PEPFAR Program Research Articles

Preliminary Evaluation of Stability Data for Dolutegravir-Containing Triple Active Formulations Intended for PEPFAR. Degradation of Tenofovir Disoproxil Fumarate and Tenofovir Alafenamide as the Limiting Factor

FDA reviews applications that are filed under the PEPFAR program to ensure that these products are manufactured to FDA's stringent requirements. Dolutegravir is a comparatively recent molecular entity that represents an advance over previous products. The stability behaviors of tablets that contain dolutegravir, lamivudine, and tenofovir disoproxil fumarate and tablets that contain dolutegravir, emtricitabine and tenofovir alafenamide were surveyed and it was found that tenofovir-related degradants increase the most and are the parameters most likely to result in product failure. A desiccant is advantageous and this desiccant should remain in the bottle after it has been opened. In-use studies simulate consumer use. Bottles are stored at 30 °C/75% RH and opened for about 1 min a day. Water content increased significantly and the rate of degradation was faster than the degradation rate observed during long-term storage. The data predict that most formulations containing TDF will stay within specification over 4 years of long-term storage followed by dispensing one tablet per day. With the current data it appears that some TAF-containing formulations may fail under similar conditions. However, the data are limited and preliminary and it is possible that the situation may improve as more stability data are acquired.

The cost-effectiveness of Pre-Exposure Prophylaxis in HIV Prevention: Analysis from A Multicentre Intervention in Northern Nigeria

Background: Pre-exposure prophylaxis (PrEP) is recommended for people at substantial risk of acquiring HIV to prevent new infections. The Nigeria PEPFAR program through USAID funded the implementation of PrEP for Key Population (KP) groups including Men Who Have Sex with Men (MSM), People who inject drugs (PWIDS), and Female sex Workers (FSW) in July 2020. We assessed the number of new infections averted and the financial resources saved because of this intervention. Methodology: HIV-negative clients from the key population community in North- East Nigeria eligible for PrEP were enrolled over a 7-month period (July 2020 – February 2021). Eligibility criteria used include being at substantial risk for HIV infection based on a screening test administered. The person-month was calculated by using the duration the participants were retained on PrEP. The incidence 15.4/100 person-years of HIV among MSM at high risk of HIV infection in the TRUST study conducted in Nigeria was used to calculate the expected positive cases if PrEP was not provided for those enrolled using the formula (15.4/100 * X) where X is number of person-years. We compared the expected positive to the actual positive seen among KPs while on PrEP within the study period. The cost-effectiveness of being on PrEP was calculated by multiplying the standard cost per HIV infection averted ($13, 267 per HIV infection averted) by the No of HIV averted. Results: We enrolled a total of 1,197 eligible HIV-negative KPs within the study period (189 were retained for seven months, 407 for four months, 585 for 3 months, and 18 for 1 month). A total of 4722 person-months (394 person-years) were accumulated over the period of the study. Using the incidence of 15.4/100 person-years, the expected positive cases if PrEP was not provided was 61 (15.4/100 *394). With the use PrEP, no client seroconverted to be HIV positive. This means that within the 7-month period, 61 HIV infections were averted. At the cost of $13,267 per HIV infection averted for PrEP, the project saved $809,287 for averting 61 HIV infections in seven months of using PrEP among HIV-negative KPs involved in high-risk behaviors. Conclusion: This study shows that PrEP is effective in averting new infections among key population groups. Placing high-risk groups such as KPs on PrEP is cost-effective due to the money saved from new infections averted. Increased funding for proven and innovative strategies on PrEP enrolment, retention, and adherence of eligible clients should be expanded for KPs.

Pre-exposure prophylaxis (PrEP) uptake and service delivery adaptations during the first wave of the COVID-19 pandemic in 21 PEPFAR-funded countries.

