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CURATOR
A pinboard by
Endre Szvetnik

I cover science and tech news for Sparrho and work with Sparrho Heroes to curate, translate and disseminate scientific research to the wider public.

PINBOARD SUMMARY

Tuberculosis is one of the most dangerous infections for people living with HIV

Scientists have found compounds that could target HIV and tuberculosis at the same time. TB and HIV mutually ‘enhance’ each other and the co-infection is a major threat to public health worldwide.

In 10 seconds? Researchers have created molecules that stop TB and the replication of the HIV virus in the body – offerring hope of a new, effective drug against the sometimes deadly double infection.

What’s the discovery? Molecules that inhibit the growth of the M. tuberculosis bacterium and the replication of HIV have been around for a while. However, researchers have managed to combine them into one in the lab and found it was effective against both infections.

Why is it good news? Because it can help fight the dangerous global epidemic of the co-infection of HIV and the multi-drug resistant variants of TB. According to WHO estimates, around 1 million people with HIV developed TB in 2016. The two conditions play off each other: HIV-patients fall ill with TB more easily and then can pass it on to healthy people.

How does that happen? TB can stay latent in otherwise healthy people for a long time, but when HIV weakens your immune system and you are not on antiretroviral therapy, it can become active in a few weeks. Having HIV is the highest risk factor of developing TB. Studies estimate that the risk can be up to 20 times higher than in the case of HIV-negative people.

Does it mean they can infect others with TB? Indeed, but for them significantly, having TB can double the risk of death compared to people only having TB. The situation has become even more complicated by the emergence of the difficult-to-treat, multidrug resistant variants of TB.

So, what can be done? Well, we’re trying to design better drugs, like the dual-action agents that can be heading for medical trials. In the meantime, scientists were involve in determining the best timing of the treatment of co-infected patients. Studies found that survival rates improved to 86% when ART and TB treatment was carried out at the same time, irrespective of the important CD4+ cell count in patients.


Thousands of pills – why people give up TB-treatment

India has seen a drop in TB, but the multidrug-resistant variant has shot up by 13% within a year.

Of the MDR-TB cases 47% were cured, but 20% died and still a lot of people drop out of treatment.

The reason for this is that people can take up to 14,600 pills during and painful daily jabs during treatment.

Based on the advice of the WHO, this regime is being changed to a shorter, 9 month course to ensure more people complete it.

14 ITEMS PINNED

How soon after infection with HIV does the risk of tuberculosis start to increase? A retrospective cohort study in South African gold miners.

Abstract: Infection with human immunodeficiency virus (HIV) increases the risk of tuberculosis (TB), but no study has assessed how this risk changes with time since HIV seroconversion.The incidence of pulmonary TB was estimated in miners with and those without HIV infection in a retrospective cohort study. HIV test results were linked to routinely collected TB, demographic, and occupational data. The rate ratio (RR) for the association between HIV status and TB was estimated by time since HIV seroconversion, calendar period, and age.Of the 23,874 miners in the cohort, 17,766 were HIV negative on entry, 3371 were HIV positive on entry, and 2737 seroconverted during follow-up (1962 had a seroconversion interval of < or =2 years). A total of 740 cases of TB were analyzed. The incidence of TB increased with time since seroconversion, calendar period, and age. TB incidence was 2.90 cases/100 person-years at risk (pyar) in HIV-positive miners and was 0.80 cases/100 pyar in HIV-negative miners (adjusted RR, 2.9 [95% confidence interval {CI}, 2.5-3.4]). TB incidence doubled within the first year of HIV infection (adjusted RR, 2.1 [95% CI, 1.4-3.1]), with a further slight increase in HIV-positive miners for longer periods, up to 7 years.The increase in the risk of TB so soon after infection with HIV was unexpected. Current predictive models of TB incidence underestimate the effect of HIV infection in areas where TB is endemic.

