G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests

Malaria elimination will be possible only with serious attempts to address asymptomatic infection and chronic infection by both Plasmodium falciparum and Plasmodium vivax. Currently available drugs that can completely clear a human of P. vivax (known as “radical cure”), and that can reduce transmission of malaria parasites, are those in the 8-aminoquinoline drug family, such as primaquine. Unfortunately, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency risk having severe adverse reactions if exposed to these drugs at certain doses. G6PD deficiency is the most common human enzyme defect, affecting approximately 400 million people worldwide. Scaling up radical cure regimens will require testing for G6PD deficiency, at two levels: 1) the individual level to ensure safe case management, and 2) the population level to understand the risk in the local population to guide Plasmodium vivax treatment policy. Several technical and operational knowledge gaps must be addressed to expand access to G6PD deficiency testing and to ensure that a patient’s G6PD status is known before deciding to administer an 8-aminoquinoline-based drug. In this report from a stakeholder meeting held in Thailand on October 4 and 5, 2012, G6PD testing in support of radical cure is discussed in detail. The focus is on challenges to the development and evaluation of G6PD diagnostic tests, and on challenges related to the operational aspects of implementing G6PD testing in support of radical cure. The report also describes recommendations for evaluation of diagnostic tests for G6PD deficiency in support of radical cure

A pilot program of HIV pre-exposure prophylaxis in Thai youth.

IntroductionThere are gaps in knowledge and experience of antiretroviral pre-exposure prophylaxis (PrEP) delivery in adolescents.MethodsThis pilot study enrolled Thai adolescents 14-20 year-old without HIV who reported risk behaviour. All participants were offered daily tenofovir/emtricitabine (TDF-FTC) and followed for 24 weeks. HIV testing, renal function, bone density scan, and sexually transmitted infection (STI) testing including syphilis serology and urine molecular testing for gonorrhoea and C. trachomatis were performed at baseline and weeks 12 and 24. Adherence was evaluated through intracellular tenofovir diphosphate (TFV-DP) levels in dried blood spots.ResultsOf the 61 enrolled adolescents, median age 18.1 (IQR: 14.8-20.9) years, 46 (75.4%) were males and 36 (59%) were MSM. Retention to week 24 was 80.3%. One third (36%) had TFV-DP levels consistent with taking ≥6 pills/week at week 12 and 29% at week 24. The factors associated with taking ≥6 pills/week were being MSM (adjusted odds ratio [aOR]: 53.2, 95% CI: 1.6-1811; p = 0.027), presence of STI at baseline (aOR: 9.4, 95% CI: 1.5-58.5; p = 0.016), and self-report of decreased condom use while taking PrEP (aOR: 8.7, 95% CI: 1.4-56.6; p = 0.023). 31% had an STI at baseline and this declined to 18% at week 24. No renal or bone toxicity was observed and there were no HIV seroconversions.ConclusionsDaily oral PrEP with FTC-TDF in high-risk Thai adolescents is feasible, accepted, well-tolerated, and had no increased risk compensation; however, low adherence was a major challenge. Adolescent-specific PrEP strategies including long-acting modalities are needed for successful HIV prevention

Bone mineral density and kidney function in adolescents taking tenofovir disoproxil fumarate-emtricitabine for pre-exposure prophylaxis.

Bone mineral density and kidney function in adolescents taking tenofovir disoproxil fumarate-emtricitabine for pre-exposure prophylaxis.</p

Factors associated with adherence to pre-exposure prophylaxis treatment among participants retained at week 24.

Factors associated with adherence to pre-exposure prophylaxis treatment among participants retained at week 24.</p

Adherence to pre-exposure prophylaxis treatment in participants determined by TFV-DP concentration at week 12 and 24.

TFV-DP categories were based on ≥ 700 fmol/punch for ≥ 4 doses/week, ≥ 1050 fmol/punch for ≥ 6 doses/week, and ≥ 1250 fmol/punch for 7 doses/week.</p

Factors associated with adherence to pre-exposure prophylaxis treatment among male participants retained at week 12.

Factors associated with adherence to pre-exposure prophylaxis treatment among male participants retained at week 12.</p

TFV-DP concentrations among participants by gender and adherence at week 12 and 24.

TFV-DP concentrations among participants by gender and adherence at week 12 and 24.</p

Factors associated with adherence to pre-exposure prophylaxis treatment among male participant retained at week 24.

Factors associated with adherence to pre-exposure prophylaxis treatment among male participant retained at week 24.</p

Factors associated with adherence to pre-exposure prophylaxis treatment among participants retained at week 12.

Factors associated with adherence to pre-exposure prophylaxis treatment among participants retained at week 12.</p

Participant demographics and characteristics.

IntroductionThere are gaps in knowledge and experience of antiretroviral pre-exposure prophylaxis (PrEP) delivery in adolescents.MethodsThis pilot study enrolled Thai adolescents 14–20 year-old without HIV who reported risk behaviour. All participants were offered daily tenofovir/emtricitabine (TDF-FTC) and followed for 24 weeks. HIV testing, renal function, bone density scan, and sexually transmitted infection (STI) testing including syphilis serology and urine molecular testing for gonorrhoea and C. trachomatis were performed at baseline and weeks 12 and 24. Adherence was evaluated through intracellular tenofovir diphosphate (TFV-DP) levels in dried blood spots.ResultsOf the 61 enrolled adolescents, median age 18.1 (IQR: 14.8–20.9) years, 46 (75.4%) were males and 36 (59%) were MSM. Retention to week 24 was 80.3%. One third (36%) had TFV-DP levels consistent with taking ≥6 pills/week at week 12 and 29% at week 24. The factors associated with taking ≥6 pills/week were being MSM (adjusted odds ratio [aOR]: 53.2, 95% CI: 1.6–1811; p = 0.027), presence of STI at baseline (aOR: 9.4, 95% CI: 1.5–58.5; p = 0.016), and self-report of decreased condom use while taking PrEP (aOR: 8.7, 95% CI: 1.4–56.6; p = 0.023). 31% had an STI at baseline and this declined to 18% at week 24. No renal or bone toxicity was observed and there were no HIV seroconversions.ConclusionsDaily oral PrEP with FTC-TDF in high-risk Thai adolescents is feasible, accepted, well-tolerated, and had no increased risk compensation; however, low adherence was a major challenge. Adolescent-specific PrEP strategies including long-acting modalities are needed for successful HIV prevention.</div