BackgroundMitigation measures for the first wave of the COVID-19 pandemic and burden on health systems created challenges for pre-exposure prophylaxis (PrEP) service delivery. We examined PrEP uptake in PEPFAR programs before and after the start of the COVID-19 pandemic.MethodsWe studied two PEPFAR program monitoring indicators, using routine Monitoring, Evaluation, Reporting (MER) indicators capturing uptake of PrEP (PrEP_NEW) and overall use of PrEP (PrEP_CURR). We also analyzed descriptive program narratives to understand successes and challenges field teams encountered after the start of the COVID-19 pandemic. To assess changes in coverage of PrEP across 21 countries, we calculated the “PrEP to need ratio” (PnR) using a published methodology. We defined the pre-COVID time period as April 1, 2019 –March 31, 2020 and the COVID time period as April 1, 2020 –March 31, 2021.FindingsThe total number of persons who initiated PrEP increased by 157% from 233,250 in the pre-COVID-19 period compared with 599,935 in the COVID-19 period. All countries, except five, noted significant increases in PrEP uptake. PrEP uptake among adolescent girls and young women (AGYW) increased by 159% from 80,452 AGYW in the pre-COVID-19 period to 208,607 AGYW in the COVID-19 period. There were 77,430 key populations (KP) initiated on PrEP in the pre-COVID-19 period and 209,114 KP initiated in the COVID-19 period (a 170% increase). The PnR increased 214% in the COVID-19 period across all PEPFAR-supported countries. Adaptations, such as multi-month dispensing (MMD) of PrEP; virtual demand creation activities; decentralized, community-based and virtual service delivery, were implemented to maintain PrEP services.ConclusionsPEPFAR programs continued to maintain and initiate new clients on PrEP despite the challenges posed by the COVID-19 pandemic. Adaptations such as MMD of PrEP and use of technology were vital in expanding service delivery and increasing PrEP coverage.FundingThis project has been supported by the U.S. President’s Emergency Plan for AIDS Relief.

The impact of COVID-19 on multi-month dispensing (MMD) policies for antiretroviral therapy (ART) and MMD uptake in 21 PEPFAR-supported countries: a multi-country analysis.

IntroductionIncreasing access to multi‐month dispensing (MMD) of antiretroviral therapy (ART) supports treatment continuity and viral load suppression for people living with HIV (PLHIV) and reduces burden on health facilities. During the COVID‐19 response, PEPFAR worked with ministries of health to scale up MMD and expand eligibility to new groups of PLHIV, including children and pregnant/breastfeeding women. We analysed PEPFAR program data to understand the impact of the policy changes on actual practice.MethodsWe conducted a desk review in 21 PEPFAR‐supported countries to identify and collect official documentation released between March and June 2020 addressing changes to MMD guidance during the COVID‐19 response. MMD coverage, the proportion of all ART clients on MMD, was assessed in the calendar quarters preceding the COVID‐19 response (Q4 2019, October–December 2019; and Q1, January–March 2020) and the quarters following the start of the response (Q2 2020, April–June 2020; Q3 2020, July–September, 2020; Q4 2020, October–December 2020). We used the two‐proportion Z‐test to test for differences in MMD coverage pre‐COVID‐19 (Q4 2019) and during implementation of COVID‐19 policy adaptations (Q2 2020).Results and discussionAs of June 2020, 16 of the 21 PEPFAR‐supported countries analysed adapted MMD policy or promoted intensified scale‐up of MMD in response to COVID‐19. MMD coverage for all clients on ART grew from 49% in Q4 2019 pre‐COVID‐19 to 72% in Q2 2020 during COVID‐19; among paediatric clients (< 15), MMD coverage increased from 27% to 51% in the same period. Adaptations to MMD policy were associated with a significantly accelerated growth in the proportion of clients on MMD (p < 0.001) for all populations, irrespective of age and dispensing interval.ConclusionsAccess to MMD markedly expanded during the COVID‐19 pandemic, supporting treatment continuity while mitigating exposure to COVID‐19 at health facilities. This model is beneficial in public health emergencies and during disruptions to the healthcare system. Outside emergency contexts, expanded MMD eligibility extends client‐centred care to previously excluded populations. The success in expanding MMD access during COVID‐19 should motivate countries to recommend broader MMD access as a new standard of care.

Taking tuberculosis preventive therapy implementation to national scale: the Nigerian PEPFAR Program experience.

