HIV Medicine Research Articles

Acknowledgement to reviewers

The Southern African Journal of HIV Medicine is focused on HIV/AIDS treatment, prevention and related topics relevant to clinical and public health practice. The purpose of the journal is to disseminate original research results and support high-level learning related to HIV Medicine. It publishes original research articles, editorials, case reports/case series, reviews of state-of-the-art clinical practice and correspondence.

1321. The UNZA/UMB MMed ID Collaboration: Training and Retaining HIV Specialist Physicians in Zambia

BackgroundTo mitigate the HIV pandemic and increasing outbreaks of infectious diseases, sub-Saharan African countries need increased healthcare worker capacity at all levels. We describe a successful collaboration between the Ministry of Health (MOH), the University Teaching Hospital (UTH), the University of Zambia (UNZA), and the University of Maryland Baltimore (UMB) to train Zambian physicians in advanced HIV medicine and infectious diseases.MethodsRecognizing the need for advanced HIV clinical care expertise in Zambia, UNZA, UTH and UMB partnered in 2008 to create a 1-year Postgraduate Diploma in HIV Medicine. The consortium extended this to an 18-month Master of Science in HIV Medicine to better align with existing professional advancement schema. In 2012, UNZA and UMB started a 4-year Master of Medicine in infectious diseases (MMedID), which was then expanded to a 5-year training program combining internal medicine and infectious disease (MMed IM/ID) in order to produce a cadre with wider expertise in internal medicine and infectious diseases. Instruction consists of bedside teaching, didactic lectures, case conferences, and journal clubs. The bulk of teaching came from UMB clinical faculty with expertise in HIV and ID; faculty are either based in Zambia or visit from the United States.ResultsThe MSc HIV program trained 27 physicians; of these, 24 (89%) are in health leadership positions in Zambia, with 17 (63%) directly involved in clinical care (mostly in the public sector), while 7 (15%) work for international implementing partners in Zambia. 1 physician emigrated to another African country, another one died and the third is in clinical nonleadership position in Zambia. The MMed ID program has enrolled 14 physicians. The first two graduates of the program completed the program in 2017 and took health leadership roles within the MOH as well as teaching positions at UNZA.ConclusionEducational collaborations embedded within local institutions and structures can provide advanced healthcare expertise within resource-limited settings. The UNZA/UMB MMed IM/ID collaboration is a model example of a successful university partnership that has resulted in retaining health leadership and clinical care expertise in Zambia.Disclosures L. Hachaambwa, Centers for Disease Control and Prevention (CDC): Cooperative Agreement to Institution, Financial support for the work described in this abstract was made possible by a cooperative agreement award from the Centers for Disease Control and Prevention (CDC) to the University of Zambia and to the University of Maryland School of Medicine.

592. Determining the Impact of an Antiretroviral Stewardship Team on the Care of HIV-Infected Patients Admitted to an Academic Research Institution

BackgroundThe American Society of Health-System Pharmacists and The American Academy of HIV Medicine have established guidelines on the pharmacist’s involvement in HIV care. Despite expanding roles, there is a paucity of data regarding the impact of collaboration amongst pharmacists and physicians on inpatient antiretroviral management. We evaluated the effects of an antiretroviral stewardship team, comprised of an HIV specialized pharmacist, Infectious Disease physician, and associated learners on reducing inpatient antiretroviral-related errors.MethodsIn this single-centered retrospective cohort study, electronic medical records of adult patients with an antiretroviral ordered between July 1, 2017 and December 31, 2017 were evaluated for the following outcome measures: number of interventions made, number of admissions with errors, predisposing risk factors for errors, and cost savings from interventions. Categorical data were expressed as a total (percent), continuous data were expressed as a median [interquartile range], and predisposing risk factors were analyzed by a multivariate logistic regression. Cost savings were estimated by the documentation system Clinical Measures©.ResultsTwo hundred ninety-seven admissions were evaluated of which 15 were excluded due to treatment for Hepatitis B and PrEP. Forty-eight percent of included admissions (134/282) had at least one intervention made, with 196 interventions made in total. The following variables were assessed to identify predisposing risk factors for errors: non-institutional outpatient provider (OR 1.890 [95% CI 1.136–3.143]; P = 0.014), admission to the intensive care unit (OR 3.836 [95% CI 1.192–12.340]; P = 0.024), change in GFR (OR 3.332 [95% CI 1.144–9.710]; P = 0.027), CD4 count <200 cells/mm3 (OR 1.196 [95% CI 1.015–3.617]; P = 0.045), and multi-tablet inpatient regimen (OR 1.768 [95% CI 0.916–3.412]; P = 0.090). Cost savings from interventions were estimated to be $137,040.ConclusionInterprofessional antiretroviral stewardship teams optimize patient care and provide cost savings. Patients at highest risk for errors include those with non-institutional outpatient providers, admission to the intensive care unit, changes in GFR, and CD4 counts <200 cells/mm3.Disclosures D. Koren, Gilead Sciences: Grant Investigator, Research grant. ViiV Healthcare: Scientific Advisor, Consulting fee.

