Antiretroviral Treatment Initiation Research Articles

How paediatric HIV services weathered the COVID-19 storm in Tshwane District, South Africa

Background: The coronavirus disease 2019 (COVID-19) pandemic disrupted paediatric HIV services across South Africa. Shortly before COVID-19, updated national HIV guidelines were released.Objectives: This study describes COVID-19’s impact on paediatric HIV services in Tshwane District, South Africa.Method: A retrospective review of National Institute for Communicable Diseases and District Health Information System data for Tshwane District from April 2019 to March 2022. Data included: Early Infant Diagnosis (EID), HIV viral load (VL) and CD4 monitoring and HIV management among children ( 15 years) living with HIV (CLHIV). Pre-pandemic (2019/2020) and pandemic periods (2020/2021, 2021/2022) were compared.Results: Year-on-year, HIV testing improved at 10 weeks, 6 months, and 18 months, whereas birth testing decreased. HIV EID case rates were 485 (2019/2020), 410 (2020/2021) and 454 (2021/2022). HIV EID test positivity was 0.77% – 1.2%. Antiretroviral treatment initiation declined from 2019/2020 to 2020/2021, but improved in 2021/2022.Initial HIV VL and CD4 testing declined, with HIV VL testing increasing in 2021/2022, and CD4 testing further declining. HIV VL suppression rate among CLHIV ranged from 69% to 73%.Conclusion: Initially, COVID-19 resulted in reduced paediatric HIV services as children disengaged from care. Indicators eventually recovered to proximate pre-pandemic levels; however, compensatory increases did not occur. Thus, some children may not have returned to care.

Statistical analysis on the incidence and predictors of death among second-line ART patients in public hospitals of North Wollo and Waghemira Zones, Ethiopia, 2021

Acquired immune deficiency virus, caused by the human immunodeficiency virus, is a significant global health concern. Sub-Saharan Africa particularly Ethiopia faces a high prevalence of human immunodeficiency virus. In low-income settings like Ethiopia, early mortality rates are elevated due to severe opportunistic infections and advanced disease at Anti-retroviral treatment initiation. Despite available treatments, delayed treatment initiation among Human Immunodeficiency Virus -infected individuals in Africa, including Ethiopia, leads to disease progression and increased mortality risk. This study aimed to identify the factors contributing to the death of HIV patients under treatment at second line regimen in public hospitals of North Wollo and Waghemira Zones. A retrospective cohort study with 474 patients was conducted in selected hospitals of North Wollo and Waghemira Zones. A parametric Weibull regression model was employed, and the adjusted hazard ratio served as the measure of association. Variables significantly affected the outcome of the study was determined at a p-value < 0.05, along with a 95% confidence interval for the variables. The patients were within the average age of 38.6(standard deviation ± 12.5) years and majority (45.57%) had no formal education. The overall death incidence rate among second-line anti-retroviral treatment patients was 1.98 per 100-person years [95% CI 1.4—2.9%]. Poor adherence to antiretroviral treatment, male gender, and being underweight significantly increased the hazard of death. Conversely, increased anti-retroviral treatment duration had a significant and negative impact, reducing the hazard of death among patients. The study reveals a high incidence of death among second line anti-retroviral treatment users. Independent predictors include poor adherence, male gender, and underweight status, all significantly increasing the risk of death. On the positive side, the hazard of death decreases with longer anti-retroviral treatment duration. A critical concern and counseling should be given for better ART adherence, to change their nutritional status and for males.

Mortality and its predictors among human immunodeficiency virus-infected children younger than 15 years receiving antiretroviral therapy in Ethiopia: a systematic review and meta-analysis