Tuberculosis (TB) preventive therapy (TPT), including isoniazid preventive therapy (IPT), has been implemented within the Nigerian human immunodeficiency virus (HIV) programme since 2014. However, drug procurement and logistic support has remained the responsibility of the National Tuberculosis and Leprosy Control Programme. The US President's Emergency Plan for AIDS Relief-Nigeria (PEPFAR Nigeria) reviewed the key bottlenecks to TPT implementation in 2016. The logistics of delivery of isoniazid (INH) were integrated with the antiretroviral (ARV) logistics management and information system (LMIS). Drug order and requisition forms at the facility level were revised to include INH, along with training on appropriate quantification and requisition of INH with ARVs. Support was provided for last mile delivery of INH directly to every implementing site, alongside ARV. We observed an increasing trend in TPT uptake between the pre-and-post intervention periods: 6% in fiscal year (FY) 2015, 7% in FY2016 and 12% in FY2017. Overall, the logistical changes in the LMIS to include INH in 2016 led to a 69% increase in TPT by the end of FY2017; this was statistically significant. Addressing logistical challenges to TPT implementation will ensure that the TB and HIV programmes can tackle the increasing burden of TB infection in people living with HIV. We recommended that the provider-to-client stage of TPT implementation be driven by the HIV programme and that cross-communication between the two programmes be improved.

President’s Emergency Plan for AIDS Relief

Due to lack of facilities and expensive medicines most of the patients in developing courtiers do not get adequate treatment for HIV/AIDS. Hence it was an immediate requirement that the developed countries and the developing countries walk hand in hand on the path of defeating this epi-demic monster. Emergency Plan for AIDS Relief is the largest global health initiative dedicated for the cure of a single disease by United States Government. The review article provides the information about the condition of the world before the implementation of PEPFAR program, his-tory and political framework of the organisation, the goals of PEPFAR, the funding sources and its partnership with different countries including India How to Cite this Article Pubmed Style Jadeja S, Pai G, Bhat K, Sathyanarayana MB. Emergency Plan for AIDS Relief. SRP. 2018; 9(1): 6-9. doi:10.5530/srp.2018.1.2 Web Style Jadeja S, Pai G, Bhat K, Sathyanarayana MB. Emergency Plan for AIDS Relief. http://www.sysrevpharm.org/?mno=302644540 [Access: March 28, 2021]. doi:10.5530/srp.2018.1.2 AMA (American Medical Association) Style Jadeja S, Pai G, Bhat K, Sathyanarayana MB. Emergency Plan for AIDS Relief. SRP. 2018; 9(1): 6-9. doi:10.5530/srp.2018.1.2 Vancouver/ICMJE Style Jadeja S, Pai G, Bhat K, Sathyanarayana MB. Emergency Plan for AIDS Relief. SRP. (2018), [cited March 28, 2021]; 9(1): 6-9. doi:10.5530/srp.2018.1.2 Harvard Style Jadeja, S., Pai, . G., Bhat, . K. & Sathyanarayana, . M. B. (2018) Emergency Plan for AIDS Relief. SRP, 9 (1), 6-9. doi:10.5530/srp.2018.1.2 Turabian Style Jadeja, Siddharth, Girish Pai, Krishnamurthy Bhat, and Muddukrishna Badamane Sathyanarayana. 2018. Emergency Plan for AIDS Reviews in Pharmacy, 9 (1), 6-9. doi:10.5530/srp.2018.1.2 Chicago Style Jadeja, Siddharth, Girish Pai, Krishnamurthy Bhat, and Muddukrishna Badamane Sathyanarayana. President’s Emergency Plan for AIDS Relief. Systematic Reviews in Pharmacy 9 (2018), 6-9. doi:10.5530/srp.2018.1.2 MLA (The Modern Language Association) Style Jadeja, Siddharth, Girish Pai, Krishnamurthy Bhat, and Muddukrishna Badamane Sathyanarayana. President’s Emergency Plan for AIDS Relief. Systematic Reviews in Pharmacy 9.1 (2018), 6-9. Print. doi:10.5530/srp.2018.1.2 APA (American Psychological Association) Style Jadeja, S., Pai, . G., Bhat, . K. & Sathyanarayana, . M. B. (2018) Emergency Plan for AIDS Reviews in Pharmacy, 9 (1), 6-9. doi:10.5530/srp.2018.1.2

Strengthening the Quality and Quantity of the Nursing and Midwifery Workforce: Report on Eight Years of the NEPI Project.

