Therapy In Resource-limited Settings Research Articles

Lung ultrasound for prediction of surfactant requirement in Indian preterm neonates: a diagnostic accuracy study.

Surfactant replacement for respiratory distress syndrome (RDS) is currently guided by oxygen (FiO2) requirement in preterm neonates. Lung ultrasound (LUS) has emerged as an important predictive tool; however, there is a paucity of evidence from developing countries.The objective of this study was to determine the diagnostic accuracy of the LUS score in comparison to standard criteria based on FiO2 requirement for prediction of surfactant requirement.In this prospective study, preterm neonates of < 34 weeks' gestation with RDS were included within 2 h of life. Surfactant was administered if the FiO2 requirement exceeded 30%. Baseline characteristics, respiratory parameters, and LUS clips were recorded soon after birth and compared between the surfactant and non-surfactant groups. LUS scoring was later performed by masked assessors which was not used in the management of neonates.Among 82 neonates (mean gestation 30.6 weeks and weight 1375 g) included in the study, 33 (40.2%) received surfactant. The surfactant group had a higher Silverman score, required higher FiO2 and mean airway pressure, and needed invasive ventilation more frequently. The mean (± SD) LUS score was significantly higher in the surfactant (9.4 ± 3.2) compared to the non-surfactant group (5.1 ± 2.1). The diagnostic accuracy of LUS scoring was determined by ROC curve analysis (AUC (95% CI): 0.83 (0.74-0.92), p < 0.01). A cutoff score of ≥ 8 for LUS was considered optimal for the prediction of surfactant requirement (sensitivity and specificity (95% CI) of 70% (51-84) and 80% (66-90), respectively). Conclusion:Lung ultrasound is a valid diagnostic tool for the prediction of surfactant requirements in resource-limited settings. What is Known: • Lung ultrasound has a good diagnostic accuracy in predicting the need for surfactant administration in preterm neonates in developed countries, but its role in developing countries is unclear. What is New: • Lung ultrasound proved to be a valid diagnostic tool in predicting surfactant replacement therapy in resource-limited settings. • The diagnostic performance of lung ultrasound was better in neonates on non-invasive ventilation, compared to invasive ventilation.

Exploring the Efficacy and Feasibility of Outpatient Blinatumomab Short Cycles in Pediatric Patients with Relapsed/Refractory B-ALL in LMIC: Preliminary Results

