pursued the derivation of a minimally modified HIV-1 (mmHIV-1) capable of establishing pathogenic infection in macaques that authentically recapitulates key features of HIV-1 in humans. These efforts have focused on three complementary objectives: (1) engineering HIV-1 to circumvent species-specific cellular restriction factors that otherwise potently inhibit HIV-1 in macaques, (2) introduction of a C chemokine receptor type 5 (CCR5)-tropic envelope, ideally that can efficiently engage macaque CD4, and (3) correction of gene expression defects inadvertently introduced during viral genome manipulations. While some progress has been made toward development of mmHIV-1 variants for use in each of the three macaque species (pigtail, cynomolgus, and rhesus), model development progress has been most promising in pigtail macaques (PTMs), which do not express an HIV-1-restricting tripartite motif-containing protein 5 α (TRIM5α). In our work, we have derived a CCR5-tropic mmHIV-1 clone designated stHIV-A19 that comprises 94% HIV-1 genome sequence and replicates to high acute-phase titers in PTMs. In animals treated with a cell-depleting CD8α antibody at the time of infection, stHIV-A19 maintains chronically elevated plasma viral loads with progressive CD4+ T-cell loss and the development of acquired immune-deficiency syndrome (AIDS)-defining clinical endpoints. However, in the absence of CD8α+ cell depletion, no mmHIV-1 model has yet displayed high levels of chronic viremia or AIDS-like pathogenesis. Here, we review mmHIV-1 development approaches, the phenotypes, features, limitations, and potential utility of currently available mmHIV-1s, and propose future directions to further advance these models.

BK virus associated hemorrhagic cystitis in pediatric patients undergoing hematopoietic stem cell transplantation

Abstract Background BK virus (BKV) is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic stem cell transplantation (HSCT). Methods Descriptive and retrospective study that included patients from 0-18 years old undergoing HSCT with a diagnosis of HC, admitted from 1/1/2018 to 11/30/2023 in a tertiary care pediatric hospital. Patients with HC were tested for BKV by quantitative polymerase chain reaction (PCR) in urine samples, if positive, plasma viral load was also requested. BKV-HC grading was defined by the European Conference on Infections in Leukemia (ECIL) consensus document. Asymptomatic patients did not undergo standardized screening for BKV. Results During this period 86 HSCT were performed for either malignant (75,6%) or non-malignant disorders (24,4%). Overall, 16 (18,6%) were autologous and 70 (81.4%) were allogeneic: 40 human leukocyte antigen (HLA) matched unrelated donor, 26 HLA-matched related donor and 4 haploidentical. Six patients (7%) suffered HC, all associated with BKV as the cause. These six patients underwent allogeneic HSCT, and 4 of them had HLA-matched unrelated donors. All patients were over 5 years old. Male sex predominated (n:5). All of the patients had hematologic malignancies as the underlying diagnosis (5 with acute lymphoblastic leukemia - ALL). The stem cell source was bone marrow in 3 patients and peripheral blood in the other 3. All patients received myeloablative conditioning regimen and 4 underwent total body irradiation. Only one patient received post-transplant cyclophosphamide. Symptoms (dysuria, abdominal pain, macroscopic hematuria, clots) began more than 14 days after HSCT in 100% of the cases. Hematuria was categorized as grade III in 5 patients and grade IV (severe) only in one. All patients tested positive for BKV PCR in urine samples. High-level BK viruria (&amp;gt;107 copies/mL) was found in 66,6%. BK viremia was detected in 4 patients. All of the patients had another concomitant viral infection, with cytomegalovirus reactivation being the most frequent (n:4). Two patients also had detectable adenovirus (ADV) PCR in urine samples. Acute graft versus host disease (GVHD) was diagnosed in 5 patients, all with skin involvement. All patients were hospitalized and prolonged the length of stay. Regarding treatment, they all received hyperhydration and Cidofovir (more than 3 doses). Dose of immunosuppressive treatment was reduced in 5 cases. Acute kidney failure (AKF) was found in 3 patients. One patient developed chronic kidney failure. The patient with no GVHD was the one who improved the fastest. The patient with severe hematuria required bladder irrigation, had dialysis indication and presented a related death. Conclusion The development of BKV-HC in HSCT patients results in suffering and pain, prolonged hospitalizations and significant morbidity (AKF). Literature shows that male sex, older age and acute GVHD are important risk factors, and this is what we also found in our case series. BKV-HC is considered a difficult and severe condition to manage, remaining troublesome so we should overcome this deficiency with new approaches, particularly emphasizing in preemptive or prophylaxis measures for the benefit of our patients.

