Virological Findings and Treatment Outcomes of Cases That Developed Dolutegravir Resistance in Malawi's National HIV Treatment Program.

Millions of Africans are on dolutegravir-based antiretroviral therapy (ART), but few detailed descriptions of dolutegravir resistance and its clinical management exist. We reviewed HIV drug resistance (HIVDR) testing application forms submitted between June 2019 and October 2022, data from the national HIVDR database, and genotypic test results. We obtained standardized ART outcomes and virological results of cases with dolutegravir resistance, and explored associations with dolutegravir resistance among individuals with successful integrase sequencing. All cases were on two nucleoside reverse transcriptase inhibitors (NRTIs)/dolutegravir, and had confirmed virological failure, generally with prolonged viremia. Among 89 samples with successful integrase sequencing, 24 showed dolutegravir resistance. Dolutegravir resistance-associated mutations included R263K (16/24), E138K (7/24), and G118R (6/24). In multivariable logistic regression analysis, older age and the presence of high-level NRTI resistance were significantly associated with dolutegravir resistance. After treatment modification recommendations, four individuals (17%) with dolutegravir resistance died, one self-discontinued ART, one defaulted, and one transferred out. Of the 17 remaining individuals, 12 had follow-up VL results, and 11 (92%) were <1000 copies/mL. Twenty-four cases with dolutegravir resistance among 89 individuals with confirmed virological failure suggests a considerable prevalence in the Malawi HIV program. Successful management of dolutegravir resistance was possible, but early mortality was high. More research on the management of treatment-experienced individuals with dolutegravir resistance is needed.

Dolutegravir Resistance in Malawi's National HIV Treatment Program.

Dolutegravir HIV drug resistance (HIVDR) data from Africa remain sparse. We reviewed HIVDR results of Malawians on dolutegravir-based antiretroviral therapy (November 2020-September 2021). Of 6462 eligible clients, 33 samples were submitted to South Africa, 27 were sequenced successfully, and 8 (30%) had dolutegravir HIVDR. Malawi urgently requires adequate HIVDR testing capacity.

Diagnostic Utility and Impact on Clinical Decision Making of Focused Assessment With Sonography for HIV-Associated Tuberculosis in Malawi: A Prospective Cohort Study.

BACKGROUND: The focused assessment with sonography for HIV-associated tuberculosis (TB) (FASH) ultrasound protocol has been increasingly used to help clinicians diagnose TB. We sought to quantify the diagnostic utility of FASH for TB among individuals with HIV in Malawi. METHODS: Between March 2016 and August 2017, 210 adults with HIV who had 2 or more signs and symptoms that were concerning for TB (fever, cough, night sweats, weight loss) were enrolled from a public HIV clinic in Lilongwe, Malawi. The treating clinicians conducted a history, physical exam, FASH protocol, and additional TB evaluation (laboratory diagnostics and chest radiography) on all participants. The clinician made a final treatment decision based on all available information. At the 6-month follow-up visit, we categorized participants based on clinical outcomes and diagnostic tests as having probable/confirmed TB or unlikely TB; association of FASH with probable/confirmed TB was calculated using Fisher's exact tests. The impact of FASH on empiric TB treatment was determined by asking the clinicians prospectively about whether they would start treatment at 2 time points in the baseline visit: (1) after the initial history and physical exam; and (2) after history, physical exam, and FASH protocol. RESULTS: A total of 181 participants underwent final analysis, of whom 56 were categorized as probable/confirmed TB and 125 were categorized as unlikely TB. The FASH protocol was positive in 71% (40/56) of participants with probable/confirmed TB compared to 24% (30/125) of participants with unlikely TB (odds ratio=7.9, 95% confidence interval=3.9,16.1; P<.001). Among those classified as confirmed/probable TB, FASH increased the likelihood of empiric TB treatment before obtaining any other diagnostic studies from 9% (5/56) to 46% (26/56) at the point-of-care. For those classified as unlikely TB, FASH increased the likelihood of empiric treatment from 2% to 4%. CONCLUSION: In the setting of HIV coinfection in Malawi, FASH can be a helpful tool that augments the clinician's ability to make a timely diagnosis of TB.

M#1045: Training Course in Focused Assessment with Sonography for HIV/TB in HIV Prevalent Medical Centers in Malawi.

