A national audit of the management of HIV-2 in adults in the UK.

BACKGROUND: HIV-2 is rare in the UK. Many UK centres therefore only treat small numbers of people and there are few clinical trials to guide treatment. The British HIV Association (BHIVA) 2010 guidelines for management of HIV-2 formed the basis for this national audit, which aims to describe current practice and adherence to guidelines. METHODS: All UK centres providing HIV care were contacted via the BHIVA "Members Matters" newsletter, and asked to submit anonymised, retrospective data for individuals living with HIV-2 accessing care at their service. RESULTS: Thirty-five sites responded and data were analysed for 167 individuals. Nearly half of individuals accessed care at one of four large London centres (77/167, 46%).Most people living with HIV-2 have taken antiretroviral therapy (ART) (132/167, 79%). The most common reasons for initiating treatment were clinical disease (34/89, 38%) and pregnancy (11/89, 12%). Most treatment-naïve individuals were initiated on a protease inhibitor based regimen (70/89, 79%). The use of integrase strand transfer inhibitor based regimens has increased over time.A significant minority of patients did not have baseline drug resistance testing performed, despite having a detectable viral load (15/52, 29%). Virological failure occurred in a minority of individuals (21/132, 16%); the most common drug regimen change in this context was the addition of an integrase strand transfer inhibitor (12/26 regimen changes, 46%). CONCLUSIONS: Most individuals living with HIV-2 were managed according to national guidance, with key areas for improvement including the choice of ART, drug resistance testing and the management of virological failure. It is hoped that this national audit, performed in conjunction with the updated 2021 BHIVA guidelines will improve the care of individuals living with HIV-2 in the UK.

Incidence of and risk factors for tuberculosis among people with HIV on antiretroviral therapy in the United Kingdom.

OBJECTIVE: The United Kingdom has a low tuberculosis incidence and earlier combination antiretroviral therapy (cART) is expected to have reduced incidence among people with HIV. Epidemiological patterns and risk factors for active tuberculosis were analysed over a 20-year period among people accessing HIV care at sites participating in the UK CHIC observational study. DESIGN: Cohort analysis. METHODS: Data were included for individuals over 15 years old attending for HIV care between 1996 and 2017 inclusive, with at least 3 months follow-up recorded. Incidence rates of new tuberculosis events were calculated and stratified by ethnicity (white/Black/other) as a proxy for tuberculosis exposure. Poisson regression models were used to determine the associations of calendar year, ethnicity and other potential risk factors after cART initiation. RESULTS: Fifty-eight thousand seven hundred and seventy-six participants (26.3% women; 54.5% white, 32.0% Black, 13.5% other/unknown ethnicity; median (interquartile range) age 34 (29-42) years) were followed for 546 617 person-years. Seven hundred and four were treated for active tuberculosis [rate 1.3; 95% confidence interval (CI) 1.2-1.4/1000 person-years). Tuberculosis incidence decreased from 1.3 (1.2-1.5) to 0.6 (0.4-0.9)/1000 person-years from pre-2004 to 2011-2017. The decline among people of Black ethnicity was less steep than among those of white/other ethnicities, with incidence remaining high among Black participants in the latest period [2.1 (1.4-3.1)/1000 person-years]. Two hundred and eighty-three participants [191 (67%) Black African] had tuberculosis with viral load less than 50 copies/ml. CONCLUSION: Despite the known protective effect of cART against tuberculosis, a continuing disproportionately high incidence is seen among Black African people. Results support further interventions to prevent tuberculosis in this group.

Evaluating cabotegravir/rilpivirine long-acting, injectable in the treatment of HIV infection: emerging data and therapeutic potential.

