PEPFAR looks to the future

Obama vs McCain on global health

PEPFAR and the fight against HIV/AIDS

Protecting Africa's children from extreme risk: a runway of sustainability for PEPFAR programmes.

As part of the global response to the HIV/AIDS epidemic, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) is committed to the provision of high‐quality services and ensuring testing accuracy. Two recently published papers focusing on HIV testing and misdiagnosis in sub‐Saharan Africa by Kosack et al. report on evaluations of HIV rapid diagnostic tests (RDTs) and found lower than expected specificity and sensitivity on some tests when used in certain geographic locations. The magnitude of PEPFAR's global HIV response has been possible due to the extensive use of RDTs, which have made HIV diagnosis accessible all over the world. We take the opportunity to address concerns raised about the potential implications that these findings could have on real‐world HIV testing accuracy. PEPFAR supported countries adhere to the normative guidance by World Health Organization (WHO) supporting algorithms which require sequential positive tests for diagnostic accuracy. An analysis of Médecins Sans Frontières (MSF) RDT site‐specific data applied to PEPFAR in‐country protocols demonstrate a variation in the diagnostic accuracy of the testing algorithms, but with a very small population‐level effect. The data demonstrate, with the use of these algorithms, that the RDT outcomes found in the study by Kosack et al. would be largely mitigated and would not be expected to have a significant impact on diagnostic accuracy and overall programming in most countries. Avoiding any misdiagnosis is a priority for PEPFAR, and it remains vital to gain a deeper understanding of the causes and the extent of diagnostic errors and any misclassification. Extensive quality control mechanisms and continued research are essential. With a focus on epidemic control and ensuring diagnostic accuracy, PEPFAR recommends that all countries use WHO pre‐qualified RDTs within the recommended strategies and algorithms for HIV testing. We also support validation of HIV testing algorithms using in‐country specimens to determine optimal performance, and the reverification testing of all people diagnosed with HIV prior to starting treatment as an essential quality assurance measure.

What has the US Global Health Initiative achieved?

There are limited data measuring the impact of expanded human immunodeficiency virus (HIV) prevention activities on the tuberculosis epidemic at the country level. Here, we characterized the potential impact of the US President's Emergency Plan for AIDS Relief (PEPFAR) on the tuberculosis epidemic in sub-Saharan Africa. We selected 12 focus countries (countries receiving the greatest US government investments) and 29 nonfocus countries (controls). We used tuberculosis incidence and mortality rates and relative risks to compare time periods before and after PEPFAR's inception, and a tuberculosis/HIV indicator to calculate the rate of change in tuberculosis incidence relative to the HIV prevalence. Comparing the periods before and after PEPFAR's implementation, both tuberculosis incidence and mortality rates have diminished significantly and to a higher degree in focus countries. The relative risk for developing tuberculosis, comparing those with and without HIV, was 22.5 for control and 20.0 for focus countries. In most focus countries, the tuberculosis epidemic is slowing down despite some regions still experiencing an increase in HIV prevalence. This ecological study showed that PEPFAR had a more consistent and substantial effect on HIV and tuberculosis in focus countries, highlighting the likely link between high levels of HIV investment and broader effects on related diseases such as tuberculosis.

In June 2011, the Joint United Nations Programme on HIV/AIDS, the US President's Emergency Plan for AIDS Relief (PEPFAR), and other collaborators outlined a transformative plan to virtually eliminate pediatric AIDS worldwide. The ambitious targets of this initiative included a 90% reduction in new pediatric HIV infections and a 50% reduction in HIV-related maternal mortality--all by 2015. PEPFAR has made an unprecedented commitment to the expansion and improvement of prevention of mother-to-child HIV transmission (PMTCT) services globally and is expected to play a critical role in reaching the virtual elimination target. To date, PEPFAR has been instrumental in the success of many national programs, including expanded coverage of PMTCT services, an enhanced continuum of care between PMTCT and HIV care and treatment, provision of more efficacious regimens for antiretroviral prophylaxis, design of innovative but simplified PMTCT approaches, and development of new strategies to evaluate program effectiveness. These accomplishments have been made through collaborative efforts with host governments, United Nations agencies, other donors (eg, the Global Fund for AIDS, Tuberculosis, and Malaria), nongovernmental organizations, and private sector partners. To successfully meet the ambitious global targets to prevent new infant HIV infections, PEPFAR must continue to leverage the existing PMTCT platform, while developing innovative approaches to rapidly expand quality HIV services. PEPFAR must also carefully integrate PMTCT into the broader combination prevention agenda for HIV, so that real progress can be made toward an "AIDS-free generation" worldwide.

