Population uptake and effectiveness of test-and-treat antiretroviral therapy guidelines for preventing the global spread of HIV: an ecological cross-national analysis.

OBJECTIVES: Although the benefits of adopting test-and-treat antiretroviral therapy (ART) guidelines that recommend initiation of ART regardless of CD4 cell counts have been demonstrated at the individual level, there is uncertainty about how this translates to the population level. Here, we explored whether adopting ART guidelines recommending earlier treatment initiation improves population ART access and viral suppression and reduces overall disease transmission. METHODS: Data on ART initiation guidelines and treatment coverage, viral suppression, and HIV incidence from 37 European and Central Asian countries were collected from the European Centre for Disease Prevention and Control and the Global HIV Policy Watch and HIV 90-90-90 Watch databases. We used multivariate linear regression models to quantify the association of ART initiation guidelines with population ART access, viral suppression, and HIV incidence, adjusting for potential confounding factors. RESULTS: Test-and-treat policies were associated with 15.2 percentage points (pp) [95% confidence interval (CI) 0.8-29.6 pp; P = 0.039] greater treatment coverage (proportion of HIV-positive people on ART) compared with countries with ART initiation at CD4 cell counts ≤ 350 cells/µL. The presence of test-and-treat policies was associated with 15.8 pp (95% CI 2.4-29.1 pp; P = 0.023) higher viral suppression rates (people on ART virally suppressed) compared with countries with treatment initiation at CD4 counts ≤ 350 cells/µL. ART initiation at CD4 counts ≤ 500 cells/µL did not significantly improve ART coverage compared to initiation at CD4 counts ≤ 350 cells/µL but achieved similar degrees of viral suppression as test-and-treat. CONCLUSIONS: Test-and-treat was found to be associated with substantial improvements in population-level access to ART and viral suppression, further strengthening evidence that rapid initiation of treatment will help curb the spread of HIV.

Building the Case for Localized Approaches to HIV: Structural Conditions and Health System Capacity to Address the HIV/AIDS Epidemic in Six US Cities.

Since the discovery of the secondary preventive benefits of antiretroviral therapy, national and international governing bodies have called for countries to reach 90% diagnosis, ART engagement and viral suppression among people living with HIV/AIDS. The US HIV epidemic is dispersed primarily across large urban centers, each with different underlying epidemiological and structural features. We selected six US cities, including Atlanta, Baltimore, Los Angeles, Miami, New York, and Seattle, with the objective of demonstrating the breadth of epidemiological and structural differences affecting the HIV/AIDS response across the US. We synthesized current and publicly-available surveillance, legal statutes, entitlement and discretionary funding, and service location data for each city. The vast differences we observed in each domain reinforce disparities in access to HIV treatment and prevention, and necessitate targeted, localized strategies to optimize the limited resources available for each city's HIV/AIDS response.

Surgery as an Adjunctive Treatment for Multidrug-Resistant Tuberculosis: An Individual Patient Data Metaanalysis.

BACKGROUND: Medical treatment for multidrug-resistant (MDR)-tuberculosis is complex, toxic, and associated with poor outcomes. Surgical lung resection may be used as an adjunct to medical therapy, with the intent of reducing bacterial burden and improving cure rates. We conducted an individual patient data metaanalysis to evaluate the effectiveness of surgery as adjunctive therapy for MDR-tuberculosis. METHODS: Individual patient data, was obtained from the authors of 26 cohort studies, identified from 3 systematic reviews of MDR-tuberculosis treatment. Data included the clinical characteristics and medical and surgical therapy of each patient. Primary analyses compared treatment success (cure and completion) to a combined outcome of failure, relapse, or death. The effects of all forms of resection surgery, pneumonectomy, and partial lung resection were evaluated. RESULTS: A total of 4238 patients from 18 surgical studies and 2193 patients from 8 nonsurgical studies were included. Pulmonary resection surgery was performed on 478 patients. Partial lung resection surgery was associated with improved treatment success (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.5-5.9; I(2)R, 11.8%), but pneumonectomy was not (aOR, 1.1; 95% CI, .6-2.3; I(2)R, 13.2%). Treatment success was more likely when surgery was performed after culture conversion than before conversion (aOR, 2.6; 95% CI, 0.9-7.1; I(2)R, 0.2%). CONCLUSIONS: Partial lung resection, but not pneumonectomy, was associated with improved treatment success among patients with MDR-tuberculosis. Although improved outcomes may reflect patient selection, partial lung resection surgery after culture conversion may improve treatment outcomes in patients who receive optimal medical therapy.

