Abstract HIV-2 group A is predominant in different parts of the world, especially Africa, Portugal, Spain, France, the United Kingdom, the United States, Korea, and India. Among the Asian countries, India accounts for about 95% of all HIV-2 infections. The prevalence of HIV-2 has been reported from various states of India such as Maharashtra, Goa, Tamil Nadu, West Bengal, and Uttar Pradesh. In the present study, we analyzed transmembrane region (gp36) sequences of 10 HIV-2 group A Indian strains, isolated from Indian HIV-2-seropositive individuals. HIV Blast analysis for the 1.0-Kb region of the gp36 transmembrane region has shown that all these sequences belong to HIV-2 group A. Phylogenetic analysis indicated that the sequences cluster with HIV-2 group A sequences of Cameroon and Senegal. The epitope found at position 645-656 (YELQKLNSWDVF), previously reported as a broadly neutralizing determinant, was very well conserved in all 10 study sequences. The percentage similarity between Indian and South African HIV-2 group A gp36 sequences was 90% (range 86-100, SD 2.8) and with other nonsubtype A clades was 84% (range 77-100, SD 6.06) indicating overall less variability among the reported HIV-2 sequences. Similarly, the consensus amino acid sequences of the envelope transmembrane region of HIV-1 (gp41) and HIV-2 (gp36) is quite synonymous, indicating 87% similarity; however, limited information is available about the gp36 transmembrane region of the prevalent HIV 2 group A Indian strain. The rate of synonymous substitutions reported in the gp105 region was significantly higher, suggesting lower virulence of HIV-2, which does translate into a lower rate of evolution, while the dN/dS ratio for the gp36 transmembrane region was less than one, indicating its conservation and significance (p<0.05) in structural and functional constraints.

BACKGROUND: Universal testing and treatment holds promise for reducing the burden of human immunodeficiency virus (HIV) in sub-Saharan Africa, but linkage from testing to treatment sites and retention in care are inadequate.

METHODS: We developed a simulation of the HIV epidemic and HIV disease progression in South Africa to compare the outcomes of the present HIV treatment campaign (status quo) with 4 HIV testing and treating strategies that increase access to antiretroviral therapy: (1) universal testing and treatment without changes in linkage to care and loss to follow-up; (2) universal testing and treatment with improved linkage to care; (3) universal testing and treatment with reduced loss to follow-up; and (4) comprehensive HIV care with universal testing and treatment, improved linkage to care, and reduced loss to follow-up. The main outcome measures were survival benefits, new HIV infections, and HIV prevalence. 

RESULTS: Compared with the status quo strategy, universal testing and treatment (1) was associated with a mean (95% uncertainty bounds) life expectancy gain of 12.0 months (11.3-12.2 months), and 35.3% (32.7%-37.5%) fewer HIV infections over a 10-year time horizon. Improved linkage to care (2), prevention of loss to follow-up (3), and comprehensive HIV care (4) provided substantial additional benefits: life expectancy gains compared with the status quo strategy were 16.1, 18.6, and 22.2 months, and new infections were 55.5%, 51.4%, and 73.2% lower, respectively. In sensitivity analysis, comprehensive HIV care reduced new infections by 69.7% to 76.7% under a broad set of assumptions.

CONCLUSIONS: Universal testing and treatment with current levels of linkage to care and loss to follow-up could substantially reduce the HIV death toll and new HIV infections. However, increasing linkage to care and preventing loss to follow-up provides nearly twice the benefits of universal testing and treatment alone.

Abstract 

Background

Adherence is crucial for public health program effectiveness, though the benefits of increasing adherence must ultimately be weighed against the associated costs. We sought to determine the relationship between investment in community health worker (CHW) home visits and increased attendance at cervical cancer screening appointments in Cape Town, South Africa.

Methodology/Principal Findings

We conducted an observational study of 5,258 CHW home visits made in 2003–4 as part of a community-based screening program. We estimated the functional relationship between spending on these visits and increased appointment attendance (adherence). Increased adherence was noted after each subsequent CHW visit. The costs of making the CHW visits was based on resource use including both personnel time and vehicle-related expenses valued in 2004 Rand. The CHW program cost R194,018, with 1,576 additional appointments attended. Adherence increased from 74% to 90%; 55% to 87%; 48% to 77%; and 56% to 80% for 6-, 12-, 24-, and 36-month appointments. Average per-woman costs increased by R14–R47. The majority of this increase occurred with the first 2 CHW visits (90%, 83%, 74%, and 77%; additional cost: R12–R26).

Conclusions/Significance

We found that study data can be used for program planning, identifying spending levels that achieve adherence targets given budgetary constraints. The results, derived from a single disease program, are retrospective, and should be prospectively replicated.

Background: Since 2003, the President's Emergency Plan for AIDS Relief (PEPFAR) has been the most ambitious initiative to address the global HIV epidemic. However, the effect of PEPFAR on HIV-related outcomes is unknown.

Objective: To assess the effect of PEPFAR on HIV-related deaths, the number of people living with HIV, and HIV prevalence in sub-Saharan Africa.

Design: Comparison of trends before and after the initiation of PEPFAR's activities.

Setting: 12 African focus countries and 29 control countries with a generalized HIV epidemic from 1997 to 2007 (451 country-year observations).

Intervention: A 5-year, $15 billion program for HIV treatment, prevention, and care that started in late 2003.

