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Introduction: Transcriptomic analyses from early human immunodeficiency virus (HIV) infection have the potential to reveal how HIV causes widespread and lasting damage to biological functions, especially in the immune system. Previous studies have been limited by difficulties in obtaining early specimens. Methods: A hospital symptom-based screening approach was applied in a rural Mozambican setting to enrol patients with suspected acute HIV infection (Fiebig stage I-IV). Blood samples were collected from all those recruited, so that acute cases and contemporaneously recruited, uninfected controls were included. PBMC were isolated and sequenced using RNA-seq. Sample cellular composition was estimated from gene expression data. Differential gene expression analysis was completed, and correlations were determined between viral load and differential gene expression. Biological implications were examined using Cytoscape, gene set enrichment analysis, and enrichment mapping. Results: Twenty-nine HIV infected subjects one month from presentation and 46 uninfected controls were included in this study. Subjects with acute HIV infection demonstrated profound gene dysregulation, with 6131 (almost 13% of the genome mapped in this study) significantly differentially expressed. Viral load was correlated with 1.6% of dysregulated genes, in particular, highly upregulated genes involved in key cell cycle functions, were correlated with viremia. The most profoundly upregulated biological functions related to cell cycle regulation, in particular, CDCA7 may drive aberrant cell division, promoted by overexpressed E2F family proteins. Also upregulated were DNA repair and replication, microtubule and spindle organization, and immune activation and response. The interferome of acute HIV was characterized by broad activation of interferon-stimulated genes with antiviral functions, most notably IFI27 and OTOF. BCL2 downregulation alongside upregulation of several apoptotic trigger genes and downstream effectors may contribute to cycle arrest and apoptosis. Transmembrane protein 155 (TMEM155) was consistently highly overexpressed during acute infection, with roles hitherto unknown. Discussion: Our study contributes to a better understanding of the mechanisms of early HIV-induced immune damage. These findings have the potential to lead to new earlier interventions that improve outcomes. [ABSTRACT FROM AUTHOR]

Objective: Despite the high HIV associated burden, Mozambique lacks data on HIV counselling and testing (HCT) costs. To help guide national HIV/AIDS programs, we estimated the cost per test for voluntary counselling and testing (VCT) from the patient's perspective and the costs per person tested and per HIV-positive individual linked to care to the healthcare provider for VCT, provider-initiated counselling and testing (PICT) and home-based testing (HBT). We also assessed the cost-effectiveness of these strategies for linking patients to care. Methods: Data from a cohort study conducted in the Manhiça District were used to derive costs and linkage-to-care outcomes of the three HCT strategies. A decision tree was used to model HCT costs according to the likelihood of HCT linking individuals to care and to obtain the incremental cost-effectiveness ratios (ICERs) of PICT and HBT with VCT as the comparator. Sensitivity analyses were performed to assess robustness of base-case findings. Findings: Based on costs and valuations in 2015, average and median VCT costs to the patient per individual tested were US$1.34 and US$1.08, respectively. Costs per individual tested were greatest for HBT (US$11.07), followed by VCT (US$7.79), and PICT (US$7.14). The costs per HIV-positive individual linked to care followed a similar trend. PICT was not cost-effective in comparison with VCT at a willingness-to-accept threshold of US$4.53, but only marginally given a corresponding base-case ICER of US$4.15, while HBT was dominated, with higher costs and lower impact than VCT. Base-case results for the comparison between PICT and VCT presented great uncertainty, whereas findings for HBT were robust. Conclusion: PICT and VCT are likely equally cost-effective in Manhiça. We recommend that VCT be offered as the predominant HCT strategy in Mozambique, but expansion of PICT could be considered in limited-resource areas. HBT without facilitated linkage or reduced costs is unlikely to be cost-effective. [ABSTRACT FROM AUTHOR]