Cabotegravir and rilpivirine long-acting injectable antiretroviral therapy for the treatment of HIV-1 infection brings promise of a new mode of delivery and potential solutions to some problems of oral therapy, but also new challenges and unanswered questions. Adding to the increasing body of evidence for newer two-drug combinations, phase II and phase III trial data to date demonstrate cabotegravir and rilpivirine combination injectable therapy to be non-inferior to selected oral triple-therapy alternatives. Most importantly, this therapy is reported to be acceptable to individuals taking the 4-weekly or 8-weekly injections, despite frequent injection-site reactions. Key outstanding questions include management of missed or delayed dosing, drug interactions and management of virological failure, as well as the efficacy of cabotegravir and rilpivirine in all HIV-1 subtypes. We describe clinical evidence to date and efficacy and challenges in selected populations, including women; those with prior virological failure; individuals with a history of difficulty adhering to oral therapy and individuals with co-infections. We await real-world data and longer-term evidence while moving forward to this new era of antiretroviral therapy.

Brief Report: The Effect of Antiretroviral Therapy and CD4 Count on Markers of Infectiousness in HIV-Associated Tuberculosis.

Clinical features of tuberculosis influence infectiousness. This cross-sectional study examined the effect of combination antiretroviral therapy (cART) and CD4 on sputum smear-positivity (SS+) and pulmonary cavitation among 1589 (1185/1589 HIV-positive) miners in South Africa. Proportions SS+ varied nonlinearly by CD4 with greatest proportions SS+ (55.3%) in the lowest stratum (<100 cells/µL). Adjusted prevalence ratio for SS+; on vs. off cART was 0.90 (95% confidence interval: 0.73 to 1.11). Proportions with cavitation varied linearly with CD4, with no independent cART effect (adjusted prevalence ratio 1.17; 95% confidence interval: 0.80 to 1.71). cART did not independently affect SS+ or cavitation but may increase infectiousness through CD4 recovery.

Raised Venous Lactate and Markers of Intestinal Translocation Are Associated With Mortality Among In-Patients With HIV-Associated TB in Rural South Africa.

INTRODUCTION: Case fatality among in-patients with HIV-associated tuberculosis (HIV-TB) in Africa is high. We investigated the factors associated with mortality in a rural South African hospital. METHODS: This was a prospective observational study of HIV-TB in-patients, with death by 8 weeks the endpoint. RESULTS: Of 99 patients (median CD4 count 72 cells/mm³), 32 (32%) died after median 8-day TB treatment. TB was diagnosed microbiologically in 75/99 and clinico-radiologically in 24, with no mortality difference between these groups [31% versus 38% (P = 0.53)]. Median venous lactate was 5.5 mmol/L (interquartile range 3.9-6.2) in those who died and 3.1 mmol/L (interquartile range 2.2-4.1) in survivors (P < 0.001). In multivariable analysis, lactate ≥4 mmol/L [adjusted odds ratio (aOR) 9.8, 95% confidence interval (CI): 3.0 to 32.2], Glasgow Coma Score <15 (aOR 6.6, 95% CI: 1.5 to 29.6), CD4 count <50 cells per cubic millimeter (aOR 5.5, 95% CI: 1.6 to 18.5), and age ≥50 (aOR 7.7, 95% CI: 1.2 to 46.9) independently predicted death. In a nested case-control study, comparing those who died versus CD4-matched survivors, median plasma lipopolysaccharide concentrations were 93 and 57 pg/mL (P = 0.026) and intestinal fatty acid-binding protein, 132 and 0 pg/mL (P = 0.002). CONCLUSIONS: Mortality was high and predicted by elevated lactate, likely reflecting a sepsis-syndrome secondary to TB or bacterial coinfection with intestinal barrier dysfunction appearing to contribute.

Clinical Relevance of Nontuberculous Mycobacteria Isolated from Sputum in a Gold Mining Workforce in South Africa: An Observational, Clinical Study.

BACKGROUND: The clinical relevance of nontuberculous mycobacteria (NTM), detected by liquid more than solid culture in sputum specimens from a South African mining workforce, is uncertain. We aimed to describe the current spectrum and relevance of NTM in this population. METHODS: An observational study including individuals with sputum NTM isolates, recruited at workforce tuberculosis screening and routine clinics. Symptom questionnaires were administered at the time of sputum collection and clinical records and chest radiographs reviewed retrospectively. RESULTS: Of 232 individuals included (228 (98%) male, median age 44 years), M. gordonae (60 individuals), M. kansasii (50), and M. avium complex (MAC: 38) were the commonest species. Of 38 MAC isolates, only 2 (5.3%) were from smear-positive sputum specimens and 30/38 grew in liquid but not solid culture. MAC was especially prevalent among symptomatic, HIV-positive individuals. HIV prevalence was high: 57/74 (77%) among those tested. No differences were found in probability of death or medical separation by NTM species. CONCLUSIONS: M. gordonae, M. kansasii, and MAC were the commonest NTM among miners with suspected tuberculosis, with most MAC from smear-negative specimens in liquid culture only. HIV testing and identification of key pathogenic NTM in this setting are essential to ensure optimal treatment.