Pub.: 21 Dec '04, Pinned: 03 May '18

Survival of patients with multidrug-resistant TB in Eastern Europe: what makes a difference?

Abstract: The quality of care for patients with TB in Eastern Europe has improved significantly; nevertheless drug resistance rates remain high. We analysed survival in a cohort of patients with multidrug-resistant and extensively drug-resistant (MDR-/XDR-) TB from Latvia, Lithuania, Estonia and Bucharest city.Consecutive adult new and retreatment patients with culture-confirmed pulmonary MDR-TB registered for treatment in 2009 (and in 2007 in Latvia) were enrolled; prospective survival information was collected.A total of 737 patients were included into the cohort. Of all MDR-TB cases, 46% were newly diagnosed; 56% of all MDR-TB cases had no additional resistance to fluoroquinolones or injectable agents, 33% had pre-XDR-TB and 11% XDR-TB. Median survival was 5.9 years in patients with MDR-TB and XDR-TB; 1.9 years in patients coinfected with HIV. Older age, male gender, alcohol abuse, retirement, co-morbidities, extrapulmonary involvement and HIV coinfection independently worsened survival. Inclusion of fluoroquinolones and injectable agents improves survival in patients with MDR-TB. Pre-XDR and XDR status did not significantly shorten survival as long as fluoroquinolones and injectable agents were part of the regimen. Moxifloxacin seems to improve survival in ofloxacin-susceptible patients when compared with older generation fluoroquinolones.The burden of additional resistances in patients with MDR-TB is high likely due to primary transmission of resistant strains. Social and programmatic factors including management of alcohol dependency, expansion of HIV testing and antiretroviral treatment need to be addressed in order to achieve cure and to interrupt transmission. The role of last generation fluoroquinolones and injectable agents in treatment of patients with pre-XDR and XDR-TB needs to be further investigated.

Pub.: 26 Mar '16, Pinned: 03 May '18

Improved survival and cure rates with concurrent treatment for MDR-TB/HIV co-infection in South Africa.

Abstract: The global epidemic of multidrug-resistant tuberculosis (MDR-TB) threatens gains in TB and HIV outcomes over the past two decades. Mortality in MDR-TB/HIV co-infection has historically been high, but most studies predated the availability of antiretroviral therapy (ART). We prospectively compared survival and treatment outcomes in MDR-TB/HIV co-infected patients on ART to those in patients with MDR-TB alone.This prospective, observational study enrolled culture-confirmed MDR-TB patients, with and without HIV co-infection, in South Africa between 2011-2013. Participants received standardized MDR-TB and HIV regimens and were followed monthly for treatment response, adverse events, and adherence. The primary outcome was survival.Among 206 participants, 150 were HIV-infected, 131 (64%) were female, and the median age was 33 years (IQR 26-41). Of the 191 participants with a final MDR-TB outcome, 130 (73%) were cured or successfully completed treatment, which did not differ by HIV status (p=0.50). After two years, the median CD4 count was 386 cells/mm3 (IQR 219-510), an increase of 140 cells/mm3 from baseline (p=0.005), and 64% had an undetectable HIV viral load. HIV-infected and HIV-uninfected participants had high rates of survival (86% and 94%, respectively; p=0.34). The strongest risk factor for mortality was having a CD4 count ≤100 cells/mm3 (aHR 15.6, 95%CI 4.4-55.6).Survival and treatment outcomes among MDR-TB/HIV individuals receiving concurrent ART were improved, approaching those of HIV-uninfected MDR-TB patients. The greatest risk of death was among HIV-infected individuals with CD4 counts ≤100 cells/mm3. These findings provide critical evidence to support concurrent treatment of MDR-TB and HIV.

Pub.: 03 Jan '18, Pinned: 01 May '18

Time to ART Initiation among Patients Treated for Rifampicin-Resistant Tuberculosis in Khayelitsha, South Africa: Impact on Mortality and Treatment Success.