In response to the urgent need to scale up access to antiretroviral therapy, the Global Nursing Education Partnership Initiative (GNCBP), a PEPFAR program administered by the U.S. Department of Health Resources and Services Administration (HRSA), was implemented from 2011 to 2018 by ICAP at Columbia University. Working closely together, HRSA and ICAP partnered with local nursing leaders and ministries of health to strengthen the nursing and midwifery workforce across 11 countries. This multi-country project, developed to address critical gaps in nursing education and training worked across six building blocks of health workforce strengthening: infrastructure improvement, curricula revision, clinical skills development, in-service training, faculty development and building partnerships for policy and regulation to increase the quality and quantity of the nursing and midwifery workforce. As a result, 13,387 nursing and midwifery students graduated from schools supported under GNCBP. A total of 5,554 nurses received critical in-service training and 4,886 faculty, clinical mentors and preceptors received training in key clinical care areas and modern teaching methodologies. ICAP completed 43 infrastructure enhancements to ensure environments conducive to learning and strengthened nursing leaders as best evidenced by the election and formation of Mozambique’s first national nursing council and the NEPI Network. Going forward, efforts to strengthen nursing and midwifery can build on the results of the GNCBP project. Going forward, a new group of African nursing leaders are being supported to advocate for high quality patient-care led through inter-professional collaboration and participation in international efforts championing the critical role of nurses in achieving universal health coverage.

The Islamification of antiretroviral therapy: Reconciling HIV treatment and religion in northern Nigeria

Access and adherence to antiretroviral therapy (ART) are essential to HIV treatment success and epidemic control. This article is about how HIV-positive Muslims and providers balance ART with religious tenets and obligations. I conducted 17 months of multi-site ethnographic research between 2007 and 2010, including participant-observation in an urban HIV clinic in Kano, Nigeria and a support group for people living with HIV, as well as in-depth interviews with 30 HIV-positive men and 30 key informants with caregiving, clinical, or policy roles related to HIV/AIDS. Patients migrated from Islamic prophetic medicine to ART when it became more widely available in the mid-2000s through the U.S. PEPFAR program. At the same time, a conceptual shift occurred away from considering HIV immediately curable through spiritual and herbal-based Islamic prophetic medicine toward considering HIV as a chronic infection that requires adherence to daily pill regimens. Hope for a complete cure and encouragement from some Islamic prophetic healers resulted in some patients forgoing ART. Patients and providers adapted biomedical treatment guidelines to minimize disruption to religious practices also considered essential to Muslims' wellbeing, irrespective of HIV status. Providers discouraged patients on second-line ART from fasting because such patients had fewer treatment options and, often, poorer health. However, patients’ medication adherence was affected by the desire to fulfill fasting obligations and to avoid questions from family and friends unaware of their HIV-positive status. This study is one of few ethnographic accounts of HIV treatment in a Muslim-majority society and contributes to understanding the significance of religion for HIV treatment in northern Nigeria. It has implications for public health programming and clinical approaches to HIV treatment in medically pluralistic Muslim societies.

Delegated Service Authority: Institutional Evolution of PEPFAR Health‐Based Program Implementing Units in Tanzania

AbstractThe critical development literature examines donor interventions' institutions and institutional impact. Donor agencies examine specific intervention mechanisms to improve intervention effectiveness or conformity with given development trends. Both literatures insufficiently address the potential evolution of program implementing units (PIUs) deployed by donor agencies according to the units' respective technical capacities. This article assesses PIU evolution using specific units contracted under the United States Government's PEPFAR program in Tanzania. These units evolved in their respective operational space that exists in the interactions between three stakeholder categories: (1) the contracting agency of PEPFAR; (2) relevant Tanzanian national public institutions; and (3) local Tanzanian authorities responsible for HIV/AIDS or health service delivery. This article examines how stakeholders' delegation of authority to PIUs for technical management and/or implementation of HIV/AIDS prevention and treatment services drive the units' institutional evolution. This evolution is ongoing given iterative PIU‐stakeholder interaction expanding units' services along with delegated authority. In the Tanzanian case, evolved PIUs became essential to the national health system with few institutions able to re‐assume the units' services or delegated authority. They also fostered a new domestic technocracy with transnational network connections to the global public health epistemic community offering new policy platform voice and exit opportunities.