SARS-CoV-2 RNAemia as a reliable predictor of long-term mortality among older adults hospitalized in pulmonary intermediate care units: a prospective cohort study

BackgroundSARS-CoV-2 viremia is associated with disease severity and high risk for in-hospital mortality. However, the impact of SARS-CoV-2 viremia on long-term outcomes in hospitalized patients with COVID-19 is poorly understood.MethodsWe conducted a prospective cohort study and recruited a group of older adult patients with COVID-19 admitted to pulmonary intermediate care units of Peking University Third Hospital during December 2022 and January 2023. The plasma level of SARS-CoV-2 RNA was determined by a standardized RT-PCR technique, and SARS-CoV-2 RNAemia was defined as a plasma viral load ≥ 50 copies/ml. In-hospital and follow-up (180-day) outcome data were collected.ResultsA total of 101 patients with an average of 80.4 years were recruited, and 63.4% of them were severe or very severe cases. Twenty-eight patients (27.7%) had SARS-CoV-2 RNAemia, with a median viral RNA load of 422.1 [261.3, 1085.6] copies/ml. Patients with SARS-CoV-2 RNAemia were more likely to develop critical cases and had a higher incidence of sepsis. Accordingly, they had a higher 180-day mortality (57.1% vs. 19.7%, P < 0.001), as well as in-hospital mortality (50.0% vs. 13.7%, P < 0.001), independent of age, disease severity, sepsis, lymphocyte count and C-Reactive protein. In addition, the risk for 180-day mortality increased with the SARS-CoV-2 RNA load in plasma. Plasma cytokines, including IL-6, IL-8 and IL-10, were higher in patients with SARS-CoV-2 RNAemia.ConclusionsOur study indicates that SARS-CoV-2 RNAemia serves as a useful biomarker for predicting mortality, especially long-term mortality, in older adult patients hospitalized in pulmonary intermediate care units.Trial registrationChinese Clinical Trial Registry website (No. ChiCTR2300067434).

HIV-1 inhibits IFITM3 expression to promote the infection of megakaryocytes.

Despite an undetectable plasma viral load as a result of antiretroviral therapy, HIV-1-infected individuals with poor immune reconstitution harbor infectious HIV-1 within their platelets. Megakaryocytes, as platelet precursors, are the likely cellular origin of these HIV-1-containing platelets. To investigate the mechanisms that allow megakaryocytes to support HIV-1 infection, we established in vitro models of viral infection using hematopoietic stem cell-derived megakaryocytes and the megakaryocytic MEG-01 cell line. We observed HIV-1 DNA provirus integration into the megakaryocyte cell genome, self-limiting virus production, and HIV-1 protein and RNA compartmentalization, which are hallmarks of HIV-1 infection in myeloid cells. In addition, following HIV-1 infection of megakaryocyte precursors, the expression of interferon-induced transmembrane protein 3 (IFITM3), an antiviral factor constitutively expressed in megakaryocytes, was inhibited in terminally differentiated HIV-1-infected megakaryocytes. IFITM3 knockdown in MEG-01 cells prior to infection led to enhanced HIV-1 infection, indicating that IFITM3 acts as an HIV-1 restriction factor in megakaryocytes. Together, these findings indicate that megakaryocyte precursors are susceptible to HIV-1 infection, leading to terminally differentiated megakaryocytes harboring virus in a process regulated by IFITM3. Megakaryocytes may thus constitute a neglected HIV-1 reservoir that warrants further study in order to develop improved antiretroviral therapies and to facilitate HIV-1 eradication.