Expanding human immunodeficiency virus testing and counseling to reach tuberculosis clients' partners and families.

Recent years have shown important increases in human immunodeficiency virus (HIV) testing and counseling (HTC), diagnosis, and coverage of antiretroviral therapy (ART) among HIV-infected tuberculosis (TB) patients. Expansion of HTC for partners and families are critical next steps to increase earlier HIV diagnoses and access to ART, and to achieve international goals for reduced TB and HIV-related morbidity, mortality, transmission and costs. TB and HIV programs should develop and evaluate feasible and effective strategies to increase access to HTC among the partners and families of TB patients, and ensure that newly diagnosed people living with HIV and HIV-infected TB patients who complete anti-tuberculosis treatment are successfully linked to ongoing HIV clinical care.

Review of policy and status of implementation of collaborative HIV-TB activities in 23 high-burden countries.

Issuance of national policy guidance is a critical step to ensure quality HIV-TB (human immunodeficiency virus-tuberculosis) coordination and programme implementation. From the database of the Joint United Nations Programme on HIV/AIDS (UNAIDS), we reviewed 62 national HIV and TB guidelines from 23 high-burden countries for recommendations on HIV testing for TB patients, criteria for initiating antiretroviral therapy (ART) and the Three I's for HIV/TB (isoniazid preventive treatment [IPT], intensified TB case finding and TB infection control). We used UNAIDS country-level programme data to determine the status of implementation of existing guidance. Of the 23 countries representing 89% of the global HIV-TB burden, Brazil recommends ART irrespective of CD4 count for all people living with HIV, and four (17%) countries recommend ART at the World Health Organization (WHO) 2013 guidelines level of CD4 count â©¿500 cells/mm(3) for asymptomatic persons. Nineteen (83%) countries are consistent with WHO 2013 guidelines and recommend ART for HIV-positive TB patients irrespective of CD4 count. IPT is recommended by 16 (70%) countries, representing 67% of the HIV-TB burden; 12 recommend symptom-based screening alone for IPT initiation. Guidelines from 15 (65%) countries with 79% of the world's HIV-TB burden include recommendations on HIV testing and counselling for TB patients. Although uptake of ART, HIV testing for TB patients, TB screening for people living with HIV and IPT have increased significantly, progress is still limited in many countries. There is considerable variance in the timing and content of national policies compared with WHO guidelines. Missed opportunities to implement new scientific evidence and delayed adaptation of existing WHO guidance remains a key challenge for many countries.

Cost-effectiveness of the Three I's for HIV/TB and ART to prevent TB among people living with HIV.

OBJECTIVE: To evaluate the cost-effectiveness of the Three I's for HIV/TB (human immunodeficiency virus/tuberculosis): antiretroviral therapy (ART), intensified TB case finding (ICF), isoniazid preventive treatment (IPT), and TB infection control (IC). METHODS: Using a 3-year decision-analytic model, we estimated the cost-effectiveness of a base scenario (55% ART coverage at CD4 count â©¿350 cells/mm(3)) and 19 strategies that included one or more of the following: 1) 90% ART coverage, 2) IC and 3) ICF using four-symptom screening and 6- or 36-month IPT. The TB diagnostic algorithm included 1) sputum smear microscopy with chest X-ray, and 2) Xpert® MTB/RIF. RESULTS: In resource-constrained settings with a high burden of HIV and TB, the most cost-effective strategies under both diagnostic algorithms included 1) 55% ART coverage and IC, 2) 55% ART coverage, IC and 36-month IPT, and 3) expanded ART at 90% coverage with IC and 36-month IPT. The latter averted more TB cases than other scenarios with increased ART coverage, IC, 6-month IPT and/or IPT for tuberculin skin test positive individuals. The cost-effectiveness results did not change significantly under the sensitivity analyses. CONCLUSION: Expanded ART to 90% coverage, IC and a 36-month IPT strategy averted most TB cases and is among the cost-effective strategies.

How can mathematical models advance tuberculosis control in high HIV prevalence settings?

