Tuberculosis (TB) and its strong association with HIV infection are the most important causes of the high rates of infectious morbidity and mortality in South African adults. The interaction between HIV and TB leads to more frequent smear-negative and extrapulmonary disease, resulting in atypical clinical presentations and altered performance characteristics of diagnostic tests. New and emerging diagnostics are being used to support earlier initiation of therapy and detection of drug resistance, although these have inherent limitations and empirical therapy is often still required. The management of HIV-associated TB is complicated by rapid clinical progression of disease, immune reconstitution inflammatory syndrome, drug-drug interactions and shared toxicities. A strong evidence base now provides guidance on the timing of initiation of antiretroviral therapy, the use of corticosteroids in TB and the use of isoniazid preventive therapy. This article provides a clinically oriented overview of the diagnosis, management and prevention of HIV-associated TB, with a focus on recent evidence in the field.
Detection of drug-resistant tuberculosis (DR-TB) increases each year in South Africa (SA). Most cases result from airborne transmission of already resistant TB strains. Epidemic control relies on rapid diagnosis and initiation of effective treatment to reduce the period of infectiousness and ongoing transmission.
The rapid diagnostic test, Xpert MTB/RIF, has replaced smear microscopy for routine screening of all cases of presumptive TB in SA. Xpert also detects rifampicin (RIF) resistance, an indicator of more extensive drug resistance, allowing rapid initiation of effective second-line treatment. Definitive diagnosis of DR-TB relies on laboratory confirmation of MTB, along with drug-susceptibility testing (DST) using culture-based (phenotypic) and/or molecular (genotypic) techniques.
A standardised treatment regimen, consisting of five (or six) drugs (pyrazinamide, (ethambutol), kanamycin, moxifloxacin, ethionamide, terizidone), is offered to individuals following initial diagnosis of RIF resistance. Treatment regimens are individualised if and when molecular mutation details and second-line DST results indicate more extensive second-line drug resistance.
DR-TB treatment outcomes are poor owing to death, and interruption and failure of current treatment. Reliable access to newer, more effective drugs within shorter, more tolerable regimens is desperately needed to improve the chance of a cure for DR-TB patients.
Tuberculous meningitis (TBM) is a medical emergency for which tuberculosis (TB) treatment should be initiated as soon as possible after diagnosis. Owing to the low diagnostic yields of confirmatory tests, TBM is often diagnosed based on suggestive clinical and cerebrospinal fluid findings, evidence for TB outside the central nervous system (CNS), typical brain imaging features and exclusion of other causes of meningitis. TB drug regimens used in TBM may be suboptimal as they are informed by studies of TB outside the CNS, rather than being based on randomised controlled trials in TBM. TBM has a high mortality and the management of HIV-co-infected patients is further complicated by neurological TB-immune reconstitution inflammatory syndrome (IRIS), which frequently occurs after starting antiretroviral therapy (ART) during TBM treatment and contributes to the poor outcome in HIV-associated TBM. HIV-infected TBM patients due to start ART should be counselled about the risk of developing neurological TB-IRIS, typical symptoms that could be expected and need to return to hospital should any of these develop. Currently, the only evidence-based treatment for TB-IRIS is with corticosteroids, which should be considered in all cases of neurological TB-IRIS.
In routine-care settings, the 10-week mortality associated with cryptococcal meningitis (CM) is high, even with prompt, appropriate antifungal treatment and correctly timed initiation of antiretroviral therapy (ART). While early diagnosis of HIV infection and initiation of ART prior to the development of AIDS is the most important way to reduce the incidence of CM, a cryptococcal antigenaemia screen-and-treat intervention has the potential to reduce mortality by identifying patients prior to onset of CM. Antifungal treatment for HIV-associated CM is divided into three phases over a minimum period of 1 year: (i) a 2-week induction phase, including intravenous amphotericin B deoxycholate as a backbone; (ii) an 8-week consolidation phase with fluconazole 400 mg daily; and (iii) a maintenance phase with fluconazole 200 mg daily. Amphotericin B should be paired with another antifungal agent to maximise cerebrospinal fluid fungal clearance. World Health Organization guidelines emphasise that patients receiving amphotericin B-containing regimens should have access to a 'minimum package of toxicity prevention, monitoring and management to minimise the serious amphotericin B-related toxicities particularly hypokalaemia and nephrotoxicity'. Raised intracranial pressure is a serious and often fatal complication of CM, which requires good pressure management with repeat lumbar punctures. ART should be initiated 4 - 6 weeks after starting antifungal therapy. In many cases, relapse CM among South African patients occurs because of suboptimal adherence to secondary prophylaxis with fluconazole and/or the antifungal not being prescribed.
Adolescents living with HIV, including those infected perinatally and non-perinatally, bear a disproportionate burden of the HIV epidemic in South Africa. This article discusses HIV management in adolescents including the following aspects: (i) burden of HIV disease, modes of HIV acquisition and implications for management; (ii) initiation of combination antiretroviral therapy (ART), outcomes and complications of ART in adolescents, including virological failure and switching regimens; (iii) adherence in adolescence, including factors that may contribute to poor adherence and advice to improve adherence; (iv) issues particular to adolescents, including sexual and reproductive health needs, disclosure to adolescents and by adolescents, and transition to adult care. This article aims to provide insights based on the literature and experience to assist the clinician to navigate the difficulties of managing HIV in adolescence and achieving successful transition to adult care.
Since 2004, when antiretroviral therapy (ART) was first available to children through the National Department of Health, there has been significant progress in preventing and treating paediatric HIV. Large cohort studies and prospective trials confirmed that young children require early diagnosis with rapid access to ART regardless of CD4+ lymphocyte count. Studies also confirmed the importance of ritonavir-boosted protease inhibitors during therapy, regardless of prior nevirapine exposure. As prevention strengthens and the paediatric population ages, the goal posts are shifting towards even earlier diagnosis, targeting newborn infants on the first day of life and also the perinatally infected adolescent.
There is an increasing focus on the long-term health, social, developmental and scholastic outcomes of HIV-infected children. Clinicians require new skills to assist children with transition into adulthood. In this article we focus on the care of infants and children.