CONCLUSIONS In low- and middle-income countries (LMIC) like Mexico, the treatment of patients with refractory or relapsed acute lymphoblastic leukemia (r/r ALL) represents a significant challenge due to limited access to immunotherapy and hematopoietic stem cell transplantation (HSCT). As a result, the one-year survival rate is reported to be less than 20%. The use of intensive chemotherapy has not improved survival in this group due to its high toxicity. Blinatumomab uses the patient's own cytotoxic T-cells to induce lysis of the leukemia cells expressing CD19 and has been established as a bridge therapy for transplant in patients with r/r B-ALL. The usual pattern of administration is a dose scaled up to complete a total of 28 days of infusion. According to various studies, it is considered appropriate to use repeated cycles of this antibody to achieve the desired response. However, there are also reports of patients achieving complete responses within the first 15 days of the cycle. The high costs of Blinatumomab's administration present a significant barrier to its use in LMIC. As a consequence, the application of prolonged or multiple cycles of the drug becomes unaffordable for a substantial portion of the global population. Demonstrate the safety and efficacy of utilizing short cycles of Blinatumomab (21 days) as a bridge therapy to HSCT in pediatric patients with r/r ALL to explore the potential cost-reduction benefits and increased access to this therapy in resource-limited settings. A pilot clinical trial was conducted. Pediatric patients (&amp;lt;16 y) diagnosed with r/r B- ALL between the years 2020-2022 were included. The usual Blinatumomab dosing regimen was adopted, but the total duration of the cycle was reduced. Continuous infusion was initiated at a dose of 5 mcg/m2/day for the first 7 days, followed by an increase to 15 mcg/m2/day for 14 days (21-day total treatment duration). To mitigate cytokine release syndrome (CRS) a single dose of dexamethasone was administered at the start of the infusion and after the dose escalation. The entire regimen was administered on an outpatient basis, with an infusion pump at home. Caregivers were instructed on the operation of the pump and detection of any signs of toxicity, with 24/7 contact with the medical team and the option to hospitalize if necessary. A total of 7 patients were included, and all of them received Blinatumomab in a single 21-day cycle. The median age was 5 years (15 mo- 13 y). The majority of patients were stratified as high-risk at the time of diagnosis (85.7%). Among the patients, 4 had relapsed ALL, while 3 had refractory disease. The median time from the initial diagnosis to the use of Blinatumomab was 16 months (ranging 7-29 mo), and the median number of treatment lines before Blinatumomab administration was 3 (ranging 2-4). The highest level of minimal residual disease (MRD) detected before the Blinatumomab treatment was 4.2% (by flow cytometry). Remarkably, all patients (100%, n=7) achieved a complete response, with MRD being negative for flow cytometry after the 21-day cycle of Blinatumomab. In 5 out of 7 patients, the administration of the drug was completely ambulatory. Only 2 patients experienced grade I CRS which was successfully managed with steroids. No adverse effects greater than grade 2 were reported, and no patient required support with transfusion therapy during or after the infusion. There were no reports of profound neutropenia, and no treatment-related deaths occurred. HSCT was conducted in all patients to consolidate the response, with 6 patients undergoing haploidentical and 1 patient undergoing identical allogeneic HSCT. At present, 5 out of 7 patients are alive and in complete remission. One patient died on day +51 post-HSCT due to pulmonary thromboembolism, and the second patient experienced relapse on day +395 post-HSCT and subsequently died on day +640 due to disease progression. The median overall survival at 3 years was 66.7%, with a median follow-up period of 21 months (4 -30mo). An alternative outpatient, low-toxicity and cost-effective treatment approach was implemented. The findings from this study could shed light on a promising strategy to improve the outcomes for patients with ALL patients with limited therapeutic options, particularly in the context of resource-constrained settings.

Performance of two plasma separation devices for HIV-1 viral load measurement in primary healthcare settings.

Dried blood spot (DBS) may overestimate the viral RNA, mainly in patients with low viral load (VL), due to proviral DNA and intracellular RNA. The Burnett and HemaSpot provide integrated solutions for the collection, separation, and drying of plasma from whole blood. This study aims to evaluate the performance of both devices compared to plasma to identify antiretroviral therapy (ART) failure. The devices were separately evaluated in a cross-sectional design. Patients on ART were included for the studies (Burnett: 611, October 2019 to January 2020) and (HemaSpot: 620, November 2020 to April 2021). VL was tested using CAP/CTM96. The sensitivity and specificity of DBS, Burnett, and HemaSpot were determined, and plasma results were considered as a reference at a threshold of 1,000 copies/ml. For the Burnett study, 2,444 specimens, including plasma, DBS, venous Burnett (vBurnett), and capillary Burnett (cBurnett), were collected. Sensitivity of DBS, vBurnett, and cBurnett was 97.4%, 98.3%, and 97.5%, respectively, whereas specificity was 86.8% for DBS, 96.9% for vBurnett, and 93.9% for cBurnett. For the HemaSpot study, 1,860 specimens were collected, including plasma, DBS, and vHemaSpot. Sensitivity of DBS and vHemaSpot was 95.0% and 91.3%, respectively, whereas specificity was 86.9% for DBS and 94.5% for vHemaSpot. The misclassification rate was more prominent in DBS (4.8%) and HemaSpot (8.4%) but lower in vBurnett (2.0%) and cBurnett (3.2%). The Burnett showed better performance than DBS, whereas HemaSpot showed poorer performance than DBS. Nevertheless, both Burnett and HemaSpot have high rate of non-reportable results. In the current format, neither of the two devices is feasible for VL scale-up in resource-limited settings.IMPORTANCEBurnett and HemaSpot are two novel technologies that allow whole blood collection and plasma separation and stabilization at room temperature without the need of additional equipment. Hence, these devices are potential alternatives to fresh plasma as a suitable specimen for viral load scale-up to monitor antiretroviral therapy in resource-limited settings.