The President's Emergency Plan for AIDS Relief (PEPFAR) has provided billions of US tax dollars to expand HIV treatment, care, and prevention programs in sub-Saharan Africa. This investment has generated significant health gains, but much less is known about PEPFAR's population-level economic effects. We used a difference-in-differences approach to compare employment trends between ten countries that received a large amount of PEPFAR funding (focus countries) and eleven countries that received little or no funding (control countries). We found that PEPFAR was associated with a 13percent differential increase in employment among males in focus countries, compared to control countries. However, we observed no change in employment among females. In addition, we found that increasing PEPFAR per capita funding by $100 was associated with a 9.1-percentage-point increase in employment among males. This rise in employment generates economic benefits equal to half of PEPFAR's cost. These findings suggest that PEPFAR's economic impact should be taken into account when making aid allocation decisions.

Alex Coutinho: transforming HIV care in Africa

HIV and AIDS continue to have a calamitous effect on individuals living on the continent of Africa. U.S. President George W. Bush implemented the President's Emergency Plan for AIDS Relief (PEPFAR) with the objective of committing approximately $15 billion from 2004 through 2008 to assist with the reduction of the HIV pandemic worldwide. The majority of the PEPFAR policy and funding focused on 12 countries in sub-Saharan Africa: Botswana, Cote d'Ivoire, Ethiopia, Kenya, Mozambique, Namibia, Nigeria, Rwanda, South Africa, Tanzania, Uganda, and Zambia. The policy question this research paper seeks to analyze is whether the PEPFAR funding (as a % of Gross Domestic Product (GDP)) allocated to the 12 countries in Africa had any effect on the decrease of HIV infection rates of males and females between the ages of 15 and 49. A fixed-effects panel regression analysis was conducted to determine if this association exists. This study examined the 12 African countries that received PEPFAR funding over the years 2002 to 2010; even though PEPFAR was only active from 2004 through 2008, this research included two years prior and two years after this timeframe in order to better estimate the effect of PEPFAR funding on HIV reduction. The results illustrate that on average, ceteris paribus, for every 1 percentage point increase in PEPFAR funding per GDP a country received, the country's HIV infection rate decreased by 0.355 percentage points. While the empirical findings in this study suggested that the correlation between PEPFAR funding and HIV reduction is statistically significant, the practical significance is perhaps less obvious. Arguably, the reduction rate should be higher given the extent of funding targeted to this project. The conclusion of this research provides suggestions on future research and the policy implications of PEPFAR.