Effect of highly-active antiretroviral therapy on neuroendocrine regulation of immunogenesis in HIV-infected children

Comparative assay has been made against the parameters of the immune and endocrine systems in 84 HIV-infected children born from HIV-infected mothers. One group of analyzed children (36 patients) did not receive highly-active antiretroviral therapy. Another group (48 patients) received different variants of highly-active antiretroviral therapy. Children aged from 1 to 182 months were examined. Venous blood samples taken from young patients were used to determine leukocyte blood composition considering the relative (%) and absolute number of blood cell counts. Hormone concentration was determined concurrently. CD-molecule expression by mononuclear cells was registered using flow cytofluorimeter. Plasma viral load in HIV-infected children was quantitatively detected with RT-PCR. Statistically significant lowering in the levels of free thyroxin, cortisol and progesterone was observed in children against a background of highly-active antiretroviral therapy as compared to those without HAART use. Correlation assay between the hormone level and the immunological parameters in children not receiving the antiretroviral preparations revealed marked positive correlations among the somatotropic hormone level and CD3+, CD4+ and CD8+ absolute numbers. Similar positive correlation with absolute T-subset number was found against free T4. The progesterone level also positively correlated with relative CD3+ and CD8+ numbers and showed negative correlation with absolute CD4+ amount. There is another positive correlation with relative T-subset number against the dehydroepiandrosterone level in the group of children without antiretroviral preparation therapy. As for HIV-infected group of children, against a background of highly-active antiretroviral therapy, the results of correlation assay between the hormone concentrations and cell parameters were found to significantly vary. There were observed positive correlations between the levels of cortisol and CD3+ (%), cortisol and CD8+ (%), estradiol and CD4/CD8, progesterone and absolute CD8+ number. As with children not receiving the antiretroviral preparations marked positive relation was revealed between the concentration of free thyroxin and absolute values of CD4+. Negative correlations were recorded between the estradiol level and the relative CD3+ numbers. Against a background of applying the antiretroviral preparations the correlation assay conducted between the viral RNA concentration (lg of copy number of mRNA/ml) and analyzed endocrinological parameters was found to have marked positive correlation with HIV concentration demonstrated by estradiol and testosterone. During the antiretroviral therapy, however, the negative correlation between the thyrotropin level and lg concentration of viral RNA was observed. Analytical results of correlation among the viral RNA concentration (lg copy number of mRNA/ml) and analyzed immunological parameters in this group of children evidence for specific ‘normalization’ due to highly-active antiretroviral therapy as the only positive correlation with virus concentration was detected for CD4+T subsets. Therefore, the alteration in endocrine system state in children born from HIV-infected mothers could be of great significance while monitoring the systemic regulation of the immunogenesis.

Empowering adolescents living with perinatally-acquired HIV: tailored CD4+ count assessment for optimized care, the EDCTP READY-study.

