Articles tagged as "Laos"

High mortality persists among people presenting with advanced HIV disease

Mortality in the first 3 months on antiretroviral therapy among HIV-positive adults in low- and middle-income countries: a meta-analysis.

Brennan AT, Long L, Useem J, Garrison L, Fox MP. J Acquir Immune Defic Syndr. 2016 Sep 1;73(1):1-10. doi: 10.1097/QAI.0000000000001112.

Previous meta-analyses reported mortality estimates of 12-month post-antiretroviral therapy (ART) initiation; however, 40%-60% of deaths occur in the first 3 months on ART, a more sensitive measure of averted deaths through early ART initiation. To determine whether early mortality is dropping as treatment thresholds have increased, we reviewed studies of 3 months on ART initiation in low- to middle-income countries. Studies of 3-month mortality from January 2003 to April 2016 were searched in 5 databases. Articles were included that reported 3-month mortality from a low- to middle-income country; nontrial setting and participants were ≥15. We assessed overall mortality and stratified by year using random effects models. Among 58 included studies, although not significant, pooled estimates show a decline in mortality when comparing studies whose enrollment of patients ended before 2010 (7.0%; 95% CI: 6.0 to 8.0) with the studies during or after 2010 (4.0%; 95% CI: 3.0 to 5.0). To continue to reduce early HIV-related mortality at the population level, intensified efforts to increase demand for ART through active testing and facilitated referral should be a priority. Continued financial investments by multinational partners and the implementation of creative interventions to mitigate multidimensional complex barriers of accessing care and treatment for HIV are needed.

Abstract access  

Editor’s notes: Early mortality among people initiating antiretroviral therapy (ART) remains high, presumed to be because many people living with HIV present when already very sick with advanced HIV disease. This systematic review included 43 studies from Africa and 13 from Asia. Its main aim was to see whether the evolution of guidelines recommending ART initiation at progressively higher CD4 counts over this period had reduced early mortality (defined as death within three months of ART start) and, by implication, the proportion of people starting ART who had advanced disease. To investigate this, the authors compared studies where enrolment ended before 2010 with studies that had started later.

Overall early mortality was six percent.  Because of the large numbers lost to follow up this will be an underestimate. The authors attempted to compensate for this, and calculated an adjusted overall figure of more than 10%. There was a fall in early mortality from seven percent to four percent (unadjusted) between the early and late periods but although the trend was consistent the difference was not significant.

In only four of the 58 studies was the median CD4 count at ART initiation above 200x106/l. It seems likely that even when policies to initiate ART at high CD4 counts are adopted, additional efforts will be necessary to promote initiation of ART and retention in care for people who feel well.  This is in order to reduce the number of people starting ART with advanced disease and consequently at very high risk of early death.   

Africa, Asia, Latin America
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Routine use of steroids harmful in cryptococcal meningitis

Adjunctive Dexamethasone in HIV-Associated Cryptococcal Meningitis.

Beardsley J, Wolbers M, Kibengo FM, Ggayi AB, Kamali A, Cuc NT, Binh TQ, Chau NV, Farrar J, Merson L, Phuong L, Thwaites G, Van Kinh N, Thuy PT, Chierakul W, Siriboon S, Thiansukhon E, Onsanit S, Supphamongkholchaikul W, Chan AK, Heyderman R, Mwinjiwa E, van Oosterhout JJ, Imran D, Basri H, Mayxay M, Dance D, Phimmasone P, Rattanavong S, Lalloo DG, Day JN, CryptoDex Investigations. N Engl J Med. 2016 Feb 11;374(6):542-54. doi: 10.1056/NEJMoa1509024.

Background: Cryptococcal meningitis associated with human immunodeficiency virus (HIV) infection causes more than 600 000 deaths each year worldwide. Treatment has changed little in 20 years, and there are no imminent new anticryptococcal agents. The use of adjuvant glucocorticoids reduces mortality among patients with other forms of meningitis in some populations, but their use is untested in patients with cryptococcal meningitis.

Methods: In this double-blind, randomized, placebo-controlled trial, we recruited adult patients with HIV-associated cryptococcal meningitis in Vietnam, Thailand, Indonesia, Laos, Uganda, and Malawi. All the patients received either dexamethasone or placebo for 6 weeks, along with combination antifungal therapy with amphotericin B and fluconazole.

Results: The trial was stopped for safety reasons after the enrollment of 451 patients. Mortality was 47% in the dexamethasone group and 41% in the placebo group by 10 weeks (hazard ratio in the dexamethasone group, 1.11; 95% confidence interval [CI], 0.84 to 1.47; P=0.45) and 57% and 49%, respectively, by 6 months (hazard ratio, 1.18; 95% CI, 0.91 to 1.53; P=0.20). The percentage of patients with disability at 10 weeks was higher in the dexamethasone group than in the placebo group, with 13% versus 25% having a prespecified good outcome (odds ratio, 0.42; 95% CI, 0.25 to 0.69; P<0.001). Clinical adverse events were more common in the dexamethasone group than in the placebo group (667 vs. 494 events, P=0.01), with more patients in the dexamethasone group having grade 3 or 4 infection (48 vs. 25 patients, P=0.003), renal events (22 vs. 7, P=0.004), and cardiac events (8 vs. 0, P=0.004). Fungal clearance in cerebrospinal fluid was slower in the dexamethasone group. Results were consistent across Asian and African sites.

Conclusions: Dexamethasone did not reduce mortality among patients with HIV-associated cryptococcal meningitis and was associated with more adverse events and disability than was placebo.

Abstract  Full-text [free] access 

Editor’s notes: Outcomes from cryptococcal meningitis in people living with HIV are very poor. This was highlighted here. Three out of five people overall had died or were severely disabled ten weeks after enrolment. This clinical trial provides strong evidence that steroids cause more harm than good and therefore routine use should not be recommended. Dexamethasone was not only associated with higher risk of death or disability but also with higher risk of significant adverse events, particularly bacterial sepsis.

The majority of deaths occurred early, in the first three weeks. Most participants were ART naïve and severely immunosuppressed (CD4+ cell count <50 cells/µL) and most deaths look to have occurred prior to the scheduled start of antiretroviral therapy. This may also partly explain the low frequency of immune reconstitution inflammatory syndrome (IRIS) and the lack of any observed benefit of dexamethasone in reducing IRIS.

Although dexamethasone was associated with greater decline in intracranial pressure, this did not translate into improved neurological outcomes. All participants had regular lumbar punctures for pressure monitoring. This might have limited the potential to observe a benefit from dexamethasone. Some explanation for the adverse outcomes might come from the impaired fungal clearance in cerebrospinal fluid – a marker of poor outcomes in previous studies. It should be noted that antifungal treatment in this trial was suboptimal. The combination of amphotericin and flucytosine was not used, despite evidence of improved outcomes and more rapid fungal clearance with this regimen.

While the search should go on for better treatment strategies, the findings in this study emphasise the importance of prevention, focused firmly, on earlier HIV diagnosis and treatment.  

Comorbidity, HIV Treatment
Indonesia, Laos, Malawi, Thailand, Uganda, Viet Nam
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