Estimating prognostic relevant cutoff values for a multiplex PCR detecting BCR::ABL1 in chronic myeloid leukemia patients on tyrosine kinase inhibitor therapy in resource-limited settings

The prognosis of chronic myeloid leukemia (CML) on tyrosine kinase inhibitor (TKI) treatment is based on the quantification of BCR::ABL1 fusion gene transcript copy number, harmonized by an international scale (IS) based on TaqMan-based real-time quantitative PCR (qRT-PCR). In Ethiopia, as in most low- and middle-income countries (LMICs), access to standard diagnostic, follow-up, and prognostic tools is very limited, and it has been challenging to strictly follow international guidelines. This seriously compromises clinical outcome, despite the availability of TKIs through the Glivec International Patient Assistance Program (GIPAP). Multiplex PCR (mpx-PCR), conventionally regarded as a “screening tool,” offers a potential solution to this problem. A total of 219 samples from confirmed CML patients were assayed. In reference to qRT-PCR, the AUC of ROC curve for mpx-PCR was 0.983 (95% CI: 0.957 to 0.997). At the optimum cut-off value, equivalent to BCR::ABL1 (IS) transcript copy number of 0.6%, the specificity and sensitivity were 93% and 95%, respectively, with 94% accuracy. Albeit the sensitivity and accuracy of mpx-PCR decrease below the optimum cutoff of 0.6% (IS), the specificity at 0.1% (IS) was 100%, making it an attractive means to rule-out relapse and drug non-adherence at later stages of treatment, which is particularly an issue in a low income setting. We conclude that the relative simplicity and low cost of mpx-PCR and prognostic relevant cutoff values (0.1–0.6% IS) should allow its use in peripheral clinics and thus maximize the positive impact of TKIs made available through GIPAP in most LMICs.

Second-Line Antiretroviral Treatment Outcome in HIV-Infected Patients Coinfected with Tuberculosis in Pakistan.

Tuberculosis (TB) coinfection in human immunodeficiency virus- (HIV-) infected patients is considered a risk of antiretroviral therapy (ART) failure. Coadministration of antitubercular therapy (ATT) with ART is another challenge for TB management. The study was aimed at investigating contributing factors affecting treatment outcomes in HIV-/TB-coinfected patients. Cross-sectional. Setting. Samples were collected from the Pakistan Institute of Medical Sciences Hospital Islamabad. Subject and Methods. Clinicodemographic and immunovirological factors between the two groups were compared. The Student t-test and chi-square test were applied to compare outcome variables, and logistic regression was applied to determine the effect of TB on virological failure (VF). Main Outcome Measures. TB coinfection did not increase VF even in univariate (p = 0.974) and multivariate analysis at 6 and 12 months of 2nd-line ART start. ARV switching was significant (p = 0.033) in TB-coinfected patients. VF was significantly high in ATT-coadministered patients along with a viral load of ≥1000 (p = 0.000). Sample Size and Characteristics. We recruited seventy-four HIV patients on 2nd-line ART; 33 coinfected with TB were followed for at least 12 months. In HIV-/TB-coinfected patients, CD4 count, CD4 gain, and VF remained comparable to HIV patients with no TB infection. ATT significantly affects the treatment outcome, suggesting drug-to-drug interactions. These factors are important to revisit the therapeutic guidelines to maximize the benefit of dual therapy in resource-limited settings.

Urine tenofovir-monitoring predicts HIV viremia in patients treated with high genetic-barrier regimens.

