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In order to determine inpatient hospital mortality rates, causes of mortality and characteristics of inpatients at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi, we conducted a prospective observational study of all patients admitted to KCH medical ward from 20 September 2008 to April 2, 2009. All admission diagnoses, HIV status and antiretroviral therapy (ART) use were recorded. Patients' vital status was determined at discharge. A descriptive analysis and two logistic regression models were used for the analysis. Of the 1895 enrolled patients, the overall hospital mortality rate was 14.6%, substantially higher among known HIV-infected patients (24.?% versus 1 0.8%, P = 0.0009) and men (17.1% versus 12%, P = 0.033). Patients with multiple diagnoses had significantly higher mortality (odds ratio [OR] 2.33; 95% confidence interval [Cl] 1.47, 3.71). Most patients (62.3%) had unknown HIV status at admission. Among HIV-infected patients, ART use did not reduce hospital mortality or alter the spectrum of diseases. The majority of diagnoses were infectious (63.4%). The high inpatient mortality rate, especially among HIV-infected patients combined with the limited spectrum of diagnoses, emphasizes the need for improved inpatient management and diagnostic services. Expansion of HIV testing is warranted. Despite the rollout of ART, there remains a significant need for treatment of HIV-infected individuals. [ABSTRACT FROM AUTHOR]

Objectives The Malawi antiretroviral therapy (ART) programme uses the public health approach to identify ART failure. Advanced disease progression may occur before switching to second-line ART. We report outcomes for patients evaluated and initiated on second-line treatment in Malawi. Methods Patients meeting Malawi immunological or clinical criteria for ART failure in two large urban ART clinics were evaluated for virological failure (viral load >400 HIV-1 RNA copies/mL) and, if failure was confirmed, initiated on second-line ART (zidovudine/lamivudine/tenofovir/lopinavir/ritonavir). Patients were seen monthly and laboratory evaluations were performed quarterly and as needed. We performed logistic regression modelling to identify factors associated with mortality, mortality or new HIV illnesses, and virological suppression at 12 months. Results Of the 109 patients with confirmed virological failure, five patients died prior to initiation, three declined switching and 101 patients initiated second-line treatment. Over 12 months, 10 additional patients died, 34 patients experienced 45 HIV-related events, and 19 patients experienced grade 3 or 4 toxicities. Among survivors, 85.2% had HIV-1 RNA<400 copies/mL at 12 months. While power to distinguish differences was limited, response rates were similar regardless of baseline resistance level. The median CD4 count increase was 142 cells/μL. World Health Organization clinical failure at baseline [odds ratio (OR) 3.47; 95% confidence interval (CI) 1.14–10.59] and body mass index <18.5 (OR 4.43; 95% CI 1.15–17.12) were risk factors for death. Baseline CD4 count <50 cells/μL was associated with increased risk for death or morbidity at 12 months (OR 2.57; 95% CI 1.01–6.52). Conclusions Second-line treatment in Malawi was associated with substantial mortality, morbidity and toxicity but, among survivors, virological outcomes were favourable. [ABSTRACT FROM AUTHOR]

BACKGROUND Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)- related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known. METHODS In this phase 3 randomized, controlled, noninferiority trial conducted in five African countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 Ing per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization-recommended treatment, which includes amphotericin B deoxycholate (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin. RESULTS A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 participants (24.8%; 95% confidence interval ICI], 20.7 to 29.3) in the liposomal amphotericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (difference, -3.9 percentage points); the upper boundary of the one-sided 95°6 confidence interval was 1.2 percentage points (within the noninferiority margin; P<0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was -0.40 log~ colonyforming units (CFU) per milliliter per day in the liposomal amphotericin B group and -0.42 logio CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.090 vs. 62.3%). CONCLUSIONS Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis and was associated with fewer adverse events. [ABSTRACT FROM AUTHOR]

Background: An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission.Methods: We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis.Results: Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant.Conclusions: The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 ClinicalTrials.gov number, NCT00074581 .). [ABSTRACT FROM AUTHOR]

BACKGROUND: Study A5274 was an open-label trial of people with HIV (PLHIV) with CD4 cell count <50 cells/µL who were randomized to empirical TB treatment vs. isoniazid preventive therapy (IPT) in addition to antiretroviral therapy (ART). We evaluated health-related quality of life (HRQoL) by study arm, changes over time, and association with sociodemographic and clinical factors. METHODS: Participants aged >13 years were enrolled from outpatient clinics in 10 countries. HRQoL was assessed at Weeks 0, 8, 24 and 96 with questions about daily activity, hospital or emergency room visits, and general health status. We used logistic regression to examine HRQoL by arm and association with sociodemographic and clinical factors. RESULTS: Among 850 participants (424 empiric arm, 426 IPT arm), HRQoL improved over time with no difference between arms. At baseline and Week 24, participants with WHO Stage 3 or 4 events, or those who had Grade 3 or 4 signs/symptoms, were significantly more likely to report poor HRQoL using the composite of four HRQoL measures. CONCLUSION: HRQoL improved substantially in both arms during the study period. These findings show that ART, TB screening, and IPT can not only reduce mortality, but also improve HRQoL in PLHIV with advanced disease.