Building HIV Workforce Capacity Through a Residency Pathway: Outcomes and Challenges.

To help address the impending HIV physician shortage, we launched an HIV Medicine Pathway within our Internal Medicine Residency in 2008. Between 2015 and 2017, surveys showed a decrease in the number of graduates providing primary care for people living with HIV. We suggest evaluation of long-term outcomes from similar training programs and stronger support for HIV primary care career development.

GSK invests in APIs in Scotland

GlaxoSmithKline has opened a $70 million facility in Montrose, Scotland, where it will manufacture fluticasone furoate and vilanterol trifenatate, the active pharmaceutical ingredients in its Ellipta respiratory inhaler. Last year, GSK launched a $57 million plant at the site, which produces aluminum salt adjuvants for vaccines. CEO Emma Walmsley says GSK has targeted Montrose for further growth based on new vaccines and medicines for respiratory illness and HIV.

Policy Recommendations for Optimizing the Infectious Diseases Physician-Scientist Workforce.

The Infectious Diseases Society of America, HIV Medicine Association, and Pediatric Infectious Diseases Society are concerned by the continued decline in the number of infectious diseases trainees pursuing careers as physician-scientists and the attrition of junior and midcareer physician-scientists. The inability to replace the aging physician-scientist workforce will have a negative, long-lasting impact our biomedical research enterprise and its ability to drive the discovery of new treatments for important infectious diseases. We discuss policy recommendations for securing and optimizing the infectious diseases physician-scientist workforce in the areas of education, training, compensation, and mentorship, as well as ways to improve federal research funding, cross-sector collaboration, and workforce diversity.

THE 10th ANNIVERSARY OF THE JOURNAL «HIV INFECTION AND IMMUNOSUPPRESSIVE DISORDERS»: WE DO IT OUR WAY

The history of the journal «HIV Infection and Immunosuppressive States» from its launching in 2009 up to now is reviewed. The missions of the journal are to highlight the latest advances in HIV medicine, epidemiology, pharmacy and biology, to foster the interest of researches in Russia to these fields, to help young scientists in data processing and publishing, to expand the scope of HIV research to neighboring research fields, including comorbid conditions, to consolidated research conducted in different regions of Russia, to backup scientific forums, to publish monographs and manuals as supplements to the journal and thus to compile journal library, and to contribute to advanced postgraduate education. The list of monographs, bulletins, manuals and thematic paper compilations included in journal library is presented.

Social capital and resilience among people living on antiretroviral therapy in resource-poor Uganda.

BackgroundDespite the national roll-out of free HIV medicines in Uganda and other sub-Saharan African countries, many HIV positive patients on antiretroviral therapy (ART) are at risk of non-adherence due to poverty and other structural and health system related constraints. However, several patients exhibit resilience by attaining and sustaining high levels of adherence amid adversity. Social capital, defined as resources embedded within social networks, is key in facilitating resilience but the mechanism through which it operates remains understudied. This article provides insights into mechanisms through which social capital enables patients on ART in a resource-poor setting to overcome risk and sustain adherence to treatment.MethodologyThe article draws from an ethnographic study of 50 adult male and female HIV patients enrolled at two treatment sites in Uganda, 15 of whom were followed-up for an extended period of six months for narrative interviews and observation. The patients were selected purposively on the basis of socio-demographic and treatment related criteria.FindingsSocial capital protects patients on ART against the risk of non-adherence in three ways. 1) It facilitates access to scarce resources; 2) encourages HIV patients to continue on treatment; and 3) averts risk for non-adherence.ConclusionsSocial capital is a key resource that can be harnessed to promote resilience among HIV patients in a resource-limited setting amid individual, structural and health system related barriers to ART adherence. Invigoration and maintenance of collectivist norms may however be necessary if its protective benefits are to be fully realized.