The elevated rate of AIDS-related mortality in Sub-Saharan Africa among adolescents living with HIV (ALHIV) is influenced by various factors, notably immunosuppression, within a framework of limited therapeutic alternatives. We aimed to enhance the management of pediatric HIV by assessing the immune response and associated factors in perinatally-infected ALHIV on antiretroviral therapy (ART) in Cameroon. A cohort study was conducted from 2018-2020 among 271 ART-experienced ALHIV in Cameroon. Sociodemographic data, immunological (CD4), and virological (plasma viral load, PVL) responses were measured at enrolment (T0), 6-months (T1), and 12-months (T2) using PIMA CD4 (Abbott/Pantech (Pty) Ltd) and Abbott Applied Biosystem platform (Real-Time PCR m2000RT) respectively. Immunological failure (IF) was defined as absolute CD4 < 250 cells/mm3, and Virological failure (VF) as PVL ≥ 1,000 copies/ml. A linear mixed-effects model with R version 4.4.1 was used to estimate both fixed and random effects, with significance set at p < 0.05. Of the 271 perinatally-infected ALHIV enrolled over three phases, females were predominant (55.7, 55.1, and 56.0%); median age was 14 (IQR: 12-17); majority of the participants were followed-up in urban areas (77.5, 74.5, and 78.6%); and the age distribution favored older adolescents (48.7, 61.2, and 58.5%). Most participants achieved clinical success (93.1, 89.7, 88.9%), predominantly on first-line ART (80.8, 66.2, and 53.0%), with good adherence (64.2, 58.9, and 64.5%). Most participants had secondary education (67.2, 70.1, and 67.5%). Median CD4+ counts fluctuated overtime, with values of 563 (IQR: 249.0-845.0), 502 (IQR: 319.0-783.5), and 628 (IQR: 427.5-817.5), respectively. Of note, being male was linked to a reduction in CD4+ count compared to females, [-200.63 (-379.32 to -21.95), p = 0.028]. Similarly, late adolescence was associated with lower CD4+ counts compared to early adolescence, [-181.08 (-301.08 to -61.09), p = 0.003]. Moreover, participants experiencing VF showed significantly lower CD4+ counts compared to those with undetectable viral loads, [-353.08 (-465.81 to -240.36), p < 0.001]. Additionally, there was a marginally significant interaction between male gender and secondary educational level, [209.78 (-6.94-426.51), p = 0.058]. Among perinatally-infected ALHIV, age, gender, educational level, and virological status are key factors influencing their immune health and treatment outcomes. Prioritizing targeted interventions and close monitoring within these subgroups is crucial for optimal management, employing holistic care strategies that consider not only medical interventions but also psychosocial support and education.

Immuno-virological and Clinical Follow-up of Persons Living With HIV-2 (PWHIV-2) Receiving Bictegravir/Emtricitabine/Tenofovir Alafenamide Fumarate (BIC/FTC/TAF): A Retrospective Study.

This retrospective study evaluated Bictegravir/FTC/TAF in 24 PWHIV, 5 naive and 19 pretreated. After a median follow-up of 37.5 months, all PWHIV-2 had a plasma viral load < 40 copies/mL. Median CD4 count increased significantly from 580 to 625 cells/mm3, suggesting the effectiveness of Bictegravir/FTC/TAF to treat HIV-2 infection.

Performance of patient-collected dried blood spot specimens for HIV-1 viral load testing: evidence from the DO ART Study in South Africa.

Evaluate the clinical utility of patient-collected dried blood spots (DBS) in measuring HIV-1 viral load (VL) for monitoring antiretroviral therapy (ART) compared to provider-collected DBS and blood plasma. In a randomized trial of community-based delivery of ART in South Africa, we assessed performance of: (1) DBS specimens compared to plasma, and (2) participant-collected versus staff-collected DBS specimens, to measure HIV-1 VL. The bioMérieux NucliSENS EasyQ HIV-1 v2.0 assay was used for VL measurement. From October 2017 to November 2019, we collected 996 pairs of plasma/DBS specimens from 760 participants and 315 pairs of staff-/participant-collected DBS cards from 261 participants. We assessed DBS test sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) using the WHO failure threshold of 1000 copies/mL. Log-transformed VL was compared using concordance correlation coefficients (CCC) and mean differences from linear mixed models. In a population with 13% detectable VL, DBS VL compared with plasma VL had 91% (95% CI: 86-95) sensitivity, 99% (98-100) specificity, 94% (90-98) PPV, and 99% (98-99) NPV. We observed high agreement between staff-collected DBS VL and plasma VL (CCC: 0.94), and between participant-collected DBS VL and plasma VL (CCC: 0.92). Correlation between participant- and staff-collected DBS was very high (CCC: 0.97; mean difference for those with a detectable result: -0.10 log 10 copies/mL [-0.21-0.02]). VL results from participant-collected DBS are clinically comparable with those collected by clinical staff and using blood plasma. Self-collected DBS has potential for use for ART monitoring outside the clinic.

