How far will we need to go to reach HIV-infected people in rural South Africa?

Background: The South African Government has outlined detailed plans for antiretroviral (ART) rollout in KwaZulu-Natal Province, but has not created a plan to address treatment accessibility in rural areas in KwaZulu-Natal. Here, we calculate the distance that People Living With HIV/AIDS (PLWHA) in rural areas in KwaZulu-Natal would have to travel to receive ART. Specifically, we address the health policy question 'How far will we need to go to reach PLWHA in rural KwaZulu-Natal?'. Methods: We developed a model to quantify treatment accessibility in rural areas; the model incorporates heterogeneity in spatial location of HCFs and patient population. We defined treatment accessibility in terms of the number of PLWHA that have access to an HCF. We modeled the treatment-accessibility region (i.e. catchment area) around an HCF by using a two-dimensional function, and assumed that treatment accessibility decreases as distance from an HCF increases. Specifically, we used a distance-discounting measure of ART accessibility based upon a modified form of a two-dimensional gravity-type model. We calculated the effect on treatment accessibility of: (1) distance from an HCF, and (2) the number of HCFs. Results: In rural areas in KwaZulu-Natal even substantially increasing the size of a small catchment area (e.g. from 1 km to 20 km) around an HCF would have a negligible impact (~2%) on increasing treatment accessibility. The percentage of PLWHA who can receive ART in rural areas in this province could be as low as ~16%. Even if individuals were willing (and able) to travel 50 km to receive ART, only ~50% of those in need would be able to access treatment. Surprisingly, we show that increasing the number of available HCFs for ART distribution ~ threefold does not lead to a threefold increase in treatment accessibility in rural KwaZulu-Natal. Conclusion: Our results show that many PLWHA in rural KwaZulu-Natal are unlikely to have access to ART, and that the impact of an additional 37 HCFs on treatment accessibility in rural areas would be less substantial than might be expected. There is a great length to go before we will be able to reach many PLWHA in rural areas in South Africa, and specifically in KwaZulu-Natal.David P Wilson and Sally Blowe

Diagnosis and management of antiretroviral-therapy failure in resource-limited settings in sub-Saharan Africa: challenges and perspectives.

Despite the enormous progress made in scaling up antiretroviral therapy (ART) in sub-Saharan Africa, many challenges remain, not least of which are the identification and management of patients who have failed first-line therapy. Less than 3% of patients are receiving second-line treatment at present, whereas 15-25% of patients have detectable viral loads 12 months or more into treatment, of whom a substantial proportion might have virological failure. We discuss the reasons why virological ART failure is likely to be under-diagnosed in the routine health system, and address the current difficulties with standard recommended second-line ART regimens. The development of new diagnostic tools for ART failure, in particular a point-of-care HIV viral-load test, combined with simple and inexpensive second-line therapy, such as boosted protease-inhibitor monotherapy, could revolutionise the management of ART failure in resource-limited settings

Universal access: the benefits and challenges in bringing integrated HIV care to isolated and conflict affected populations in the Republic of Congo

The Pool region of the Republic of Congo is an isolated, conflict-affected area with under-resourced and poorly functioning health care services. Despite significant AIDS-related mortality and morbidity in this area, and a national level commitment to universal HIV care, HIV has been largely neglected. In 2005 Médecins Sans Frontières decided to introduce HIV care activities. However, in this setting of high basic health care needs, limited medical resources and competing medical priorities, a vertical HIV programme was not suitable. This paper describes the process of integrating HIV care and treatment into basic health services, the clinical outcomes of 222 patients started on antiretroviral treatment (ART), and the benefits to communities and health care systems. Key lessons learned include the use of multi-skilled human resources, the step-wise implementation of HIV activities, the initial engagement of an HIV experienced staff member, the use of simplified and adapted testing, clinical and monitoring protocols and drug regimens, the introduction of more complex monitoring tools to simplify clinical management decisions and intensive staff education regarding the benefits of HIV integration. This project in a rural and remote conflict-affected setting demonstrates that integrated HIV programs can save lives and play a key role in helping to achieve universal access to ART in Africa

Preliminary outcomes of a paediatric highly active antiretroviral therapy cohort from KwaZulu-Natal, South Africa

BACKGROUND: Few studies address the use of paediatric highly active antiretroviral therapy (HAART) in Africa. METHODS: We performed a retrospective cohort study to investigate preliminary outcomes of all children eligible for HAART at Sinikithemba HIV/AIDS clinic in KwaZulu-Natal, South Africa. Immunologic, virologic, clinical, mortality, primary caregiver, and psychosocial variables were collected and analyzed. RESULTS: From August 31, 2003 until October 31, 2005, 151 children initiated HAART. The median age at HAART initiation was 5.7 years (range 0.3–15.4). Median follow-up time of the cohort after HAART initiation was 8 months (IQR 3.5–13.5). The median change in CD4% from baseline (p < 0.001) was 10.2 (IQR 5.0–13.8) at 6 months (n = 90), and 16.2 (IQR 9.6–20.3) at 12 months (n = 59). Viral loads (VLs) were available for 100 children at 6 months of which 84% had HIV-1 RNA levels ≤ 50 copies/mL. At 12 months, 80.3% (n = 61) had undetectable VLs. Sixty-five out of 88 children (73.8%) reported a significant increase (p < 0.001) in weight after the first month. Eighty-nine percent of the cohort (n = 132) reported ≤ 2 missed doses during any given treatment month (> 95%adherence). Seventeen patients (11.3%) had a regimen change; two (1.3%) were due to antiretroviral toxicity. The Kaplan-Meier one year survival estimate was 90.9% (95%confidence interval (CI) 84.8–94.6). Thirteen children died during follow-up (8.6%), one changed service provider, and no children were lost to follow-up. All 13 deaths occurred in children with advanced HIV disease within 5 months of treatment initiation. In multivariate analysis of baseline variables against mortality using Cox proportional-hazards model, chronic gastroenteritis was associated with death [hazard ratio (HR), 12.34; 95%CI, 1.27–119.71) and an HIV-positive primary caregiver was found to be protective against mortality [HR, 0.12; 95%CI, 0.02–0.88). Age, orphanhood, baseline CD4%, and hemoglobin were not predicators of mortality in our cohort. Fifty-two percent of the cohort had at least one HIV-positive primary caregiver, and 38.4% had at least one primary caregiver also on HAART at Sinikithemba clinic. CONCLUSION: This report suggests that paediatric HAART can be effective despite the challenges of a resource-limited setting