Access to viral load measurements is constrained in resource-limited settings. A lateral flow urine tenofovir (TFV) rapid assay (UTRA) for patients whose regimens include TFV offers an affordable approach to frequent adherence monitoring. We conducted a cross-sectional study of patients to assess the utility of UTRA to predict virologic failure, defined as a viral load greater than 400 copies/ml. We assessed urine TFV among 113 participants at increased risk of viral failure (who had previous viral failure on this regimen or had previously been ≥30 days out of care), comparing low genetic-barrier efavirenz (EFV) regimens (n = 60) to dolutegravir (DTG)-boosted or ritonavir-boosted protease inhibitor (PI/r)-based high genetic-barrier regimens (n = 53). Dried blood spots (DBS) for TFV-diphosphate and plasma for TFV concentrations were collected, with drug resistance assessed if viral failure present. Among 113 participants, 17 of 53 received DTG or PI/r had viral failure at the cross-sectional visit, with 11 (64.7%) demonstrating an undetectable urine TFV; the negative-predictive value (NPV) of undetectable UTRA for viral failure was 85% (34/40); none of the 16 sequenced had dual class drug resistance. In those treated with EFV regimens the sensitivity was lower, as only 1 (4.8%) of 21 with viral failure had an undetectable UTRA (P < 0.001). Urine tenofovir-testing had a high negative-predictive value for viral failure in patients treated with DTG or ritonavir-boosted protease inhibitor regimens, where viral failure was largely explained by poor drug adherence. Frequent monitoring with inexpensive lateral flow urine TFV testing should be investigated prospectively in between viral load visits to improve viral load suppression on DTG-based first-line therapy in resource-limited settings.

Antimicrobial therapy in resource-limited settings with high antimicrobial resistance: a case-based approach.

Choosing antimicrobial therapy in resource-limited settings is challenging because of the lack of advanced diagnostics and limited treatment options. Furthermore, since most international guidelines do not account for settings with high antimicrobial resistance, it is difficult for primary care physicians to choose the right antibiotic. This review, therefore, attempts to summarise the principles of antimicrobial therapy in such settings through six hypothetical case scenarios.

Efficacy of pulse dexamethasone in non-systemic juvenile idiopathic arthritis: a double-blind randomized controlled trial.

Early aggressive therapy using biologicals is increasingly being used in JIA for early disease remission. Pulse steroids are used in induction regimes for rheumatic disorders such as SLE and systemic JIA; however, no controlled studies have demonstrated their use in non-systemic JIA. The objective of the present study was to evaluate the efficacy and safety of pulse dexamethasone therapy in children with treatment-naïve non-systemic JIA as early aggressive therapy in resource-limited settings. Sixty treatment-naïve children with non-systemic JIA with an active joint count of ≥5 and/or involvement of hip or cervical joints were randomized to receive either pulse dexamethasone (3 mg/kg/day, max 100 mg/day) or placebo (normal saline) for three consecutive days during each visit at 0, 6 (±2) and 12 (±2) weeks; along with standard therapy (MTX and NSAIDs). The use of oral bridge steroids was permissible for persistent severe disease as per predefined criteria. The primary outcome was ACR-Pedi 70 response at 16 (±2) weeks after enrolment in the two groups. The proportion of children achieving ACR-Pedi 70 in the two groups at last follow-up was 11/30 (36.7%) in pulse dexamethasone arm vs 11/28 (39.3%) in the placebo arm (P-value 0.837, relative risk 0.93, 95% CI 0.48, 1.80). We did not observe any significant difference in the proportion of children requiring bridge steroids. Adverse events were comparable in the two groups. The addition of pulse dexamethasone to standard treatment may not add any advantage in improving ACR-Pedi 70 scores at medium-term follow-up. Clinical Trial Registry-India; www.ctri.nic.in CTRI/2018/08/015151.

Growing data for recycling tenofovir and lamivudine with dolutegravir as empiric second-line antiretroviral therapy in resource-limited settings.

Growing data for recycling tenofovir and lamivudine with dolutegravir as empiric second-line antiretroviral therapy in resource-limited settings.