Background: Eliminating mother-to-child HIV-transmission (EMTCT) implies a case rate target of new pediatric HIV-infections< 50/100,000 live-births and a transmission rate < 5%. We assessed these indicators at community-level in Mozambique, where MTCT is the second highest globally..Methods: A cross-sectional household survey was conducted within the Manhiça Health Demographic Surveillance System in Mozambique (October 2017-April 2018). Live births in the previous 4 years were randomly selected, and mother/child HIV-status was ascertained through documentation or age-appropriate testing. Estimates on prevalence and transmission were adjusted by multiple imputation chained equation (MICE) for participants with missing HIV-status. Retrospective cumulative mortality rate and risk factors were estimate by Fine-Gray model.Results: Among 5000 selected mother-child pairs, 3486 consented participate. Community HIV-prevalence estimate in mothers after MICE adjustment was 37.6% (95%CI:35.8-39.4%). Estimates doubled in adolescents aged < 19 years (from 8.0 to 19.1%) and increased 1.5-times in mothers aged < 25 years. Overall adjusted vertical HIV-transmission at the time of the study were 4.4% (95% CI:3.1-5.7%) in HIV-exposed children (HEC). Pediatric case rate-infection was estimated at 1654/100,000 live-births. Testing coverage in HEC was close to 96.0%; however, only 69.1% of them were tested early(< 2 months of age). Cumulative child mortality rate was 41.6/1000 live-births. HIV-positive status and later birth order were significantly associated with death. Neonatal complications, HIV and pneumonia were main pediatric causes of death.Conclusions: In Mozambique, SPECTRUM modeling estimated 15% MTCT, higher than our district-level community-based estimates of MTCT among HIV-exposed children. Community-based subnational assessments of progress towards EMTCT are needed to complement clinic-based and modeling estimates. [ABSTRACT FROM AUTHOR]

Background: The implementation of quality HIV control programs is crucial for the achievement of the UNAIDS 90-90-90 targets and to motivate people living with HIV (PLWHIV) to link and remain in HIV-care. The aim of this mixed method cross-sectional study was to estimate the linkage and long-term retention in care of PLWHIV and to identify factors potentially interfering along the HIV-care continuum in southern Mozambique. Methods: A home-based semi-structured interview was conducted in 2015 to explore barriers and facilitators to the HIV-care cascade among individuals that had been newly HIV-diagnosed in community testing campaigns in 2010 or 2012. Linkage and long-term retention were estimated retrospectively through client self-reports and clinical records. Cohen's Kappa coefficient was calculated to measure the agreement between participant self-reported and documented cascade outcomes. Results: Among the 112 interviewed participants, 24 (21.4%) did not disclose their HIV-positive serostatus to the interviewer. While 84 (75.0%) self-reported having enrolled in care, only 69 (61.6%) reported still being in-care 3–5 years after diagnosis of which 17.4% reported having disengaged and re-engaged. An important factor affecting optimal continuum in HIV-care was the impact of the fear-based authoritarian relationship between the health system and the patient that could act as both driver and barrier. Conclusion: Special attention should be given to quantify and understand repeated cycles of patient disengagement and re-engagement in HIV-care. Strategies to improve the relationship between the health system and patients are still needed in order to optimally engage PLWHIV for long-term periods. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Awareness of HIV‐infection goes beyond diagnosis, and encompasses understanding, acceptance, disclosure and initiation of the HIV‐care. We aimed to characterize the HIV‐positive population that underwent repeat HIV‐testing without disclosing their serostatus and the impact on estimates of the first UNAIDS 90 target. Methods: This analysis was nested in a prospective cohort established in southern Mozambique which conducted three HIV‐testing modalities: voluntary counselling and testing (VCT), provider‐initiated counselling and testing (PICT) and home‐based testing (HBT). Participants were given the opportunity to self‐report their status to lay counsellors and HIV‐positive diagnoses were verified for previous enrolment in care. This study included 1955 individuals diagnosed with HIV through VCT/PICT and 11,746 participants of a HBT campaign. Those who did not report their serostatus prior to testing, and were found to have a previous HIV‐diagnosis, were defined as non‐disclosures. Venue‐stratified descriptive analyses were performed and factors associated with non‐disclosure were estimated through log‐binomial regression. Results: In the first round of 2500 adults randomized for HBT, 1725 were eligible for testing and 18.7% self‐reported their HIV‐positivity. Of those tested with a positive result, 38.9% were found to be non‐disclosures. Similar prevalence of non‐disclosures was found in clinical‐testing modalities, 29.4% (95% CI 26.7 to 32.3) for PICT strategy and 13.0% (95% CI 10.9 to 15.3) for VCT. Prior history of missed visits (adjusted prevalence ratio (APR) 4.2, 95% CI 2.6 to 6.8), younger age (APR 2.5, 95% CI 1.4 to 4.4) and no prior history of treatment ((APR) 1.4, 95% CI 1.0 to 2.1) were significantly associated with non‐disclosure as compared to patients who self‐reported. When considering non‐disclosures as people living with HIV (PLWHIV) aware of their HIV‐status, the proportion of PLWHIV aware increased from 78.3% (95% CI 74.2 to 81.6) to 86.8% (95% CI 83.4 to 89.6). Conclusion: More than one‐third of individuals testing HIV‐positive did not disclose their previous positive HIV‐diagnosis to counsellors. This proportion varied according to testing modality and age. In the absence of an efficient and non‐anonymous tracking system for HIV‐testers, repeat testing of non‐disclosures leads to wasted resources and may distort programmatic indicators. Developing interventions that ensure appropriate psychosocial support are needed to encourage this population to disclose their status and optimize scarce resources. [ABSTRACT FROM AUTHOR]

