Doravirine-associated resistance mutations in antiretroviral therapy naïve and experienced adults with HIV-1 subtype C infection in Botswana.

OBJECTIVES: There are limited data on the prevalence of doravirine (DOR)-associated drug resistance mutations in people with HIV (PWH) in Botswana. This cross-sectional, retrospective study aimed to explore the prevalence of DOR-associated resistance mutations among ART-naïve and -experienced PWH in Botswana enrolled in the population-based Botswana Combination Prevention Project (BCPP). METHODS: A total of 6078 HIV-1C pol sequences were analysed for DOR-associated resistance mutations using the Stanford HIV drug resistance database, and their levels were predicted according to the Stanford DRM penalty scores and resistance interpretation. Virologic failure was defined as HIV-1 RNA load (VL) >400 copies/mL. RESULTS: Among 6078 PWH, 5999 (99%) had known ART status, and 4529/5999 (79%) were on ART at time of sampling. The suppression rate among ART-experienced was 4517/4729 (96%). The overall prevalence of any DOR-associated resistance mutations was 181/1473 (12.3% [95% confidence interval {CI}: 10.7-14.1]); by ART status: 42/212 (19.8% [95% CI: 14.7-25.4]) among ART-failing individuals (VL ≥400 copies/mL) and 139/1261 (11.0% [95% CI: 9.3-12.9]) among ART-naïve individuals (P < 0.01). Intermediate DOR-associated resistance mutations were observed in 106/1261 (7.8% [95% CI: 6.9-10.1]) in ART-naïve individuals and 29/212 (13.7% [95% CI: 9.4-8.5]) among ART-experienced participants (P < 0.01). High-level DOR-associated resistance mutations were observed in 33/1261 (2.6% [95% CI: 1.8-3.7]) among ART-naïve and 13/212 (6.1% [95% CI: 3.6-10.8]) among ART-failing PWH (P < 0.01). PWH failing ART with at least one EFV/NVP-associated resistance mutation had high prevalence 13/67 (19.4%) of high-level DOR-associated resistance mutations. CONCLUSION: DOR-associated mutations were rare (11.0%) among ART-naive PWH but present in 62.7% of Botswana individuals who failed NNRTI-based ART with at least one EFV/NVP-associated resistance mutation. Testing for HIV drug resistance should underpin the use of DOR in PWH who have taken first-generation NNRTIs.

Leveraging Partnerships to Maximize Global Health Security Improvements in Guinea, 2015-2019.

In response to the 2014-2016 West Africa Ebola virus disease (EVD) outbreak, a US congressional appropriation provided funds to the US Centers for Disease Control and Prevention (CDC) to support global health security capacity building in 17 partner countries, including Guinea. The 2014 funding enabled CDC to provide more than 300 deployments of personnel to Guinea during the Ebola response, establish a country office, and fund 11 implementing partners through cooperative agreements to support global health security engagement efforts in 4 core technical areas: workforce development, surveillance systems, laboratory systems, and emergency management. This article reflects on almost 4 years of collaboration between CDC and its implementing partners in Guinea during the Ebola outbreak response and the recovery period. We highlight examples of collaborative synergies between cooperative agreement partners and local Guinean partners and discuss the impact of these collaborations in strengthening the above 4 core capacities. Finally, we identify the key elements of the successful collaborations, including communication and information sharing as a core cooperative agreement activity, a flexible funding mechanism, and willingness to adapt to local needs. We hope these observations can serve as guidance for future endeavors seeking to establish strong and effective partnerships between government and nongovernment organizations providing technical and operational assistance.

Prevalence of transmitted HIV drug resistance in Botswana: lessons learned from the HIVDR-Threshold Survey conducted among women presenting for routine antenatal care as part of the 2007 national sentinel survey.

The emergence and spread of transmitted drug resistance (TDR) poses a major threat to the success of the rapidly expanding antiretroviral treatment (ART) programs in resource-limited countries. The World Health Organization recommends the use of the HIV Drug Resistance Threshold Survey (HIVDR-TS) as an affordable means to monitor the presence of TDR in these settings. We report our experiences and results of the 2007 HIVDR-TS in Botswana, a country with one of the longest-existing national public ART programs in Africa. The HIVDR-TS and HIV-1 incidence testing were performed in the two largest national sites as part of the 2007 antenatal Botswana Sentinel Survey. The HIVDR-TS showed no significant drug resistance mutations (TDR less than 5%) in one site. TDR prevalence, however, could not be ascertained at the second site due to low sample size. The agreement between HIVDR-TS eligibility criteria and laboratory-based methodologies (i.e., BED-CEIA and LS-EIA) in identifying recently HIV-1 infected adults was poor. Five years following the establishment of Botswana's public ART program, the prevalence of TDR remains low. The HIVDR-TS methodology has limitations for low-density populations as in Botswana, where the majority of antenatal sites are too small to recruit sufficient numbers of patients. In addition, the eligibility criteria (age <25 years and parity (first pregnancy)) of the HIVDR-TS performed poorly in identifying recent HIV-1 infections in Botswana. An alternative sampling strategy should be considered for the surveillance of HIVDR in Botswana and similar geographic settings.

Ensuring the quality of HIV rapid testing in resource-poor countries using a systematic approach to training.

HIV rapid testing is a key tool in the fight against the HIV/AIDS epidemic; it enables the rapid expansion of prevention and treatment programs in resource-limited countries. Meeting the goals of these programs means that millions of people will need testing annually. Accuracy and reliability of these tests are critical to the success of these programs. Given the enormous number of rapid tests that are performed each year, even a low error rate of 0.5% applied to 100 million people will result in 500,000 erroneous results. Ensuring the quality of HIV rapid testing presents unique challenges in that testing is often performed in various settings by personnel without formal laboratory training. This article describes the development and implementation of a generic HIV rapid test training package using a systems approach in an effort to standardize training and ensure the quality of rapid tests. It also highlights achievements from Uganda, Haiti, and Botswana.