Antiviral capacity of the early CD8 T-cell response is predictive of natural control of SIV infection: Learning in vivo dynamics using ex vivo data.

While most individuals suffer progressive disease following HIV infection, a small fraction spontaneously controls the infection. Although CD8 T-cells have been implicated in this natural control, their mechanistic roles are yet to be established. Here, we combined mathematical modeling and analysis of previously published data from 16 SIV-infected macaques, of which 12 were natural controllers, to elucidate the role of CD8 T-cells in natural control. For each macaque, we considered, in addition to the canonical in vivo plasma viral load and SIV DNA data, longitudinal ex vivo measurements of the virus suppressive capacity of CD8 T-cells. Available mathematical models do not allow analysis of such combined in vivo-ex vivo datasets. We explicitly modeled the ex vivo assay, derived analytical approximations that link the ex vivo measurements with the in vivo effector function of CD8-T cells, and integrated them with an in vivo model of virus dynamics, thus developing a new learning framework that enabled the analysis. Our model fit the data well and estimated the recruitment rate and/or maximal killing rate of CD8 T-cells to be up to 2-fold higher in controllers than non-controllers (p = 0.013). Importantly, the cumulative suppressive capacity of CD8 T-cells over the first 4-6 weeks of infection was associated with virus control (Spearman's ρ = -0.51; p = 0.05). Thus, our analysis identified the early cumulative suppressive capacity of CD8 T-cells as a predictor of natural control. Furthermore, simulating a large virtual population, our model quantified the minimum capacity of this early CD8 T-cell response necessary for long-term control. Our study presents new, quantitative insights into the role of CD8 T-cells in the natural control of HIV infection and has implications for remission strategies.

Clinical-Laboratory Outcome of Cryptococcus sp. Multifocal Choroiditis in Acquired Immunodeficiency Syndrome Patients

ABSTRACT Purpose This study aims to describe the clinical and laboratory outcomes of patients with Acquired Immunodeficiency Syndrome (AIDS) presenting multifocal choroiditis secondary to Cryptococcus sp. infection. Methods We reviewed the clinical records of AIDS patients diagnosed with cryptococcal multifocal choroiditis at the Laboratory of Infectious Disease in Ophthalmology, Oswaldo Cruz Foundation, from January 2022 to March 2024. Patients meeting the criteria of typical fundus appearance associated with disseminated cryptococcosis laboratory diagnosis were included. Data collected included age, gender, symptoms, plasma HIV viral load, serum T-CD4+ cell count (cells/mm3), initial visual acuity (VA), laboratory methods for cryptococcosis diagnosis, treatment, and final VA. All patients underwent multimodal evaluation including spectral domain optical coherence tomography, fluorescein angiography (FA), and indocyanine green angiography (ICG). Results Six patients were evaluated, comprising five males (83%) and one female (17%), with a mean age of 36.5 years (standard deviation, SD: 10,46). Five patients (83%) presented with meningeal syndrome. Mean HIV plasma viral load was 262.959 copies/mm3 (SD: 209.469), and the mean serum T-CD4 count was 13.33 cells/mL (SD: 14,63). All patients tested positive for serum cryptococcal antigen (CRAG). Four patients (67%) had positive cerebrospinal fluid (CSF) culture and CRAG. Treatment included intravenous Amphotericin B and oral Fluconazole. Among twelve eyes (100%), four (33%) achieved visual recovery, while eight (67%) maintained initial VA. Lesions were more numerous and distinct on ICG compared to fundus examination and FA. Conclusion This study underscores the importance of clinical, laboratory, and multimodal evaluations in AIDS patients presenting with cryptococcal multifocal choroiditis.