Abstract: Khayelitsha, South Africa, with high burdens of rifampicin-resistant tuberculosis (RR-TB) and HIV co-infection.To describe time to antiretroviral treatment (ART) initiation among HIV-infected RR-TB patients initiating RR-TB treatment and to assess the association between time to ART initiation and treatment outcomes.A retrospective cohort study of patients with RR-TB and HIV co-infection not on ART at RR-TB treatment initiation.Of the 696 RR-TB and HIV-infected patients initiated on RR-TB treatment between 2009 and 2013, 303 (44%) were not on ART when RR-TB treatment was initiated. The median CD4 cell count was 126 cells/mm3. Overall 257 (85%) patients started ART during RR-TB treatment, 33 (11%) within 2 weeks, 152 (50%) between 2-8 weeks and 72 (24%) after 8 weeks. Of the 46 (15%) who never started ART, 10 (21%) died or stopped RR-TB treatment within 4 weeks and 16 (37%) had at least 4 months of RR-TB treatment. Treatment success and mortality during treatment did not vary by time to ART initiation: treatment success was 41%, 43%, and 50% among patients who started ART within 2 weeks, between 2-8 weeks, and after 8 weeks (p = 0.62), while mortality was 21%, 13% and 15% respectively (p = 0.57). Mortality was associated with never receiving ART (adjusted hazard ratio (aHR) 6.0, CI 2.1-18.1), CD4 count ≤100 (aHR 2.1, CI 1.0-4.5), and multidrug-resistant tuberculosis (MDR-TB) with second-line resistance (aHR 2.5, CI 1.1-5.4).Despite wide variation in time to ART initiation among RR-TB patients, no differences in mortality or treatment success were observed. However, a significant proportion of patients did not initiate ART despite receiving >4 months of RR-TB treatment. Programmatic priorities should focus on ensuring all patients with RR-TB/HIV co-infection initiate ART regardless of CD4 count, with special attention for patients with CD4 counts ≤ 100 to initiate ART as soon as possible after RR-TB treatment initiation.

Pub.: 12 Nov '15, Pinned: 01 May '18

High Treatment Success Rates among HIV-infected Multidrug-resistant Tuberculosis Patients after Expansion of Antiretroviral Therapy in Botswana, 2006-2013.

Abstract: Few studies have examined multidrug-resistant (MDR) tuberculosis (TB) treatment outcomes among HIV-infected persons after widespread expansion of antiretroviral therapy (ART). We describe MDR-TB treatment outcomes among HIV-infected and HIV-uninfected patients in Botswana after ART expansion.We retrospectively reviewed data from patients who started MDR-TB therapy in Botswana during 2006-2013. Multivariable regression models were used to compare treatment outcomes between HIV-infected and HIV-uninfected patients.We included 588 MDR-TB patients in the analysis, of whom, 47 (8.0%) and 9 (1.5%) were diagnosed with pre-extensively drug-resistant (XDR)-TB and XDR-TB, respectively. Of the 408 (69.4%) HIV-infected patients, 352 (86.0%) were on ART or started ART during treatment, and median baseline CD4+ T cell count was 234 cells/mm. Treatment success rates were 79.4% and 73.0% among HIV-uninfected and HIV-infected patients, respectively (P = 0.121). HIV-infected patients with CD4+ T cell count <100 cells/mm were more likely to die during treatment compared to HIV-uninfected patients (adjusted risk ratio=1.890; 95% CI=1.098-3.254).High rates of treatment success were achieved with programmatic management of MDR-TB and HIV in Botswana after widespread expansion of ART. However, a two-fold increase in mortality was observed among HIV-infected persons with baseline CD4 <100 cells/mm compared with HIV-uninfected persons.

Pub.: 24 Aug '16, Pinned: 01 May '18

Time to initiate antiretroviral therapy between 4 weeks and 12 weeks of tuberculosis treatment in HIV-infected patients: results from the TIME study.

