• Antiretroviral Therapy Adherence Interruptions Are Associated With Systemic Inflammation Among Ugandans Who Achieved Viral Suppression

      Musinguzi, N; Castillo-Mancilla, J; Morrow, M; Byakwaga, H; Mawhinney, S; Burdo, TH; Boum, Y; Muzoora, C; Bwana, BM; Siedner, MJ; et al. (Lippincott, Williams & Wilkins, 2019-12-01)
      Background: Residual systemic inflammation, which is associated with non-AIDS clinical outcomes, may persist despite viral suppression. We assessed the effect of antiretroviral therapy (ART) adherence interruptions on systemic inflammation among Ugandans living with HIV who were virally suppressed. Setting: We evaluated adults initiating first-line ART at a regional referral hospital clinic in Mbarara, Uganda. Methods: Plasma concentrations of interleukin-6 (IL-6), D-dimer, soluble sCD14, sCD163, the kynurenine/tryptophan (K/T) ratio, and CD8+ T-cell activation (HLA-DR+/CD38+ coexpression) were measured at baseline and 6 months after ART initiation among participants who achieved viral suppression (<400 copies/mL) at 6 months. ART adherence was monitored electronically. Time spent in an adherence interruption was computed as the percentage of days when the running average adherence was ≤10%. We fit adjusted linear regressions to evaluate the effect of time spent in an interruption on the log-transformed plasma concentrations of the inflammation biomarkers. Results: Of 282 participants, 70% were women, and the median age was 34 years. At baseline, median CD4 and median log viral load were 135 cells per microliter and 5.1 copies per milliliter, respectively. In the adjusted analysis, a running average adherence of <10% was associated with higher sCD14 (+3%; P < 0.008), sCD163 (+5%; P = 0.002), D-dimer (+10%; P = 0.007), HLA-DR+/CD8+ (+3%; P < 0.025), IL-6 (+14%; P = 0.008), and K:T ratio (+5%; P = 0.002). These findings were largely robust to adjustment for average adherence, as well as higher thresholds of running average adherence, albeit with decreased statistical significance. Conclusions: Increased time spent in adherence interruptions is associated with increased levels of inflammation, despite viral suppression above and beyond average adherence.
    • Correction of Tuberous Nipple Areolar Complex Deformity in Gynecomastia: The Deformity That Can Get Forgotten.

      Godwin, Y (Lippincott, Williams & Wilkins, 2018-07-01)
      The desired end point of surgical reduction of gynecomastia is a masculine breast appearance and symmetry. This article concentrates on the tuberous deformity of the nipple areolar complex (NAC) that can present in gynecomastia and is sometimes overlooked at surgical correction.This deformity can be corrected at primary surgery if it is recognized preoperatively. If missed, or not adequately corrected, the postoperative result of primary reduction may be deemed incomplete by the patient and they will request revision.The deformity involves overprojection of the NAC in an anteroposterior direction, yet the base diameter may be close to normal. Correction involves reduction of the herniated breast bud, excision of excess areolar tissue, and careful radial scoring to flatten the NAC to a normal level of projection.For the NAC to have a masculine appearance, the areolae need to be symmetrical, of normal male size, and slightly oval in a transverse direction. The projection of both areola and nipple needs to be low, but present: not flattened. This article presents an operative technique to address primary or residual tuberous NAC deformity in the treatment of gynecomastia.
    • Demanding an end to tuberculosis: treatment of tuberculosis infection among persons living with and without HIV

      Fargher, J; Reuter, A; Furin, J (Lippincott, Williams & Wilkins, 2019-01-01)
      More than two billion people are infected with Mycobacterium tuberculosis and few of them are ever offered therapy in spite of such treatment being associated with reduced rates of morbidity and mortality. This article reviews the current recommendations on the diagnosis and treatment of TB infection (or what is commonly referred to as 'prophylaxis' or 'preventive therapy' of latent TB) and discusses barriers to implementation that have led to low demand for this life-saving therapeutic intervention.
    • Extremely Low Hepatitis C prevalence among HIV co-infected individuals in 4 countries in sub-Saharan Africa

      Loarec, A; Carnimeo, V; Molfino, L; Kizito, W; Muyindike, W; Andrieux-Meyer, I; Balkan, S; Nzomukunda, Y; Mwanga-Amumpaire, J; Ousley, J; et al. (Lippincott, Williams & Wilkins, 2018-11-16)
      : A multicentric, retrospective case-series analysis (facility-based) in five sites across Kenya, Malawi, Mozambique, and Uganda screened HIV-positive adults for hepatitis C virus (HCV) antibodies using Oraquick rapid testing and viral confirmation (in three sites). Results found substantially lower prevalence than previously reported for these countries compared with previous reports, suggesting that targeted integration of HCV screening in African HIV programs may be more impactful than routine screening.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.
    • Field Suitability and Diagnostic Accuracy of the Biocentric Open Real-Time PCR Platform for Dried Blood Spot-Based HIV Viral Load Quantification in Eswatini.