On Partial Identification of the Natural Indirect Effect.

In causal mediation analysis, nonparametric identification of the natural indirect effect typically relies on, in addition to no unobserved pre-exposure confounding, fundamental assumptions of (i) so-called "cross-world-countterfactuals" independence and (ii) no exposure-induced confounding. When the mediator is binary, bounds for partial identification have been given when neither assumption is made, or alternatively when assuming only (ii). We extend existing bounds to the case of a polytomous mediator, and provide bounds for the case assuming only (i). We apply these bounds to data from the Harvard PEPFAR program in Nigeria, where we evaluate the extent to which the effects of antiretroviral therapy on virological failure are mediated by a patient's adherence, and show that inference on this effect is somewhat sensitive to model assumptions.

HIV Exceptionalism: Development through Disease in Sierra Leone by Adia Benton

Adia Benton, HIVExceptionalism: Development through Disease in Sierra Leone. Minneapolis: University of Minnesota Press, 2015. 192 pp.Among many books written about HIV epidemic in Africa over past few decades, book-length anthropological studies remain a rarity. Adia Benton's new book, HIV Exceptionalism-Development through Disease in Sierra Leone, helps to fill that gap. Through fine-grained accounts describing how individuals navigated new structures, new relationships, and new expectations that came along with being beneficiaries of global HIV funding, Benton reveals jagged edges and uncomfortable truths about broader global-local health encounters. This book tells a compelling story about an entire society adapting to a sudden infusion of donor money for a disease that, in this particular context, barely existed.The book is about HIV in Sierra Leone, but issue of local responses to global health initiatives has relevance beyond HIV or any particular country context. What makes this particular disease in this particular country an interesting case for ethnographic study is fact that HIV rates here have been historically very low, both before and after 1991-2002 civil war, and yet country received a large infusion of foreign aid money specifically for HIV/AIDS prevention and care programs. HIV services were initially introduced on a pilot basis in 2004, and by 2007 Global Fund had secured enough funding to open a network of treatment centers that offered anti-AIDS treatment free of charge. By 2012, country had spent more than $12 million USD on HIV/AIDS services, and all while HIV prevalence rates remained essentially no different than pre-war figure of 1.5 percent. How did country and its war-ravaged health systems adapt to absorb those funds? How did people adjust their behavior to become models of positive living? How were hierarchies of power established between transnational donors, local health officials, NGOs, AIDS activists, and expert patients? What made HIV so exceptional in comparison to all other challenges confronting country at time? All these questions are explored in Benton's anthropological project to hold lived experience in focus while mapping networks, institutions, beliefs, and conceptions that emerged with flood of post-war HIV/AIDS money.Sierra Leone's civil war was winding down just as international HIV/ AIDS was revving up. With 2001 launch of PEPFAR program (President's Emergency Program for AIDS Relief) by US President George W. Bush, a multi-billion dollar fund to address global HIV/AIDS epidemic became available. What some had called the AIDS industry roared into action at that time and search was on for worthy projects and countries to target for assistance. The newly launched PEPFAR program with its billions of dollars was actively searching for worthy projects and countries to target for HIV assistance. Expert consensus then was that war and HIV always conspired against affected populations and constituted a double emergency. When it was found that HIV prevalence in conflict-affected Sierra Leone was lower than anticipated, experts argued that normalization in post-conflict period would lead to increased HIV transmission. While this never happened, it did not stop international funders or Sierra Leonean officials from making a case to secure attractive emergency HIV/AIDS funds. And why not? With those funds, nearly $80 million allocated over a five-year period, came a wide-range of services-medical care, support groups, income generation projects, education, food supplements, and skills training, among others. All of these were welcomed in dire social and economic circumstances of postwar Sierra Leone. But HIV was, and remains, exceptional among diseases, and exceptionalism created what Benton refers to as an economy of suffering, whereby those who had AIDS could claim unique hardship in a context where daily suffering was norm. …

Loss to Follow-Up within the Prevention of Mother-to-Child Transmission Care Cascade in a Large ART Program in Nigeria.