BackgroundDespite antiretroviral treatment (ART), the human immunodeficiency virus (HIV) continues to pose a considerable health burden in resource-poor countries. This systematic review and meta-analysis aimed to determine the pooled incidence density of mortality and identify potential predictors among HIV-infected children receiving ART, from studies conducted in various parts of Ethiopia.MethodsA comprehensive database search was made in Excerpta Medica, PubMed, Web of Science, African Journals Online, Google Scholar, and Scopus. We reported results following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020. Excel Spreadsheet and STATA Version 14 software were used for data abstraction and meta-analysis, respectively. Statistical heterogeneity among studies was assessed using I2 statistics. Meta-regression and subgroup analysis were performed to further explore the sources of statistical heterogeneity. Moreover, publication bias and a leave-out-one sensitivity analysis were performed.ResultsTwenty-two articles involving 8,731 participants met inclusion criteria and were included. The pooled incidence density of mortality was 3.08 (95% confidence interval (CI), 2.52 to 3.64) per 100 child years. Predictors of mortality were living in rural areas (hazard ratio (HR), 2.18 [95% CI, 1.20 to 3.98]), poor adherence to ART (HR, 2.85 [ 95% CI, 1.39 to 5.88]), failure to initiate co-trimoxazole preventive therapy (HR, 2.16 [95% CI, 1.52 to 3.07]), anemia (HR, 2.28 [95% CI, 1.51 to 3.45]), opportunistic infections (HR, 1.52 [ 95% CI, 1.15 to 2.00]), underweight (HR, 1.74 [95% CI, 1.26 to 2.41]), wasting (HR, 2.54 [95% CI, 1.56 to 4.16]), stunting (HR, 2.02 [95% CI, 1.63 to 2.51]), World Health Organization classified HIV clinical stages III and IV (HR, 1.71 [95% CI, 1.42 to 2.05]), and Nevirapine-based regimens (HR, 3.91 [95% CI, 3.09 to 4.95]).ConclusionsThis study found that the overall mortality rate among HIV-infected children after ART initiation was high. Therefore, high-level commitment and involvement of responsible caregivers, healthcare providers, social workers, and program managers are of paramount importance to identify these risk factors and thus enhance the survival of HIV-infected children receiving ART.

Characterization and Determinants of Long-Term Immune Recovery Under Suppressive Antiretroviral Therapy.

We developed a robust characterization of immune recovery trajectories in people living with HIV on antiretroviral treatment (ART) and relate our findings to epidemiological risk factors and bacterial pneumonia. Using data from the Swiss HIV Cohort Study and the Zurich Primary HIV Infection Cohort Study (n = 5907), we analyzed the long-term trajectories of CD4 cell and CD8 cell counts and their ratio in people living with HIV on ART for at least 8 years by fitting nonlinear mixed-effects models. The determinants of long-term immune recovery were investigated using generalized additive models. In addition, prediction accuracy of the modeled trajectories and their impact on the fit of a model for bacterial pneumonia was assessed. Overall, our population showed good immune recovery (median plateau [interquartile range]-CD4: 718 [555-900] cells/μL, CD8: 709 [547-893] cells/μL, CD4/CD8: 1.01 [0.76-1.37]). The following factors were predictive of recovery: age, sex, nadir/zenith value, pre-ART HIV-1 viral load, hepatitis C, ethnicity, acquisition risk, and timing of ART initiation. The fitted models proved to be an accurate and efficient way of predicting future CD4 and CD8 cell recovery dynamics: Compared with carrying forward the last observation, mean squared errors of the fitted values were lower by 1.3%-18.3% across outcomes. When modeling future episodes of bacterial pneumonia, using predictors derived from the recovery dynamics improved most model fits. We described and validated a method to characterize individual immune recovery trajectories of people living with HIV on suppressive ART. These trajectories accurately predict long-term immune recovery and the occurrence of bacterial pneumonia.

Reduction in time to viral suppression among persons living with HIV in Jamaica between 2017-2019.

HIV viral suppression is important for effective treatment and for reducing new infections. In 2019, only 66% of persons on antiretroviral treatment (ART) in Jamaica were virally suppressed. We aim to compare time to viral suppression by ART initiation year and type of treatment site to understand the implications for programming. We assessed time to viral suppression among 4560 persons who received viral load testing either pre or post ART initiation from 2017-2019. We used descriptive statistics and Kaplan-Meier estimates to compare survival curves by ART year (2017, 2018, 2019), sex and type of treatment site (public and non-governmental organizations). Persons were censored if suppression was not achieved. Mixed effects Cox regression was used to determine the effect of covariates on the likelihood of viral suppression. We report hazard ratios and 95% confidence intervals. Pre-ART viral load testing decreased from 36% in 2017 to 30% in 2019. For post-ART viral load tests, approximately 78% (n = 1589) of persons achieved suppression, 51% (n = 809) were female and 86% (n = 1341) used a public treatment site. The median time to suppression decreased by 3 months from 2017 to 2019. The likelihood of suppression was almost 2 times greater in 2018 (HR = 1.56, CI = 1.39-1.75) and 3 times greater in 2019 (HR = 3.17, CI = 2.76-3.64) compared to 2017. NGO treatment sites were also significantly associated with the likelihood of viral suppression compared to public sites. Pre-ART viral load testing and the time to viral suppression decreased over three years. Initiating ART after 2017 and early use of NGO treatment sites were found to significantly increase the likelihood of achieving suppression. This demonstrates improvements in the national HIV response but there is need to increase the number of persons on ART and achieving viral suppression.

