Individual and healthcare supply-related barriers to treatment initiation in HIV-positive patients enrolled in the Cameroonian antiretroviral treatment access programme

International audienceIncreasing demand for antiretroviral treatment (ART) together with a reduction in international funding during the last decade may jeopardize access to ART. Using data from a cross-sectional survey conducted in 2014 in 19 HIV services in the Centre and Littoral regions in Cameroon, we investigated the role of healthcare supply-related factors in time to ART initiation in HIV-positive patients eligible for ART at HIV diagnosis. HIV service profiles were built using cluster analysis. Factors associated with time to ART initiation were identified using a multilevel Cox model. The study population included 847 HIV-positive patients (women 72%, median age: 39 years). Median (interquartile range) time to ART initiation was 1.6 (0.5-4.3) months. Four HIV service profiles were identified: (1) small services with a limited staff practising partial task-shifting (n = 4); (2) experienced and well-equipped services practising task-shifting and involving HIV community-based organizations (n = 5); (3) small services with limited resources and activities (n = 6); (4) small services providing a large range of activities using task-shifting and involving HIV community-based organizations (n = 4). The multivariable model showed that HIV-positive patients over 39 years old [hazard ratio: 1.26 (95% confidence interval) (1.09-1.45), P = 0.002], those with disease symptoms [1.21 (1.04-1.41), P = 0.015] and those with hepatitis B co-infection [2.31 (1.15-4.66), P = 0.019] were all more likely to initiate ART early. However, patients in the first profile were less likely to initiate ART early [0.80 (0.65-0.99), P = 0.049] than those in the second profile, as were patients in the third profile [association only significant at the 10% level; 0.86 (0.72-1.02), P = 0.090]. Our findings provide a better understanding of the role played by healthcare supply-related factors in ART initiation. In HIV services with limited capacity, task-shifting and support from community-based organizations may improve treatment access. Additional funding is required to relieve healthcare supply-related barriers and achieve the goal of universal ART access

Role of active metabolites in the use of opioids

The opioid class of drugs, a large group, is mainly used for the treatment of acute and chronic persistent pain. All are eliminated from the body via metabolism involving principally CYP3A4 and the highly polymorphic CYP2D6, which markedly affects the drug's function, and by conjugation reactions mainly by UGT2B7. In many cases, the resultant metabolites have the same pharmacological activity as the parent opioid; however in many cases, plasma metabolite concentrations are too low to make a meaningful contribution to the overall clinical effects of the parent drug. These metabolites are invariably more water soluble and require renal clearance as an important overall elimination pathway. Such metabolites have the potential to accumulate in the elderly and in those with declining renal function with resultant accumulation to a much greater extent than the parent opioid. The best known example is the accumulation of morphine-6-glucuronide from morphine. Some opioids have active metabolites but at different target sites. These are norpethidine, a neurotoxic agent, and nordextropropoxyphene, a cardiotoxic agent. Clinicians need to be aware that many opioids have active metabolites that will become therapeutically important, for example in cases of altered pathology, drug interactions and genetic polymorphisms of drug-metabolizing enzymes. Thus, dose individualisation and the avoidance of adverse effects of opioids due to the accumulation of active metabolites or lack of formation of active metabolites are important considerations when opioids are used.Janet K. Coller, Lona L. Christrup, Andrew A. Somogy