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Background: The lack of acute and early HIV infection (AEHI) diagnosis and care contributes to high HIV incidence in resource-limited settings. We aimed to assess the yield of AEHI, predict and diagnose AEHI, and describe AEHI care outcomes in a public sector setting in Eswatini., Setting: This study was conducted in Nhlangano outpatient department from March 2019 to March 2020., Methods: Adults at risk of AEHI underwent diagnostic testing for AEHI with the quantitative Xpert HIV-1 viral load (VL) assay. AEHI was defined as the detection of HIV-1 VL on Xpert and either an HIV-seronegative or HIV-serodiscordant third-generation antibody-based rapid diagnostic test (RDT) result. First, the cross-sectional analysis obtained the yield of AEHI and established a predictor risk score for the prediction of AEHI using Lasso logistic regression. Second, diagnostic accuracy statistics described the ability of the fourth-generation antibody/p24 antigen-based Alere HIV-Combo RDT to diagnose AEHI (vs Xpert VL testing). Third, we described acute HIV infection care outcomes of AEHI-positive patients using survival analysis., Results: Of 795 HIV-seronegative/HIV-serodiscordant outpatients recruited, 30 (3.8%, 95% confidence interval: 2.6% to 5.3%) had AEHI. The predictor risk score contained several factors (HIV-serodiscordant RDT, women, feeling at risk of HIV, swollen glands, and fatigue) and had sensitivity and specificity of 83.3% and 65.8%, respectively, to predict AEHI. The HIV-Combo RDT had sensitivity and specificity of 86.2% and 99.9%, respectively, to diagnose AEHI. Of 30 AEHI-positive patients, the 1-month cumulative treatment initiation was 74% (95% confidence interval: 57% to 88%), and the 3-month viral suppression (<1000 copies/mL) was 87% (67% to 98%)., Conclusion: AEHI diagnosis and care seem possible in resource-limited settings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Xpert MTB/RIF rapidly detects resistance to rifampicin (RR); however, this test misses I491F-RR conferring rpoB mutation, common in southern Africa. In addition, Xpert MTB/RIF does not distinguish between viable and dead Mycobacterium tuberculosis (MTB). We aimed to investigate the ability of thin-layer agar (TLA) direct drug-susceptibility testing (DST) to detect MTB and its drug-resistance profiles in field conditions in Eswatini. Consecutive samples were tested in parallel with Xpert MTB/RIF and TLA for rifampicin (1.0 μg/ml) and ofloxacin (2.0 μg/ml). TLA results were compared at the Reference Laboratory in Antwerp with indirect-DST on Löwenstein-Jensen or 7H11 solid media and additional phenotypic and genotypic testing to resolve discordance. TLA showed a positivity rate for MTB detection of 7.1% versus 10.0% for Xpert MTB/RIF. Of a total of 4,547 samples included in the study, 200 isolates were available for comparison to the composite reference. Within a median of 18.4 days, TLA detected RR with 93.0% sensitivity (95% confidence interval [CI], 77.4 to 98.0) and 99.4% specificity (95% CI, 96.7 to 99.9) versus 62.5% (95% CI, 42.7 to 78.8) and 99.3% (95% CI, 96.2 to 99.9) for Xpert MTB/RIF. Eight isolates, 28.6% of all RR-confirmed isolates, carried the I491F mutation, all detected by TLA. TLA also correctly identified 183 of the 184 ofloxacin-susceptible isolates (99.5% specificity; 95% CI, 97.0 to 99.9). In field conditions, TLA rapidly detects RR, and in this specific setting, it contributed to detection of additional RR patients over Xpert MTB/RIF, mainly but not exclusively due to I491F. TLA also accurately excluded fluoroquinolone resistance., (Copyright © 2021 Ardizzoni et al.)