Background: In Malawi, passive partner notification is the mainstay method of partner notification (PN). Despite its wide use, the proportion of sexual partners referred for care through this method is very low. We aimed to increase the proportion of sexual partner referral through passive PN., Methods: We implemented a quality improvement (QI) project at Bwaila STI unit in Lilongwe, Malawi between January and June 2017 using a pre- and post- intervention quasi-experimental study design. Pre-intervention, we conducted key-informant interviews and clinic observations and used the findings to design a QI project using expert opinion. The intervention included three change ideas: early start time of the clinic, shortening of the group health talk and expedited clinic flow for sexual partners. Each change idea was tested twice through 1-week long Plan-Do-Study-Act cycles using the model for improvement (MFI) and then combined and tested twice. Process data were collected and monitored using run charts. Post-intervention, we evaluated the proportion of sexual partners who presented to the clinic, to detect a 10% increase at 95% power and α=0.05, between pre- and post-intervention periods., Results: The average duration of the group health talk dropped from 56 minutes to 38 minutes and the duration of clinic stay for sexual partners reduced by 45 minutes (from 1hour 36 minutes to 51 minutes). The average clinic start time improved from 09:02 hours to 08:17 hours. The proportion of sexual partner referral increased by 37% (P=0.04) - from 15.6% to 21.4%. We observed an upward trend in the proportion of sexual partners referred in the post-intervention period., Conclusion: The yield of sexual partners through passive PN was improved using a simple QI intervention implemented using the MFI. However, the proportion of sexual partner referral remains suboptimal. More effort is required to increase the proportion of sexual partner referral in Malawi.

Scale-up of viral load (VL) monitoring for HIV-infected patients on antiretroviral therapy (ART) is a priority in many resource-limited settings, and ART providers are critical to effective program implementation. We explored provider-perceived barriers and facilitators of VL monitoring. We interviewed all providers (n = 17) engaged in a public health evaluation of dried blood spots for VL monitoring at five ART clinics in Malawi. All ART clinics were housed within district hospitals. We grouped themes at patient, provider, facility, system, and policy levels. Providers emphasized their desire for improved ART monitoring strategies, and frustration in response to restrictive policies for determining which patients were eligible to receive VL monitoring. Although many providers pled for expansion of monitoring to include all persons on ART, regardless of time on ART, the most salient provider-perceived barrier to VL monitoring implementation was the pressure of work associated with monitoring activities. The work burden was exacerbated by inefficient data management systems, highlighting a critical interaction between provider-, facility-, and system-level factors. Lack of integration between laboratory and clinical systems complicated the process for alerting providers when results were available, and these communication gaps were intensified by poor facility connectivity. Centralized second-line ART distribution was also noted as a barrier: providers reported that the time and expenses required for patients to collect second-line ART frequently obstructed referral. However, provider empowerment emerged as an unexpected facilitator of VL monitoring. For many providers, this was the first time they used an objective marker of ART response to guide clinical management. Providers' knowledge of a patient's virological status increased confidence in adherence counseling and clinical decision-making. Results from our study provide unique insight into provider perceptions of VL monitoring and indicate the importance of policies responsive to individual and environmental challenges of VL monitoring program implementation. Findings may inform scale-up by helping policy-makers identify strategies to improve feasibility and sustainability of VL monitoring.

In order to determine inpatient hospital mortality rates, causes of mortality and characteristics of inpatients at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi, we conducted a prospective observational study of all patients admitted to KCH medical ward from 20 September 2008 to April 2, 2009. All admission diagnoses, HIV status and antiretroviral therapy (ART) use were recorded. Patients' vital status was determined at discharge. A descriptive analysis and two logistic regression models were used for the analysis. Of the 1895 enrolled patients, the overall hospital mortality rate was 14.6%, substantially higher among known HIV-infected patients (24.2% versus 10.8%, P = 0.0009) and men (17.1% versus 12%, P = 0.033). Patients with multiple diagnoses had significantly higher mortality (odds ratio [OR] 2.33; 95% confidence interval [CI] 1.47, 3.71). Most patients (62.3%) had unknown HIV status at admission. Among HIV-infected patients, ART use did not reduce hospital mortality or alter the spectrum of diseases. The majority of diagnoses were infectious (63.4%). The high inpatient mortality rate, especially among HIV-infected patients combined with the limited spectrum of diagnoses, emphasizes the need for improved inpatient management and diagnostic services. Expansion of HIV testing is warranted. Despite the rollout of ART, there remains a significant need for treatment of HIV-infected individuals.

A parallel-plate flow chamber was used to quantify the detachment of normal, transformed, and reverted rat fibroblasts from a confluent monolayer of normal fibroblasts. In this method, known shear stresses were applied to the adherent cells and the percent of cells detached from the monolayer was determined. Results indicate that the detachment of all cell types increased with increasing shear stress and detachment of highly metastatic ras-transformed cells was significantly higher than that of either nonmetastatic normal cells or transformed cells reverted with the Kirsten ras revertant (K-rev 1a) gene, which are lowly metastatic. From these results, it is concluded that a correlation exists between the metastatic phenotype of the cell and its ability to detach from normal cells.