Early antiretroviral therapy in SIV-infected rhesus macaques reveals a multiphasic, saturable dynamic accumulation of the rebound competent viral reservoir.

The rebound competent viral reservoir (RCVR)-virus that persists during antiretroviral treatment (ART) and can reignite systemic infection when treatment is stopped-is the primary barrier to eradicating HIV. We used time to initiation of ART during primary infection of rhesus macaques (RMs) after intravenous challenge with barcoded SIVmac239 as a means to elucidate the dynamics of RCVR establishment in groups of RMs by creating a multi-log range of pre-ART viral loads and then assessed viral time-to-rebound and reactivation rates resulting from the discontinuation of ART after one year. RMs started on ART on days 3, 4, 5, 6, 7, 9 or 12 post-infection showed a nearly 10-fold difference in pre-ART viral measurements for successive ART-initiation timepoints. Only 1 of 8 RMs initiating ART on days 3 and 4 rebounded after ART interruption despite measurable pre-ART plasma viremia. Rebounding plasma from the 1 rebounding RM contained only a single barcode lineage detected at day 50 post-ART. All RMs starting ART on days 5 and 6 rebounded between 14- and 50-days post-ART with 1-2 rebounding variants each. RMs starting ART on days 7, 9, and 12 had similar time-to-measurable plasma rebound kinetics despite multiple log differences in pre-ART plasma viral load (pVL), with all RMs rebounding between 7- and 16-days post-ART with 3-28 rebounding lineages. Calculated reactivation rates per pre-ART pVL were highest for RMs starting ART on days 5, 6, and 7 after which the rate of accumulation of the RCVR markedly decreased for RMs treated on days 9 and 12, consistent with multiphasic establishment and near saturation of the RCVR within 2 weeks post infection. Taken together, these data highlight the heterogeneity of the RCVR between RMs, the stochastic establishment of the very early RCVR, and the saturability of the RCVR prior to peak viral infection.

Differences in neuroinflammation in people who started antiretroviral treatment during primary versus chronic HIV infection: an 18kDa Translocator protein (TSPO) positron emission tomography (PET) study.

Persistent inflammation is described in people with HIV (PWH) on antiretroviral treatment (ART). Early ART initiation is associated with reduced inflammation. We aimed to evaluate neuroinflammation, using translocator protein (TSPO) [11C]PBR28 PET neuroimaging in PWH who initiated ART during acute HIV (aPWH) versus chronic HIV infection (cPWH) versus a control population. This was a cross-sectional, observational study. All participants underwent [11C]PBR28 PET-CT neuroimaging. Using a two-tissue compartment model, total volume of distribution (VT) and distribution volume ratios (DVR) using cortical grey matter as a pseudo-reference region at 20 regions of interest (ROIs) were calculated. Differences in VT and DVR were compared between groups using the Kruskall-Wallis test. Seventeen neuro-asymptomatic male PWH on ART (9 aPWH, 8 cPWH) and 8 male control participants (CPs) were included. Median (interquartile range, IQR) age was 40 (30, 46), 44 (41, 47) and 21 (20, 25) years in aPWH, cPWH and CPs, respectively. Median (IQR) CD4 (cells/µL) and CD4:CD8 were 687 (652, 1014) and 1.37 (1.24, 1.42), and 700 (500, 720) and 0.67 (0.64, 0.82) in aPWH and cPWH, respectively. Overall, no significant difference in VT and DVR were observed between the three groups at any ROIs. cPWH demonstrated a trend towards higher mean VT compared with aPWH and CPs at most ROIs. No significant differences in neuroinflammation, using [11C]PBR28 binding as a proxy, were identified between cPWH, aPWH and CPs. A trend towards lower absolute [11C]PBR28 binding was seen amongst aPWH and CPs, suggesting early ART may mitigate neuroinflammation.

Does HIV index testing bring patients into treatment at earlier stages of HIV disease? Results from a retrospective study in Ukraine.