Community involvement in biomedical research conducted in the global health context; what can be done to make it really matter?

BackgroundCommunity involvement in research has been advocated by researchers, communities, regulatory agencies, and funders with the aim of reinforcing subjects’ protection and improving research efficiency. Community involvement also has the potential to improve dissemination, uptake, and implementation of research findings. The fields of community based participatory research conducted with indigenous populations and of participatory action research offer a large base of experience in community involvement in research. Rules on involving the population affected when conducting research have been established in these fields. But what is the role of community engagement in clinical research and observational studies conducted in biomedical research outside of these specific areas?Main body of the abstractMore than 20 years ago, in the field of HIV medicine, regulatory bodies and funding agencies (such as the US National Institutes of Health) recommended the constitution of a formal organism, the Community Advisory Board (CAB), as part of the study requirements for HIV trials. More recently, CABs have been adopted and used in other fields of medical research, such as malaria. CABs are not without limitations, however, and there is little research on the effectiveness of their use in achieving community protection and participation. Nevertheless, CABs could be a model to import into clinical trials and observational research where no alternative model of community representation is currently being used.ConclusionsAllocating more resources to training and shifting more power to community representatives could be part of the solution to current CAB limitations. However, for researchers to be able to apply these recommendations on community involvement, certain conditions need to be met. In particular, funding agencies need to recognize the human and financial resources required for serious community involvement, and the academic environment needs to take community involvement into account when appraising, mentoring, and training researchers.

AIDS Clinical Research in Spain-Large HIV Population, Geniality of Doctors, and Missing Opportunities.

The first cases of AIDS in Spain were reported in 1982. Since then over 85,000 persons with AIDS have been cumulated, with 60,000 deaths. Current estimates for people living with HIV are of 145,000, of whom 20% are unaware of it. This explains the still high rate of late HIV presenters. Although the HIV epidemic in Spain was originally driven mostly by injection drug users, since the year 2000 men having sex with men (MSM) account for most new incident HIV cases. Currently, MSM represent over 80% of new yearly HIV diagnoses. In the 80s, a subset of young doctors and nurses working at Internal Medicine hospital wards became deeply engaged in attending HIV-infected persons. Before the introduction of antiretrovirals in the earlier 1990s, diagnosis and treatment of opportunistic infections was their major task. A new wave of infectious diseases specialists was born. Following the wide introduction of triple combination therapy in the late 1990s, drug side effects and antiretroviral resistance led to built a core of highly devoted HIV specialists across the country. Since then, HIV medicine has improved and currently is largely conducted by multidisciplinary teams of health care providers working at hospital-based outclinics, where HIV-positive persons are generally seen every six months. Antiretroviral therapy is currently prescribed to roughly 75,000 persons, almost all attended at clinics belonging to the government health public system. Overall, the impact of HIV/AIDS publications by Spanish teams is the third most important in Europe. HIV research in Spain has classically been funded mostly by national and European public agencies along with pharma companies. Chronologically, some of the major contributions of Spanish HIV research are being in the field of tuberculosis, toxoplasmosis, leishmaniasis, HIV variants including HIV-2, drug resistance, pharmacology, antiretroviral drug-related toxicities, coinfection with viral hepatitis, design and participation in clinical trials with antiretrovirals, immunopathogenesis, ageing, and vaccine development.

HIV Medicine As double-sided Sword: Care and Prevention

The 20th Bangkok International Symposium on HIV Medicine Queen Sirikit National Convention Centre, Bangkok, Thailand, 17–19 January 2018.The HIV Netherlands Australia Thailand research collaboration (HIV-NAT) convened the 20th Bangkok Symposium on HIV medicine. The symposium, considered one of the most comprehensive clinical conferences on HIV in the Asia Pacific region, is held annually in January. The 2018 symposium was the second year straight in which the sessions were live webcast via the internet. The highlights of this year's sessions included prevention for HIV, the potentials for an end to HIV, management of hepatitis C infection, and a special session on same-day ART initiation.