Possible role of plasma Galectin-9 levels as a surrogate marker of viremia in HIV infected patients on antiretroviral therapy in resource-limited settings

BackgroundEarly detection of viremia in HIV infected patients on anti-retroviral therapy (ART) is important to prevent disease progression as well as accumulation of drug resistance mutations. This makes HIV viral load (VL) monitoring indispensable in HIV infected patients on ART. However VL, being an expensive test, results in heavy financial burden on health services. Hence, cheaper surrogate markers of viremia are desired to reduce overall cost of management of HIV infected patients.MethodsWe enrolled aviremic (n = 63, M:F = 31:32) and viremic (n = 43, M:F = 21:22) HIV infected patients at 1 year after ART initiation. Viremic individuals were identified as those having a plasma VL of more than 1000 copies/µl and aviremic individuals as less than 40 copies/µl. The study participants also included immuno-virologically discordant patients as they demonstrate differential degrees of immune-reconstitution and are likely to harbour concomitant infections influencing levels of immune-activation markers screened as the surrogate markers. Immune activation markers viz. plasma hs-CRP, soluble-CD14 and Galectin-9 levels were estimated by ELISA, IL-6 by luminex assay and percentages of CD38+ CD8+ cells were determined by flow cytometry. The levels were compared between viremic and aviremic patients and correlated with plasma viral load. Receiver operated curve (ROC) analysis was done for plasma Galectin-9 levels.ResultsViremic patients had significantly higher levels of Galectin-9 and %CD38+ CD8+ cells (p values < 0.0001) than aviremic patients. Levels of the other activation markers did not differ between viremic and aviremic individuals. Galectin-9 levels (r = 0.76) and %CD38+ CD8+ cells (r = 0.39) correlated positively with VL. Area under curve for Galectin-9 levels for distinguishing between viremic and aviremic individuals was 0.98. Youden index, sensitivity, specificity, positive predictive value and negative predictive value for Galectin-9 levels were 0.87, 0.97, 0.90, 0.87 and 0.98, respectively, at the cut-off value of 5.79 ng/ml.ConclusionsPlasma Galectin-9 levels could identify viremic individuals with sensitivity and specificity of more than 90%. Thus, they showed a potential to serve as a surrogate marker of viremia in HIV infected patients on ART and would have cost implications on HIV management especially in resource-limited settings. However, the findings need to be confirmed in the patients on ART for different durations of time.

Diverse Human Immunodeficiency Virus-1 Drug Resistance Profiles at Screening for ACTG A5288: A Study of People Experiencing Virologic Failure on Second-line Antiretroviral Therapy in Resource-limited Settings.

Human immunodeficiency virus (HIV) drug resistance profiles are needed to optimize individual patient management and to develop treatment guidelines. Resistance profiles are not well defined among individuals on failing second-line antiretroviral therapy (ART) in low- and middle-income countries (LMIC). Resistance genotypes were performed during screening for enrollment into a trial of third-line ART (AIDS Clinical Trials Group protocol 5288). Prior exposure to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs and confirmed virologic failure on a protease inhibitor-containing regimen were required. Associations of drug resistance with sex, age, treatment history, plasma HIV RNA, nadir CD4+T-cell count, HIV subtype, and country were investigated. Plasma HIV genotypes were analyzed for 653 screened candidates; most had resistance (508 of 653; 78%) to 1 or more drugs. Genotypes from 133 (20%) showed resistance to at least 1 drug in a drug class, from 206 (32%) showed resistance to at least 1 drug in 2 drug classes, and from 169 (26%) showed resistance to at least 1 drug in all 3 commonly available drug classes. Susceptibility to at least 1 second-line regimen was preserved in 59%, as were susceptibility to etravirine (78%) and darunavir/ritonavir (97%). Susceptibility to a second-line regimen was significantly higher among women, younger individuals, those with higher nadir CD4+ T-cell counts, and those who had received lopinavir/ritonavir, but was lower among prior nevirapine recipients. Highly divergent HIV drug resistance profiles were observed among candidates screened for third-line ART in LMIC, ranging from no resistance to resistance to 3 drug classes. These findings underscore the need for access to resistance testing and newer antiretrovirals for the optimal management of third-line ART in LMIC.