Over one-third of people living with HIV (PLH) in Ukraine are not on treatment. Index testing services, which link potentially exposed partners (named partners) of known PLH (index patients) with testing and treatment services, are being scaled in Ukraine and could potentially close this gap. This retrospective study included patient data from 14,554 adult PLH who initiated antiretroviral treatment (ART) between October 2018 and May 2021 at one of 35 facilities participating in an intervention to strengthen index testing services. Mixed effects modified Poisson models were used to assess differences between named partners and other ART initiators, and an interrupted time series (ITS) analysis was used to assess changes in ART initiation over time. Compared to other ART initiators, named partners were significantly less likely to have a confirmed TB diagnosis (aRR = 0.56, 95% CI = 0.40, 0.77, p < 0.001), a CD4 count less than 200 cells/mm3 (aRR = 0.84, 95% CI = 0.73, 0.97, p = 0.017), or be categorized as WHO HIV stage 4 (aRR = 0.68, 9% CI = 0.55, 0.83, p < 0.001) at the time of ART initiation, and were significantly more likely to initiate ART within seven days of testing for HIV (aRR = 1.36, 95% CI = 1.22, 1.50, p < 0.001). Our ITS analysis showed a modest 2.34% (95% CI = 0.26%, 4.38%; p = 0.028) month-on-month reduction in mean ART initiations comparing the post-intervention period to the pre-intervention period, although these results were likely confounded by the COVID epidemic. Our findings suggest that index testing services may be beneficial in bringing PLH into treatment at an earlier stage of HIV disease and decreasing delays between HIV testing and ART initiation, potentially improving patient outcomes and retention in the HIV care cascade.

Persistent poor clinical outcomes of people living with HIV presenting with AIDS and late HIV diagnosis – results from the ICONA cohort in Italy, 2009-2022

ObjectivesLimited data are available on the long-term outcomes in recent years for late HIV diagnosis (LD). MethodsAll subjects with HIV enrolled in the ICONA cohort in 2009-2022 who started antiretroviral treatment (ART) within 4 months from diagnosis were included and divided into: (i) pre-ART CD4 count ≥350/mm3 without AIDS (non-LD), (ii) pre-ART CD4 count <350/mm3 without AIDS (LD asymptomatic), and (iii) with AIDS events pre-ART (LD-AIDS). The estimated probability and independent risk for mortality (all-cause and cause-specific) and treatment failure were evaluated. ResultsOf 6813 participants (2448 non-LD, 3198 LD asymptomatic, and 1167 LD-AIDS), 161 (2.4%) died after ART initiation. At survival analysis, a higher probability of all-cause mortality has been identified for LD than non-LD (P <0.001) and within the former, for LD-AIDS over LD asymptomatic (P <0.001). After adjusting for confounders, LD showed a higher risk of all-cause mortality (vs non-LD adjusted hazard ratio (aHR) 5.51, P <0.001) and, in particular, being an AIDS presenter predicted a greater risk of all-cause (aHR = 4.42, P <0.001), AIDS-related (adjusted subhazard ratio [aSHR] = 16.86, P <0.001), and non-AIDS–related mortality (aSHR = 1.74, P = 0.022) than the rest of the late presenters. Among the short-term survivors in the LD-AIDS group, the long-term mortality was mediated by the lack of immune recovery at 2 years. Finally, LD compared with non-LD and, particularly, among the former, LD-AIDS over LD asymptomatic showed a greater risk of treatment failure. ConclusionsIn recent years, LD subjects, particularly, AIDS presenters, remained at a higher risk of poorer outcomes. Public health strategies for early HIV diagnosis are urgently needed to constrain the mortality gap.

Heavily treatment-experienced persons living with HIV currently in care in Italy: characteristics, risk factors, and therapeutic options—the ICONA Foundation cohort study

ObjectivesHeavily treatment-experienced (HTE) people living with HIV (PLWH) pose unique challenges due to limited antiretroviral treatment (ART) options. Our study aimed to investigate the prevalence and features of HTE individuals followed up in the Italian Cohort Naïve Antiretrovirals (ICONA) cohort as of December 31, 2021. MethodsHTE were defined based on meeting specific conditions concerning their current ART and their ART history up to December 31, 2021. Descriptive statistics were performed by HTE status. Regression analyses explored factors associated with becoming HTE based on pre-ART patients' characteristics. Cluster dendrogram analysis provided insights into subgroups with inadequate responses based on clusters of differentiation (CD4) counts and viral load (VL) trajectories. ResultsAmong the 8758 PLWH actively followed in our cohort, 163 individuals (1.9%), mainly female, younger, Italian, and infected through heterosexual contact, met the HTE criteria. A lower CD4 count at ART initiation (odds ratio [OR] 1.60 per 100 cells/mmc lower CD4, 95% confidence interval [CI] 1.06-2.41, P = 0.03) and hepatitis C virus antibody positivity (OR 1.90, 95% CI 1.16-3.11, P = 0.01) were associated with higher HTE risk. Thirty PLWH exhibited ongoing immune-virological failure (18% of the HTE subgroup and 0.003% of the total population). Thirty PLWH exhibited ongoing immune-virological failure (i.e., with a current CD4 count <200 cells/mmc or VL>200 copies/mL). A cluster analysis identified 13 (43%) with a current CD4 count <200 cells/mmc. Also, notably, 19/30 (63%) had major acquired resistance-associated mutations to at least one antiretroviral drug class. ConclusionsHTE is rare in our cohort and tends to co-exist with major resistance mutations. A focused investigation into treatment history and immuno-virological response is warranted, particularly given the availability of new antiretroviral drugs.