Background: Pre-exposure-prophylaxis (PrEP) has been heralded for its potential to put women in control of preventing HIV infection, but uptake and continuation rates have been disappointing in high-incidence settings in sub-Saharan Africa. We explored structural and social factors that influenced PrEP use among young women and pregnant or breastfeeding women in rural Eswatini., Methods: We conducted two in-depth interviews with ten women on PrEP, and one-time in-depth interviews with fourteen women who declined or discontinued PrEP. Interviews covered decision-making processes around PrEP initiation and experiences with pill-taking. In-depth interviews were conducted with nine health workers, covering experiences in delivering PrEP services, and two focus group discussions were held with men to elicit their perceptions of PrEP. Interviews and discussions were audio-recorded, translated, transcribed and analysed thematically, using an inductive approach., Results: PrEP initiation and use were experienced by many women as empowering them to take control of their health and well-being, and stay HIV free, facilitating them to realise their aspirations relating to motherhood and educational attainment. However, the social norms that defined relationship dynamics with partners or family members either undermined or promoted this empowerment potential. In particular, young women were rarely supported by family members to take PrEP unless it was perceived to be for protecting an unborn child. Stigmatisation of pill-taking through its associations with HIV and the burden of daily pill-taking also contributed to PrEP discontinuation., Conclusions: Unlike many prevention tools, PrEP enabled women to achieve a sense of control over their lives. Nevertheless, women's agency to continue and adhere to PrEP was influenced by social and structural factors including gender norms, family expectations of young women, relationship dynamics and stigma related to HIV. Future interventions should address these barriers to promote PrEP use among sexually-active women.

Background: To assess the performance and suitability of dried blood spot (DBS) sampling using filter paper to collect blood for viral load (VL) quantification under routine conditions., Methods: We compared performance of DBS VL quantification using the Biocentric method with plasma VL quantification using Roche and Biocentric as reference methods. Adults (≥18 years) were enrolled at 2 health facilities in Eswatini from October 12, 2016 to March 1, 2017. DBS samples were prepared through finger-prick by a phlebotomist (DBS-1), and through the pipetting of whole venous blood by a phlebotomist (DBS-2) and by a laboratory technologist (DBS-3). We calculated the VL-testing completion rate, correlation, and agreement, as well as diagnostic accuracy estimates at the clinical threshold of 1000 copies/mL., Results: Of 362 patients enrolled, 1066 DBS cards (DBS-1: 347; DBS-2: 359; DBS-3: 360) were tested. Overall, test characteristics were comparable between DBS-sampling methods, irrespective of the reference method. The Pearson correlation coefficients ranged from 0.67 to 0.82 (P < 0.001) for different types of DBS sampling using both reference methods, and the Bland-Altman difference ranged from 0.15 to 0.30 log10 copies/mL. Sensitivity estimates were from 85.3% to 89.2% and specificity estimates were from 94.5% to 98.6%. The positive predictive values were between 87.0% and 96.5% at a prevalence of 30% VL elevations, and negative predictive values were between 93.7% and 95.4%., Conclusions: DBS VL quantification using the newly configured Biocentric method can be part of contextualized VL-testing strategies, particularly for remote settings and populations with higher viral failure rates.

Background: Viral load (VL) testing is being scaled up in resource-limited settings. However, not all commercially available VL testing methods have been evaluated under field conditions. This study is one of a few to evaluate the Biocentric platform for VL quantification in routine practice in Sub-Saharan Africa., Methods: Venous blood specimens were obtained from patients eligible for VL testing at two health facilities in Swaziland from October 2016 to March 2017. Samples were centrifuged at two laboratories (LAB-1, LAB-2) to obtain paired plasma specimens for VL quantification with the national reference method and on the Biocentric platform. Agreement (correlation, Bland-Altman) and accuracy (sensitivity, specificity) indicators were calculated at the VL thresholds of 416 (2.62 log 10 ) and 1000 (3.0 log 10 ) copies/mL. Leftover samples from patients with discordant VL results were re-quantified and accuracy indicators recalculated. Logistic regression was used to compare laboratory performance., Results: A total of 364 paired plasma samples (LAB-1: n = 198; LAB-2: n = 166) were successfully tested using both methods. The correlation was high (R = 0.82, p < 0.01), and the Bland-Altman analysis showed a minimal mean difference (- 0.03 log 10 copies/mL; 95% CI: -1.15 to 1.08). At the clinical threshold level of 3.0 log 10 copies/mL, the sensitivity was 88.6% (95% CI: 78.7 to 94.9) and the specificity was 98.3% (95% CI: 96.1 to 99.4). Sensitivity was higher in LAB-1 (100%; 95% CI: 71.5 to 100) than in LAB-2 (86.4%; 95% CI: 75.0 to 94.0). Most upward (n = 8, 2.2%) and downward (n = 11, 3.0%) misclassifications occurred at the 2.62 log threshold, with LAB-2 having a 16 (95% CI: 2.26 to 113.27; p = 0.006) times higher odds of downward misclassification. After retesting of discordant leftover samples (n = 17), overall sensitivity increased to 93.5% (95% CI: 85.5 to 97.9) and 97.1% (95% CI: 90.1 to 99.7) at the 2.62 and 3.0 thresholds, and specificity increased to 98.6% (95% CI: 96.5 to 99.6) and 99.0% (95% CI: 97.0 to 99.8) respectively., Conclusions: The test characteristics of the Biocentric platform were overall comparable to the national reference method for VL quantification. One laboratory tended to misclassify VL results downwards, likely owing to unmet training needs and lack of previous hands-on practice.