Cost-Effectiveness of Preventing Loss to Follow-up in HIV Treatment Programs: A Côte d'Ivoire Appraisal

Based on data from West Africa, Elena Losina and colleagues predict that interventions to reduce dropout rates from HIV treatment programs (such as eliminating copayments) will be cost-effective

Women experience a better long-term immune recovery and a better survival on HAART in Lao People's Democratic Republic.

<p>Abstract</p> <p>Background</p> <p>In April 2003, Médecins Sans Frontières launched an HIV/AIDS programme to provide free HAART to HIV-infected patients in Laos. Although HIV prevalence is estimated as low in this country, it has been increasing in the last years. This work reports the first results of an observational cohort study and it aims to identify the principal determinants of the CD4 cells evolution and to assess mortality among patients on HAART.</p> <p>Methods</p> <p>We performed a retrospective database analysis on patients initiated on HAART between 2003 and 2009 (CD4<200cells/μL or WHO stage 4). We excluded from the analysis patients who were less than 16 years old and pregnant women. To explore the determinants of the CD4 reconstitution, a linear mixed model was adjusted. To identify typical trajectories of the CD4 cells, a latent trajectory analysis was carried out. Finally, a Cox proportional-hazards model was used to reveal predictors of mortality on HAART including appointment delay greater than 1 day.</p> <p>Results</p> <p>A total of 1365 patients entered the programme and 913 (66.9%) received an HAART with a median CD4 of 49 cells/μL [IQR 15–148]. High baseline CD4 cell count and female gender were associated with a higher CD4 level over time. In addition, this gender difference increased over time. Two typical latent CD4 trajectories were revealed showing that 31% of women against 22% of men followed a high CD4 trajectory. In the long-term, women were more likely to attend appointments without delay. Mortality reached 6.2% (95% CI 4.8-8.0%) at 4 months and 9.1% (95% CI 7.3-11.3%) at 1 year. Female gender (HR=0.17, 95% CI 0.07-0.44) and high CD4 trajectory (HR=0.19, 95% CI 0.08-0.47) were independently associated with a lower death rate.</p> <p>Conclusions</p> <p>Patients who initiated HAART were severely immunocompromised yielding to a high early mortality. In the long-term on HAART, women achieved a better CD4 cells reconstitution than men and were less likely to die. This study highlights important differences between men and women regarding response to HAART and medical care, and questions men’s compliance to treatment.</p

Gender distribution of adult patients on highly active antiretroviral therapy (HAART) in Southern Africa: a systematic review

Background: HIV and AIDS are significant and growing public health concerns in southern Africa. The majority of countries in the region have national adult HIV prevalence estimates exceeding 10 percent. The increasing availability of highly active antiretroviral therapy (HAART) has potential to mitigate the situation. There is however concern that women may experience more barriers in accessing treatment programs than men. Methods: A systematic review of the literature was carried out to describe the gender distribution of patients accessing highly active antiretroviral therapy (HAART) in Southern Africa. Data on number of patients on treatment, their mean or median age and gender were obtained and compared across studies and reports. Results: The median or mean age of patients in the studies ranged from 33 to 39 years. While female to male HIV infection prevalence ratios in the southern African countries ranged from 1.2:1 to 1.6:1, female to male ratios on HAART ranged from 0.8: 1 to 2.3: 1. The majority of the reports had female: male ratio in treatment exceeding 1.6. Overall, there were more females on HAART than there were males and this was not solely explained by the higher HIV prevalence among females compared to males. Conclusion: In most Southern African countries, proportionally more females are on HIV antiretroviral treatment than men, even when the higher HIV infection prevalence in females is accounted for. There is need to identify the factors that are facilitating women's accessibility to HIV treatment. As more patients access HAART in the region, it will be important to continue assessing the gender distribution of patients on HAART.Peer Reviewe

Progress and Research Needs of Plant Biomass Degradation by Basidiomycete Fungi

Peer reviewe

Genome-Wide Functional Profiling Reveals Genes Required for Tolerance to Benzene Metabolites in Yeast

Benzene is a ubiquitous environmental contaminant and is widely used in industry. Exposure to benzene causes a number of serious health problems, including blood disorders and leukemia. Benzene undergoes complex metabolism in humans, making mechanistic determination of benzene toxicity difficult. We used a functional genomics approach to identify the genes that modulate the cellular toxicity of three of the phenolic metabolites of benzene, hydroquinone (HQ), catechol (CAT) and 1,2,4-benzenetriol (BT), in the model eukaryote Saccharomyces cerevisiae. Benzene metabolites generate oxidative and cytoskeletal stress, and tolerance requires correct regulation of iron homeostasis and the vacuolar ATPase. We have identified a conserved bZIP transcription factor, Yap3p, as important for a HQ-specific response pathway, as well as two genes that encode putative NAD(P)H:quinone oxidoreductases, PST2 and YCP4. Many of the yeast genes identified have human orthologs that may modulate human benzene toxicity in a similar manner and could play a role in benzene exposure-related disease