Motivational Interviewing as an Intervention to Improve Antiretroviral Treatment Initiation among People who Inject Drugs (PWID): A Pilot Study in Jakarta and Bandung, Indonesia.

Progress towards the 95-95-95 target among People Who Inject Drugs (PWID) with Human Immunodeficiency Virus (HIV) infection was considerably low. A behavioral approach, such as motivational interviewing (MI), has been recognized as an effective strategy for improving HIV treatment outcomes among PWID. This study aimed at assessing the impact of MI counselling to improve ARV initiation among HIV-positive PWID. A cohort design pilot study was performed, and participants were recruited using a convenience sampling technique. Participants were PWID with HIV who accessed healthcare facilities in two Indonesian cities. Selected participants were assigned to an intervention group and a control group. The intervention group followed MI counselling, while the control group received ART following the standard of care. The participants were assigned to each group based on their preferences. The data was collected between January 2018 and January 2019. In total, 115 PWID with HIV participated in this study in the intervention (n=30) and control (n=85) groups. All but one intervention group's participants started ART, while 68/85 in the control group did so. Receiving MI counselling significantly contributed to ART initiation. In addition, the participants were followed-up until 12 months after ARV initiation. During this period, we found that similar proportions of participants in both groups discontinued the treatment, and only a small number achieved HIV viral suppression. The positive effect of MI counselling on ART initiation provides insight into the possibility of its wider implementation. Further studies are needed to gain a deeper understanding of MI counselling and its effect on other outcomes of the HIV treatment cascade.

Mortality Among HIV-Infected Adults on Antiretroviral Therapy in Southern Uganda.

Monitoring and evaluation of clinical programs requires assessing patient outcomes. Numerous challenges complicate these efforts, the most insidious of which is loss to follow-up (LTFU). LTFU is a composite outcome, including individuals out of care, undocumented transfers, and unreported deaths. Incorporation of vital status information from routine patient outreach may improve the mortality estimates for those LTFU. We analyzed routinely collected clinical and patient tracing data for individuals (15 years or older) initiating antiretroviral treatment between January 2014 and December 2018 at 2 public HIV care clinics in greater Rakai, Uganda. We derived unadjusted mortality estimates using Kaplan-Meier methods. Estimates, adjusted for unreported deaths, applied weighting through the Frangakis and Rubin method to represent outcomes among LTFU patients who were successfully traced and for whom vital status was ascertained. Confidence intervals were determined through bootstrap methods. Of 1969 patients with median age at antiretroviral treatment initiation of 31 years (interquartile range: 25-38), 1126 (57.2%) were female patients and 808 (41%) were lost. Of the lost patients, 640 patient files (79.2%) were found and reviewed, of which 204 (31.8%) had a tracing attempt. Within the electronic health records of the program, 28 deaths were identified with an estimated unadjusted mortality 1 year after antiretroviral treatment initiation of 2.5% (95% CI: 1.8% to 3.3%). Using chart review and patient tracing data, an additional 24 deaths (total 52) were discovered with an adjusted 1-year mortality of 3.8% (95% CI: 2.6% to 5.0%). Data from routine outreach efforts by HIV care and treatment programs can be used to support plausible adjustments to estimates of client mortality. Mortality estimates without active ascertainment of vital status of LTFU patients may significantly underestimate program mortality.

Mapping factors influencing initiation of antiretroviral treatment among adolescents living with HIV/AIDS in sub-Saharan Africa: A scoping review protocol.