Abstract: Optimal timing for initiation of antiretroviral therapy (ART) among HIV-infected patients with tuberculosis (TB) is not well established.HIV/TB-coinfected patients were randomized to initiate tenofovir/lamivudine/efavirenz at 4 weeks (4-week group) or 12 weeks (12-week group) of TB treatment. The primary outcome was 1-year all-cause mortality.Of 156 patients, 79 were in 4-week group and 77 in 12-week group. Overall, median (interquartile range) CD4 was 43 (47-106) cells per cubic millimeter and median (interquartile range) HIV-1 RNA was 5.8 (5.4-6.3) log copies per milliliter. Eleven (7%) mortalities occurred in a total follow-up period of 137 patient-years. Seven percent (6/79, 8.76 per 100 patient-years) mortalities were in 4-week group, and 6% (5/77, 7.25 per 100 person-years) mortalities were in 12-week group [relative risk (RR) = 0.845, 95% confidence interval (CI) = 0.247 to 2.893]. Twenty-eight (35%) patients in 4-week group and 25 (32%) patients in 12-week group were hospitalized (RR = 1.142, 95% CI = 0.588 to 2.217). Grade 2-4 adverse events were 39% (31/79) in 4-week group and 34% (26/77) in 12-week group (RR = 1.267, 95% CI = 0.659 to 2.435). In multivariate analysis, "low albumin" (RR = 2.695, 95% CI = 1.353 to 5.475) and "low baseline CD4 count" (RR = 4.878, 95% CI = 1.019 to 23.256) were the independent predictors of mortality. Immune reconstitution inflammatory syndrome was more frequent in 4-week group with an incidence of 8.86 versus 5.02 per 100 person-months in 12-week group over the first 6 months of ART (P = 0.069).In middle-income countries where ART is initiated at CD4 count of <350 cells per cubic millimeter, immediate initiation of ART in HIV-infected patients with active TB was not associated with survival advantage when compared to initiation of ART at 12 weeks.

Pub.: 18 May '12, Pinned: 01 May '18

Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection.

Abstract: Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter.We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause.A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions.The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.).

Pub.: 21 Jul '15, Pinned: 01 May '18

Delayed antiretroviral therapy despite integrated treatment for tuberculosis and HIV infection.

Abstract: Five primary health care clinics in Kinshasa, Democratic Republic of Congo.To examine timing and predictors of delayed initiation of antiretroviral therapy (ART) during anti-tuberculosis treatment.Prospective observational cohort of adult patients receiving integrated treatment for tuberculosis (TB) and human immunodeficiency virus (HIV) who are expected to initiate ART at 1 month if CD4 count is <100 cells/mm(3) or if patient is World Health Organization (WHO) Clinical Stage 4 for reasons other than extra-pulmonary TB, at 2 months if CD4 count is 100-350 cells/mm(3), or at completion of anti-tuberculosis treatment if subsequently CD4 count is ≤ 350 cells/mm(3) or patient has WHO Clinical Stage 4.Of 492 patients, 235 (47.8%) experienced delayed initiation of ART: 171 (72.8%) initiated ART late, after a median delay of 12 days (interquartile range [IQR] 4-27) and 64 (27.2%) never initiated ART. Contraindication to any antiretroviral drug (aOR 2.91, 95%CI 1.22-6.95), lower baseline CD4 count (aOR 1.20, 95%CI 1.08-1.33/100 cells/mm(3)), TB drug intolerance (aOR 1.93, 95%CI 1.23-3.02) and non-disclosure of HIV infection (aOR 1.50, 95%CI 1.03-2.18) predicted delayed ART initiation.Despite fully integrated treatment, half of all patients experienced delayed ART initiation. Pragmatic approaches to ensure timely ART initiation in those at risk of delayed ART initiation are needed.

Pub.: 07 Jun '14, Pinned: 01 May '18