Transfer is not a transition – voices of Jamaican adolescents with HIV and their health care providers

ABSTRACTIncreasing access to antiretroviral therapy in resource-limited settings (RLS) has resulted in the survival of perinatally HIV-infected children into adulthood. We characterized the transition process from pediatric to adult care by conducting semi-structured interviews of HIV-infected adolescents and health care providers in Jamaica. Using an inductive content analytic approach, four themes emerged: (1) Transition should be holistic and a process; (2) Pediatric clinics were like families; (3) Rootedness in the pediatric clinic; and (4) Need for adolescent-centered services to bridge the gap between pediatric and adult-centered services. Adolescent informed- and centered-transition approach may result in better outcomes for HIV-infected adolescents.

Characteristics of patients with thromboembolic disorders on warfarin therapy in resource limited settings

BackgroundWarfarin is a drug with narrow therapeutic index used in the management of thromboembolic disorders. Several factors affect its plasma concentrations with a resultant risk of toxicity. We examined the database of patients on warfarin therapy in order to establish the factors that affect the stability of INR and correlated them to clinical outcomes in resource limited settings.MethodsWe analysed retrospective data of patients admitted to adult medical wards at Moi Teaching and Referral Hospital (MTRH) in 2015. Inclusion criteria were patients with thromboembolic and related disorders and on warfarin treatment. Derived data included demographics, indications for warfarin use, co-prescribed drugs, co-morbidities, INR measurements, duration of hospital stay and clinical outcomes. Descriptive statistics were used to summarize the data. Pearson’s correlation coefficient was used to assess relationships between duration of hospitalization and number of INR tests. Regression splines were used to capture INR trends during the follow up period. Data was analysed using R v. 3.3.1.ResultsA total of 310 patients had thromboembolic disorders, out of which 63 met the study criteria.The median age was 48 years, while the mean number of INR measurements was once every four days. Majority of patients did not achieve stable INR values, with only two having consecutive INR values within therapeutic goal. Patients who died had high INR levels. The median duration of hospital stay was 9 days (IQR: 7.0, 16.5). There was a significant correlation between length of stay in hospital and the number of times that INR were measured (Corr = 0.667, p < 0.001). The two most common indications for warfarin were DVT (64.4%) and atrial fibrillation (24.7%). All the patients had one or more comorbid conditions except for 11 with DVT alone, with cardiovascular diseases and infections being the most frequent, and on concomitant medications, majority of which are known to interact with warfarin.ConclusionsIt was difficult to achieve stable INR under the prevailing conditions despite the frequent tests.The potential factors that may have contributed to the fluctuations include drug-drug interactions, frequency of INR tests, comorbidities and the short duration of hospital stay.

Predicting death and lost to follow-up among adults initiating antiretroviral therapy in resource-limited settings: Derivation and external validation of a risk score in Haiti.

