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Summary Background Directly observed therapy has been recommended to improve adherence for patients with HIV infection who are on highly active antiretroviral therapy, but the benefit and cost-effectiveness of this approach has not been established conclusively. We did a systematic review and meta-analysis of randomised trials of directly observed versus self-administered antiretroviral treatment. Methods We did duplicate searches of databases (from inception to July 27, 2009), searchable websites of major HIV conferences (up to July, 2009), and lay publications and websites (March–July, 2009) to identify randomised trials assessing directly observed therapy to promote adherence to antiretroviral therapy in adults. Our primary outcome was virological suppression at study completion. We calculated relative risks (95% CIs), and pooled estimates using a random-effects method. Findings 12 studies met our inclusion criteria; four of these were done in groups that were judged to be at high risk of poor adherence (drug users and homeless people). Ten studies reported on the primary outcome (n=1862 participants); we calculated a pooled relative risk of 1·04 (95% CI 0·91–1·20, p=0·55), and noted moderate heterogeneity between the studies ( I 2 = 53·8%, 95% CI 0–75·7, p=0·0247) for directly observed versus self-administered treatment. Interpretation Directly observed antiretroviral therapy seems to offer no benefit over self-administered treatment, which calls into question the use of such an approach to support adherence in the general patient population. Funding None.

Shortages of health-care staff are endemic in sub-Saharan Africa (table). Overall, there is one physician for every 8000 people in the region. In the worst affected countries, such as Malawi, the physician-to-population ratio is just 0·02 for every 1000 (one per 50 000). There are also huge disparities between rural and urban areas: rural parts of South Africa have 14 times fewer doctors than the national average. These numbers are very different to those in developed countries: the UK, for example, has over 100 times more physicians per population than Malawi. Furthermore, almost one in ten doctors working in the UK are from Africa. The insufficiency of health staff to provide even basic services is one of the most pressing impediments to health-care delivery in resource-poor settings. The consequences are clearly shown by the inverse relation that exists between health-care worker density and mortality.

BACKGROUND: The recording of outcomes from large-scale, simplified HAART (highly active antiretroviral therapy) programmes in sub-Saharan Africa is critical. We aimed to assess the effectiveness of such a programme held by Médecins Sans Frontières (MSF) in the Chiradzulu district, Malawi. METHODS: We scaled up and simplified HAART in this programme since August, 2002. We analysed survival indicators, CD4 count evolution, virological response, and adherence to treatment. We included adults who all started HAART 6 months or more before the analysis. HIV-1 RNA plasma viral load and self-reported adherence were assessed on a subsample of patients, and antiretroviral resistance mutations were analysed in plasma with viral loads greater than 1000 copies per mL. Analysis was by intention to treat. FINDINGS: Of the 1308 patients who were eligible, 827 (64%) were female, the median age was 34.9 years (IQR 29.9-41.0), and 1023 (78%) received d4T/3TC/NVP (stavudine, lamivudine, and nevirapine) as a fixed-dose combination. At baseline, 1266 individuals (97%) were HAART-naive, 357 (27%) were at WHO stage IV, 311 (33%) had a body-mass index of less than 18.5 kg/m2, and 208 (21%) had a CD4 count lower than 50 cells per muL. At follow-up (median 8.3 months, IQR 5.5-13.1), 967 (74%) were still on HAART, 243 (19%) had died, 91 (7%) were lost to follow-up, and seven (0.5%) discontinued treatment. Low body-mass index, WHO stage IV, male sex, and baseline CD4 count lower than 50 cells per muL were independent determinants of death in the first 6 months. At 12 months, the probability of individuals still in care was 0.76 (95% CI 0.73-0.78) and the median CD4 gain was 165 (IQR 67-259) cells per muL. In the cross-sectional survey (n=398), 334 (84%) had a viral load of less than 400 copies per mL. Of several indicators measuring adherence, self-reported poor adherence (

This critique talks about the evidence that indicates we are doing a poor job of providing men with the medical assistance they need in the fight against HIV/AIDS. Addressing these issues effectively means moving beyond laying blame and starting to develop interventions to encourage uptake of prevention testing and treatment for men—for everyone’s sake.

