Tuberculosis (TB) is the leading cause of death among persons with HIV. In 2022, an estimated 167,000 TB-related deaths occurred globally among persons with HIV. TB preventive treatment (TPT) helps prevent TB disease and is recommended for persons at high risk for developing TB, including those with HIV. TPT, when taken with antiretroviral treatment (ART), can reduce TB-attributable deaths among persons with HIV. In 2018, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) program committed to offer one course of TPT to all eligible clients receiving ART. This analysis describes trends in TPT initiation and completion among PEPFAR-supported programs in 36 countries in Africa, Central and South America, and Asia during fiscal years (FYs) 2017-2023. Overall, TPT initiation rates peaked in FY19, a possible sign of programmatic saturation. TPT initiation among clients who had been on ART <6 months reached 59%, and overall completion rates up to 87% were reported. Approximately 13 million persons with HIV have completed TPT since FY17, but widespread adoption of shorter regimens, patient-centered approaches, and electronic medical record systems might be needed to ensure full TPT coverage. Through PEPFAR's partnership with national HIV programs, TPT has become the standard of care for persons with HIV.

BACKGROUND: Tuberculosis remains the leading cause of death by an infectious disease among people living with HIV (PLHIV). TB Preventive Treatment (TPT) is a cost-effective intervention known to reduce morbidity and mortality. We used data from ZIMPHIA 2020 to assess TPT uptake and factors associated with its use. METHODOLOGY: ZIMPHIA a cross-sectional household survey, estimated HIV treatment outcomes among PLHIV aged ≥15 years. Randomly selected participants provided demographic and clinical information. We applied multivariable logistic regression models using survey weights. Variances were estimated via the Jackknife series to determine factors associated with TPT uptake. RESULTS: The sample of 2419 PLHIV ≥15 years had 65% females, 44% had no primary education, and 29% lived in urban centers. Overall, 38% had ever taken TPT, including 15% currently taking TPT. Controlling for other variables, those screened for TB at last HIV-related visit, those who visited a TB clinic in the previous 12 months, and those who had HIV viral load suppression were more likely to take TPT. CONCLUSION: The findings show suboptimal TPT coverage among PLHIV. There is a need for targeted interventions and policies to address the barriers to TPT uptake, to reduce TB morbidity and mortality among PLHIV.

SETTING: Peri-urban health facilities providing HIV and TB care in Zambia. OBJECTIVE: To evaluate 1) the impact of Xpert(®) MTB/RIF on time-to-diagnosis, treatment initiation, and outcomes among adult people living with HIV (PLHIV) on antiretroviral therapy (ART); and 2) the diagnostic performance of Xpert and Determine™ TB-LAM Ag assays. DESIGN: Quasi-experimental study design with the first cohort evaluated per standard-of-care (SOC; first sputum tested using smear microscopy) and the second cohort per an algorithm using Xpert as initial test (intervention phase; IP). Xpert testing was provided onsite in Chongwe District, while samples were transported 5-10 km in Kafue District. TB was confirmed using mycobacterial culture. RESULTS: Among 1350 PLHIV enrolled, 156 (15.4%) had confirmed TB. Time from TB evaluation to diagnosis (P = 0.018), and from evaluation to treatment initiation (P = 0.03) was significantly shorter for IP than for SOC. There was no difference in all-cause mortality (7.0% vs. 8.6%). TB-LAM Ag showed higher sensitivity with lower CD4 cell count: 81.8% at CD4 < 50 cells/mm(3) vs. 31.7% overall. CONCLUSION: Xpert improved time to diagnosis and treatment initiation, but there was no difference in all-cause mortality. High sensitivity of Determine TB-LAM Ag at lower CD4 count supports increased use in settings providing care to PLHIV, particularly with advanced HIV disease.

Wallis et al recently reviewed key determinants of human immunodeficiency virus (HIV) drug resistance in low- and middle-income countries (LMICs) [1]. In addition to the determinants that were reviewed, we believe the quality of antiretrovirals (ARVs) available in antiretroviral therapy regimens also merits attention. | | The World Health Organization (WHO) recently released a report on the burden of substandard and falsified antimicrobials. Based on their global analysis, 11% of antimicrobials contained subtherapeutic concentrations of active pharmaceutical ingredients [2]. The proportion for ARVs was 4.2% [2]. People with HIV exposed to subtherapeutic ARVs are at increased risk of developing HIV drug resistance [3, 4]. Continued vigilance to ensure use of quality ARVs is critical for three reasons. First, in many countries procurement is transitioning to domestic mechanisms that may not have the same stringent requirements for quality as the President’s Emergency Plan for AIDS Relief (PEPFAR) and Global Fund (GF). Second, there may not be enough supply from qualified manufacturers to supply all countries with newly recommended ARVs, such as dolutegravir-containing regimens, increasing the risk of a possible influx of nonquality-assured ARVs in some countries. Finally, in countries moving toward national and privatized health insurance schemes as part of universal health coverage, different pharmacies may procure ARVs through different manufacturers (some of which may not adhere to stringent quality standards).

