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Background HIV-1 incidence calculation currently includes recency classification by HIV-1 incidence assay and unsuppressed viral load (VL ≥ 1000 copies/mL) in a recent infection testing algorithm (RITA). However, persons with recent classification not virally suppressed and taking antiretroviral (ARV) medication may be misclassified. Setting We used data from 13 African household surveys to describe the impact of an ARV-adjusted RITA on HIV-1 incidence estimates. Methods HIV-seropositive samples were tested for recency using the HIV-1 Limiting Antigen (LAg)-Avidity enzyme immunoassay, HIV-1 viral load, ARVs used in each country, and ARV drug resistance. LAg-recent result was defined as normalized optical density values ≤1.5. We compared HIV-1 incidence estimates using 2 RITA: RITA1: LAg-recent + VL ≥ 1000 copies/mL and RITA2: RITA1 + undetectable ARV. We explored RITA2 with self-reported ARV use and with clinical history. Results Overall, 357 adult HIV-positive participants were classified as having recent infection with RITA1. RITA2 reclassified 55 (15.4%) persons with detectable ARV as having long-term infection. Those with detectable ARV were significantly more likely to be aware of their HIV-positive status (84% vs. 10%) and had higher levels of drug resistance (74% vs. 26%) than those without detectable ARV. RITA2 incidence was lower than RITA1 incidence (range, 0%-30% decrease), resulting in decreased estimated new infections from 390,000 to 341,000 across the 13 countries. Incidence estimates were similar using detectable or self-reported ARV (R2 > 0.995). Conclusions Including ARV in RITA2 improved the accuracy of HIV-1 incidence estimates by removing participants with likely long-term HIV infection.

BACKGROUND Measurement of mother-to-child HIV transmission through population-based surveys requires large sample sizes because of low HIV prevalence among children. We estimate potential improvements in sampling efficiency resulting from a targeted sample design. SETTING Eight countries in sub-Saharan Africa with completed Population-based HIV Impact Assessment (PHIA) surveys as of 2017. METHODS The PHIA surveys used a geographically stratified 2-stage sample design with households sampled from randomly selected census enumeration areas. Children (0-14 years of age) were eligible for HIV testing within a random subsample of households (usually 50%). Estimates of child HIV prevalence in each country were calculated using jackknife replicate weights. We compared sample sizes and precision achieved using this design with a 2-phase disproportionate sample design applied to strata defined by maternal HIV status and mortality. RESULTS HIV prevalence among children ranged from 0.4% (95% confidence interval: 0.2 to 0.6) in Tanzania to 2.8% (95% confidence interval: 2.2 to 3.4) in Eswatini with achieved relative standard errors between 11% and 21%. The expected precision improved in the targeted design in all countries included in the analysis, with proportionate reductions in mean squared error ranging from 27% in Eswatini to 61% in Tanzania, assuming an equal sample size. CONCLUSIONS Population-based surveys of adult HIV prevalence that also measure child HIV prevalence should consider targeted sampling of children to reduce required sample size, increase precision, and increase the number of positive children tested. The findings from the PHIA surveys can be used as baseline data for informing future sample designs.

Supplemental Digital Content is Available in the Text., 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 log10) and 1000 (3.0 log10) 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

Background: Children and adolescents living with human immune-deficiency virus (C/ALHIV) have increased tuberculosis (TB) risk compared to HIV-negative peers. Anti-retroviral therapy (ART) reduces TB risk among adults living with HIV, but data is limited in C/ALHIV. Methods: Patient data from seven pediatric HIV centers that adhere to national guidelines in Botswana, Eswatini, Lesotho, Malawi, Tanzania, and Uganda were analyzed. Standardized HIV and TB classification and outcomes were reported following WHO guidelines. A Bayesian mixed effects model assessed association between ART coverage and TB period prevalence. Findings: The analytic period (2013-2017) encompassed 57,525 patient-years and captured 1,217 cases of HIV-associated child and adolescent TB. Favorable TB outcomes were associated with increased length of time in care and early ART initiation. Severe immunosuppression at TB diagnosis was associated with death. The TB incidence was 2,017/100,000 patient-years. With every 10% increase in C/ALHIV receiving ART, there was a 2.33% (95% Credible interval; 0.58%-4.40%) reduction in TB prevalence. Clinics with lower TB prevalence experienced less dramatic declines in TB incidence. Interpretation: These findings support continued need to advocate for policies and implement practices that optimize integrated pediatric and adolescent HIV and TB services. Although ART use is associated with decreased TB prevalence among C/ALHIV, novel TB interventions are likely required to achieve TB elimination and HIV epidemic control in TB/HIV high-burden settings. Funding Statement: This material has been supported by the U.S. President’s Emergency Plan for AIDS Relief through the United States Agency for International Development (USAID) under the terms of USAID Award Number AID-674-A-16-00003. In addition, funds were leveraged from Texas Children’s Hospital to support completion of this research and dissemination of findings. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: No individual participant consent was required for this retrospective analysis of programmatic data. Approval was obtained from all necessary ethical bodies in each country including the Baylor College of Medicine Children’s Foundation or Trust, the national ethics committees in each country, and the Baylor College of Medicine Institutional Review Board.

A quantifiable, stool-based, Mycobacterium tuberculosis (Mtb) test has potential complementary value to respiratory specimens. Limit of detection (LOD) was determined by spiking control stool. Clinical test performance was evaluated in a cohort with pulmonary tuberculosis (TB) (N = 166) and asymptomatic household TB child contacts (N = 105). Stool-quantitative polymerase chain reaction (qPCR) results were compared with sputum acid-fast bacilli (AFB) microscopy, GeneXpert MTB/RIF (Xpert MTB/RIF), and cultures. In Mtb stool-spiking studies, the LOD was 96 colony-forming units/50 mg of stool (95% confidence interval [CI]: 84.8-105.6). Among specimens collected within 72 hours of antituberculosis treatment (ATT) initiation, stool qPCR detected 22 of 23 (95%) of culture-positive cases. Among clinically diagnosed cases that were Xpert MTB/RIF and culture negative, stool qPCR detected an additional 8% (3/37). Among asymptomatic, recently TB-exposed participants, stool PCR detected Mtb in two of 105 (1.9%) patients. Two months after ATT, the Mtb quantitative burden in femtogram per microliters decreased (Wilcoxon signed-rank P < 0.001) and persistent positive stool PCR was associated with treatment failure or drug resistance (relative risk 2.8, CI: 1.2-6.5; P = 0.012). Stool-based qPCR is a promising complementary technique to sputum-based diagnosis. It detects and quantifies low levels of stool Mtb DNA, thereby supporting adjunct diagnosis and treatment monitoring in pulmonary TB.

Directed acyclic graph (DAG) presenting possible relationships between Biocentric laboratory (LAB-1/LAB-2) and the probability of VL misclassification. (PDF 194 kb)