On June 1 the G8 leaders will gather in Evian France where access to medicines is again at the top of the their agenda. (The G8 countries are: Canada France Germany Italy Japan Russia UK USA.) That same day according to far too familiar disease statistics 19 000 people will die from AIDS tuberculosis malaria African trypanosomiasis and visceral leishmaniasis. These five diseases represent the failure of the pharmaceutical industry to deliver medicines for the developing world and the non-response from governments to this market failure. The G8 has an enormous political and financial potential to curb this death toll. However while several important commitments have been made to improve access to medicines in the past 3 years few have been achieved and many have been forgotten. (excerpt)

This letter comments on Keertan Dheda and colleagues report of extremely poor treatment outcomes for patients with extensively drug-resistant (XDR) tuberculosis in South Africa. It states that an important strategy to prevent XDR tuberculosis is to ensure adequate treatment for multidrug-resistant (MDR) tuberculosis.

Sir—Carmen Perez-Casas and colleagues (Dec 16, p 2102) argue that many drugs, exemplified by fluconazole, are not accessible to patients in less-developed countries essentially because of their high cost. Although this issue is important and the international pricing structures used by multinational pharmaceutical companies contribute, issues of affordability, health-system resources, and priority setting must be taken into account. Even if drugs are made available at low cost to less-developed countries, they might not be affordable to them. According to the information given by Perez-Casas and colleagues and the lowest price in their list, a 12-week course of fluconazole plus 6 months of secondary prophylaxis would cost about US$100 per patient, almost 20% of the annual gross domestic product per person in Zimbabwe. This calculation is rough, but the message holds: where there are large numbers of patients, long treatment periods, or both, cut-price drugs still require a large capital outlay. In terms of health-system resources, successful treatment of cryptococcal meningitis, as well as fluconazole treatment, requires accurate and timely diagnostic tests and facilities; treatment with amphotericin B, flucytosine, or both for the acute stages; monitoring and management of adverse drug reactions; acute-care facilities for control of raised intracranial pressure, which is known to lessen the risk of mortality and morbidity; HIV testing and counselling for surviving patients; and adequate drug-distribution networks in urban and rural areas. Most of these resources are, however, limited or prohibitively expensive in many developing countries. Cryptococcal meningitis generally presents at an advanced stage of immunosuppression and has a poor prognosis with only supportive care (22% survival beyond 30 days). Improvement in survival has been seen only in patients who also receive highly active antiretroviral therapy. Marginal increases in survival in this patient group are not cost effective when the money could be used in primary prevention strategies for HIV infection and AIDS or for support measures such as prophylaxis or treatment of tuberculosis. Lobby groups in more-developed countries tend to start well-meaning 1 Ogutu BR, Smoak BL, Nduati RW, Mbori-Ngacha DA, Mwathe F, Shanks GD. The efficacy of pyrimethaminesulfadoxine (Fansidar) in the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children. Trans R Soc Trop Med Hyg 2000; 94: 83–84. 2 Hogh B, Gamage-Mendis A, Butcher GA, et al. The differing impact of chloroquine and pyrimethamine/sulfadoxine upon the infectivity of malaria species to the mosquito vector. Am J Trop Med Hyg 1998; 58: 176–82. 3 von Seidlein L, Milligan P, Pinder M, et al. Efficacy of artesunate plus pyrimethaminesulphadoxine for uncomplicated malaria in Gambian children: a double-blind, randomised, controlled trial. Lancet 2000; 355: 352–57. 4 Luxemburger C, Nosten F, Raimond SD, Chongsuphajaisiddhi T, White NJ. Oral artesunate in the treatment of uncomplicated hyperparasitemic falciparum malaria. Am J Trop Med Hyg 1995; 53: 522–25. 5 Nosten F, van Vugt M, Price R, et al. Effects of artesunate-mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand: a prospective study. Lancet 2000; 356: 297–302.

There is strong evidence that Marburg hemorrhagic fever which presents with symptoms similar to Ebola was the cause of a recent epidemic in the Democratic Republic of the Congo that left 60 people dead. As with Ebola there is no specific treatment for Marburg which has also recently been linked with "Durba syndrome." Because only one of six cases from the current epidemic tested positive for Marburg further epidemiological studies are being conducted by an international team. Most of the cases have occurred among men working illegally in abandoned unhygienic mines near Durba. These mines are littered with excreta from rats and bats and may offer researchers the first opportunity to study Marburgs transmission routes reservoirs and vectors. Medecins Sans Frontieres has created an isolation unit for patient care is advising local health authorities and the general public and is distributing barrier nursing materials to health workers.