PURPOSE: Training medical providers of different backgrounds the "focused assessment with sonography for HIV-associated TB" (FASH) exam to expand the availability of ultrasound for TB diagnosis in resource poor settings in the central region of Malawi. METHODS AND MATERIALS: A survey was completed by the 19 eligible participants before and after a 4-day training course regarding the utility of the FASH exam. A six-question quiz was used to assess knowledge of the use of ultrasound in the FASH exam before and after the course. RESULTS: Participants' knowledge of the FASH technique significantly improved after the four-day course with a 32% increase in total quiz questions answered correctly (p<0.001).Ninety-five percent (n= 18) of participants answered that they would "likely" incorporate FASH in their clinical practice. Furthermore, 100% (n=19) of participants agreed that the FASH exam would improve their ability to diagnose TB and 95% (n=18) agreed that FASH would improve patient care in their clinic. CONCLUSIONS: After completing a 4-day training course, medical providers were more knowledgeable about the FASH exam and its findings, and felt more comfortable using ultrasound for the diagnosis of TB. Participants were also unanimous in opinion that the FASH ultrasound exam would improve their ability to diagnose TB.

Supporting Quality Data Systems: Lessons Learned from Early Implementation of Routine Viral Load Monitoring at a Large Clinic in Lilongwe, Malawi.

Successful viral load programs rely on the presence of data systems and high quality of patient data. Using a cohort of 49 patients at Partners in Hope, a large, urban HIV clinic in Malawi, we performed a quality improvement assessment of a new viral load program with a focus on accuracy of data collected from patients as well as adherence to Malawi HIV Guidelines in regard to response to elevated viral loads (≥1,000 copies/mL). Data were obtained from three parallel medical record systems to investigate the proportion of patients with a repeat viral load and whether the three data systems agreed in regard to sociodemographic and clinical data. Fewer than 30% of patients had a repeat viral load within six months, as recommended in the Malawi HIV Guidelines. There were significant problems with data agreement across the three parallel databases used for care. Date of birth was consistent for 55.1% (N=27) of patients, while a different date of birth was noted in all three sources for 10.2% of pateints (N=1). For 65.3% (N=32), the viral load from the laboratory did not match the recorded viral load in the electronic or paper record. Scale-up of viral load monitoring must be accompanied by the development of data systems that support workflow from sample collection to lab and back to provider. Education of providers and strategies for data collection with minimal errors can facilitate scale-up of high quality programs.

Feasibility and Acceptability of Cryptococcal Antigen Screening and Prevalence of Cryptocococcemia in Patients Attending a Resource-Limited HIV/AIDS Clinic in Malawi.

BACKGROUND: The World Health Organization (WHO) recommends screening patients living with AIDS to detect and treat early cryptococcal infection. METHODS: The authors evaluated a cryptococcal antigen (CrAg) screening and treatment program at an HIV/AIDS clinic in Malawi. Eligible patients were of age >18 years, had a CD4 count <100 cells/µL or WHO clinical HIV/AIDS stage III or IV. RESULTS: Of 552 patients who presented for care, 113 were eligible, and all (100%) agreed to CrAg screening. Of them, 2 (1.8%; 95% confidence interval [CI]: 0-4.2%) patients were CrAg positive. Among those with CD4 count <100 cells/µL or WHO stage IV, the CrAg prevalence was 3.5% (95% CI: 0-8.4%) and 5.0% (95% CI: 0-15%), respectively. CONCLUSION: A CrAg screening program was acceptable to new patients in a Malawian HIV/AIDS clinic. The CrAg prevalence for patients with CD4 count < 100 cells/µL and WHO stage IV was consistent with cost-effectiveness estimates. CrAg screening and treatment programs for patients living with AIDS should be expanded.

Validation of rapid HIV antibody tests in 5 African countries.

The sensitivity and specificity of 3 rapid HIV antibody tests were assessed at 5 clinical trial sites in Africa and 1 site in the United States using a minimum of 100 HIV antibody positive samples and 100 HIV antibody negative samples at each site. The overall sensitivity and specificity for the OraSure OraQuick, Abbott Determine, and Trinity Unigold tests were 99.3%, 99.8%, and 98.5%, respectively, and 99.3%, 99.4%, and 99.5%, respectively. There were no instances at any site in which false-negative or false-positive results were obtained for the same sample on more than 1 rapid test kit. The results of this study provide assurance that for these diverse sites in Africa, the accuracy of these kits is quite good. Given the excellent accuracy, relatively fast turnaround time, and minimal infrastructure required, these rapid tests for HIV antibody provide a very attractive and accurate testing format.