Adverse events with isoniazid preventive therapy: experience from a large trial.

OBJECTIVES: We describe isoniazid-related adverse events in Thibela TB, a cluster-randomized study of community-wide isoniazid preventive therapy (IPT) among gold miners in South Africa, where HIV prevalence is estimated at 30%. METHODS: Consenting employees were screened prior to IPT for active tuberculosis and increased risk of isoniazid toxicity using a questionnaire and chest radiograph. Study-defined IPT-related adverse events were sought at each study visit: liver function tests were only performed if clinically indicated. In a substudy, we questioned consecutive participants at baseline and months 1, 3, and 6 concerning minor IPT-related adverse events. RESULTS: Among 24,221 participants (95.2% men, median age 40 years), 130 individuals had 132 study-defined adverse events (0.54%); 61 (0.25%) possible hypersensitivity rash, 50 (0.21%) peripheral neuropathy, 17 (0.07%) clinical hepatotoxicity, and four (0.02%) convulsions. Four events (two hepatotoxicity, one fatal, and two convulsions) fulfilled criteria for seriousness. Clinical hepatotoxicity was associated with consumption of alcohol [0.11 vs. 0.03% if no alcohol consumed, odds ratio 3.9 (95% confidence interval 1.2-12.1)], but not with sex, age, weight, or concurrent antiretroviral therapy. In the substudy, 324 of 498 (65.1%) participants reported better health since starting IPT; 180 of 324 (55.6%) reported that this was because of increased appetite. The frequency of specific minor symptoms was low among those taking IPT, and all symptoms were reported less often than at baseline. CONCLUSION: The risk of adverse events, particularly hepatotoxicity, was very low in this population. Our data suggest that clinical criteria can safely be used for screening prior to and monitoring during IPT.

Tuberculosis outcomes and drug susceptibility in individuals exposed to isoniazid preventive therapy in a high HIV prevalence setting.

OBJECTIVE: Despite World Health Organization recommendations, concerns about promoting resistance have impeded implementation of isoniazid preventive therapy (IPT) for tuberculosis (TB). We describe characteristics of TB in individuals previously exposed to IPT as part of 'Thibela TB', a cluster-randomized trial of community-wide IPT in gold miners in South Africa. DESIGN: Case series including participants who were dispensed IPT, attended at least one follow-up visit and were subsequently treated for TB. METHODS: TB episodes were detected through surveillance and through follow-up if IPT was stopped early. Drug susceptibility data were compared with TB episodes detected through surveillance in control clusters (where IPT use was minimal) and a laboratory substudy of mycobacterial sputum culture from TB suspects in control clusters. RESULTS: Among 126 eligible individuals (125 men, median age 43 years), median time from starting IPT to TB treatment was 316 days (interquartile range 174-491). Ninety-four of the 126 (75%) were first episodes. Eighty-nine of 103 (86%) tested HIV-infected, with the median CD4 cell count of 196 cells/microl (n = 51). Sixty-four of 108 (59%) with known treatment outcomes were cured or completed treatment. Among 71 isolates with drug susceptibility results available, 12.1% [95% confidence interval (CI) 5.0-23.3] and 7.7% (95% CI 0.2-36.0) from first and retreatment episodes, respectively, had isoniazid resistance, compared with 6.0% (95% CI 3.1-10.2) and 18.7% (95% CI 10.6-29.3) in control clusters and 11.8% (95% CI 8.2-16.3) among first TB episodes in the laboratory substudy. CONCLUSION: TB after recent IPT has prevalence of drug resistance similar to background and treatment outcomes typical of this setting. These data support wider implementation of IPT.