Casting a Wide Net: HIV Drug Resistance Monitoring in Pre-Exposure Prophylaxis Seroconverters in the Global Evaluation of Microbicide Sensitivity Project

Lisa Levy; Jill M. Peterson; Lauren D. Kudrick; Bhavna Chohan; Everline Bosek; Irene Mukui; Mary Mugambi; Sarah Masyuko; Owen Mugurungi; Nonhlanhla Ndlovu; Imelda Mahaka; Megan Dunbar; Anita Hettema; Rudo A.P. Kuwengwa; Sindy Matse; Saiqa Mullick; Letitia Greener; Cara O'Connor; Diantha Pillay; Maria Fawzy; John W. Mellors; Urvi M. Parikh; the Global Evaluation of Microbicide Sensitivity (GEMS) project

doi:10.9745/GHSP-D-21-00122

Figures & Tables

Figures

Tables
Additional Files

Download figure
Open in new tab
Download powerpoint
FIGURE
Global Evaluation of Microbicide Sensitivity HIV Drug Resistance Monitoring Toolkit^a
Abbreviations: DBS, dried blood spot; HIVDR, HIV drug resistance; PrEP, pre-exposure prophylaxis; SOP, standard operating procedure.
^aThe Global Evaluation of Microbicide Sensitivity HIV Drug Resistance Monitoring Toolkit was developed to support implementation for pre-exposure prophylaxis resistance monitoring. The toolkit contains customizable materials for health care workers, laboratory personnel, policy makers, and project implementers including standard operating procedures, job aids, fact sheets, monitoring and evaluation plans, and training modules. The toolkit is available online at prepwatch.org/gems and gems.pitt.edu.
Download figure
Open in new tab
Download powerpoint
A Global Evaluation of Microbicide Sensitivity specimen collection kit was provided to pre-exposure prophylaxis (PrEP) delivery sites that included the following components: (A) Laboratory requisition form that includes date of PrEP initiation, date of detected seroconversion, client demographics, and self-reported adherence information; Chain of custody form for sample tracking; and Informed consent form to be signed by the client before sample collection. (B) Venipuncture blood collection materials including sterile wipe, ethylenediamine tetraacetic acid (EDTA) blood collection tube, needle, cotton wool, and plaster bandage; (C) Blood transfer materials including transfer pipette and 2 dried blood spot cards (one each for HIV drug resistance and drug-level testing); (D) Dried blood spot shipment and storage materials including desiccants, glassine envelopes, and sealable plastic bags. A shipping envelope with the address of the laboratory and prepaid postage was also provided. © 2018 Lauren Kudrick/University of Pittsburgh.

View popup

TABLE 1.

Considerations for Collecting Blood Samples for HIV Drug Resistance Monitoring^32–34

Sample Type	Storage	Transport and Shipment	Equipment	Training Needed	Blood Testing Capability
DBS	Ambient temperature storage for up to 14^{^a} days; Long term storage in non-frost-free -20°C freezer or ≤-70°C freezer	DBS cards may be transported in an envelope to the lab at ambient temperature within 14 days	DBS cards, blood tube, and pipette to spot the cards	Minimal training required; clinical staff may have DBS experience with infant HIV testing	Five spots (per DBS card), limiting amount of blood available for testing; quality control or troubleshooting
Whole blood (for plasma)	Whole blood can be refrigerated prior to shipment (up to 24 hours) or immediately processed for plasma to be kept in ≤-70°C freezer for storage	Whole blood optimally shipped using ice packs; Plasma must be shipped on dry ice and stored at ≤-70°C	EDTA blood tube to collect whole blood (heparin not suitable); centrifuge needed to separate plasma from blood	Minimal training required for whole blood collection; additional laboratory training required for plasma preparation	Quantity of blood collected in tube allows for HIVDR, with leftover blood available for quality control or troubleshooting

Abbreviations: DBS, dried blood spot; EDTA, ethylenediaminetetraacetic acid; HIVDR, HIV drug resistance.
↵a The GEMS project aimed to complete sample transport within 5 days.

