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

BACKGROUND: Evidence of HIV drug resistance (HIVDR) in individuals using oral pre-exposure prophylaxis (PrEP) who acquire HIV is limited to clinical trials and case studies. More data are needed to understand the risk of HIVDR with oral PrEP during PrEP rollout. Mechanisms to collect these data vary, and are dependent on cost, scale of PrEP distribution, and in-country infrastructure for the identification, collection, and testing of samples from PrEP seroconverters. METHODS: The Global Evaluation of Microbicide Sensitivity (GEMS) project, in collaboration with country stakeholders, initiated HIVDR monitoring among new HIV seroconverters with prior PrEP use in Eswatini, Kenya, South Africa, and Zimbabwe. Standalone protocols were developed to assess HIVDR among a national sample of PrEP users. In addition, HIVDR testing was incorporated into existing demonstration projects for key populations. LESSONS LEARNED: Countries are supportive of conducting a time-limited evaluation of HIVDR during the early stages of PrEP rollout. As PrEP rollout expands, the need for long-term HIVDR monitoring with PrEP will need to be balanced with maintaining national HIV drug resistance surveillance for pretreatment and acquired drug resistance. Laboratory capacity is a common obstacle to setting up a monitoring system. CONCLUSIONS: Establishing HIV resistance monitoring within PrEP programs is feasible. Approaches to drug resistance monitoring may evolve as the PrEP programs mature and expand. The methods and implementation support offered by GEMS assisted countries in developing methods to monitor for drug resistance that best fit their PrEP program needs and resources.

The Impact of Same-Day Antiretroviral Therapy Initiation Under the World Health Organization Treat-All Policy.

Rapid initiation of antiretroviral therapy (ART) is recommended for people living with human immunodeficiency virus (HIV), with the option to start treatment on the day of diagnosis (same-day ART). However, the effect of same-day ART remains unknown in realistic public sector settings. We established a cohort of ≥16-year-old patients who initiated first-line ART under a treat-all policy in Nhlangano (Eswatini) during 2014-2016, either on the day of HIV care enrollment (same-day ART) or 1-14 days thereafter (early ART). Directed acyclic graphs, flexible parametric survival analysis, and targeted maximum likelihood estimation (TMLE) were used to estimate the effect of same-day-ART initiation on a composite unfavorable treatment outcome (loss to follow-up, death, viral failure, treatment switch). Of 1,328 patients, 839 (63.2%) initiated same-day ART. The adjusted hazard ratio of the unfavorable outcome was higher, 1.48 (95% confidence interval: 1.16, 1.89), for same-day ART compared with early ART. TMLE suggested that after 1 year, 28.9% of patients would experience the unfavorable outcome under same-day ART compared with 21.2% under early ART (difference: 7.7%; 1.3%-14.1%). This estimate was driven by loss to follow-up and varied over time, with a higher hazard during the first year after HIV care enrollment and a similar hazard thereafter. We found an increased risk with same-day ART. A limitation was that possible silent transfers that were not captured.

Assessing the adoption of lopinavir/ritonavir oral pellets for HIV-positive children in Zimbabwe.

INTRODUCTION: Heat-stable lopinavir/ritonavir (LPV/r) oral pellets were developed to overcome challenges with administration and storage experienced with previously available tablet and syrup forms of LPV/r prescribed to paediatric HIV patients. We report on the adoption of LPV/r pellets for infants living with HIV in the public sector antiretroviral therapy (ART) programme in Zimbabwe. METHODS: Infants aged three months to three years who had been prescribed a LPV/r-based regimen (including ART-naïve patients) in fourteen facilities across the country were eligible to receive the pellets. Caregivers were counselled on the new formulation and provided with administration guides. A caregiver questionnaire was administered three to four months after the child initiated on pellets. Data were also extracted from patient ART records. RESULTS AND DISCUSSION: One hundred and fifty-seven children were enrolled (median age: 21 months; interquartile range 11.8 to 29.4). Survey data from 74 caregivers were included for analysis. Eighty-one per cent of the caregivers preferred pellets while 19% preferred the syrup formulation. Eighty-nine per cent assessed their child's response to taking the pellets as good or very good. Overall, 46% did not report any challenges while 54% reported one or more challenges with using the pellets. Difficulties with administration included: poor taste (36%; 26 participants); swallowing pellets (16%; 12 participants); finishing the dose (14%; 10 participants); and opening the capsule (10%; seven participants). Caregivers who were not confident to instruct others on pellet administration were 5.64 (95% confidence interval 1.45 to 21.95, p = 0.013) times as likely to experience a challenge. CONCLUSIONS: A large proportion of caregivers preferred pellets to other formulations of LPV/r and reported a good response to pellets; however, they also reported challenges with administration. Counselling should focus on ensuring that caregivers can confidently administer pellets and are able to instruct others, to ensure high uptake and good adherence to treatment. LPV/r pellets may be an acceptable substitute for other available forms of LPV/r for eligible children under three years if they are currently on or in need of LPV/r-containing regimens; however, challenges with administration still highlight the need for improved drug formulations for paediatric ART patients.