Existing approaches to tuberculosis (TB) control have been no more than partially successful in areas with high human immunodeficiency virus (HIV) prevalence. In the context of increasingly constrained resources, mathematical modelling can augment understanding and support policy for implementing those strategies that are most likely to bring public health and economic benefits. In this paper, we present an overview of past and recent contributions of TB modelling in this key area, and suggest a way forward through a modelling research agenda that supports a more effective response to the TB-HIV epidemic, based on expert discussions at a meeting convened by the TB Modelling and Analysis Consortium. The research agenda identified high-priority areas for future modelling efforts, including 1) the difficult diagnosis and high mortality of TB-HIV; 2) the high risk of disease progression; 3) TB health systems in high HIV prevalence settings; 4) uncertainty in the natural progression of TB-HIV; and 5) combined interventions for TB-HIV. Efficient and rapid progress towards completion of this modelling agenda will require co-ordination between the modelling community and key stakeholders, including advocates, health policy makers, donors and national or regional finance officials. A continuing dialogue will ensure that new results are effectively communicated and new policy-relevant questions are addressed swiftly.

From caution to urgency: the evolution of HIV testing and counselling in Africa.

OBJECTIVE: To describe recent changes in policy on provider-initiated testing and counselling (PITC) for human immunodeficiency virus (HIV) infection in African countries and to investigate patients' experiences of and views about PITC. METHODS: A review of the published literature and of national HIV testing policies, strategic frameworks, plans and other relevant documents was carried out. FINDINGS: Of the African countries reviewed, 42 (79.2%) had adopted a PITC policy. Of the 42, all recommended PITC for the prevention of mother-to-child HIV transmission, 66.7% recommended it for tuberculosis clinics and patients, and 45.2% for sexually transmitted infection clinics. Moreover, 43.6% adopted PITC in 2005 or 2006. The literature search identified 11 studies on patients' experiences of and views about PITC in clinical settings in Africa. The clear majority regarded PITC as acceptable. However, women in antenatal clinics were not always aware that they had the right to decline an HIV test. CONCLUSION: Policy and practice on HIV testing and counselling in Africa has shifted from a cautious approach that emphasizes confidentiality to greater acceptance of the routine offer of HIV testing. The introduction of PITC in clinical settings has contributed to increased HIV testing in several of these settings. Most patients regard PITC as acceptable. However, other approaches are needed to reach people who do not consult health-care services.

Community-based multi-disease prevention campaigns for controlling human immunodeficiency virus-associated tuberculosis.

Human immunodeficiency virus (HIV) infection increases the risk of tuberculosis (TB) 21-34 fold, and has fuelled the resurgence of TB in sub-Saharan Africa. The World Health Organization (WHO) recommends the Three I's for HIV/TB (infection control, intensified case finding [ICF] and isoniazid preventive therapy) and earlier initiation of antiretroviral therapy for preventing TB in persons with HIV. Current service delivery frameworks do not identify people early enough to maximally harness the preventive benefits of these interventions. Community-based campaigns were essential components of global efforts to control major public health threats such as polio, measles, guinea worm disease and smallpox. They were also successful in helping to control TB in resource-rich settings. There have been recent community-based efforts to identify persons who have TB and/or HIV. Multi-disease community-based frameworks have been rare. Based on findings from a WHO meta-analysis and a Cochrane review, integrating ICF into the recent multi-disease prevention campaign in Kenya may have had implications in controlling TB. Community-based multi-disease prevention campaigns represent a potentially powerful strategy to deliver prevention interventions, identify people with HIV and/or TB, and link those eligible to care and treatment.

Protease inhibitor-containing antiretroviral treatment and tuberculosis: can rifabutin fill the breach?

OBJECTIVE: To assess how to best manage co-administration of rifabutin (RFB) and human immunodeficiency virus 1 (HIV-1) protease inhibitor (PI) containing antiretroviral treatment (ART). Recommended for initial anti-tuberculosis treatment, rifampicin (RMP) lowers PI concentrations below therapeutic levels, posing significant challenges for ART. As RFB has little effect on PI concentrations, it could be an alternative to RMP. METHODS: A review of the scientific literature on the safety and efficacy of RFB for adult tuberculosis (TB) treatment was conducted, focusing on ART-TB co-therapy. A cost comparison was performed between treatment regimens, and estimates of the burden of TB disease in patients on ART were used to model RFB demand in low- and middle-income countries (LMICs). RESULTS: Eleven clinical studies were identified, comprising 1543 TB patients treated with RFB; 980 (64%) were living with HIV. RFB was as safe and effective as RMP, including in 313 patients receiving co-administered ART (unboosted PIs included indinavir, nelfinavir or saquinavir; a minority received ritonavir [RTV] boosted amprenavir or saquinavir). The total cost for 6 months of all HIV and TB treatment containing RTV-boosted lopinavir (LPV) and RFB is US$410, compared to US$455 if RMP is used with LPV super-boosted with RTV. Our model suggests that demand for RFB in LMICs could be between 10,000 and 18,000 courses by 2012. CONCLUSION: RFB is effective and safe in combination with the PIs studied, cost-saving for co-therapy with currently recommended boosted PIs, and may have a pivotal role in the roll-out of ART. Further research into a daily dose of RFB to simplify dosing regimens and developing fixed-dose combinations can enhance the public sector roll-out of ART.