View popup

TABLE 2.

HIVDR Monitoring Project Initiation by Country

Country	HIVDR Monitoring Approach	Implementing Partners	Timeline for IRB/EC Approvals^{^a}	Training Strategy	Laboratory Location and Sample Type
Eswatini	National seroconverter protocol, led by MOH	MOH, CHAI, private, and public national health facilities offering PrEP	3 months	Regional training approach (11 trainings/ 231 participants) and 5 add-on trainings (143 participants)	Johannesburg, South Africa; DBS and whole blood collected
Kenya	National seroconverter protocol, led by Kenyan investigators including MOH	MOH, CASCOs, POWER, Partners-Scale Up, PrIMA, PrIYA, LVCT Health, Jilinde, SWOP, CHAK, CHS, IRDO, PATH, APHIA, KEMRI Welcome Trust, Kilifi, NRHS, NOPE, I Choose Life, EGPAF, KENSHE, DPEP	3 months	Train-the-trainer approach (20 individual trainings conducted at county level and with individual partner organizations); additional training of PrEP service providers in the 10 highest incidence counties	Kisumu Kenya; DBS is primary method; however, plasma samples collected where possible, in case of DBS testing challenges
Zimbabwe	National seroconverter protocol, led by Zimbabwean investigators including MOHCC	MOHCC, PZAT, PSI, Zim-TTECH, CeSSHAR, OPHID, and national health clinics	4 months	Train-the-trainer approach (25 individual trainings conducted across project partners)	Johannesburg, South Africa; DBS is primary method; however, plasma samples collected where possible, in case of DBS testing challenges
South Africa	Individual demonstration projects providing PrEP to a limited number of health facilities	POWER, CHARISMA, Project PrEP Wits RHI/Unitaid, Wits RHI/Key Populations, Wits RHI/PrEP SMART	Approximately 4-5 months for various projects	Comprehensive approach; all sites trained through project partners (9 individual trainings conducted across project partners)	Johannesburg, South Africa; whole blood sample collected and sent to laboratory for any site with laboratory pick up capabilities within one day; DBS samples collected at all other clinics

Abbreviations: APHIA, AIDS, Population & Health Integrated Assistance; CASCO, County AIDS and Sexually Transmitted Infection Coordinator; CeSSHAR, Centre for Sexual Health and HIV AIDS Research Zimbabwe; CHAI, Clinton Health Access Initiative; CHAK, Christian Health Association of Kenya; CHARISMA, Community Health Clinical Model for Agency in Relationships and Safer Microbicide Adherence; CHS, Center for Health Solutions-Kenya; DBS, dried blood spot; DPEP, doxycycline post-exposure prophylaxis for prevention of sexually transmitted infections; EGPAF, Elizabeth Glaser Pediatric AIDS Foundation; HIVDR, HIV drug resistance; IRDO, Impact Research and Development Organization; KEMRI, Kenya Medical Research Institute; The KEN-SHE Study, KENya Single-dose HPV-vaccine Efficacy; MOH, Ministry of Health; MOHCC, Ministry of Health and Child Care; NOPE, National Organization of Peer Educators; NRHS, Nyanza Reproductive Health Society; OPHID, Organization for Public Health Interventions & Development; POWER, Prevention Options for Women Evaluation Research; PrEP, pre-exposure prophylaxis; PrIMA, PrEP Implementation for Mothers in Antenatal Care, PrIYA, PrEP Implementation in Young Women and Adolescents; PSI, Population Services International; PZAT, Pangaea Zimbabwe AIDS Trust; SWOP, Sex Workers Outreach Project; Wits RHI/Unitaid, Project PrEP Wits Reproductive Health and HIV Institute Wits RHI/PrEP SMART (Sequential multiple assignment randomized trial); Zim-TTECH, Zimbabwe Training, Technical Assistance and Education Center for Health.
↵a Time from initial protocol submission to final institutional review board (IRB)/ethics committee (EC) approval.