In order to examine the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-P) in combination with bevacizumab (B) and gemcitabine (G) for the first-line treatment of patients with HER2-negative metastatic breast cancer (MBC). In this single-center, open-label phase II trial, patients with HER2-negative MBC received gemcitabine 1500 mg/m(2), nab-paclitaxel 150 mg/m(2), and bevacizumab 10 mg/kg (each administered intravenously) on days 1 and 15 of a 28-day cycle. The primary end point was progression free survival (PFS); secondary end points were overall response rate (ORR), complete (CR) and partial (PR) response rates, clinical benefit (ORR + stable disease), overall survival (OS), and safety. Thirty patients were enrolled. One patient was ineligible and was not included in analysis. Median PFS was 10.4 months (95% CI: 5.6-15.2 months). ORR was 75.9%, comprising eight (27.6%) CRs and 14 (48.3%) PRs; five patients had stable disease (SD) and two patients (6.9%) had progressive disease (PD) as their best response. The clinical benefit rate was 93.1% (27/29) in the overall group and 84.6% in the triple-negative cohort (11/13). The 18-month survival rate was 77.2% (95% CI: 51.1-90.5%). Eight (27.6%) patients experienced grade 3 or 4 toxicity: grade 4 neutropenic fever (n = 1) and grade 3 infection (n = 6), leukopenia, thrombocytopenia, peripheral neuropathy, seizure, shortness of breath, hematuria, and cardiac tamponade (one each). First-line therapy with nab-P, B, and G demonstrated a median PFS of 10.4 months and a 75.9% ORR with acceptable toxicity; this novel combination warrants investigation in a randomized study.

Objectives PEPFAR’s initial rapid scale-up approach was largely a vertical effort focused fairly exclusively on AIDS. The purpose of our research was to identify spill-over health system effects, if any, of investments intended to stem the HIV epidemic over a 6-year period with evidence from Uganda. The test of whether there were health system expansions (aside from direct HIV programming) was evidence of increases in utilization of non-HIV services—such as outpatient visits, in-facility births or immunizations—that could be associated with varying levels of PEPFAR investments at the district level.Methods Uganda’s Health Management Information System article-based records were available from mid-2005 onwards. We visited all 112 District Health offices to collect routine monthly reports (which contain data aggregated from monthly facility reports) and annual reports (which contain data aggregated from annual facility reports). Counts of individuals on anti-retroviral therapy (ART) at year-end served as our primary predictor variable. We grouped district-months into tertiles of high, medium or low PEPFAR investment based on their total reported number of patients on ART at the end of the year. We generated incidence-rate ratios, interpreted as the relative rate of the outcome measure in relation to the lowest investment PEPFAR tertile, holding constant control variables in the model.Results We found PEPFAR investment overall was associated with small declines in service volumes in several key areas of non-HIV care (outpatient care for young children, TB tests and in-facility deliveries), after adjusting for sanitation, elementary education and HIV prevalence. For example, districts with medium and high ART investment had 11% fewer outpatient visits for children aged 4 and younger compared with low investment districts, incidence rate ratio (IRR) of 0.89 for high investment compared with low (95% CI, 0.85–0.94) and IRR of 0.93 for medium compared with low (0.90–0.96). Similarly, 22% fewer TB sputum tests were performed in high investment districts compared with low investment, [IRR 0.78 (0.72–0.85)] and 13% fewer in medium compared with low, [IRR 0.88 (0.83–0.94)]. Districts with medium and high ART investment had 5% fewer in-facility deliveries compared with low investment districts [IRR 0.95 for high compared with low, (91–1.00) and 0.96 for medium compared with low (0.93–0.99)]. Although not statistically significant, the rate of maternal deaths in high investment district-months was 13% lower than observed in low investment districts.Conclusions This study sought to understand whether PEPFAR, as a vertical programme, may have had a spill-over effect on the health system generally, as measured by utilization. Our conclusion is that it did not, at least not in Uganda.

Achieving an AIDS-free generation will require the adoption and implementation of critical health policy reforms. However, countries with high HIV burden often have low policy development, advocacy, and monitoring capacity. This lack of capacity may be a significant barrier to achieving the AIDS-free generation goals. This manuscript describes the increased focus on policy development and implementation by the United States President’s Emergency Plan for AIDS Relief (PEPFAR). It evaluates the curriculum and learning modalities used for two regional policy capacity building workshops organized around the PEPFAR Partnership Framework agreements and the Road Map for Monitoring and Implementing Policy Reforms. A total of 64 participants representing the U.S. Government, partner country governments, and civil society organizations attended the workshops. On average, participants responded that their policy monitoring skills improved and that they felt they were better prepared to monitor policy reforms three months after the workshop. When followed-up regarding utilization of the Road Map action plan, responses were mixed. Reasons cited for not making progress included an inability to meet or a lack of time, personnel, or governmental support. This lack of progress may point to a need for building policy monitoring systems in high HIV burden countries. Because the success of policy reforms cannot be measured by the mere adoption of written policy documents, monitoring the implementation of policy reforms and evaluating their public health impact is essential. In many high HIV burden countries, policy development and monitoring capacity remains weak. This lack of capacity could hinder efforts to achieve the ambitious AIDS-free generation treatment, care and prevention goals. The Road Map appears to be a useful tool for strengthening these critical capacities.