Although efficacy of 36 months isoniazid preventive therapy (IPT) among HIV-positive individuals has been proven in trial settings, outcome, tolerance, and adherence have rarely been evaluated in real-life settings.This is a prospective observational cohort study conducted in 2 primary care rural clinics in Swaziland.After negative tuberculosis symptom screening, patients either with the positive tuberculin skin test (TST) or after tuberculosis treatment were initiated on IPT for 144 weeks. In addition to routine clinic visits, adherence was assessed every semester.Of 288 eligible patients, 2 patients never started IPT (1 refusal, 1 contraindication), and 253 (87.8%), 234 (81.3%), and 228 (79.2%) were still on IPT after 48, 96, and 144 weeks, respectively (chiP = .01). Of 41 patients who interrupted IPT before 144 weeks, 21 defaulted (of which 17 also defaulted HIV care); 16 stopped because of adverse drug reactions; 2 were discontinued by clinicians' mistake and 1 because of TB symptoms. Five patients (1.7%) died of causes not related to IPT, 5 (1.7%) developed TB of which 2 were isoniazid-resistant, and 9 (3.1%) were transferred to another clinic. As an indicator of adherence, isoniazid could be detected in the urine during 86.3% (302/350) and 73.6% (248/337) of patient visits in the 2 clinics, respectively (chiP < .001).The routine implementation of IPT 36 months was feasible and good patient outcomes were achieved, with low TB incidence, good tolerance, and sustained adherence.

Introduction: The tuberculin skin test (TST) can be used to identify HIV-infected people who would benefit the most from long-term isoniazid preventive therapy (IPT). However, in resource-constrained settings, implementation of the TST can be challenging. The objectives of this study were to assess the feasibility of implementing the TST for IPT initiation and to estimate the proportion of TST-positive incidence among HIV-positive patients in 2 high tuberculosis and HIV burden settings., Methods: Two prospective observational cohort studies were conducted under programmatic conditions in Mathare, an urban slum of Nairobi, Kenya, and in rural Shiselweni, Swaziland. HIV-positive adults with negative tuberculosis symptomatic screening underwent the TST. Those testing positive were started on 36-month IPT., Results: Of 897 and 1021 patients screened in Mathare and Shiselweni, 550 and 696, respectively, were included. Median age was 38 years, 67.7% were female, and 86.8% were on antiretroviral therapy. Among TST-eligible participants, 88.0% (491/558) and 81.8% (694/848) accepted TST and 74.2% (414/558) and 77.1% (654/858) returned for test reading in Mathare and Shiselweni, respectively. The TST was positive in 49.8% (95% confidence interval: 44.9 to 54.6) in Mathare and 33.2% (95% confidence interval: 29.6 to 36.8) in Shiselweni. The 36-month IPT was accepted by 96.1% (198/206) patients in Mathare and 99.5% (216/217) in Shiselweni. IPT implementation at the clinics was managed with no additional staff or extra space., Conclusion: Implementing the TST for IPT initiation was feasible and acceptable in both urban and rural resource-constrained settings. This strategy allows patients who can benefit the most to receive long-term IPT and avoids unnecessarily treating a significant number of patients who do not stand to benefit.