Sexually transmitted infections and bacterial vaginosis among adolescent girls and young women in the early postpartum period: a cross-sectional study

BackgroundUniversal antiretroviral treatment (ART) for pregnant women has reduced mother-to-child transmission risk significantly. However, not all women on ART are virally suppressed during pregnancy and lactation. In addition to poor adherence to ART, co-infections particularly other sexually transmitted infections (STIs) are known to increase the risk of HIV acquisition and HIV transmission. While the prevalence of STIs during pregnancy has been well studied, the prevalence of STIs in the postpartum period and its association with HIV viral suppression are underreported.MethodsIn this cross-sectional study, we determined the prevalence of STIs among adolescent girls and young women (AGYW) living with HIV (WLHIV) and without HIV (WNLHIV) at their 6–14 week postnatal clinic visit in a high HIV prevalence district in South Africa. All women were examined for STI-related symptoms and had vaginal swabs collected and stored for later STI testing. Vaginal swabs were tested for Trichomonas vaginalis (T.vaginalis), Chlamydia trachomatis (C. trachomatis), Neisseria gonorrhoeae (N. gonorrhoea) and herpes simplex virus-2 (HSV-2) using PCR. All women were tested for bacterial vaginosis (BV) using the Nugent scoring criteria. WLHIV had a blood sample collected for HIV viral load, Hepatitis B and syphilis.ResultsIncluded in this analysis were 82 WLHIV and 102 WNLHIV. Between 6 and 14 weeks postpartum, 40 (21.7%) AGYW tested positive for any STI and among these 15 (37.5%) were symptomatic and received empirical treatment. C. trachomatis was most commonly detected (10.9%), followed by HSV-2 (7.7%), T. vaginalis (3.8%) and N. gonorrhoea (1.6%). WLHIV were more likely to test positive for an STI (OR 2.0; 0.96–3.96) and BV (OR 4.2; 95%CI 2.1–8.1) compared to WNLHIV. Among WLHIV on ART, 70.5% had an undetectable plasma viral load (PVL) and 20.5% had a PVL > 1000 copies/ml. Testing positive for any STI or BV at the postpartum visit was not associated with PVL > 1000 copies/ml (OR 1.33; 95%CI 0.38–4.64).ConclusionWe report a high prevalence of largely asymptomatic STIs and BV in the early postpartum period and STIs in WLHIV were not associated with unsuppressed PVL.The high STI positivity rate among WNLHIV has implications for HIV risk during the postpartum period, and subsequently breastfeeding transmission.

Sustained HIV remission after allogeneic hematopoietic stem cell transplantation with wild-type CCR5 donor cells.

HIV cure has been reported for five individuals who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with cells from CCR5Δ32 homozygous donors. By contrast, viral rebound has occurred in other people living with HIV who interrupted antiretroviral treatment after undergoing allo-HSCT, with cells mostly from wild-type CCR5 donors. Here we report the case of a male individual who has achieved durable HIV remission following allo-HSCT with cells from an unrelated HLA-matched (9 of 10 matching for HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 alleles) wild-type CCR5 donor to treat an extramedullary myeloid tumor. To date, plasma viral load has remained undetectable for 32 months after the interruption of antiretroviral treatment. Treatment with ruxolitinib has been maintained during this period to treat chronic graft-versus-host disease. Low levels of proviral DNA were detected sporadically after allo-HSCT, including defective but not intact HIV DNA. No virus could be amplified in cultures of CD4+ T cells obtained after antiretroviral treatment interruption, while CD4+ T cells remained susceptible to HIV-1 infection in vitro. Declines in HIV antibodies and undetectable HIV-specific T cell responses further corroborate the absence of viral rebound after antiretroviral treatment interruption. These results suggest that HIV remission could be achieved in the context of allo-HSCT with wild-type CCR5.