Treatment advocate tactics to expand access to antiviral therapy for HIV and viral hepatitis C in low- to high-income settings: making sure no one is left behind.

IntroductionWorldwide, 71 million people are infected with hepatitis C virus (HCV), which, without treatment, can lead to liver failure or hepatocellular carcinoma. HCV co‐infection increases liver‐ and AIDS‐related morbidity and mortality among HIV‐positive people, despite ART. A 12‐week course of HCV direct‐acting antivirals (DAAs) usually cures HCV – regardless of HIV status. However, patents and high prices have created access barriers for people living with HCV, especially people who inject drugs (PWID). Inadequate access to and coverage of harm reduction interventions feed the co‐epidemics of HIV and HCV; as a result, the highest prevalence of HCV is found among PWID, who face additional obstacles to treatment (including stigma, discrimination and other structural barriers). The HIV epidemic occurred during globalization of intellectual property rights, and highlighted the relationship between patents and the high prices that prevent access to medicines. Indian generic manufacturers produced affordable generic HIV treatment, enabling global scale‐up. Unlike HIV, donors have yet to step forward to fund HCV programmes, although DAAs can be mass‐produced at a low and sustainable cost. Unfortunately, although voluntary licensing agreements between originators and generic manufacturers enable low‐income (and some lower‐middle income countries) to buy generic versions of HIV and HCV medicines, most middle‐income countries with large burdens of HCV infection and HIV/HCV co‐infection are excluded from these agreements. Our commentary presents tactics from the HIV experience that treatment advocates can use to expand access to DAAs.DiscussionA number of practical actions can help increase access to DAAs, including new research and development (R&D) paradigms; compassionate use, named‐patient and early access programmes; use of TRIPS flexibilities such as compulsory licences and patent oppositions; and parallel importation via buyers’ clubs. Together, these approaches can increase access to antiviral therapy for people living with HIV and viral hepatitis in low‐, middle‐ and high‐income settings.ConclusionsThe HIV example provides helpful parallels for addressing challenges to expanding access to HCV DAAs. HCV treatment access – and harm reduction – should be massively scaled‐up to meet the needs of PWID, and efforts should be made to tackle stigma and discrimination, and stop criminalization of drug use and possession.

Access to hepatitis C virus treatment: Lessons from implementation of strategies for increasing access to antiretroviral treatment

At September’s 2017 United Nations General Assembly, a state-of-the-art HIV medicine was announced to be made available at just $75 per person per year. There have been a number of strategies that the global AIDS community and countries have utilized to reduce prices and make antiretrovirals (ARVs) accessible for people living with HIV/AIDS. There appears to be an opportunity for the treatment of hepatitis C virus infection using direct-acting antivirals (DAAs) to benefit from the often painful and laboured history of driving down the prices of ARVs. In general, the success of lowering prices for ARVs has stemmed from the politics needed to initially support generic entry into the on-patent market. The use of flexibilities present in the World Trade Organization’s Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) have been used to overcome patent barriers, with the use of compulsory licenses and/or the threat of their use as instruments for strengthening the bargaining power in price negotiations.These strategies have been combined with new financing mechanisms that have promoted more effective procurement and price negotiations. Partnership among the different stakeholders has also been critical in this regard. Countries have also invested in their health systems and implemented several strategies to reduce stigma and discrimination to increase access to and improve utilization of ARVs. This article suggests that any future international initiatives to increase access to DAAs can learn from these lessons surrounding price reduction, improved financing, advocacy, as well as health systems strengthening and stigma reduction. Adopting and reconfiguring these strategies will also incur substantial savings in time, money and lives.

Editorial introductions

Editorial introductions

Chromatographic methods in HIV medicine: Application to therapeutic drug monitoring.