Measurements: HIV-related deaths, the number of people living with HIV, and HIV prevalence.

Results: Between 2004 and 2007, the difference in the annual change in the number of HIV-related deaths was 10.5% lower in the focus countries than the control countries (P = 0.001). The difference in trends between the groups before 2003 was not significant. The annual growth in the number of people living with HIV was 3.7% slower in the focus countries than the control countries from 1997 to 2002 (P = 0.05), but during PEPFAR's activities, the difference was no longer significant. The difference in the change in HIV prevalence did not significantly differ throughout the study period. These estimates were stable after sensitivity analysis.

Limitation: The selection of the focus countries was not random, which limits the generalizability of the results.

Conclusion: After 4 years of PEPFAR activity, HIV-related deaths decreased in sub-Saharan African focus countries compared with control countries, but trends in adult prevalence did not differ. Assessment of epidemiologic effectiveness should be part of PEPFAR's evaluation programs.

Primary Funding Source: Agency for Healthcare Research and Quality.

Background Current World Health Organization (WHO) guidelines for treatment of HIV in resource-limited settings call for 2 antiretroviral regimens. The effectiveness and cost-effectiveness of increasing the number of antiretroviral regimens is unknown.

Methods Using a simulation model, we compared the survival and costs of current WHO regimens with two 3-regimen strategies: an initial regimen of 3 nucleoside reverse transcriptase inhibitors followed by the WHO regimens and the WHO regimens followed by a regimen with a second-generation boosted protease inhibitor (2bPI). We evaluated monitoring with CD4 counts only and with both CD4 counts and viral load. We used cost and effectiveness data from Cape Town and tested all assumptions in sensitivity analyses.

Results Over the lifetime of the cohort, 25.6% of individuals failed both WHO regimens by virologic criteria. However, when patients were monitored using CD4 counts alone, only 6.5% were prescribed additional highly active antiretroviral therapy due to missed and delayed detection of failure. The life expectancy gain for individuals who took a 2bPI was 6.7-8.9 months, depending on the monitoring strategy. When CD4 alone was available, adding a regimen with a 2bPI was associated with an incremental cost-effectiveness ratio of $2581 per year of life gained, and when viral load was available, the ratio was $6519 per year of life gained. Strategies with triple-nucleoside reverse transcriptase inhibitor regimens in initial therapy were dominated. Results were sensitive to the price of 2bPIs.

Conclusions About 1 in 4 individuals who start highly active antiretroviral therapy in sub-Saharan Africa will fail currently recommended regimens. At current prices, adding a regimen with a 2bPI is cost effective for South Africa and other middle-income countries by WHO standards.

Introduction: Little is known about the natural history of malignant solitary pulmonary nodules (SPN). Experts' beliefs may help fill these knowledge gaps and explain variation in clinical practices.

Methods: Using a modified Delphi process, we surveyed a group of lung cancer experts about tumor growth, disease progression, and prognosis in patients with malignant SPN. After completing the first survey, experts were given the opportunity during a second survey to revise their responses in light of their peers' beliefs.

Results: The response rate was 100% (14 of 14) for both surveys. There was consensus that disease progression depends on the tumor growth rate, that survival for patients with untreated lung cancer is approximated by a declining exponential function, and that treatment is delayed by approximately 1 tumor volume doubling time (TVDT) in patients who undergo a period of watchful waiting. Just over half of experts (8 of 14) agreed that lung cancer progresses in three steps (from local to regional to distant disease), whereas 43% (6 of 14) preferred a 2-step model (from local to systemic disease). Likewise, 64% of experts (9 of 14) believed that malignant nodules grow exponentially, whereas 36% (5 of 14) believed that growth is slower than exponential. Experts' estimates of the risk of disease progression during a period of observation lasting 1 TVDT varied from 1 to 50%. Estimates of 5-year survival for patients in whom diagnosis and treatment were delayed by 1 TVDT varied between 40% and 80%.

Conclusions: There is substantial variability in experts' beliefs about the natural history of untreated, malignant SPN. Different beliefs may be partly responsible for variation in management practices.

Methods: Test characteristics for the noninvasive staging studies were updated from the first iteration of the lung cancer guidelines using systematic searches of the MEDLINE, HealthStar, and Cochrane Library databases up to May 2006, including selected metaanalyses, practice guidelines, and reviews. Study designs and results are summarized in evidence tables.

Results: The pooled sensitivity and specificity of CT scanning for identifying mediastinal lymph node metastasis were 51% (95% confidence interval [CI], 47 to 54%) and 85% (95% CI, 84 to 88%), respectively, confirming that CT scanning has limited ability either to rule in or exclude mediastinal metastasis. For PET scanning, the pooled estimates of sensitivity and specificity for identifying mediastinal metastasis were 74% (95% CI, 69 to 79%) and 85% (95% CI, 82 to 88%), respectively. These findings demonstrate that PET scanning is more accurate than CT scanning. If the clinical evaluation in search of metastatic disease is negative, the likelihood of finding metastasis is low.

Conclusions: CT scanning of the chest is useful in providing anatomic detail, but the accuracy of chest CT scanning in differentiating benign from malignant lymph nodes in the mediastinum is poor. PET scanning has much better sensitivity and specificity than chest CT scanning for staging lung cancer in the mediastinum, and distant metastatic disease can be detected by PET scanning. With either test, abnormal findings must be confirmed by tissue biopsy to ensure accurate staging.