Considerable delay in switching to second-line cART may occur despite an observed high rate of failure. Factors including WHO clinical stage and tuberculosis co-infection should be evaluated before starting cART. Toxicity and drug adherence should be monitored to minimize drug substitution in LMIC.

Highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) infection has been widely available in industrialized countries since 1996; its widespread use determined a dramatic decline in acquired immunodeficiency syndrome (AIDS)-related mortality, and consequently, a significant decrease of AIDS-defining cancers. However the increased mean age of HIVinfected patients, prolonged exposure to environmental and lifestyle cancer risk factors, and coinfection with oncogenic viruses contributed to the emergence of other malignancies that are considered non-AIDS-defining cancers (NADCs) as a relevant fraction of morbidity and mortality among HIV-infected people twenty years after HAART introduction. The role of immunosuppression in the pathogenesis of NADCs is not well defined, and future researches should investigate the etiology of NADCs. In the last years there is a growing evidence that intensive chemotherapy regimens and radiotherapy could be safely administrated to HIV-positive patients while continuing HAART. This requires a multidisciplinary approach and a close co-operation of oncologists and HIV-physicians in order to best manage compliance of patients to treatment and to face drug-related side effects. Here we review the main epidemiological features, risk factors and clinical behavior of the more common NADCs, such as lung cancer, hepatocellular carcinoma, colorectal cancer and anal cancer, Hodgkin's lymphoma and some cutaneous malignancies, focusing also on the current therapeutic approaches and preventive screening strategies.

Because of a lack of prevention policies or problems in implementing prevention of mother-to-child transmission (P-MTCT), most of the 1500 daily new HIV infections in children aged<15 years are caused by MTCT. Fifteen percent of all HIV-infected individuals are children, but the vast majority lack access to highly active antiretroviral therapy (HAART), which can drastically reduce morbidity and mortality. There are 22 antiretroviral drugs currently approved by the US FDA for use in the treatment of HIV-infected adults and adolescents, but only 12 of these drugs are approved for use in children. Antiretroviral drugs belong to four major classes: nucleoside and nucleotide analogue reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors and fusion inhibitors. According to international guidelines developed by organizations including WHO, the Paediatric European Network for Treatment of AIDS (PENTA) and the US National Institutes of Health (US-NIH), the treatment of choice for HIV-infected children and adults is a combination of two NRTIs (backbone treatment) plus a third potent agent from a different class, either an NNRTI or a ritonavir-boosted protease inhibitor. There are specific challenges in treating HIV-infected children, including uncertainty about the best time to start treatment, the need for more paediatric formulations, the lack of pharmacokinetic studies for new drugs, and incomplete dosing guidelines. Furthermore, the most appropriate regimen for an individual child depends on a variety of factors, including the age of the child; the availability of appropriate drug formulations; the potency, complexity and toxicity of the drug regimen; the home situation; the child and caregiver's ability to adhere to the regimen; and the child's antiretroviral treatment history. In addition, antiretroviral drugs are not licensed for all age groups and the drugs are often not affordable. This review describes NNRTI and protease inhibitors as key components of first- and second-line antiretroviral therapy (ART), focusing on the rationale for choosing an NNRTI- versus protease inhibitor-based regimen based on the results of available phase II and III studies. Some of the new agents available for children as second-line and salvage therapy both on- and off-label are also discussed. The drug regimens described in this review are relevant to clinicians in developed and developing countries. The availability of new, potent compounds with different resistance and toxicity profiles may represent an alternative option to interclass switching and could redefine ART strategy, including the option of first-line NRTI-sparing regimens.

In resource-constrained settings, considerable delays in IPT initiation may occur, particularly in children with HIV who are presenting with cough at TB screening. The good safety profile of isoniazid in antiretroviral-therapy-experienced children provides further support to IPT implementation in this population.

No abstract