IntroductionIn 2004, the US government began to utilize the Food and Drug Administration's (USFDA) tentative approval process (tFDA) as a basis to determine which HIV drugs are appropriate to be purchased and used in resource‐constrained settings. This process permits products that are not approved for marketing in the US, including medicines with active patents or marketing restrictions in the US, to be purchased and distributed in resource‐constrained settings. Although the tFDA was originally intended to support the United States’ President's Emergency Plan for AIDS Relief (PEPFAR), the USFDA list has become a cornerstone of international HIV programmes that support procurement of ARVs, such as the World Health Organization and the Global Fund to Fight AIDS, Tuberculosis, and Malaria. Our objective in this article is to help the global HIV policy makers and implementers of HIV programmes better understand the benefits and limitations of the tFDA by providing an in‐depth review of the relevant legal and regulatory processes.DiscussionUSFDA's dedicated tFDA process for ARVs used by the PEPFAR programme has a wide impact globally; however, the implementation and the regulatory processes governing the programme have not been thoroughly described in the medical literature. This paper seeks to help stakeholders better understand the legal and regulatory aspects associated with review of ARVs under the tFDA by describing the following: (1) the tFDA and its importance to global ARV procurement; (2) the regulatory pathways for applications under tFDA for the PEPFAR programme, including modifications to applications, review timelines and costs; (3) the role of US patents, US marketing exclusivity rights, and the Medicines Patents Pool in tFDA; and (4) an overview of how applications for PEPFAR programme are processed through the USFDA. We also provide a case study of a new ARV, tenofovir alafenamide fumarate (TAF), not yet reviewed by USFDA for PEPFAR use.ConclusionsIn this paper, we describe the importance and implementation of USFDA's tentative approval process to review ARVs for resource‐constrained settings. We also highlight the impact of patents and exclusivities on review of HIV drugs under tFDA and illustrate the concepts using a new HIV drug as an example.

IntroductionSince 2003, US government funding to address the HIV and AIDS pandemic has been subject to an anti-prostitution clause. Simultaneously, the efficacy of some HIV prevention efforts for sex work in areas receiving US government funding has diminished. This article seeks to explain why.MethodsThis analysis utilizes a case story approach to build a narrative of defining features of organizations in receipt of funding from the President's Emergency Plan for AIDS Relief (PEPFAR) and other US funding sources. For this analysis, multiple cases were compiled within a single narrative. This helps show restrictions imposed by the anti-prostitution clause, any lack of clarity of guidelines for implementation and ways some agencies, decision-making personnel, and staff on the ground contend with these restrictions.ResultsResponses to PEPFAR's anti-prostitution clause vary widely and have varied over time. Organizational responses have included ending services for sex workers, gradual phase-out of services, cessation of seeking US government HIV funds and increasing isolation of sex workers. Guidance issued in 2010 did not clarify what was permitted. Implementation and enforcement has been dependent in part on the interpretations of this policy by individuals, including US government representatives and organizational staff.ConclusionsDifferent interpretations of the anti-prostitution clause have led to variations in programming, affecting the effectiveness of work with sex workers. The case story approach proved ideal for working with information like this that is highly sensitive and vulnerable to breach of anonymity because the method limits the potential to betray confidences and sources, and limits the potential to jeopardize funding and thereby jeopardize programming. This method enabled us to use specific examples without jeopardizing the organizations and individuals involved while demonstrating unintended consequences of PEPFAR's anti-prostitution pledge in its provision of services to sex workers and clients.

The US Food and Drug Administration (FDA) program to review antiretroviral drugs for use in low-resource settings via the US President's Emergency Plan for AIDS Relief (PEPFAR) now supports treatment of more than 14 million patients with HIV. However, an in-depth evaluation of the program has not been undertaken. To conduct a quantitative analysis of the FDA-reviewed antiretroviral drug applications in order to assess the contributions of PEPFAR and to identify areas for improvement. A cross-sectional study was conducted of all PEPFAR applications submitted to the FDA from December 1, 2004, to May 31, 2018. The analyses were conducted between October 2018 and February 2019. Numbers and types of applications reviewed, how long it took for applications to obtain approval or tentative approval (time to registration), how often the FDA issued a complete response letter (CRL) identifying deficiencies precluding application approval or tentative approval and their reasons, and the association between CRLs and time to registration. Overall, 260 PEPFAR applications for 327 antiretroviral therapies were reviewed by FDA, of which 216 applications (83%) for 272 drugs were authorized for use. Of the 216 authorized applications, 184 applications for 231 drugs remain in active status and, thus, are available for use. Twenty-six percent (56 of 216) of the applications were for pediatric-specific formulations or strengths; the remainder were for adults. For all 216 applications, the median (interquartile range) time to registration was 10.0 (7.0-17.5) months. Thirty-seven percent (95 of 260) of the applications received 1 or more CRLs, resulting in a total of 172 CRLs; most applications received 1 CRL, whereas some were issued up to 6 CRLs. Among all CRLs, 264 deficiency reasons were identified; the most common deficiencies were associated with manufacturing processes (155 [44%]), followed by product labeling (62 [23%]), and failing facility inspections (54 [20%]). Complete response letters were associated with an increased time to registration. Applications without CRLs had a median (interquartile range) time to registration of 9.0 (5.5-12.0) months, whereas those with at least 1 CRL took a median (interquartile range) of 22.0 (14.0-38.0) months (P < .001). The FDA's PEPFAR program has made many antiretroviral drugs available for global use. However, FDA and the pharmaceutical companies could take steps to improve the quality of applications submitted to prevent avoidable deficiencies in manufacturing processes and labeling. Further efforts to develop better, easier to use pediatric-specific therapies are needed.

