Management challenges in tuberculosis and HIV

Globally, South Africa (SA) is disproportionately affected by the epidemics of  tuberculosis (TB) and the human immunodeficiency virus-1 (HIV-1). The intersection of these two diseases has resulted in an unprecedented disease burden. It is estimated that 12.2% of South Africans are HIV-infected – a total of 6.4 million people, the largest number in any country in the world.SA has the second highest annual incidence of TB after Swaziland – approximately 1% of the population develop active TB disease each year (an estimated 530 000 people in 2012). While SA comprises 0.7% of the world’s population, it is estimated that of all cases of HIVassociated TB that occur worldwide annually, 30% are in SA

Diagnosis, treatment and immunopathogenesis of the HIV-associated tuberculosis immune reconstitution inflammatory syndrome

The paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of antiretroviral therapy (ART) among patients who start ART while on treatment for tuberculosis (TB). The condition manifests with new, worsening or recurrent inflammatory features of TB due to immunopathology attendant on rapidly recovering immune function

Testing but not treating: missed opportunities and lost lives in the South African ART programme

Recently published WHO guidance recommends starting ART in HIV-infected adults with CD4 counts of ≤350 cells/μl [1]. There is mounting evidence that such a policy will lead to lower mortality among HIV-infected individuals [2]. Also modeling data suggests that expanded testing and earlier treatment will reduce HIV transmission [3]. In South Africa ART coverage is not meeting current needs, even using the CD4 count criteria of <200 cells/μl, and mortality early in ART programmes is high due to advanced immunosuppression at initiation [4]. Fortunately, following limited government leadership around HIV in the past, South African President Jacob Zuma has encouraged widespread HIV testing, and announced that he will undertake an HIV test [5]

Antiretroviral treatment outcomes amongst older adults in a large multicentre cohort in South Africa

Introduction Increasing numbers of patients are starting antiretroviral treatment (ART) at advanced age or reaching advanced age while on ART. We compared baseline characteristics and ART outcomes of older adults (aged ≥55 years) vs. younger adults (aged 25-54 years) in routine care settings in South Africa. METHODS: A multicentre cohort study of ART-naïve adults starting ART at 89 public sector facilities was conducted. Mortality, loss to follow-up (LTFU), immunological and virological outcomes until five years of ART were compared using competing-risks regression, generalised estimating equations and mixed-effects models. RESULTS: 4065 older adults and 86,006 younger adults were included. There were more men amongst older adults; 44.7% vs. 33.4%; RR = 1.34 (95% CI: 1.29-1.39). Mortality after starting ART was substantially higher amongst older adults, adjusted sub-hazard ratio (asHR) = 1.44 over 5 years (95% CI: 1.26-1.64), particularly for the period 7-60 months of treatment, asHR = 1.73 (95% CI: 1.44-2.10). LTFU was lower in older adults, asHR = 0.87 (95% CI: 0.78-0.97). Achievement of virological suppression was greater in older adults, adjusted odds ratio = 1.42 (95% CI: 1.23-1.64). The probabilities of viral rebound and confirmed virological failure were both lower in older adults, adjusted hazard ratios = 0.69 (95% CI: 0.56-0.85) and 0.64 (95% CI: 0.47-0.89), respectively. The rate of CD4 cell recovery (amongst patients with continuous viral suppression) was 25 cells/6 months of ART (95% CI: 17.3-33.2) lower in older adults. CONCLUSIONS: Although older adults had better virological outcomes and reduced LTFU, their higher mortality and slower immunological recovery warrant consideration of age-specific ART initiation criteria and management strategies

Failure to eradicate Isospora belli diarrhoea despite immune reconstitution in adults with HIV--a case series

Isospora belli causes diarrhoea in patients with AIDS. Most respond to targeted therapy and recommendations are that secondary prophylaxis can be stopped following immune reconstitution with ART. We report eight cases of chronic isosporiasis that persisted despite standard antimicrobial therapy, secondary prophylaxis, and good immunological and virological response to ART. Median CD4 nadir was 175.5 cells/mm 3 and median highest CD4 while symptomatic was 373 cells/mm 3 . Overall 34% of stool samples and 63% of duodenal biopsy specimens were positive for oocytes. Four patients died, two remain symptomatic and two recovered. Possible explanations for persistence of symptoms include host factors such as antigen specific immune deficiency or generalised reduction in gut immunity. Parasite factors may include accumulating resistance to co-trimoxazole. Research is required to determine the optimum dose and duration of co-trimoxazole therapy and whether dual therapy may be necessary. Mortality was high and pending more data we recommend extended treatment with high-dose co-trimoxazole in similar cases

Risk Factors for Acquired Rifamycin and Isoniazid resistance: A systematic review and meta-analysis

BACKGROUND: Studies looking at acquired drug resistance (ADR) are diverse with respect to geographical distribution, HIV co-infection rates, retreatment status and programmatic factors such as regimens administered and directly observed therapy. Our objective was to examine and consolidate evidence from clinical studies of the multifactorial aetiology of acquired rifamycin and/or isoniazid resistance within the scope of a single systematic review. This is important to inform policy and identify key areas for further studies. METHODS: Case-control and cohort studies and randomised controlled trials that reported ADR as an outcome during antitubercular treatment regimens including a rifamycin and examined the association of at least 1 risk factor were included. Post hoc, we carried out random effects Mantel-Haenszel weighted meta-analyses of the impact of 2 key risk factors 1) HIV and 2) baseline drug resistance on the binary outcome of ADR. Heterogeneity was assessed used I 2 statistic. As a secondary outcome, we calculated median cumulative incidence of ADR, weighted by the sample size of the studies. RESULTS: Meta-analysis of 15 studies showed increased risk of ADR with baseline mono- or polyresistance (RR 4.85 95% CI 3.26 to 7.23, heterogeneity I 2 58%, 95% CI 26 to 76%). Meta-analysis of 8 studies showed that HIV co-infection was associated with increased risk of ADR (RR 3.02, 95% CI 1.28 to 7.11); there was considerable heterogeneity amongst these studies (I 2 81%, 95% CI 64 to 90%). Non-adherence, extrapulmonary/disseminated disease and advanced immunosuppression in HIV co-infection were other risk factors noted. The weighted median cumulative incidence of acquired multi drug resistance calculated in 24 studies (assuming whole cohort as denominator, regardless of follow up DST) was 0.1% (5 th to 95 th percentile 0.07 to 3.2%). CONCLUSION: Baseline drug resistance and HIV co-infection were significant risk factors for ADR. There was a trend of positive association with non-adherence which is likely to contribute to the outcome of ADR. The multifactorial aetiology of ADR in a programmatic setting should be further evaluated via appropriately designed studies