Cascade of care for people living with HIV infection in the Wellington region.

AIM: Antiretroviral therapy (ART) is highly effective in providing better outcomes for people living with HIV infection (PLHIV) and reducing the risk of transmission to others. The 'cascade of care' describes steps in delivering care: diagnosis, linkage and retention in care, and the provision and success of ART. METHODS: The cascade of care for PLHIV in the Wellington region was reviewed during 2015. An estimate of 20% undiagnosed HIV infection was used from past New Zealand research. 'Suppression of HIV infection' by ART was defined as a viral load less than 200 RNA copies/mL as commonly used in other cascade of care studies. RESULTS: There were 307 people identified with HIV infection. The median age was 48 years, and 54 (18%) were women. At the time of the audit, each of the 307 PLHIV were accounted for and not lost to follow-up. ART was being taken by 272 (89%). Those with a CD4 count >500 x 10^6/L accounted for 26/35 not on ART. Of those on ART 254/272 (93.3%) had a suppressed viral load, including 252/259 (97.3%) of those established on treatment >6 months. Overall, 254/384 (66.1%) were estimated to have a suppressed viral load. CONCLUSIONS: The study indicated a high level of retention in care, and of effective HIV suppression, with ART. The main gaps in the cascade of care were the people with undiagnosed HIV infection and those in whom treatment had not yet been initiated because their CD4 count was above 500 cells/10^6/L.

Peloruside A synergizes with other microtubule stabilizing agents in cultured cancer cell lines.

The microtubule stabilizing agent peloruside A binds to a unique site on the tubulin alpha,beta-heterodimer compared to taxoid site drugs such as paclitaxel (Taxol), docetaxel (Taxotere), epothilone A, and discodermolide. Because the binding sites differ, peloruside A may be able to synergize with these taxoid site drugs when added in combination to cultured cells. Ovarian carcinoma cells (1A9) and myeloid leukemic cells (HL-60) were treated with different concentrations of peloruside A and taxoid site drugs, both compounds given singly and in combination in the nanomolar range, and the antiproliferative activity, G2/M blocking potency, and microtubule stabilizing activity of the treatments assessed. Cell proliferation was monitored using the MTT cell proliferation assay, cell cycle block was determined by flow cytometry, and stabilization of the tubulin polymer was assessed by Western blotting for beta-tubulin distributions in supernatant and pellet fractions of cell lysates. A combination index (CI) was calculated from the equation CI = D1/Dx1 + D2/Dx2 in which D1 and D2 are the concentrations of drug 1 and drug 2 that in combination give the same response as drug 1 alone (Dx1) or drug 2 alone (Dx2). A CI of less than 1 indicates synergy, equal to 1, additivity, and greater than 1, antagonism. Confidence intervals for each CI value were obtained using a bootstrapping procedure. In cell proliferation assays, statistically significant synergy was found between peloruside A and paclitaxel and epothilone A. Combinations of these two taxoid site drugs, however, also showed synergy in their effects on cell proliferation. These results confirm that peloruside A, when added in combination with other microtubule stabilizing agents, acts synergistically to enhance the antimitotic action of the drugs, but also highlight the complexity of drug interactions in intact cells.