Drug Interactions in the Treatment of Malignancy in HIV-Infected Patients.

The number of patients with HIV (human immunodeficiency virus) requiring treatment for malignancy is increasing worldwide. Concurrent treatment of HIV and malignancy is complicated by unpredictable drug-drug interactions, which can cause potentially life-threatening toxicities and ineffective treatment of either disease. This article aims to provide a practical approach to drug interactions and their management in this context to help deliver effective and safe treatment of both the malignancy and HIV.

Effects of vitamin D deficiency and combination antiretroviral therapy on bone in HIV-positive patients.

OBJECTIVES: In the era of combination antiretroviral therapy (cART), vitamin D deficiency, low bone mineral density (BMD) and fractures have emerged as subjects of concern in HIV-positive patients. Testing for vitamin D deficiency has been widely adopted in clinical practice even though the benefits of vitamin D supplementation in this population remain uncertain. The objective of this review was to evaluate the evidence for such a strategy. DESIGN: Systematic review of the literature on vitamin D deficiency in HIV infection, the effects of cART on vitamin D status, and the effects of vitamin D deficiency and cART on parathyroid hormone (PTH), bone turnover, BMD and the incidence of fractures in HIV-positive patients. METHODS: PubMed was used to identify relevant articles up to September 2011. RESULTS: Vitamin D deficiency, secondary hyperparathyroidism and low BMD are common in HIV-positive patients. Efavirenz is associated with a reduction in 25-hydroxy vitamin D levels, tenofovir with secondary hyperparathyroidism, and cART with increased bone turnover and low BMD. The clinical significance of low BMD, however, remains unclear, especially in younger patients. Although the incidence of fractures may be increased in HIV-positive patients, the contribution of low BMD and vitamin D deficiency to these fractures is uncertain. Limited data on vitamin D supplementation in HIV-positive patients have shown transient, beneficial effects on PTH, but no effects on BMD. CONCLUSION: The benefits of vitamin D supplementation in this population need to be demonstrated before widespread 'test and treat' policies can be recommended as part of routine clinical practice.

Efavirenz is associated with severe vitamin D deficiency and increased alkaline phosphatase.

OBJECTIVE(S): To identify factors (including exposure to specific antiretroviral drugs) associated with severe vitamin D deficiency (VDD) in HIV-infected individuals and to explore the effects of severe VDD and antiretroviral drug exposure on serum alkaline phosphatase (ALP) as surrogate marker of bone turnover. DESIGN: Cross-sectional survey of vitamin D status among HIV-infected patients attending for routine clinical care at a large London HIV clinic. METHODS: Severe VDD was defined as 25(OH)D levels of less than 10 microg/l (<25 nmol/l). Multivariate logistic regression analysis was used to identify factors associated with severe VDD and upper quartile ALP levels. RESULTS: Vitamin D levels were measured in 1077 patients and found to be suboptimal in 91%. One-third of patients had severe VDD. Black ethnicity, sampling in winter, nadir CD4 cell count less than 200 cells/microl, and exposure to combination antiretroviral therapy were associated with severe VDD. In analyses restricted to patients on combination antiretroviral therapy, current efavirenz use was significantly associated with severe VDD [adjusted odds ratio 2.0 (95% confidence interval 1.5-2.7)]. Current tenofovir [adjusted odds ratio 3.5 (95% confidence interval 2.3-5.2)] and efavirenz use [adjusted odds ratio 1.6 (95% confidence interval 1.02-2.4)], but not severe VDD [odds ratio 1.1 (0.8-1.5)], were associated with increased bone turnover (upper quartile ALP). CONCLUSION: Efavirenz was associated with severe VDD, a condition associated with multiple adverse health outcomes, and efavirenz and tenofovir with increased ALP. The clinical significance of these findings requires further investigation, given the widespread use of efavirenz and tenofovir in first-line combination antiretroviral therapy.

Population and antenatal-based HIV prevalence estimates in a high contracepting female population in rural South Africa.