The 2013 WHO guidelines incorporated simplified and more effective antiretroviral regimens for the purposes of preventing mother-to-child transmission of HIV. With ideal implementation of these recommendations, perinatal HIV transmission could be reduced to less than 2%. However, loss to follow-up (LTFU) has the potential to erode the success of programs and a number of studies report high rates of LTFU within the prevention of mother-to-child transmission (PMTCT) care cascade. We evaluated the timing and magnitude of LTFU in a large programmatic PMTCT cohort in Nigeria in order to focus future efforts to reduce loss in this high burden setting. From 2004-2014, the APIN/Harvard PEPFAR program supported antenatal HIV screening for nearly one million pregnant women and provided PMTCT care to over 30,000 women. The care cascade for women enrolling in the PMTCT program includes antenatal, delivery, and infant follow-up services through 12-18 months of life. In this retrospective cohort analysis, we examined data collected between 2004-2014 from 31 clinical sites in Nigeria and assessed the numbers of mothers and infants enrolled and LTFU at various points along the care cascade. Among 31,504 women (median age 30, IQR: 27-34) entering PMTCT care during the antenatal period, 20,679 (66%) completed the entire cascade of services including antenatal, delivery, and at least one infant follow-up visit. The median gestational age at presentation for antenatal care services was 23 weeks (IQR: 17-29). The median infant age at last follow-up visit was 12 months (IQR: 5-18). The greatest loss in the PMTCT care cascade occurred prior to delivery care (21%), with a further 16% lost prior to first infant visit. Of the 38,223 women who entered at any point along the PMTCT cascade, an HIV DNA PCR was available for 20,202 (53%) of their infants. Among infants for whom DNA PCR results were available, the rate of HIV transmission for infants whose mothers received any antenatal and/or delivery care was 2.8% versus 20.0% if their mother received none. In this large cohort analysis, the proportion of women LTFU in the PMTCT care cascade was lower than that reported in previous cohort analyses. Nevertheless, this proportion remains unacceptably high and inhibits the program from maximally achieving the goals of PMTCT care. We also provide the largest analysis to date on rates of perinatal HIV transmission, with low rates among women receiving NNRTI- or PI-based regimens, approaching that reported in clinical trials. However, among mothers who received any antenatal care, infant outcomes were unknown for 48%, and women presented later in pregnancy than that recommended by current guidelines. Implementation research to evaluate ways to improve integration of services, particularly transitions from antenatal to delivery and pediatric care, are critically needed to reduce LTFU within PMTCT programs and achieve the ultimate goal of eliminating pediatric HIV infection.

Overview of recently approved 505(b)(2) new drug applications (2010-2012): role of clinical pharmacology.

The role of clinical pharmacology (CP) in the approval of 505(b)(2) NDAs was explored with the goal of sharing with the drug development community, some of the critical CP aspects that need to be considered and addressed during the planning and submission of a 505(b)(2) NDA. Among the 106 505(b)(2) NDAs approved in 2010-2012 (excluding those that were approved under the PEPFAR program), 25% included only CP information, no supportive clinical safety/efficacy was necessary for their approval and 43% included both clinical and CP information. A review of the pre-submission interaction discussion held for 58% of the non-PEPFAR NDAs, indicated that CP-related aspects discussed at this avenue included study design of the pivotal BA/BE study, biowaiver related discussion, need for additional or supportive pharmacokinetic information to be included in the NDA, selection of the most appropriate reference drug product for 505(b)(2) purpose, as well as acceptability of publicly available information to address data gaps in knowledge. Further, we also noted that 505(b)(2) NDAs that did not report having a pre-submission interaction with the Agency had twice the rate of receiving a complete response action in the first cycle as compared to the NDAs that did meet with the Agency.

Short communication: east meets west: a description of HIV-1 drug resistance mutation patterns of patients failing first line therapy in PEPFAR clinics from Uganda and Nigeria.