HIV antiretroviral therapy spans several different drug classes, meant to combat various aspects of viral infection and replication. Many authors have argued the benefits of therapeutic drug monitoring (TDM) for the HIV patient including compliance assurance and assessment of appropriate drug concentrations; however, the array of drug chemistries and combinations makes TDM an arduous task. HPLC-UV and LC-MS/MS are both frequent instruments for the quantification of HIV drugs in biological matrices with investigators striving to balance sensitivity and affordability. Plasma, the dominant matrix for these analyses, is prepared using protein precipitation, liquid-liquid extraction or solid-phase extraction depending on the specific complement of analytes. Despite the range of polarities found in drug classes relevant to HIV therapeutics, most chromatographic separations utilize a hydrophobic column (C18 ). Additionally, as the clinically relevant samples for these assays are infected with HIV, along with possible co-infections, another important aspect of sample preparation concerns viral inactivation. Although not routine in clinical practice, many published analytical methods from the previous two decades have demonstrated the ability to conduct TDM in HIV patients receiving various medicinal combinations. This review summarizes the analytical methods relevant to TDM of HIV drugs, while highlighting respective challenges.

Assessment of the benefits of and barriers to HIV pharmacist credentialing

ObjectivesTo ascertain the reasons for, benefits of, and barriers to pursuing the American Academy of HIV Medicine (AAHIVM) HIV Pharmacist (AAHIVP) credential. MethodsA cross-sectional study using an electronic self-administered survey was used. Two separate invitations to participate in online surveys were sent to pharmacists who practice in HIV-related settings: 1 to pharmacists with the AAHIVP credential and 1 to members of key pharmacy organizations and employers without the credential. The surveys assessed demographics, concurrent credentials and certifications, and factors influencing the pursuit of and benefits gained from having the AAHIVP credential (credentialed population) or barriers to pursuing the AAHIVP credential (credentialed and noncredentialed populations). ResultsThere were 192 participants (survey response rate 38.8%) in the credentialed population and 212 participants in the noncredentialed population. Perceived recognition as an HIV expert from pharmacist (n = 174; 90.6%) and physician (n = 162; 84.4%) peers was the main reason for credentialing; only 20.4% (n = 23/113) of participants’ employers reimbursed for the credential. Common reasons for nonpursuit included lack of employer incentive (n = 46; 26.6%) and lack of fee reimbursement (n = 38; 21.9%) in those aware of the credential. However, a majority of these noncredentialed participants reported they would be interested in pursuing credentialing (n = 152; 80.4%). ConclusionAAHIVP credentialing is sought and maintained on the basis of perceived intangible benefits, such as peer recognition, over tangible benefits, such as increased salary and reimbursement by third-party payers. Despite interest, a lack of employer reimbursement is perceived to be a barrier to AAHIVP credentialing among those who have not yet been credentialed.

Stockouts of HIV commodities in public health facilities in Kinshasa: Barriers to end HIV.

Stockouts of HIV commodities increase the risk of treatment interruption, antiretroviral resistance, treatment failure, morbidity and mortality. The study objective was to assess the magnitude and duration of stockouts of HIV medicines and diagnostic tests in public facilities in Kinshasa, Democratic Republic of the Congo. This was a cross-sectional survey involving visits to facilities and warehouses in April and May 2015. All zonal warehouses, all public facilities with more than 200 patients on antiretroviral treatment (ART) (high-burden facilities) and a purposive sample of facilities with 200 or fewer patients (low-burden facilities) in Kinshasa were selected. We focused on three adult ART formulations, cotrimoxazole tablets, and HIV diagnostic tests. Availability of items was determined by physical check, while stockout duration until the day of the survey visit was verified with stock cards. In case of ART stockouts, we asked the pharmacist in charge what the facility coping strategy was for patients needing those medicines. The study included 28 high-burden facilities and 64 low-burden facilities, together serving around 22000 ART patients. During the study period, a national shortage of the newly introduced first-line regimen Tenofovir-Lamivudine-Efavirenz resulted in stockouts of this regimen in 56% of high-burden and 43% of low-burden facilities, lasting a median of 36 (interquartile range 29–90) and 44 days (interquartile range 24–90) until the day of the survey visit, respectively. Each of the other investigated commodities were found out of stock in at least two low-burden and two high-burden facilities. In 30/41 (73%) of stockout cases, the commodity was absent at the facility but present at the upstream warehouse. In 30/57 (54%) of ART stockout cases, patients did not receive any medicines. In some cases, patients were switched to different ART formulations or regimens. Stockouts of HIV commodities were common in the visited facilities. Introduction of new ART regimens needs additional planning.