Potential utility of empirical tuberculosis treatment for HIV-infected patients with advanced immunodeficiency in high TB-HIV burden settings.

The human immunodeficiency virus (HIV) and HIV-associated tuberculosis (TB-HIV) epidemics remain uncontrolled in many resource-limited regions, especially in sub-Saharan Africa. The scale of these epidemics requires the consideration of innovative bold interventions and 'out-of-the-box' thinking. To this end, a symposium entitled 'Controversies in HIV' was held at the 40th Union World Conference on Lung Health in Cancun, Mexico, in December 2009. The first topic debated, entitled 'Annual HIV testing and immediate start of antiretroviral therapy for all HIV-infected persons', received much attention at international conferences and in the literature in 2009. The second topic forms the subject of this article. The rationale for the use of empirical TB treatment is premised on the hypothesis that in settings worst affected by the TB-HIV epidemic, a subset of HIV-infected patients have such a high risk of undiagnosed TB and of associated mortality that their prognosis may be improved by immediate initiation of empirical TB treatment used in conjunction with antiretroviral therapy. In addition to morbidity and mortality reduction, additional benefits may include prevention of nosocomial TB transmission and TB preventive effect. Potential adverse consequences, however, may include failure to consider other non-TB diagnoses, drug co-toxicity, compromised treatment adherence, and logistical and resource challenges. There may also be general reluctance among national TB programmes to endorse such a strategy. Following fruitful debate, the conclusion that this strategy should be carefully evaluated in randomised controlled trials was strongly supported. This paper provides an in-depth consideration of this proposed intervention.

Cross-referral between voluntary HIV counselling and testing centres and TB services, Maharashtra, India, 2003-2004.

SETTING: India has a high tuberculosis (TB) burden, with 1.8 million new cases per year. Although an estimated 2.5 million people are infected with human immunodeficiency virus (HIV), the national HIV prevalence is <1%. India's size and diverse TB-HIV epidemiology pose a major challenge to the implementation of links between TB and HIV/AIDS programme services. METHODS: A pilot cross-referral initiative was instituted between voluntary counselling and testing centres (VCT) and the diagnostic and treatment facilities of the Revised National TB Control Programme (RNTCP) in four districts of Maharashtra, India. OBJECTIVE: To detect TB disease among VCT patients and selectively screen TB patients for referral to VCT services. RESULTS: Between July 2003 and June 2004, 336 (3%) of 9921 VCT patients were identified as TB suspects and 83 (29%) were diagnosed with TB disease. Of the 765 selectively referred TB cases, 181 (24%) were found to be HIV-positive, representing 11% of the newly detected persons living with HIV in the four districts. CONCLUSIONS: The pilot cross-referral initiative yielded significant numbers of active TB cases among VCT patients and HIV-positive persons among TB patients. Collaborative activities between HIV/AIDS and TB programmes need to be rapidly scaled up to other states in India.

Cost and cost-effectiveness of a public-private mix project in Kannur District, Kerala, India, 2001-2002.

BACKGROUND: Little is known yet about the cost-effectiveness of public-private mix (PPM) collaborations for the delivery of tuberculosis (TB) diagnostic and treatment services. DESIGN: We evaluated the cost and cost-effectiveness of a PPM project targeting private laboratories in Kannur district, India, from the perspective of the Revised National TB Control Programme (RNTCP). We estimated the cost per provider recruited and retained, the cost per additional patient notified under various effectiveness scenarios and the cost per additional patient successfully treated. Intervention cost data were abstracted from RNTCP records. Treatment costs were estimated based on RNTCP case management protocols. RESULTS: The annual total estimated cost of the project was US$8712-$11611. The cost per private provider recruited varied between US$22 and US$54. The cost per additional pulmonary TB patient privately diagnosed was US$14-$18. In the most conservative scenario, the cost per additional patient notified was US$29-$36. The cost per new acid-fast bacilli-positive patient successfully treated was US$47-$51. Higher notification rates would improve cost-effectiveness. CONCLUSIONS: Comparisons with public sector diagnostic costs are required to determine if this intervention remains economically attractive to the public health care system at different activity levels and to determine the supplemental resources needed if scale-up is pursued.

Tuberculosis case finding and preventive therapy in an HIV voluntary counseling and testing center in Uganda.