HIV-1 viral load (VL) monitoring is recommended but seldom performed in resource-constrained countries. An evaluation of patients receiving first-line antiretroviral therapy in a multicountry PEPFAR program (RV288) was performed to determine the rates and predictors of virologic suppression. Resistance data from treatment failures are available from Uganda and Nigeria. Each country enrolled 325 subjects into this cross-sectional study. Subjects on first-line therapy were randomly selected for HIV RNA testing (viral load). Regimens included efavirenz or nevirapine with zidovudine/lamivudine or tenofovir/lamivudine. VL was determined from plasma using the Roche COBAS TaqMan HIV-1 Test, High Pure System v1.0 (47 copies/ml). Genotypic resistance testing was performed on samples with VL>1,000 copies/ml. From Uganda, 85% of subjects were undetectable while 7% (23/325) had VL>1,000 copies/ml. The HIV-1 subtype distribution was as follows: A=47.6%, C=14.3%, and D=38.1%. No resistance mutations were found in 14% of subjects. All subjects with resistance had the M184V mutation. Of subjects failing a zidovudine regimen less than 1 year, 88% (7/8) had no thymidine analogue mutations (TAMs), compared to 50% (4/8) failing greater than 1 year. Four subjects (25%) had more than two mutations from the TAM-1 pathway (41L, 210W, 215Y). In Nigeria, 82% were undetectable while 14% (45/325) had VL>1,000 copies/ml. HIV-1 subtype distribution was as follows: 62.8%=CRF02_AG, 34%=pure G, and 2.8%=A. Of the 35 genotyped subjects, 14% (5/35) had no resistance mutations. Of the remainder, 10% (3/30) had no nucleoside analogue mutations while 33% (10/30) had only M184V along with nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations. Forty percent (10/25) of subjects on zidovudine failed without TAMs. Another 25% (5/25) of subjects failing on zidovudine had more than two TAM-1 mutations. Individuals failing first-line antiretroviral therapy (ART) may retain sensitivity to one or more nucleoside analogues from the regimen. Knowledge of drug resistance patterns allow for selection of drugs that can be recycled in future regimens. Accumulation of resistance mutations may compromise future treatment options.

Response to 'PEPFAR Program Expenditures (Form Number: DS-4213, OMB Control Number: 1405-0208) Third Revision

This response document will briefly address concerns about the ethical, legal and methodological flaws with past research informing aspects of present PEPFAR program areas; concerns about adverse consequences of PEPFAR program areas; and concerns about the absence of oversight of the activities of PEPFAR funding recipients.

Accumulation of protease mutations among patients failing second-line antiretroviral therapy and response to salvage therapy in Nigeria.

BackgroundTo date, antiretroviral therapy (ART) guidelines and programs in resource-limited settings (RLS) have focused on 1st- and 2nd-line (2 L) therapy. As programs approach a decade of implementation, policy regarding access to 3rd-line (3 L) ART is needed. We aimed to examine the impact of maintaining patients on failing 2 L ART on the accumulation of protease (PR) mutations.Methods and FindingsFrom 2004–2011, the Harvard/APIN PEPFAR Program provided ART to >100,000 people in Nigeria. Genotypic resistance testing was performed on a subset of patients experiencing 2 L failure, defined as 2 consecutive viral loads (VL)>1000 copies/mL after ≥6 months on 2 L. Of 6714 patients who received protease inhibitor (PI)-based ART, 673 (10.0%) met virologic failure criteria. Genotypes were performed on 61 samples. Patients on non-suppressive 2 L therapy for <12 months prior to genotyping had a median of 2 (IQR: 0–5) International AIDS Society (IAS) PR mutations compared with 5 (IQR: 0–6) among patients failing for >24 months. Patients developed a median of 0.6 (IQR: 0–1.4) IAS PR mutations per 6 months on failing 2 L therapy. In 38% of failing patients no PR mutations were present. For patients failing >24 months, high- or intermediate-level resistance to lopinavir and atazanavir was present in 63%, with 5% to darunavir.ConclusionsThis is the first report assessing the impact of duration of non-suppressive 2 L therapy on the accumulation of PR resistance in a RLS. This information provides insight into the resistance cost of failing to switch non-suppressive 2 L regimens and highlights the issue of 3 L access.