Real-world effectiveness and tolerability of switching to doravirine-based antiretroviral therapy in people with HIV: a nationwide, matched, prospective cohort study

Currently, real-world data on doravirine are scarce. In a national prospective cohort, we assessed the effectiveness and tolerability of switching to doravirine-based antiretroviral therapy (ART) in people with HIV. We did a nationwide, matched, prospective cohort study of people with HIV without previous virological failure and stable for at least 12 months on non-doravirine-containing triple or dual ART switching to doravirine before Sept 1, 2020 (exposed group). Participants in the exposed group were matched 1:2 to individuals continuing stable non-doravirine-containing ART, on age, sex, HIV acquisition category, time since ART initiation, calendar time, pre-ART CD4-count, pre-ART plasma viral load (PVL) and anchor drug class before switching. The primary outcome was protocol-defined virological failure (PDVF; PVL of ≥200 copies per mL) in the intention-to-treat (ITT) population at week 104, with participants modifying their regimen or becoming lost to follow-up considered as PDVF (non-inferiority margin +5%). In contrast, in the on-treatment population, those who modified their regimen or became lost to follow-up were censored from that moment onwards. Tolerability was a secondary outcome. In total, 590 participants in the exposed group and 1180 participants in the unexposed group (of whom 55·3% used integrase strand transfer inhibitor-based regimens) were included. In the ITT analysis, PDVF occurred in 135 (22·9%) exposed participants and in 295 (25·0%) unexposed participants (risk difference -2·12%, upper limit of the one-sided 95% CI +1·40%). In the on-treatment analysis, 10 (2·2%) of 455 non-censored exposed participants and 26 (2·9%) of 885 non-censored unexposed participants had PDVF (risk difference -0·70%, upper limit of the one-sided 95% CI +0·73%). All exposed participants with a PVL of 200 copies or more per mL resuppressed without regimen modification: no confirmed virological failure (two consecutive PVLs of ≥200 copies per mL) was observed. 104 (17·6%) exposed participants and 211 (17·9%) unexposed participants modified their regimen. 73 (12.4%) exposed participants discontinued doravirine due to adverse events: abnormal dreams (1·7%) and insomnia (1·5%) were most common. Switching to doravirine in well suppressed people with HIV without previous virological failure was non-inferior compared with continuing non-doravirine-containing regimens after 2 years in a real-world setting. None.

The risk of non-AIDS defining events is lower in ART-naive HIV controllers than in normal progressors on suppressive ART.

We aimed to compare the non-AIDS events (nADE) risk between normal progressors using ART (NP-ART) and people with HIV (PWH) that naturally control HIV infection (HIV controllers), as well as the outcomes after ART in HIV controllers on nADE. The primary endpoint was major nADE defined as the composite of cardiovascular disease, non-AIDS malignancy or all-cause mortality, whichever came first.. The role of ART in HIV controllers was assessed as a time-varying covariate. We included 1007 ART-naive HIV controllers (of which 60 elite controllers), 1510 Early-ART (<6 months after negative HIV test) and 15437 NP-ART (reference group), contributing 3813, 11,060 and 160,050 years of follow-up, respectively. HIV controllers had lower risk of the primary endpoint (HR 0.55, 95%CI 0.38-0.81, P = 0.0023), all-cause mortality (Adjusted Hazard ratio [aHR]: 0.45, 95% confidence interval [CI] 0.25-0.79, P = 0.0054), cardiovascular disease (aHR 0.47, 95%CI 0.22-0.99, P = 0.046) , but not non-AIDS malignancy (aHR 0.74, 95%CI 0.41-1.35, P = 0.33) than NP-ART. Among HIV controllers, each log10 lower baseline viral load further decreased the risk of nADE (aHR 0.54, 95% CI 0.29-0.99, P = 0.045). ART in HIV controllers did not reduce the risk of any nADE (aHR 1.22, 95% CI 0.66-2.29, P = 0.53). We found a lower risk of nADE in HIV controllers than NP-ART, especially in those with low plasma viral loads. Initiation of ART did not alter the nADE risk in HIV controllers. Our findings help clinicians to decide on prescribing ART in HIV controllers.