Since the Start Free, Stay Free, and AIDS-Free launch, UNAIDS targets intended to promote interventions to prevent HIV transmission and promote access to ART among adolescents and children, of which none were achieved in 2020. In the sub-Saharan African region, the number of adolescents initiated on ART drugs remained consistently low, with approximately100 000 adolescents succumbing to AIDS-related causes in 2022. Although HIV prevalence among adolescents had been reduced, several HIV- positive adolescents died without being initiated on ART drugs. Therefore, this scoping review protocol aims to map factors influencing the initiation of ART drugs among adolescents living with HIV in sub-Saharan Africa. The methodological framework for scoping reviews will guide this scoping protocol. A search strategy will be used to search literature in electronic databases, including EBSCOhost (PubMed/MEDLINE), Google Scholar, Science Direct, Scopus, BioMed Central, and the World Health Organization library for citations and literature using keywords and the Medical Subjects Heading (MeSH). The electronic databases will be supplemented by hand-searching references on the included studies. The search will be from Jan 01, 2012, to Dec 31, 2022. Articles will be searched and assessed for eligibility by two screeners uploaded on the Endnote software, and duplicates will be identified and removed before the abstract screening. The two screeners will assess the eligibility of the abstracts and the complete articles of the selected studies using the inclusion and exclusion criteria. A third screener will intervene when there is a lack of consensus between the two screeners. The selection process will be documented by following and using the PRISMA flow diagram (Fig 1). A thematic content analysis will present a narrative account of the extracted data. The results of this review will identify and describe factors influencing the initiation of Antiretroviral treatment among adolescents living with HIV in the Sub-Saharan African region. The findings will guide future research and inform tailored interventions and strategies for initiating ART among adolescents. Open Science Framework. https://doi.org/10.17605/OSF.IO/RNF2T.

Low unspliced cell-associated HIV RNA in early treated adolescents living with HIV on long suppressive ART.

Initiation of antiretroviral treatment (ART) in patients early after HIV-infection and long-term suppression leads to low or undetectable levels of HIV RNA and cell-associated (CA) HIV DNA and RNA. Both CA-DNA and CA-RNA, overestimate the size of the HIV reservoir but CA-RNA as well as p24/cell-free viral RNA can be indicators of residual viral replication. This study describes HIV RNA amounts and levels of cytokines/soluble markers in 40 well-suppressed adolescents who initiated ART early in life and investigated which viral markers may be informative as endpoints in cure clinical trials within this population. Forty adolescents perinatally infected with HIV on suppressive ART for >5 years were enrolled in the CARMA study. HIV DNA and total or unspliced CA-RNA in PBMCs were analyzed by qPCR/RT-qPCR and dPCR/RT-dPCR. Cell-free HIV was determined using an ultrasensitive viral load (US-VL) assay. Plasma markers and p24 were analyzed by digital ELISA and correlations between total and unspliced HIV RNA and clinical markers, including age at ART, Western Blot score, levels of cytokines/inflammation markers or HIV CA-DNA, were tested. CA-RNA was detected in two thirds of the participants and was comparable in RT-qPCR and RT-dPCR. Adolescents with undetectable CA-RNA showed significantly lower HIV DNA compared to individuals with detectable CA-RNA. Undetectable unspliced CA-RNA was positively associated with age at ART initiation and Western Blot score. We found that a higher concentration of TNF-α was predictive of higher CA-DNA and CA-RNA. Other clinical characteristics like US-VL, time to suppression, or percent CD4+ T-lymphocytes were not predictive of the CA-RNA in this cross-sectional study. Low CA-DNA after long-term suppressive ART is associated with lower CA-RNA, in concordance with other reports. Patients with low CA-RNA levels in combination with low CA-DNA and low Western Blot scores should be further investigated to characterize candidates for treatment interruption trials. Unspliced CA-RNA warrants further investigation as a marker that can be prioritized in paediatric clinical trials where the sample volume can be a significant limitation.

Current Resistance of HIV-1 Strains Isolated in Volunteer Blood Donors in Gabon.

Detection of drug resistance mutations (DRMs) and HIV-1 subtypes ensures effective therapeutic management for HIV-infected individuals. In Gabon, data on DRMs are very little available in the population of people living with HIV and also among voluntary HIV-positive blood donors. This study aimed to study subtypes and DRMs in HIV-1-positive volunteer blood donors in Gabon. A cross-sectional study was carried out at the National Blood Transfusion Center of Gabon. A purposive sampling method was used to collect 128 HIV-1 seropositive blood samples. Viral RNA was extracted on real-time PCR (Abbott 2000®), and sequencing was performed on ABI 3500 (Hitachi®). SPSS version 21.0 software was used for statistical analysis. Of the 128 seropositive volunteer donors included, men and the 29-39-age group were more representative at 78.9% and 49.2%, respectively. Eighty-two samples were sequenced. The majority strains identified were subtype A, subtype F, subtype G, CRF02_AG, and CRF45_cpx. The resistance mutations identified were K103N, L210W, E138G, V179D, V179T, and M46L. The prevalence of resistant subtypes was 25.6%. CRF02_AG strains exhibited high-level resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), including efavirenz and nevirapine. The study identified major DRMs in reverse transcriptase and protease that confer high-level resistance to most NNRTIs, nucleoside reverse transcriptase inhibitors, and protease inhibitors. CRF02_AG was more predominant, and the frequency of resistant subtypes was high. However, these data will contribute to the therapeutic choice during the initiation of antiretroviral treatment in treatment-naive patients in Gabon.