Response to 'PEPFAR Program Expenditures' - [Form Number: DS-4213, OMB Control Number: 1405-0208

This response document will briefly address concerns about the ethical, legal and methodological flaws with past research informing aspects of present PEPFAR program areas; concerns about adverse consequences of PEPFAR program areas; and concerns about the absence of oversight of the activities of PEPFAR funding recipients.

Prevalence and Clinical and Immunoviralogical Profile of Human Immunodeficiency Virus-Hepatitis B Coinfection among Children in an Antiretroviral Therapy Programme in Benue State, Nigeria.

Background. Nigeria has the world largest burden of paediatric HIV and is also highly endemic for Hepatitis B virus (HBV). However, relatively little is known regarding the prevalence of HBV-HIV coinfections among Nigerian children. Methods. A retrospective study among treatment naive HIV-infected children attending the pediatric clinic of the APIN Plus/Harvard PEPFAR program of the Federal Medical Centre, Makurdi, between June 2008 and June 2012. Results. The mean age of the 395 subjects studied was 7.53 ± 4.23 years. Thirty-one subjects (7.8%) were positive for HBV. No subject was HIV-HBV-HCV triply infected. Significantly higher HIV-HBC coinfections were found, in older subjects (11–15 years), subjects that did not receive nor complete Hepatitis B vaccinations, and subjects that had a severe immunosuppression of < 15% with respective P values of 0.00, 0.01, and 0.00. HIV-HBV co-infection did not significantly impact on other baseline characteristics including, gender, WHO clinical stage, median absolute CD4 count, mean viral load, median ALT, and hepatotoxicity. Conclusion. A high seroprevalence of HBV among this cohort of HIV-infected children contributes to the calls for pre-ART screening for HBV and the necessary paradigm shift in the ART nucleoside backbone to include agent(s) more dually effective against HIV and HBV.

Equitable Distribution of PEPFAR-Supported HIV/AIDS Services in South Africa

This letter to the editor describes South Africa’s lack of proper health infrastructure which has led to inequalities in access to healthcare. This primarily affects the population’s access to HIV/AIDS and tuberculosis treatments. The South African government and the U.S.’s PEPFAR program have been working to reverse this trend. Recent data indicates that there is an association between the burden of HIV/AIDS and the people tested for HIV/AIDS as well as the vulnerable populations supported by treatment. There is no association between the prevalence of HIV/AIDS and socioeconomic status or existing infrastructure. The use of PEPFAR services is intended reduce healthcare inequities in this population.

Financial Crises and Social Spending: The Impact of the 2008-2009 Crisis

Financial crises in developing and transition countries have often proven disruptive to policies and programs due to procyclical trends government spending growth. Given the importance and significant component of public budgets devoted to education and health cuts in government expenditures during recessions potentially place social programs at risk. This paper analyzes the experiences from 1995-2007 for 131 countries; projects fiscal social spending to 2013; and, examines specific issue around fiscal social spending in the current crisis including donor responses, and government and household coping mechanisms.Growth rate trends in education and health spending fluctuate overtime with greater volatility in education. Despite this pattern, absolute fiscal spending rises steadily overtime with brief periods of flat trends over one or two years, the latter reflecting periods of GDP growth declines in GDP growth. Public spending tends to be more counterclyclical for education compared to health. While sharp declines in growth rates of fiscal social spending are projected, they are balanced by projected increases in absolute spending over the 2008-2013 period.HIV/AIDS funding appears largely protected in the current crisis as the two largest programs – the US PEPFAR Program and the Global Fund for AIDS, TB and Malaria – are not expected to contract. Moreover, 38 percent of all GFATM funding over 9 rounds of funding is not yet spent by recipient governments leaving a significant cushion particularly in Sub-Saharan Africa where almost half of all allocations remain to be spent. Donor funding historically moves procyclically in developing countries, but there have been major shifts in recent years. During the current crisis World Bank lending expanded by 50 percent as governments ramped up safety nets. Regionally only Eastern Europe was hit hard. Declining spending on that region’s social programs has forced long delayed reforms, but there have been negative impacts on household spending and particularly in health, though education spending has been far less affected.