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OBJECTIVE: Antiretrovirals do not prevent anal intraepithelial neoplasia. However, the influence of antiretrovirals in the natural history of invasive anal cancer is less clear. The objective is to investigate the impact of antiretrovirals in the time to the development of anal cancer in HIV-positive MSM. DESIGN: A retrospective analysis of cases of anal cancer in a cohort of HIV-positive MSM receiving antiretrovirals between 1988 and 2008. METHODS: Time from first CD4 cell count or HIV RNA viral load test to anal cancer diagnosis was analysed using Cox regression and Kaplan-Meier curves. Anal cancer cases treated in the era prior to HAART (<1996) were compared with those treated later (1996-2008). RESULTS: Anal cancer cases (n = 37) were compared with a cohort of 1654 HIV-positive MSM on antiretrovirals. Antiretrovirals were started in the pre-HAART era by 70% of cancer cases, and median CD4 cell count nadir was 70 cells/µl (10-130). Time to development of anal cancer was shorter for cases treated during the pre-HAART era [adjusted hazard ratio (AHR) 3.04, 95% confidence interval (95% CI) 1.48-6.24, P = 0.002], with a CD4 cell count nadir less than 100 cells/µl (AHR 2.21, 95% CI 1.06-4.62, P = 0.035) and longer duration of CD4 cell count less than 100 cells/µl (AHR 1.33, 95% CI 1.11-1.58, P = 0.002). CONCLUSION: Results show that severe immunosuppression and starting therapy pre-HAART are associated with an increased risk of anal cancer. HIV-positive MSM initiating antiretrovirals during the HAART era (1996-2008) had a longer time to the development of anal cancer than those treated pre-HAART. Our results suggest that early use of HAART may delay progression to anal cancer.

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OBJECTIVE: To estimate the lost investment of domestically educated doctors migrating from sub-Saharan African countries to Australia, Canada, the United Kingdom, and the United States. DESIGN: Human capital cost analysis using publicly accessible data. SETTINGS: Sub-Saharan African countries. PARTICIPANTS: Nine sub-Saharan African countries with an HIV prevalence of 5% or greater or with more than one million people with HIV/AIDS and with at least one medical school (Ethiopia, Kenya, Malawi, Nigeria, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe), and data available on the number of doctors practising in destination countries. MAIN OUTCOME MEASURES: The financial cost of educating a doctor (through primary, secondary, and medical school), assuming that migration occurred after graduation, using current country specific interest rates for savings converted to US dollars; cost according to the number of source country doctors currently working in the destination countries; and savings to destination countries of receiving trained doctors. RESULTS: In the nine source countries the estimated government subsidised cost of a doctor's education ranged from $21,000 (£13,000; €15,000) in Uganda to $58,700 in South Africa. The overall estimated loss of returns from investment for all doctors currently working in the destination countries was $2.17bn (95% confidence interval 2.13bn to 2.21bn), with costs for each country ranging from $2.16m (1.55m to 2.78m) for Malawi to $1.41bn (1.38bn to 1.44bn) for South Africa. The ratio of the estimated compounded lost investment over gross domestic product showed that Zimbabwe and South Africa had the largest losses. The benefit to destination countries of recruiting trained doctors was largest for the United Kingdom ($2.7bn) and United States ($846m). CONCLUSIONS: Among sub-Saharan African countries most affected by HIV/AIDS, lost investment from the emigration of doctors is considerable. Destination countries should consider investing in measurable training for source countries and strengthening of their health systems.

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BACKGROUND: HIV/AIDS has orphaned 11.6 million children in sub-Saharan Africa. Expanded antiretroviral therapy (ART) use may reduce AIDS orphanhood by decreasing adult mortality and population-level HIV transmission. METHODS: We modeled two scenarios to measure the impact of adult ART use on the incidence of orphanhood in 10 sub-Saharan African countries, from 2009 to 2020. Demographic model data inputs were obtained from cohort studies, UNAIDS, UN Population Division, WHO and the US Census Bureau. RESULTS: Compared to current rates of ART uptake, universal ART access averted 4.37 million more AIDS orphans by year 2020, including 3.15 million maternal, 1.89 million paternal and 0.75 million double orphans. The number of AIDS orphans averted was highest in South Africa (901.71 thousand) and Nigeria (839.01 thousand), and lowest in Zimbabwe (86.96 thousand) and Côte d'Ivoire (109.12 thousand). CONCLUSION: Universal ART use may significantly reduce orphanhood in sub-Saharan Africa.

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BACKGROUND: In clinical and cohort research, mortality estimates are often derived from manual reports generated by physicians or electronic reports from vital event registries. We examined the rate of underreporting of deaths by manual methods as compared with electronic reports from a vital event registry. METHODS: The retrospective analyses included deaths among participants registered in an observational cohort who initiated highly-active antiretroviral therapy (HAART) between August 1, 1996 and June 30, 2006. Deaths were routinely reported manually by physicians and through annual electronic record linkages with a population-based vital event registry. Multivariate logistic regression was carried out to assess independent predictors of death reporting by manual methods. RESULTS: Of the 3,116 individuals included in the analyses, 622 (20.0%) died during follow-up. Manual reporting by physicians only identified 377 (60.6%), while electronic linkages captured 598 (96.1%) of all deaths. Multivariate analysis indicated that deaths among individuals with lower CD4 cell count, higher HIV plasma viral load, a history of injection drug use, and under the care of an HIV-experienced physicians were more likely to be reported manually. Furthermore, non-accidental deaths were more likely to be reported manually, and manual reporting of deaths increased over time. CONCLUSIONS: Relying only on manual reports to ascertain deaths significantly underestimates the total number of deaths in the population. This can generate important biases when evaluating the impact of therapeutic interventions in the populational setting.

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