Nutritional status and treatment outcomes of tuberculosis in Mizan Tepi University Teaching Hospital, a five -year retrospective study.

Public health problems related to tuberculosis (TB) remain substantial globally, particularly in resource-limited countries. Determining TB treatment outcomes and identifying contributing factors are the basic components of the TB control strategy. In Ethiopia, different studies have been done on treatment outcomes and multiple associated factors, and there is also a little information on the effect of nutritional status on TB treatment outcomes. So there is a need for comprehensive research that examines the combined effects of multiple factors along with nutritional status. A five-year institution-based retrospective cross-sectional study was conducted at Mizan Tepi University Teaching Hospital, South West Ethiopia. This study included all tuberculosis patients who were documented in the TB registration and had known treatment outcomes at the treatment facility between January 1, 2016, and December 31, 2020. Data was collected through a pretested structured data extraction checklist. Data were entered into Epidata version 3.1 and analyzed through SPSS version 22. Multiple logistic regression was employed to assess the association between dependent and independent variables. A p-value of less than 0.05 was considered statistically significant. Of the total 625 TB patients, 283 (45.3%), 175 (28%), and 167 (26.7%) had smear-positive, extra-pulmonary, and smear-negative tuberculosis, respectively. The majority of study participants had normal weight (62.2%), were in the age group of 15-44 (67.4%), were new cases (73.8%), and were from urban areas (69.4%). About 32.2% of cases were HIV-positive. The overall unsuccessful treatment rate was 25%. From the total unsuccessful treatment rates, the highest proportion was a death rate of 90 (14.4%), followed by a treatment failure of 56 (9%). Being female (AOR = 1.7, 95% CI: 1.2-2.5), HIV positive (AOR = 2.7, 95% CI: 1.9-4.1), undernutrition (BMI<18.5kg/m2) (AOR = 1.9, 95% CI: 1.3-2.9), and smear-negative pulmonary TB (AOR = 1.6, 95% CI: 1-2.5) were independent predictors of unsuccessful treatment outcomes. The treatment success rate in the study area is very poor. Poor treatment outcomes were associated with undernutrition, female gender, HIV positivity and smear-negative pulmonary TB. So, continuous and serious supervision and monitoring of directly observed treatment short course (DOTS) program accomplishment, early detection of HIV and TB, prompt anti TB and antiretroviral treatment initiation and adherence, enhanced nutritional assessment, and counseling services need to be strengthened to improve treatment outcomes.

Cytomegalovirus infection among people living with HIV in Sweden: Case profiles, treatment strategies and patient outcomes at Karolinska University Hospital 2010-2020.

In countries with access to early antiretroviral treatment (ART), opportunistic infections caused by cytomegalovirus (CMV) in people living with HIV (PLWH) are becoming increasingly rare. As potential complications are severe, it is critical to remain aware of this important diagnosis. However, clinical characteristics and prognosis of CMV infection in PLWH in the era of modern ART have not been well described. Here, we compiled the clinical presentation, management and outcome of CMV infection in PLWH treated at the infectious diseases clinic of Karolinska University Hospital during 2010-2020. We identified 51 cases of active CMV infection, based on detection of CMV-DNA, mainly diagnosed in patients with CD4 T-cell count <200 cells/μL (86%). Median time from HIV diagnosis to detection of CMV infection was 16 days. In 20 cases (39%), CMV infection was symptomatic with retinitis identified as a manifestation in 70% of cases. Symptomatic CMV infection was treated for 73 (20-313) days upon diagnosis, mostly using valganciclovir. One-year mortality was 22% and was associated with longer time to ART initiation from HIV diagnosis and with comorbidities, but not with CMV-DNA levels or CD4 count. Immune reconstitution was not significantly compromised in patients with symptomatic CMV, although CD4/8 ratio tended to be lower in patients with systemic CMV infection. Retinitis remains the most common manifestation of symptomatic CMV infection in PLWH. Recognizing CMV infection is important, especially in the management of 'late presenters'. Adequate duration of antiviral therapy and appropriate follow-up must be ensured to avoid complications.

Mental health burden among females living with HIV and AIDS in sub-Saharan Africa: A systematic review.