      Kerschberger, B; Ntshalintshali, N; Mpala, Q; Diaz Uribe, PA; Maphalala, G; Kalombola, S; Telila, AB; Chawinga, T; Maphalala, M; Jani, A; et al. (Lippincott, Williams & Wilkins, 2019-09-01)
      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.
    • The People Living with HIV Stigma Index 2.0: generating critical evidence for change worldwide.

      Friedland, BA; Gottert, A; Hows, J; Baral, SD; Sprague, L; Nyblade, L; McClair, TL; Anam, F; Geibel, S; Kentutsi, S; et al. (Lippincott, Williams & Wilkins, 2020-09-01)
      Objective(s): To describe the process of updating the People Living with HIV (PLHIV) Stigma Index (Stigma Index) to reflect current global treatment guidelines and to better measure intersecting stigmas and resilience. Design: Through an iterative process driven by PLHIV, the Stigma Index was revised, pretested, and formally evaluated in three cross-sectional studies. Methods: Between March and October 2017, 1153 surveys (n = 377, Cameroon; n = 390, Senegal; n = 391, Uganda) were conducted with PLHIV at least 18 years old who had known their status for at least 1 year. PLHIV interviewers administered the survey on tablet computers or mobile phones to a diverse group of purposively sampled respondents recruited through PLHIV networks, community-based organizations, HIV clinics, and snowball sampling. Sixty respondents participated in cognitive interviews (20 per country) to assess if questions were understood as intended, and eight focus groups (Uganda only) assessed relevance of the survey, overall. Results: The Stigma Index 2.0 performed well and was relevant to PLHIV in all three countries. HIV-related stigma was experienced by more than one-third of respondents, including in HIV care settings. High rates of stigma experienced by key populations (such as MSM and sex workers) impeded access to HIV services. Many PLHIV also demonstrated resilience per the new PLHIV Resilience Scale. Conclusion: The Stigma Index 2.0 is now more relevant to the current context of the HIV/AIDS epidemic and response. Results will be critical for addressing gaps in program design and policies that must be overcome to support PLHIV engaging in services, adhering to antiretroviral therapy, being virally suppressed, and leading healthy, stigma-free lives.
    • Should urine-LAM tests be used in TB symptomatic HIV-positive patients when no CD4 count is available? A prospective observational cohort study from Malawi

      Huerga, H; Mathabire, SR; Bastard, M; Dimba, A; Kamba, C; Amoros, I; Szumilin, E (Lippincott, Williams & Wilkins, 2019-10-16)
      Background: Current eligibility criteria for urine lateral-flow-lipoarabinomannan assay (LF-LAM) in ambulatory, HIV-positive patients rely on the CD4 count. We investigated the diagnostic yield of LF-LAM and the 6-month mortality in ambulatory, TB symptomatic, HIV-positive patients regardless of their CD4 count. Methods: We conducted a prospective, observational study that included all ambulatory, >15-year-old, TB symptomatic (cough, weight loss, fever, or night sweats) HIV-positive patients presenting at 4 health facilities in Malawi. Patients received a clinical examination and were requested urine LF-LAM, sputum microscopy and Xpert MTB/RIF. TB was defined as bacteriologically confirmed if Xpert was positive. Results: Of 485 patients included, 171 (35.3%) had a CD4<200 and 32 (7.2%) were seriously ill. Median CD4 count was 341 cells/µL (IQR: 129-256). LAM was positive in 24.9% patients with CD4<200 (50% LAM Grades 2-4) and 12.5% with CD4≥200 (12.8% LAM Grades 2-4). Xpert was positive in 14.1% (44/312). Among Xpert-positive patients, LAM-positivity was: 56.7% (CD4<200) and 42.9% (CD4≥200), p=0.393. Of the patients without an Xpert result, 13.4% (23/172) were LAM-positive (i.e. potentially missed patients). Overall mortality was 9.2% (44/478). More pronounced LAM-positive patients had higher mortality than LAM-negative (Grades 2-4: 36.0%; Grade 1: 9.1%; Negative: 7.4%; p<0.001). LAM-positive patients with CD4<200 cells/µL had higher risk of mortality than LAM-negatives (aHR:3.2, 95CI:1.4-7.2, p=0.006), particularly those with LAM Grades 2-4 (aHR:4.9, 95CI:1.8-13.3, p=0.002). Conclusions: Urine-LAM testing can be useful for TB diagnosis in HIV-positive TB-symptomatic patients with no CD4 cell count. LAM grade can identify patients at higher risk of death in this situation.