BACKGROUND: To eliminate preventable deaths, disease and suffering due to tuberculosis (TB), improved diagnostic capacity is critical. The Cepheid Xpert(R) MTB/RIF assay is recommended by the World Health Organization as the initial diagnostic test for people with suspected HIV-associated TB. However, despite high expectations, its scale-up in real-world settings has faced challenges, often due to the systems that support it. OPPORTUNITIES FOR SYSTEM STRENGTHENING: In this commentary we discuss needs and opportunities for systems strengthening to support widespread scale-up of Xpert(R) MTB/RIF as they relate to each step within the TB diagnostic cascade, from finding presumptive patients, to collecting, transporting and testing sputum specimens, to reporting and receiving results, to initiating and monitoring treatment and, ultimately, to ensuring successful and timely treatment and cure. Investments in evidence-based interventions at each step along the cascade and within the system as a whole will augment not only the utility of Xpert(R) MTB/RIF, but also the successful implementation of future diagnostic tests. CONCLUSION: Xpert(R) MTB/RIF will only improve patient outcomes if optimally implemented within the context of strong TB programs and systems. Roll-out of this technology to people living with HIV and others in resource-limited settings offers the opportunity to leverage current TB and HIV laboratory, diagnostic and programmatic investments, while also addressing challenges and strengthening coordination between laboratory systems, laboratory-program interfaces, and TB-HIV program interfaces. If successful, the benefits of this tool could extend beyond progress towards global End TB Strategy goals, to improve system-wide capacity for global disease detection and control.

Considerable progress has been made in the provision of life-saving antiretroviral therapy (ART) for persons with human immunodeficiency virus (HIV) infection worldwide, resulting in an overall decrease in HIV incidence and acquired immunodeficiency syndrome (AIDS)-related mortality. In the strategic scale-up of HIV care and treatment programs, persons with HIV and tuberculosis (TB) are a priority population for receiving ART. TB is the leading cause of death among persons living with HIV in sub-Saharan Africa and remains a potential risk to the estimated 35 million persons living with HIV globally. Of the 9 million new cases of TB disease globally in 2013, an estimated 1.1 million (13%) were among persons living with HIV; of the 1.5 million deaths attributed to TB in 2013, a total of 360,000 (24%) were among persons living with HIV. ART reduces the incidence of HIV-associated TB disease, and early initiation of ART after the start of TB treatment reduces progression of HIV infection and death among HIV-positive TB patients. To assess the progress in scaling up ART provision among HIV-positive TB patients in 19 countries in sub-Saharan Africa with high TB and HIV burdens, TB and HIV data collected by the World Health Organization (WHO) were reviewed. The results found that the percentage of HIV-positive TB patients receiving ART increased from 37% in 2010 to 69% in 2013. However, many TB cases among persons who are HIV-positive go unreported, and only 38% of the estimated number of HIV-positive new TB patients received ART in 2013. Although progress has been made, the combination of TB and HIV continues to pose a threat to global health, particularly in sub-Saharan Africa.

The US President's Emergency Plan for AIDS Relief (PEPFAR) has supported a comprehensive package of care in which interventions to address HIV-related tuberculosis (TB) have received increased funding and support in recent years. PEPFAR's TB/HIV programming is based on the World Health Organization's 12-point policy for collaborative TB/HIV activities, which are integrated into PEPFAR annual guidance. PEPFAR implementing partners have provided crucial support to TB/HIV collaboration, and as a result, PEPFAR-supported countries in sub-Saharan Africa have made significant gains in HIV testing and counseling of TB patients and linkages to HIV care and treatment, intensified TB case finding, and TB infection control. PEPFAR's support of TB/HIV integration has also included significant investment in health systems, including improved laboratory services and educating and enlarging the workforce. The scale-up of antiretroviral therapy along with support of programs to increase HIV counseling and testing and improve linkage and retention in HIV care may have considerable impact on TB morbidity and mortality, if used synergistically with isoniazid preventive therapy, intensified case finding, and infection control. Issues to be addressed by future programming include accelerating implementation of isoniazid preventive therapy, increasing access and ensuring appropriate use of new TB diagnostics, supporting early initiation of antiretroviral therapy for HIV-infected TB patients, and strengthening systems to monitor and evaluate program implementation.

Stakeholders agree that supporting high-quality diagnostics is essential if we are to continue to make strides in the fight against human immunodeficiency virus (HIV) and tuberculosis. Despite the need to strengthen existing laboratory infrastructure, which includes expanding and developing new laboratories, there are clear diagnostic needs where conventional laboratory support is insufficient. Regarding HIV, rapid point-of-care (POC) testing for initial HIV diagnosis has been successful, but several needs remain. For tuberculosis, several new diagnostic tests have recently been endorsed by the World Health Organization, but a POC test remains elusive. Human immunodeficiency virus and tuberculosis are coendemic in many high prevalence locations, making parallel diagnosis of these conditions an important consideration. Despite its clear advantages, POC testing has important limitations, and laboratory-based testing will continue to be an important component of future diagnostic networks. Ideally, a strategic deployment plan should be used to define where and how POC technologies can be most efficiently and cost effectively integrated into diagnostic algorithms and existing test networks prior to widespread scale-up. In this fashion, the global community can best harness the tremendous capacity of novel diagnostics in fighting these 2 scourges.