Impact of weight gain with dolutegravir on antiretroviral adherence and viral suppression in four African countries.

OBJECTIVE: We hypothesized that total body weight (TBW) gain after switching antiretroviral therapy (ART) regimen to tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD) may negatively impact ART adherence and viral load (VL) and therefore sought to examine these associations. METHODS: The ongoing African Cohort Study (AFRICOS) enrols people with HIV at 12 facilities in Kenya, Nigeria, Tanzania and Uganda supported by The US President's Emergency Plan for AIDS Relief. Among ART-experienced participants who switched to TLD, we used multivariable multinomial logistic regression to examine associations between pre-/post-TLD changes in percentage TBW (≥5% gain, <5% change, ≥5% loss) and changes in self-reported ART adherence (0, 1-2, ≥3 days missed doses in past 30 days) and VL [(<50 copies/mL (undetectable), 50-999 copies/mL (detectable, but suppressed), ≥1000 copies/mL (unsuppressed)]. RESULTS: Among 1508 participants, median time from starting TLD to follow-up was 9 months (interquartile range: 7-11). Overall, 438 (29.1%) participants experienced a TBW gain ≥5%, which was more common among females than among males (32.2% vs 25.2%, p = 0.005) and participants switching from efavirenz [32.0% vs nevirapine (19.9%) and boosted protease inhibitor (20.0%); p < 0.001]. Compared with a TBW change <5% [950 (63.0%) participants], TBW gain ≥5% was not significantly associated with more days with missed ART doses [adjusted odds ratio (aOR) = 0.77, 95% confidence interval (CI): 0.48-1.23] or VL becoming detectable and/or unsuppressed (aOR = 0.69, 95% CI: 0.41-1.16). CONCLUSIONS: Although a substantial proportion of participants experienced weight gain after switching to TLD, we did not identify a significant impact on adherence or virological outcomes.

Tuberculosis Preventive Treatment Scale-Up Among Antiretroviral Therapy Patients - 16 Countries Supported by the U.S. President's Emergency Plan for AIDS Relief, 2017-2019.

Tuberculosis (TB) is the leading cause of death among persons living with human immunodeficiency virus (HIV) infection. In 2018, an estimated 251,000 persons living with HIV infection died from TB, accounting for one third of all HIV-related deaths and one sixth of all TB deaths (1). TB preventive treatment (TPT) is recommended by the World Health Organization (WHO) for persons living with HIV infection without active TB disease (i.e., adults with a negative clinical symptom screen for cough, fever, night sweats, or weight loss; and children with a negative clinical screen for cough, fever, contact with a person with TB, or poor weight gain) and either without* a tuberculin skin test result or with a known positive result (2). TPT decreases morbidity and mortality among persons living with HIV infection, independent of antiretroviral therapy (ART) (3); however, in 2017, fewer than 1 million of the estimated 21.3 million ART patients started TPT worldwide. Most patients receiving TPT were treated with 6 months of daily isoniazid (1,4). This report summarizes data on TB symptom screening and TPT initiation and completion among ART patients in 16 countries supported by the U.S. President's Emergency Plan for AIDS† Relief (PEPFAR) during April 1, 2017-March 31, 2019. During this period, these 16 countries accounted for approximately 90% of PEPFAR-supported ART patients. During April 1, 2017-September 30, 2018, TB symptom screening increased from 54% to 84%. Overall, nearly 2 million ART patients initiated TPT, and 60% completed treatment during October 1, 2017-March 31, 2019. Although TPT initiations increased substantially, completion among those who initiated TPT increased only from 55% to 66%. In addition to continuing gains in initiation, improving retention after initiation and identifying barriers to TPT completion are important to increase TPT scale-up and reduce global TB mortality.

Evaluation of Automated Molecular Testing Rollout for Tuberculosis Diagnosis Using Routinely Collected Surveillance Data - Uganda, 2012-2015.