The President's Emergency Plan for AIDS Relief (PEPFAR), which began in 2003, initially responded to the global AIDS epidemic by applying lessons learned in treating the disease in the United States to addressing the emergency abroad. As the program expanded, it evolved to support interventions increasingly tailored to local needs in countries receiving PEPFAR assistance. This global experience has created a knowledge base of how to provide HIV/AIDS prevention, care, and treatment services in low-resource settings. It underscored the importance of treatment adherence, family-centered care, and integration of HIV into broader health care delivery systems. Applying these lessons can help US policy makers address existing gaps in HIV care in the United States, where the availability of HIV treatment has at times masked the continued need for testing, early diagnosis, targeted prevention for key populations, and a solid array of social services for people living with HIV/AIDS and their families. This article identifies PEPFAR practices that merit further exploration for adoption in the United States, including strategies to increase adherence to drug treatment regimens and to ensure that HIV services are broadly integrated with other aspects of health care.

IntroductionHIV prevention and treatment supported by the United States President's Emergency Plan for AIDS Relief (PEPFAR) have saved millions of lives. Rwanda is among the most successful countries worldwide in achieving global targets with PEPFAR support. Abrupt PEPFAR funding uncertainty raises concerns about continued HIV epidemic control. We projected the impact of the Government of Rwanda's (GoR's) capacity to offset PEPFAR funding elimination on adult HIV epidemic and care continuum outcomes over 10 years.MethodsUsing an HIV policy model calibrated to Rwanda, we assessed capacity to sustain HIV services at: 50% (with no capacity by GoR to cover the PEPFAR funding gap), 75%, 90% and 100% (with full capacity by GoR to cover the gap). Scenarios involved reducing the number on antiretroviral therapy (ART), immediately discontinuing ART and proportionally decreasing HIV diagnosis, ART initiation, and care re‐engagement. We projected epidemic outcomes (HIV prevalence, HIV incidence, number with HIV, new HIV infections, deaths) and care continuum outcomes (percentage diagnosed, percentage on ART among those diagnosed, percentage virally suppressed among those on ART). We calculated differences in projected outcomes for partial or no capacity versus full capacity. Secondary analyses assessed the timing of the GoR's response.ResultsCompared to full capacity at 10 years, the model projected a 13.9%–38.7% increase in HIV prevalence and 69.0%–246.7% increase in HIV incidence across coverage capacity scenarios. This translated to 29,000–64,000 additional adults with HIV and 20,000–92,000 cumulative new adult HIV infections. Cumulative projected deaths increased by 10,000–51,200. The model projected continual reductions in percentage diagnosed at 10 years; percentage virally suppressed among those on ART was similar across scenarios. Higher, and more delayed, coverage capacity had projected outcomes similar to lower, and less delayed, coverage capacity. Outcomes for gradual increases in coverage capacity were generally similar to or better than full, but delayed, coverage capacity.ConclusionsEven in countries like Rwanda that have achieved epidemic control, abrupt and persistent elimination of PEPFAR funding could drastically reverse critical gains. Evidence quantifying the consequences of different capacities to sustain HIV services underscores the high stakes of rapid and sufficient action.