SETTING: A large, urban human immunodeficiency virus (HIV) voluntary counseling and testing (VCT) center in Kampala, Uganda. OBJECTIVE: Tuberculosis (TB) is a leading cause of morbidity and mortality in persons with HIV infection in sub-Saharan Africa. Intensified TB case finding and use of isoniazid preventive therapy (IPT) for latent infection reduces the burden of TB, but few programs have been implemented due to concerns about feasibility. DESIGN: Retrospective evaluation of a TB case finding and IPT program. RESULTS: Over a 25-month period, 6305 patients newly diagnosed with HIV infection underwent evaluation: 293 (5%) had TB disease; 1955 (37%) patients were not eligible for preventive therapy because they lived > 20 km away, had advanced HIV disease, or had previously had TB. Of 3366 who had a tuberculin skin test (TST) placed, 2548 (76%) had the TST read; 894 (35%) of these were positive. Of 506 persons who started treatment, 335 (66%) completed it. CONCLUSION: This unique program was feasible, detected a high proportion of undiagnosed TB, and successfully treated persons with latent infection. Expanding access to HIV VCT as well as collaboration between HIV/ AIDS and TB programs can increase the proportion of HIV-infected persons who can benefit from these programs.

Improved tuberculosis case detection through public-private partnership and laboratory-based surveillance, Kannur District, Kerala, India, 2001-2002.

BACKGROUND: Efforts to intensify global tuberculosis (TB) control are limited by difficulties in coordinating with private doctors. More than half of Indian TB patients may initially consult a private provider, but many are neither diagnosed accurately nor treated effectively. We established and evaluated a public-private partnership based on surveillance of TB detected in private laboratories and use of standardised directly observed treatment regimens. METHODS: In one district, the governmental TB control programme offered training in microscopy to all large private sector laboratories, and educated private physicians on the importance of microscopy for TB diagnosis. We reviewed records from participating private laboratories and all publicly diagnosed patients. RESULTS: Of 2328 pulmonary TB patients registered from July 2001 to December 2002, 404 (17%) were detected in the private sector. The annual new AFB-positive case notification rate increased by 21%, from 27.8/100,000 in 2000 to 33.5/100,000 in 2002. Surveillance at private laboratories found an additional 260 nonregistered AFB-positive patients. CONCLUSIONS: This public-private partnership substantially increased TB case detection and established a sustainable framework for private sector involvement in TB control. In the setting of a strong public sector programme, the combination of active surveillance of private laboratories along with physician sensitisation is a promising approach to improve TB case detection.

The impact of HIV/AIDS on the control of tuberculosis in India.

Epidemics of HIV/AIDS have increased the tuberculosis (TB) case-load by five or more times in East Africa and southern Africa. As HIV continues to spread, warnings have been issued of disastrous AIDS and TB epidemics in "new-wave" countries, including India, which accounts for 20% of all new TB cases arising in the world each year. Here we investigate whether, in the face of the HIV epidemic, India's Revised National TB Control Program (RNTCP) could halve TB prevalence and death rates in the period 1990-2015, as specified by the United Nations Millennium Development Goals. Using a mathematical model to capture the spatial and temporal variation in TB and HIV in India, we predict that, without the RNTCP, HIV would increase TB prevalence (by 1%), incidence (by 12%), and mortality rates (by 33%) between 1990 and 2015. With the RNTCP, however, we expect substantial reductions in prevalence (by 68%), incidence (by 41%), and mortality (by 39%) between 1990 and 2015. In India, 29% of adults but 72% of HIV-positive adults live in four large states in the south where, even with the RNTCP, mortality is expected to fall by only 15% between 1990 and 2015. Nationally, the RNTCP should be able to reverse the increases in TB burden due to HIV but, to ensure that TB mortality is reduced by 50% or more by 2015, HIV-infected TB patients should be provided with antiretroviral therapy in addition to the recommended treatment for TB.

Storage of heat-fixed unstained sputum AFB smears for panel testing in a tuberculosis unit in South India.

To evaluate the suitability for panel testing of heat-fixed unstained sputum AFB smears stored for up to 10 months, panels of slides were prepared at the national laboratory and stored under ambient conditions. Every month, three slides were utilised for panel testing in each of 12 microscopy centres; 70 smears were checked in a blinded fashion after 10 months. Reading errors occurred in 15/360 slides used in panel testing and in 4/70 slides used in blinded checking. The quality and grading of heat-fixed unstained smears were unaffected for up to 10 months and were found suitable for panel testing.