Mental health problems, particularly depression and anxiety, are common in women and young girls living with HIV/ AIDS particularly in low- and middle-income (LMICs) countries where women's vulnerability to psychiatric symptoms is heightened due to the prevalent intersectional stressors such as stigma and intimate partner violence. However, no synthesized evidence exists on the mental health burden of females living with HIV/AIDS (FLWHA) in Africa. This systematic review aimed to synthesize the current evidence on the mental health burden among FLWHA in sub-Saharan Africa. A systematic literature review of articles published from 2013-2023 was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). Five electronic databases; PubMed, MEDLINE with full text, Scopus, Academic Search Complete, and Health Source: Nursing Academic Edition were searched for articles published in English. Nineteen articles (15 quantitative, 3 qualitative, and 1 case study) from over 7 African countries met the inclusion criteria. The majority of the studies' quality was determined to be moderate. The prevalence of depression ranged from 5.9 to 61% and anxiety from 28.9 to 61%. Mental health burden was a logical outcome of HIV diagnosis. Predictors of mental health outcomes in the context of HIV/AIDS were identified as intimate partner violence (IPV), stigma, childhood traumas, sexual abuse, poverty, unemployment, and social isolation. Social support and resilience were identified as protective factors against mental illness in FLWHA. Mental illness had a deleterious effect on viral suppression rates among FLWHA, resulting in delayed initiation of antiretroviral therapy treatment and increased mortality but had no impact on immune reconstitution in the face of ART adherence. Given the high prevalence rates of depression and anxiety and their relationship with HIV progression, it is crucial that mental health care services are integrated into routine HIV care.

Machine Learning Bolsters Evidence That D1, Nef, and Tat Influence HIV Reservoir Dynamics.

The primary hurdle to curing HIV is due to the establishment of a reservoir early in infection. In an effort to find new treatment strategies, we and others have focused on understanding the selection pressures exerted on the reservoir by studying how proviral sequences change over time. To gain insights into the dynamics of the HIV reservoir we analyzed longitudinal near full-length sequences from 7 people living with HIV between 1 and 20 years following the initiation of antiretroviral treatment. We used this data to employ Bayesian mixed effects models to characterize the decay of the reservoir using single-phase and multiphasic decay models based on near full-length sequencing. In addition, we developed a machine-learning approach utilizing logistic regression to identify elements within the HIV genome most associated with proviral decay and persistence. By systematically analyzing proviruses that are deleted for a specific element, we gain insights into their role in reservoir contraction and expansion. Our analyses indicate that biphasic decay models of intact reservoir dynamics were better than single-phase models with a stronger statistical fit. Based on the biphasic decay pattern of the intact reservoir, we estimated the half-lives of the first and second phases of decay to be 18.2 (17.3 to 19.2, 95%CI) and 433 (227 to 6400, 95%CI) months, respectively.In contrast, the dynamics of defective proviruses differed favoring neither model definitively, with an estimated half-life of 87.3 (78.1 to 98.8, 95% CI) months during the first phase of the biphasic model. Machine-learning analysis of HIV genomes at the nucleotide level revealed that the presence of the splice donor site D1 was the principal genomic element associated with contraction. This role of D1 was then validated in an in vitro system. Using the same approach, we additionally found supporting evidence that HIV nef may confer a protective advantage for latently infected T cells while tat was associated with clonal expansion. The nature of intact reservoir decay suggests that the long-lived HIV reservoir contains at least 2 distinct compartments. The first compartment decays faster than the second compartment. Our machine-learning analysis of HIV proviral sequences reveals specific genomic elements are associated with contraction while others are associated with persistence and expansion. Together, these opposing forces shape the reservoir over time.

Torque Teno Virus load is associated with CDC stage and CD4+ cell count in people living with HIV but unrelated to AIDS-defining events and Human Pegivirus load.

Torque Teno Virus (TTV) is a non-enveloped, circular single-strand DNA virus and part of the human virome. The replication of TTV was related to the immune status in patients treated with immunosuppressive drugs after organ transplantation. We hypothesize that TTV load could be an additional marker for immune function in people living with HIV (PLWH). In this analysis serum samples of PLWH from the RESINA multicenter cohort were reanalysed for TTV. Investigated clinical and epidemiological parameters included Pegivirus (HPgV) load, age, sex, HIV load, CD4+ cell count (CDC 1, 2, 3) and CDC clinical stages (1993 CDC classification system, A, B, C) before initiation of antiretroviral treatment. Regression analysis was used to detect possible associations among parameters. Our analysis confirmed TTV as a strong predictor of CD4+ cell count and CDC class 3. This relationship was used to propose a first classification of TTV load in regard to clinical stage. We found no association with clinical CDC stages A, B and C. HPgV load was inversely correlated with HIV load but not TTV load. TTV load was associated with immunodeficiency in PLWH. Neither TTV- nor HIV load were predictive for the clinical categories of HIV infection.