In 2012, Uganda introduced the use of GeneXpert MTB/RIF (Cepheid, Sunnyvale CA), a sensitive, automated, real-time polymerase chain reaction-based platform for tuberculosis (TB) diagnosis, for programmatic use among children, adults with presumptive human immunodeficiency virus (HIV)-associated TB, and symptomatic persons at risk for rifampicin (RIF)-resistant TB. The effect of using the platform's Xpert MTB/RIF assay on TB care and control was assessed using routinely collected programmatic data; in addition, a retrospective review of district quarterly summaries using abstracted TB register data from purposively selected facilities in the capital city of Kampala was conducted. Case notification rates were calculated and nonparametric statistical methods were used for analysis. No statistically significant differences were observed in case notification rates before and after the Xpert MTB/RIF assay became available, although four of 10 districts demonstrated a statistically significant difference in bacteriologically confirmed TB. Once the GeneXpert MTB/RIF platform is established and refined, a more comprehensive evaluation should be conducted.

Association between Mycobacterium tuberculosis complex phylogenetic lineage and acquired drug resistance.

BACKGROUND: Development of resistance to antituberculosis drugs during treatment (i.e., acquired resistance) can lead to emergence of resistant strains and consequent poor clinical outcomes. However, it is unknown whether Mycobacterium tuberculosis complex species and lineage affects the likelihood of acquired resistance. METHODS: We analyzed data from the U.S. National Tuberculosis Surveillance System and National Tuberculosis Genotyping Service for tuberculosis cases during 2004-2011 with assigned species and lineage and both initial and final drug susceptibility test results. We determined univariate associations between species and lineage of Mycobacterium tuberculosis complex bacteria and acquired resistance to isoniazid, rifamycins, fluoroquinolones, and second-line injectables. We used Poisson regression with backward elimination to generate multivariable models for acquired resistance to isoniazid and rifamycins. RESULTS: M. bovis was independently associated with acquired resistance to isoniazid (adjusted prevalence ratio = 8.46, 95% CI 2.96-24.14) adjusting for HIV status, and with acquired resistance to rifamycins (adjusted prevalence ratio = 4.53, 95% CI 1.29-15.90) adjusting for homelessness, HIV status, initial resistance to isoniazid, site of disease, and administration of therapy. East Asian lineage was associated with acquired resistance to fluoroquinolones (prevalence ratio = 6.10, 95% CI 1.56-23.83). CONCLUSIONS: We found an association between mycobacterial species and lineage and acquired drug resistance using U.S. surveillance data. Prospective clinical studies are needed to determine the clinical significance of these findings, including whether rapid genotyping of isolates at the outset of treatment may benefit patient management.

Survival among patients with HIV infection and smear-negative pulmonary tuberculosis - United States, 1993-2006.

BACKGROUND: In patients with HIV and tuberculosis (TB) in resource-constrained settings, smear-negative disease has been associated with higher mortality than smear-positive disease. Higher reported mortality may be due to misdiagnosis, diagnostic delays, or because smear-negative disease indicates more advanced immune suppression. METHODS: We analyzed culture-confirmed, pulmonary TB among patients with TB and HIV in the United States from 1993-2008 to calculate prevalence ratios (PRs) for smear-negative disease by demographic and clinical characteristics. Allowing two years for treatment outcome to be reported, we determined hazard ratios (HRs) for survival by smear status, adjusted for significant covariates on patients before 2006. RESULTS: Among 16,710 cases with sputum smear results, 6,739 (39%) were sputum smear-negative and 9,971 (58%) were sputum smear-positive. The prevalence of smear-negative disease was lower in male patients (PR: 0.89, 95% confidence interval [CI]: 0.86-0.93) and in those who were homeless (PR: 0.92, CI: 0.87-0.97) or used alcohol excessively (PR: 0.91, CI: 0.87-0.95), and higher in persons diagnosed while incarcerated (PR: 1.20, CI: 1.13-1.27). Patients with smear-negative disease had better survival compared to patients with smear-positive disease, both before (HR: 0.82, CI: 0.75-0.90) and after (HR: 0.81, CI: 0.71-0.92) the introduction of combination anti-retroviral therapy. CONCLUSIONS: In the United States, smear-negative pulmonary TB in patients with HIV was not associated with higher mortality, in contrast to what has been documented in high TB burden settings. Smear-negative TB can be routinely and definitively diagnosed in the United States, whereas high-burden countries often rely solely on AFB-smear microscopy. This difference could contribute to diagnostic and treatment delays in high-burden countries, possibly resulting in higher mortality.