BackgroundOver 18 million adults have initiated life-saving antiretroviral therapy (ART) in resource-poor settings; however, mortality and lost-to-follow-up rates continue to be high among patients in their first year after treatment start. Clinical decision tools are needed to identify patients at high risk for poor outcomes in order to provide individualized risk assessment and intervention. This study aimed to develop and externally validate risk prediction tools that estimate the probability of dying or of being lost to follow-up (LTF) during the year after starting ART.MethodsWe used a derivation cohort of 7,031 adults age 15–70 years initiating ART from 2007 to 2013 at 6 clinics in Haiti; 242 (3.5%) had documented death and 1,521 (21.6%) were LTF at 1 year after starting ART. The following routinely collected data were used as predictors in two logistic regression models (one to predict death and another to predict LTF): age, gender, weight, CD4 count, WHO Stage, and diagnosis of tuberculosis (TB). The validation cohort consisted of 1,835 adults initiating ART at a different HIV clinic in Haiti during 2012. We assessed model discrimination by measuring the C-statistic, and measured model calibration by how closely the predicted probabilities approximated actual probabilities of the two outcomes. We derived a nomogram and a point-based risk score from the predictive models.FindingsThe model predicting death within the year after starting ART had a C-statistic of 0.75 (95% CI 0.74 to 0.81). There was no evidence for significant overfitting and the predictions were well calibrated. The strongest predictors of 1-year mortality were male gender, low weight, low CD4 count, advanced WHO stage, and the absence of TB. In the validation cohort, the C-statistic was 0.69 (95% CI 0.59 to 0.77). A point-based risk score for death had a C-statistic 0.73 (95% CI 0.69 to 0.76) and categorizes patients as low risk (<2% risk of death), average risk (3–4%), and high-risk (8–10%) and very high-risk (14–19%) with likelihood ratios to be used in settings where the baseline risk is different from our study population. The model predicting LTF did not discriminate well (C-statistic 0.59).ConclusionsA simple risk-score using routinely collected data can predict 1-year mortality after ART initiation for HIV-positive adults in Haiti. However, predicting lost to follow-up using routinely collected data was not as successful. The next step is to assess whether use of this risk score can identify patients who need tailored services to reduce mortality in resource-poor settings such as Haiti.

Development of Low-Cost Locally Sourced Two-Component Compression Bandages in Western Kenya.

IntroductionCompression therapy is well-established standard of care for chronic leg ulcers from venous disease and lymphedema. Chronic leg ulcers and lymphedema have a significant impact on quality of life, driven by pain, foul odor, and restricted mobility. Provision of layered compression therapy in resource-limited settings, as in Western Kenya and other regions of sub-Saharan Africa, is a major challenge due to several barriers: availability, affordability, and access to healthcare facilities. When wound care providers from an Academic Model Providing Access to Healthcare (AMPATH) health center in Western Kenya noted that a donated, finite supply of two-component compression bandages was helping to heal chronic leg ulcers, they began to explore the potential of finding a local, sustainable solution. Dermatology and pharmacy teams from AMPATH collaborated with health center providers to address this need.MethodsFollowing a literature review and examination of ingredients in prepackaged brand-name kits, essential components were identified: elastic crepe, gauze, and zinc oxide paste. All of these materials are locally available and routinely used for wound care. Two-component compression bandages were made by applying zinc oxide to dry gauze for the inner layer and using elastic crepe as the outer layer. Feedback from wound clinic providers was utilized to optimize the compression bandages for ease of use.ResultsAdjustments to assembly of the paste bandage included use of zinc oxide paste instead of zinc oxide ointment for easier gauze impregnation and cutting the inner layer gauze in half lengthwise to facilitate easier bandaging of the leg, such that there were two rolls of zinc-impregnated gauze each measuring 5 inches × 2 m. Adjustments to use of the compression bandage have included increasing the frequency of bandage changes from 7 to 3 days during the rainy seasons, when it is difficult to keep the bandage dry. Continuous local acquisition of all components led to lower price quotes for bulk materials, driving down the production cost and enabling a cost to the patient of 200 KSh (2 USD) per two-component compression bandage kit. Wound care providers have provided anecdotal reports of healed chronic leg ulcers (from venous stasis, trauma), improved lymphedema, and patient tolerance of compression.ConclusionsLow-cost locally sourced two-component compression bandages have been developed for use in Western Kenya. Their use has been initiated at an AMPATH health center and is poised to meet the need for affordable compression therapy options in Western Kenya. Studies evaluating their efficacy in chronic leg ulcers and Kaposi sarcoma lymphedema are ongoing. Future work should address adaptation of compression bandages for optimal use in Western Kenya and evaluate reproducibility of these bandages in similar settings, as well as consider home- or community-based care delivery models to mitigate transportation costs associated with accessing healthcare facilities.