Introduction: Non-tuberculous mycobacteria (NTM) can cause disease which can be clinically and radiologically undistinguishable from tuberculosis (TB), posing a diagnostic and therapeutic challenge in high TB settings. We aim to describe the prevalence of NTM isolation and its clinical characteristics in children from rural Mozambique. Methods: This study was part of a community TB incidence study in children <3 years of age. Gastric aspirate and induced sputum sampling were performed in all presumptive TB cases and processed for smear testing using fluorochrome staining and LED Microscopy, liquid and solid culture, and molecular identification by GenoType® Mycobacterium CM/AS assays. Results: NTM were isolated in 26.3% (204/775) of children. The most prevalent NTM species was M. intracellulare (N = 128), followed by M. scrofulaceum (N = 35) and M. fortuitum (N = 9). Children with NTM were significantly less symptomatic and less likely to present with an abnormal chest radiograph than those with M. tuberculosis. NTM were present in 21.6% of follow-up samples and 25 children had the same species isolated from ≥2 separate samples. All were considered clinically insignificant and none received specific treatment. Children with NTM isolates had equal all cause mortality and likelihood of TB treatment as those with negative culture although they were less likely to have TB ruled out. Conclusions: NTM isolation is frequent in presumptive TB cases but was not clinically significant in this patient cohort. However, it can contribute to TB misdiagnosis. Further studies are needed to understand the epidemiology and the clinical significance of NTM in children. [ABSTRACT FROM AUTHOR]

Introduction: Context-specific improvements in the continuum of HIV care are needed to achieve the UNAIDS target of 90-90-90. This study aimed to assess the linkage to and retention in HIV care according to different testing modalities in rural southern Mozambique. Methods: Adults newly diagnosed with HIV from voluntary counseling and testing, provider-initiated counseling and testing, and home-based HIV testing services were prospectively enrolled between 2014 and 2015 at the Manhiça District. Patients were passively followed up through chart examination. Tracing was performed at 12 months to ascertain causes of loss to follow-up. Fine and Gray competing risk analysis was performed to determine factors associated with the each step of the cascade. Results: Overall linkage to care as defined by having a CD4 count at 3 months was 43.7% [95% confidence interval (CI): 40.8 to 46.6] and 25.2% of all participants initiated antiretroviral therapy. Factors associated with increased linkage in multivariable analysis included testing at voluntary counseling and testing, older age, having been previously tested for HIV, owning a cell phone, presenting with WHO clinical stages III/IV, self-reported illness-associated disability in the previous month, and later calendar month of participant recruitment. Ascertaining deaths and transfers allowed for adjustment of the rate of 12-month retention in treatment from 75.6% (95% CI: 70.2 to 80.5) to 84.2% (95% CI: 79.2 to 88.5). Conclusions: Home-based HIV testing reached a sociodemographically distinct population from that of clinic-based testing modalities but low linkage to care points to a need for facilitated linkage interventions. Distinguishing between true treatment defaulting and other causes of loss to follow-up can significantly change indicators of retention in care. [ABSTRACT FROM AUTHOR]