BACKGROUND: To present and compare population-based and antenatal-care (ANC) sentinel surveillance HIV prevalence estimates among women in a rural South African population where both provision of ANC services and family planning is prevalent and fertility is declining. With a need, in such settings, to understand how to appropriately adjust ANC sentinel surveillance estimates to represent HIV prevalence in general populations, and with evidence of possible biases inherent to both surveillance systems, we explore differences between the two systems. There is particular emphasis on unrepresentative selection of ANC clinics and unrepresentative testing in the population. METHODS: HIV sero-prevalence amongst blood samples collected from women consenting to test during the 2005 annual longitudinal population-based serological survey was compared to anonymous unlinked HIV sero-prevalence amongst women attending antenatal care (ANC) first visits in six clinics (January to May 2005). Both surveillance systems were conducted as part of the Africa Centre Demographic Information System. RESULTS: Population-based HIV prevalence estimates for all women (25.2%) and pregnant women (23.7%) were significantly lower than that for ANC attendees (37.7%). A large proportion of women attending urban or peri-urban clinics would be predicted to be resident within rural areas. Although overall estimates remained significantly different, presenting and standardising estimates by age and location (clinic for ANC-based estimates and individual-residence for population-based estimates) made some group-specific estimates from the two surveillance systems more predictive of one another. CONCLUSION: It is likely that where ANC coverage and contraceptive use is widespread and fertility is low, population-based surveillance under-estimates HIV prevalence due to unrepresentative testing by age, residence and also probably by HIV status, and that ANC sentinel surveillance over-estimates prevalence due to selection bias in terms of age of sexual debut and contraceptive use. The results presented highlight the importance of accounting for unrepresentative testing, particularly by individual residence and age, through system design and statistical analyses.

Continued very high prevalence of HIV infection in rural KwaZulu-Natal, South Africa: a population-based longitudinal study.

OBJECTIVE: To estimate the prevalence of HIV and associated sociodemographic factors including mobility and migration in a rural population in KwaZulu-Natal, South Africa. METHODS: A household-based HIV serosurvey of a population that has been under longitudinal demographic surveillance since 2000. All residents (women aged 15-49 years; men aged 15-54 years) and a sample of non-residents ('migrants') who return periodically to their households in the area were identified and approached for finger-prick HIV testing. RESULTS: A total of 8325/11 505 male and 11 542/14 396 female residents were traced. Of these, 4692 men and 6859 women consented to HIV testing. Overall, 27% of female and 13.5% of male residents were HIV infected. HIV prevalence peaked at 51% among resident women aged 25-29 years and 44% among resident men aged 30-34 years, with the highest infection rates of 57.5% among 26-year-old women. The female: male infection ratio for residents aged 15-19 years was 13.0. Many factors, including increased mobility, associated with an increased risk of HIV infection among residents, were also associated with non-participation. Among non-residents, 34% of men aged 15-54 years and 41% of women aged 15-49 years were HIV infected. CONCLUSION: The extremely high prevalence of HIV suggests an urgent need to allocate adequate resources for HIV prevention and treatment in rural areas. Effective monitoring of the epidemic in Africa needs to include efforts to strengthen sentinel surveillance in rural areas and strategies for the surveillance of migrants and mobile individuals.

Antiretroviral treatment in resource-poor settings: public health research priorities.

Many countries in Africa are planning to provide highly active antiretroviral therapy (HAART) to millions of people with acquired immune deficiency syndrome. This will be a highly complex therapy programme. Physician-based models of care adapted from industrialized countries will not succeed in providing treatment to the majority of those who need it in resource-constrained settings. A high priority is to identify care models for Africa that will increase coverage of HAART safely and effectively: key issues are (i) whether nursing staff or non-clinically qualified staff can take the major role in the treatment programme and reduce the workload of physicians, (ii) whether treatment and monitoring can be delivered through peripheral health centres or through home visits and achieve better adherence and be more cost-effective than delivery at hospitals and (iii) which clinical algorithms used by nursing or non-clinically qualified staff will be effective for screening, diagnosing and managing treatment-related side-effects and medical problems being incurred. Many current ART support programmes are making little or no investment in research, but answering important questions on delivery of HAART will be essential if HAART programmes are to be successful in African nations with a high burden of human immunodeficiency virus infection.