Quality of life among HIV-infected individuals failing first-line antiretroviral therapy in resource-limited settings

ABSTRACTWe evaluated health-related quality of life (QoL) in HIV infection participants with virologic failure (VF) on first-line antiretroviral therapy (ART) in 9 resource-limited settings (RLS). ACTG SF-21 was completed by 512 participants at A5273 study entry; 8 domains assessed: general health perceptions (GHP), physical functioning (PF), role functioning (RF), social functioning (SF), cognitive functioning (CF), pain (P), mental health (MH), and energy/fatigue (E/F); each was scored between 0 (worst) to 100 (best). Mean QoL scores ranged from 67 (GHP) to 91 (PF, SF, CF). QoL varied by country; high VL and low CD4 were associated with worse QoL in most domains, except RF (VL only), SF (CD4 only) and CF (neither). Number of comorbidities, BMI and history of AIDS were associated with some domains. Relationships between QoL and VL varied among countries for all domains. The association of worse disease status with worse QoL may reflect low QoL when ART was initiated and/or deterioration associated with VF.

Second-line antiretroviral therapy in resource-limited settings: what we know and the challenges of ever-changing antiretroviral therapy

Almost 22 million persons with human immunodeficiency virus (HIV) are receiving antiretroviral therapy (ART) with the majority living in resource-limited settings (RLS) (1). This remarkable achievement owes much of its success to the public health approach adopted by the World Health Organization (WHO) (2).

A cinnamon-derived procyanidin type A compound inhibits hepatitis C virus cell entry.

Chronic hepatitisC virus (HCV) infection is a major cause of liver disease worldwide. Although direct-acting antivirals can cure the large majority of treated patients, important limitations remain, including treatment failure and high costs precluding access to therapy in resource-limited settings. We report herein the anti-HCV effects of IND02, a procyanidin typeA molecule, isolated and characterized from cinnamon. Using cellculture-derived HCV (HCVcc), HCV pseudoparticles (HCVpp), and subgenomic replicons, we demonstrated that IND02 markedly and dose-dependently inhibited HCV cell entry. Kinetic assays demonstrated that IND02 inhibits HCV entry most likely at a postbinding step. Experiments performed using primary human hepatocytes confirmed inhibition of HCV entry by IND02, demonstrating the functional impact in the most physiological cell-based system for studying HCV-host interactions. The natural compound IND02 exhibits potent HCV cell entry inhibition and provides a novel perspective for development of a low-cost antiviral for treatment of HCV infection.

Compatibility of next-generation first-line antiretrovirals with rifampicin-based antituberculosis therapy in resource limited settings.

Reduced dose efavirenz, dolutegravir, and/or tenofovir alafenamide (TAF) are likely to be used in the next generation of first-line antiretroviral therapy in resource limited settings, where HIV-associated tuberculosis is common. Rifampicin, which is a key component of first-line antituberculosis therapy, is a potent inducer of many drug transporters and metabolising enzymes. We reviewed the literature for potential or actual drug--drug interactions between these antiretrovirals and rifampicin. Dose adjustments of standard dose efavirenz are not necessary with rifampicin, because auto-induction of CYP2B6 by efavirenz counteracts the induction of rifampicin. However, patients with extensive metabolizer CYP2B6 genotypes have lower efavirenz concentrations and may have less auto-induction of CYP2B6; the additive inducing effects of rifampicin on CYP2B6 could result in clinically significant reductions of efavirenz concentrations. Doubling the dose of dolutegravir overcomes induction by rifampicin. TAF is more prone to be the victim in drug--drug interactions than tenofovir disoproxil fumarate. Interactions between TAF and rifampicin have not been studied, but there is likely to be significant interaction. Further research on drug--drug interactions between rifampicin and the next generation of first-line antiretrovirals will be needed before they can be recommended in patients with HIV-associated tuberculosis.

Does early goal directed therapy in sepsis still hold relevance in low and middle-income countries?

The efficacy of early goal directed therapy in improving outcomes has been questioned in few recent studies. But, does that hold true for low and middle income countries like Nepal? This editorial expresses the views of the editors on the usual care of sepsis patients and early goal directed therapy in resource limited settings.