Thandekile Manzini

Adult antiretroviral therapy guidelines 2017

These guidelines are intended as an update to those published in the Southern African Journal of HIV Medicine in 2014 and the update on when to initiate antiretroviral therapy in 2015. Since the release of the previous guidelines, the scale-up of antiretroviral therapy (ART) in southern Africa has continued. New antiretroviral drugs have become available with improved efficacy, safety and robustness. The guidelines are intended for countries in the southern African region, which vary between lower and middle income.

Adult antiretroviral therapy guidelines 2014 : guideline

These guidelines are intended as an update to those published in the Southern African Journal of HIV Medicine in 2012. Since the release of the previous guidelines, the scale-up of antiretroviral therapy (ART) in southern Africa has continued. Cohort studies from the region show excellent clinical outcomes; however, ART is still being initiated late (in advanced disease) in some patients, resulting in relatively high early mortality rates. New data on antiretroviral drugs have become available. Although currently few, there are patients in the region who are failing protease-inhibitor-based second-line regimens. To address this, guidelines on third-line therapy have been expanded.

Southern African HIV Clinicians Society adult antiretroviral therapy guidelines: Update on when to initiate antiretroviral therapy

The most recent version of the Southern African HIV Clinicians Society’s adult antiretroviral therapy (ART) guidelines was published in December 2014. In the 27 August 2015 edition of the New England Journal of Medicine, two seminal randomised controlled trials that addressed the optimal timing of ART in HIV-infected patients with high CD4 counts were published: Strategic timing of antiretroviral therapy (START) and TEMPRANO ANRS 12136 (Early antiretroviral treatment and/or early isoniazid prophylaxis against tuberculosis in HIV-infected adults). The findings of these two trials were consistent: there was significant individual clinical benefit from starting ART immediately in patients with CD4 counts higher than 500 cells/μL rather than deferring until a certain lower CD4 threshold or clinical indication was met. The findings add to prior evidence showing that ART reduces the risk of onward HIV transmission. Therefore, early ART initiation has the public health benefits of potentially reducing both HIV incidence and morbidity. Given this new and important evidence, the Society took the decision to provide a specific update on the section of the adult ART guidelines relating to when ART should be initiated.

Recurrent giant molluscum contagiosum immune reconstitution inflammatory syndrome (IRIS) after initiation of antiretroviral therapy in an HIV-infected man

We describe an HIV-infected South African man who experienced two distinct episodes of disseminated giant molluscum contagiosum immune reconstitution inflammatory syndrome (IRIS) over a six-year period. The first episode of molluscum contagiosum IRIS occurred with rapid virologic suppression following antiretroviral therapy initiation. The second episode occurred during a rapid increase in CD4 cells following stable viral suppression with second-line antiretroviral therapy. His molluscum contagiosum lesions then completely resolved during a reduction in CD4 count, despite maintaining virologic suppression. Nearly one year after the resolution of his giant molluscum contagiosum IRIS lesions, he maintains an undetectable viral load, but his level of immune deficiency has not improved. In the absence of well-controlled therapeutic trials, molluscum contagiosum IRIS presents important management challenges.

Challenges in the Management of Disseminated Progressive Histoplasmosis in Human Immunodeficiency Virus-Infected Patients in Resource-Limited Settings

The diagnosis of histoplasmosis in patients with human immunodeficiency virus in southern Africa is complicated by the nonspecific presentation of the disease in this patient group and the unavailability of sensitive diagnostics including antigen assays. Treatment options are also limited due to the unavailability of liposomal amphotericin and itraconazole, and the inability to perform therapeutic drug monitoring further confounds management. We present 3 clinical cases to illustrate the limits of diagnosis and management in the southern African context, and we highlight the need for additional diagnostic tools and treatment options in resource-limited settings.

Appropriate clinical use of darunavir 800 mg

PREZISTA, in combination with low dose ritonavir (DRV/r) and with other antiretroviral medicines, is indicated for the treatment of human immunodeficiency virus (HIV) infection in antiretroviral treatment experienced adult patients who are protease-inhibitor-naïve or after exclusion of darunavir resistance associated mutations (DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V). Genotypic or phenotypic testing should guide the use of DRV/r. (Prezista package insert)

Southern African HIV Clinicians Society Guidance on the use of dolutegravir in first-line antiretroviral therapy

In preliminary data from the Tsepamo study in Botswana, it was found that 0.94% (95% confidence interval [CI]: 0.37 – 2.4) of babies (4/426) born to women who were taking dolutegravir periconception had neural tube defects (NTDs), compared with 0.1% of babies (14/11 173) of women taking other antiretroviral drugs (ARVs) in the periconception period.1 No NTDs were observed in pregnancies where dolutegravir was initiated later in pregnancy. Further data from the Tsepamo study were presented at AIDS 2018: the updated number of NTDs with periconception dolutegravir exposure in the Tsepamo cohort is 4/596, 0.67% (95% CI: 0.26 to 1.7). The next formal analysis will occur after 31 March 2019 and will include women exposed to dolutegravir from conception before the recent change in guidance. Tsepamo plans to expand the number of study sites, increasing the coverage from 45% to 72% of births in Botswana with a projected denominator of over 1200 by March 2019.1

Hepatitis B immune reconstitution syndrome in a patient with HIV infection

South Africa has a high rate of HIV and hepatitis B co-infection. The national HIV treatment guidelines include anti-retrovirals that treat both viruses. We describe a HIV-positive patient who presented with liver histology-confirmed hepatitis B immune reconstitution inflammatory syndrome whilst on a regimen containing lamivudine and tenofovir.

Tuberculous drug-induced liver injury and treatment re-challenge in Human Immunodeficiency Virus co-infection

Background: Tuberculosis drug-induced liver injury (TB-DILI) is the most common adverse event necessitating therapy interruption. The optimal re-challenge strategy for antituberculous therapy (ATT) remains unclear, especially in human immunodeficiency virus (HIV) co-infected individuals in high-prevalence settings such as South Africa. Objective: To determine the incidence of and risk factors for the recurrence of TB-DILI with different ATT re-challenge strategies. Materials and Methods: We conducted a retrospective chart review of patients managed for TB-DILI from 2005 to 2013 at King Edward VIII Hospital in Durban, South Africa. Relevant clinical and laboratory data at the presentation of TB-DILI, time to recovery of liver function, method of ATT re-challenge and outcome of re-challenge were documented. Results: 1016 charts were reviewed, and 53 individuals with TB-DILI (48 HIV-co-infected) were identified. Following discontinuation of ATT, the median time to alanine aminotransferase normalization was 28 days (interquartile range 13-43). Forty-two subjects were re-challenged (30 regimen re-challenges and 12 step-wise re-challenges). 5 (12%) cases of recurrent TB-DILI were noted. Recurrences were not associated with the method of re-challenge. Conclusion: Based on the data available, it appears that full ATT can be safely restarted in the majority of subjects with a recurrence of DILI occurring in about 12% of subjects. The method of re-challenge did not appear to impact on the risk of recurrence. Ideally, a prospective randomized trial is needed to determine the best method of re-challenge.