Both antiretroviral treatment interruption (TI) and cessation have been strongly discouraged since 2006. We describe the incidence, duration, and risk factors for TI and loss-to-follow-up (LTFU) rates across 13 countries. and ART with food restrictions (fasting or with food). In conclusion, since 2006, 7.8% of patients had significant time off treatment, which has the potential to compromise any 'test and treat' policy as during the interruption viral load will rebound and increase the risk of transmission.

Background: Cytopenias are the most common HIV-associated hematological abnormality. Cytopenias become more prevalent as HIV progresses and are often fatal. Sex, race, geographical location and comorbidities such as tuberculosis have been associated with cytopenias. Data from resource-limited settings about the prevalence, correlates and trends in cytopenia are limited. This analysis assessed the prevalence and correlates of cytopenia at initiation of HAART and the trend in cytopenias among HAART-treated AIDS patients in Uganda. Methods: This is a secondary analysis of hematological data of 400 adults enrolled into the Multivitamins, HAART and HIV/AIDS Trial (NCT01228578). Anemia was defined according to WHO guidelines and leucopenia and thrombocytopenia were defined using study site laboratory reference ranges for lack of generally accepted standardized definitions for these 2 cell lines. Univariate and bivariate analyses were done to describe the patient population and log-binomial regression was used to quantify the correlates of cytopenia. Multilevel mixed-effects linear regression was used to examine the change in the 3 cell lines over 18 months of HAART. Results: Sixty five percent had at least one form of cytopenia and the prevalence was higher in females (PR 1.21 CI 1.01-1.43) and higher with decreasing CD4 count and decreasing body mass index. Anemia was the most common occurring in 47.8%. Adjusted models showed that hemoglobin values were 0.03g/dl higher with each month of HAART (p < 0.001) while white blood cell counts and platelets were lower by 0.01 (p = 0.009) and 0.15 (p = 0.522) units respectively with each month of HAART. Conclusions: Cytopenias are a frequent complication in HIVinfected adults at initiation of HAART in Uganda. Females, a decreasing CD4 count and decreasing body mass index were associated with having a cytopenia. This data shows that HAART improves hemoglobin status and alters the white blood cell and platelet counts independent of sex, immunological and nutritional parameters.

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Background: Combination drug products can display thermal behaviour that is more complex than for the corresponding single drug products. For example, the contraceptive vaginal ring (VR) Nuvaring contains a eutectic (lowest melting) composition of etonogestrel (ETN) and ethinyl estradiol. Here we report the predisposition of dapivirine (DPV) to form reduced melting/eutectic mixtures when combined with other contraceptive hormones and antiretrovirals, and discuss the implications for development of combination microbicide and multipurpose prevention technology (MPT) products. Methods: Binary mixtures of DPV with darunavir (DRV), levonorgestrel (LNG), ETN or maraviroc (MVC) were prepared either by physical mixing or by solvent evaporation. Selected binary mixtures were also incorporated into silicone elastomer (SE) VR devices. Thermal behavior of the mixtures was analyzed using differential scanning calorimetry (DSC) operating in standard heating ramp mode (10°C/min). DSC data were used to construct two component phase diagrams for each binary system. Results: Drug mixtures typically showed reduced melting transitions for both drug components, with clear evidence for a eutectic mixture at a well-defined intermediate composition. Eutectic temperatures and compositions for the various mixtures were: 40% DPV / 60% ETN -170°C; 25% DPV / 75% MVC -172°C; 65% DPV / 35% LNG -192°C. In each case, the eutectic composition was also detected when the drug mixtures were incorporated into SE VRs. For the DPV/DRV system, the thermal behaviour is complicated by desolvation from the darunavir ethanolate polymorph. Conclusions: When DPV is combined with small molecular weight hydrophobic drugs, the melting temperature for both drugs is typically reduced to a degree dependent on the composition of the mixture. At specified compositions, a low melting eutectic system results. The formation of eutectic behavior in binary drug systems needs to be carefully characterised in order to define product performance and drug release.Background: A vaginal ring (VR) that can prevent both unintended pregnancy and the spread of sexually transmitted infec-tions has the potential to significantly improve women's sexual and reproductive health. Here, we report in vitro evaluation of four hormonal contraceptive compounds -levonorgestrel (LNG), ethinylestradiol (EE), etonogestrel (ET) and nestorone (NES) -for co-formulation with dapivirine (DPV) in a silicone elastomer (SE) vaginal ring device. Methods: The influence of each steroid hormone on the SE cure characteristics was assessed using flow rheology. The thermal stability of each API and the potential for drug-polymer and drugdrug interactions were assessed using thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Matrixtype and reservoir-type VRs containing various loadings of each steroid were manufactured using both a condensation-cure and an addition-cure SE systems and in vitro release rates assessed. Results: TGA confirmed all steroids were stable in the temperature...