• 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.
    • Depression During Pregnancy and the Postpartum Among HIV-Infected Women on Antiretroviral Therapy in Uganda

      Kaida, Angela; Matthews, Lynn T; Ashaba, Scholastic; Tsai, Alexander C; Kanters, Steve; Robak, Magdalena; Psaros, Christina; Kabakyenga, Jerome; Boum, Yap; Haberer, Jessica E; et al. (Lippincott Williams & Wilkins, 2014-12-01)
      Among HIV-infected women, perinatal depression compromises clinical, maternal, and child health outcomes. Antiretroviral therapy (ART) is associated with lower depression symptom severity but the uniformity of effect through pregnancy and postpartum periods is unknown.
    • 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.
    • For Family-Centered Differentiated Service Delivery for HIV

      Grimsrud, A; Bygrave, H; Wilkinson, L (Lippincott Williams & Wilkins, 2018-08-15)
      Differentiated care, or differentiated service delivery (DSD), is increasingly being promoted as one of the possible ways to address and improve access, quality, and efficiency of HIV prevention, care, and treatment. Family-centered care has long been promoted within the provision of HIV services, but the full benefits have not necessarily been realized. In this article, we bring together these two approaches and make the case for how family-centered DSD can offer benefits to both people affected by HIV and the health system. Family-centered DSD approaches are presented for HIV testing and antiretroviral therapy (ART) delivery, referencing policies, best practice examples, and evidence from the field. With differentiated family-centered ART delivery, the potential efficiencies gained by extending ART refills can both benefit clients by reducing the frequency and intensity of contact with the health service and lead to health system gains by not requiring multiple providers to care for one family. A family-centered DSD approach should also be leveraged along the HIV care cascade in the provision of prevention technologies and mobilizing family members to receive regular HIV testing. Furthermore, a family-centered lens should be applied wherever DSD is implemented to ensure that, for example, adolescents who are pregnant receive an adapted package of quality care.
    • Higher Art Adherence is Associated with Lower Systemic Inflammation in Treatment-Naïve Ugandans Who Achieve Virologic Suppression

      Castillo-Mancilla, JR; Morrow, M; Boum, Y; Byakwaga, H; Haberer, JE; Martin, JN; Bangsberg, D; Mawhinney, S; Musinguzi, N; Huang, Y; et al. (Wolters Kluwer Health / Lippincott; Williams & Wilkins, 2018-01-16)
      Residual systemic inflammation persists despite suppressive antiretroviral therapy (ART) and is associated with non-AIDS clinical outcomes. We aimed to evaluate the association between ART adherence and inflammation in Ugandans living with HIV who were predominantly receiving nevirapine-based ART with a thymidine analog backbone and were virologically suppressed by conventional assays.
    • Implementation and Operational Research: Feasibility of Using Tuberculin Skin Test Screening for Initiation of 36-Month Isoniazid Preventive Therapy in HIV-Infected Patients in Resource-Constrained Settings

      Huerga, H; Mueller, Y; Ferlazzo, G; Mpala, Q; Bevilacqua, P; Vasquez, B; Noël Mekiedje, C; Ouattara, A; Mchunu, G; Weyenga, HO; et al. (Lippincott Williams & Wilkins, 2016-04-01)
      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.
    • Incidence Rate of Kaposi Sarcoma in HIV-Infected Patients on Antiretroviral Therapy in Southern Africa: A Prospective Multicohort Study

      Rohner, Eliane; Valeri, Fabio; Maskew, Mhairi; Prozesky, Hans; Rabie, Helena; Garone, Daniela; Dickinson, Diana; Chimbetete, Cleophas; Lumano-Mulenga, Priscilla; Sikazwe, Izukanji; et al. (Lippincott Williams & Wilkins, 2014-12-15)
      The risk of Kaposi sarcoma (KS) among HIV-infected persons on antiretroviral therapy (ART) is not well defined in resource-limited settings. We studied KS incidence rates and associated risk factors in children and adults on ART in Southern Africa.
    • Risk factors and mortality associated with resistance to first line antiretroviral therapy: multicentric cross-sectional and longitudinal analyses

      Pinoges, Loretxu; Schramm, Birgit; Poulet, Elisabeth; Balkan, Suna; Szumilin, Elisabeth; Ferreyra, Cecilia; Pujades-Rodríguez, M (Lippincott Williams & Wilkins, 2015-01-12)
      Understanding the factors associated with HIV drug resistance development and subsequent mortality is important to improve clinical patient management.
    • Safety, Feasibility, and Acceptability of the PrePex Device for Adult Male Circumcision in Malawi

      Kohler, PK; Tippett Barr, BA; Kangʼombe, A; Hofstee, C; Kilembe, F; Galagan, S; Chilongozi, D; Namate, D; Machaya, M; Kabwere, K; et al. (Lippincott Williams & Wilkins, 2016-06-01)
      Nonsurgical adult male circumcision devices present an alternative to surgery where health resources are limited. This study aimed to assess the safety, feasibility, and acceptability of the PrePex device for adult male circumcision in Malawi.
    • Treatment outcomes from the largest antiretroviral treatment program in Myanmar (Burma): a cohort analysis of retention after scale-up.

      Sabapathy, Kalpana; Ford, Nathan; Chan, Khin Nyein; Kyaw, Moe Kyaw; Elema, Riekje; Smithuis, Frank; Floyd, Sian; Imperial College London, London, United Kingdom; Medecins Sans Frontieres, Amsterdam, The Netherlands, Medecins Sans Frontieres, Geneva, Switzerland; Medecisn Sans Frontieres, Yangon, Myanmar; Medical Action Myanmar, Yangon, Myanmar; London School of Hygiene and Tropical Medicine, London, United Kingdom. (2012-06-01)
      Antiretroviral treatment (ART) coverage in Myanmar is well below average. This study describes retention and baseline predictors of prognosis from the largest ART program in the country.