Capacity building in HIV/AIDS care in antiretroviral therapy center through open and distance learning

The number of people living with HIV (PLHIV) in India is 26.26 lakhs (18.00–27.85 lakhs) as per annual report 2016–2017 of the National AIDS Control Organization (NACO). Till September 2016, 361 care and support centers were functional, and a total of 10,70,928 PLHIV received care and support services. There are 528 functional antiretroviral therapy (ART) centers and 1108 linked ART centers across the country including 88 ART plus centers till September 2016. About 2000 trained doctors would be needed to man these facilities. It is planned that MBBS doctors with Postgraduate (PG) Diploma in HIV Medicine (PGDHIVM) shall be considered for the post of senior medical officer at ART centers. The PGDHIVM would help to standardize HIV Medicine training and also help to bridge the gap in trained workforce for ART centers. With the above background, Indira Gandhi National Open University developed a 1-year program on HIV Medicine for MBBS doctors, which is being offered through open and distance learning in collaboration with NACO with the objectives that the learner would be able to imbibe comprehensive knowledge on basic of HIV as related to details of management of HIV/AIDS in tertiary care setup, manage all complications as well as opportunistic infections due to HIV/AIDS at time of need, and recognize and handle emergencies related to HIV/AIDS and its complication and take bedside decision for management whenever is required. This program comprises 36 credits (1 credit = 30 study hours), which is divided into four theory and two practical courses. All learners have been provided a total of 20 blocks having 76 units along with three practical logbooks as learning materials for this program. There are 28 days of hands-on skill training in medical colleges identified as the center of excellence by NACO and another 30-day training in an ART center. The program was launched in 2012, and 122 candidates have successfully completed it so far.

Concurrent HIV and Zika Virus Infection, A Problem to be Address in HIV Medicine

Dear Editor, the HIV infection is a worldwide distributed disease at present. The infection is the most common immunodeficiency disorder and is still the global public health threat. This disease is still non-curable and the continuous research aiming at the successful management of the disease is required. Mainly, HIV is transmitted by sexually contact, blood and blood contact, transplacental from mother to infant or organ receipt. The concurrence between HIV and other medical disorder is an interesting issue in HIV medicine. Of several medical disorders, the new emerging infection should be mentioned.

Assessment of a quality improvement intervention to strengthen pharmaceutical human resources and improve availability and use of HIV medicines in Uganda.

Inadequate medication dispensing and management by healthcare providers can contribute to poor outcomes among HIV-positive patients. Gaps in medication availability, often associated with pharmacy workforce shortages, are an important barrier to retention in HIV care in Uganda. An intervention to address pharmacy staffing constraints through strengthening pharmaceutical management, dispensing practices, and general competencies of facility clinical and pharmacy staff was implemented in 14 facilities in three districts in eastern Uganda. Teams of staff were organised in each facility and supported to apply quality improvement (QI) methods to address deficits in availability and rational use of HIV drugs. To evaluate the intervention, baseline and end line data were collected 24 months apart. Dispensing practices, clinical wellness and adherence to antiretrovirals improved by 45%, 28% and 20% from baseline to end line, respectively. All clients at end line received the medications prescribed, and medications were correctly, completely and legibly labelled more often. Clients better understood when, how much and for how long they were supposed to take their prescribed medicines at end line. Pharmaceutical management practices also improved from baseline in most categories by statistically significant margins. Facilities significantly improved on correctly recording stock information about antiretroviral drugs (53%vs100%, P<0.0001). Coinciding with existing staff taking on pharmaceutical roles, facilities improved management of unwanted and expired drugs, notably by optimising use of existing health workers and making pharmaceutical management processes more efficient. Implementation of this improvement intervention in the 14 facilities appeared to have a positive impact on client outcomes, pharmacy department management and providers’ self-reported knowledge of QI methods. These results were achieved at a cost of about US$5.50 per client receiving HIV services at participating facilities.