Raltegravir-intensified initial antiretroviral therapy in advanced HIV disease in Africa: A randomised controlled trial

In sub-Saharan Africa, individuals infected with HIV who are severely immunocompromised have high mortality (about 10%) shortly after starting antiretroviral therapy (ART). This group also has the greatest risk of morbidity and mortality associated with immune reconstitution inflammatory syndrome (I...

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Bibliographic Details
Published in:PLoS medicine 2018-12, Vol.15 (12), p.e1002706-e1002706
Main Authors: Kityo, Cissy, Szubert, Alexander J, Siika, Abraham, Heyderman, Robert, Bwakura-Dangarembizi, Mutsa, Lugemwa, Abbas, Mwaringa, Shalton, Griffiths, Anna, Nkanya, Immaculate, Kabahenda, Sheila, Wachira, Simon, Musoro, Godfrey, Rajapakse, Chatu, Etyang, Timothy, Abach, James, Spyer, Moira J, Wavamunno, Priscilla, Nyondo-Mipando, Linda, Chidziva, Ennie, Nathoo, Kusum, Klein, Nigel, Hakim, James, Gibb, Diana M, Walker, A Sarah, Pett, Sarah L
Format: Article
Language:English
Subjects:
Abacavir
Adolescent
Adolescents
Adult
Africa - epidemiology
Anti-HIV Agents - administration & dosage
Anti-Retroviral Agents - administration & dosage
Antiretroviral agents
Antiretroviral drugs
Antiretroviral therapy
Biology and Life Sciences
Biomarkers
CD4 antigen
Child
Child, Preschool
Children
Clinical trials
Councils
Disease Progression
Drug Administration Schedule
Drug therapy
Female
Follow-Up Studies
Funding
Genotypes
Health Services Accessibility - trends
HIV
HIV infections
HIV Infections - diagnostic imaging
HIV Infections - drug therapy
HIV Infections - epidemiology
Human immunodeficiency virus
Humans
Immune reconstitution
Infections
Inflammation
Inhibitors
Integrase
Kenya - epidemiology
Malawi - epidemiology
Male
Medical research
Medicine
Medicine and Health Sciences
Morbidity
Mortality
Mutation
Non-nucleoside reverse transcriptase inhibitors
Nucleoside reverse transcriptase inhibitors
Nucleosides
Raltegravir
Raltegravir Potassium - administration & dosage
Randomization
Research and Analysis Methods
RNA-directed DNA polymerase
Supervision
Tenofovir
Testing
Uganda - epidemiology
University colleges
Viremia
Viruses
Walker, Sarah
Young Adult
Zimbabwe - epidemiology
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Summary:In sub-Saharan Africa, individuals infected with HIV who are severely immunocompromised have high mortality (about 10%) shortly after starting antiretroviral therapy (ART). This group also has the greatest risk of morbidity and mortality associated with immune reconstitution inflammatory syndrome (IRIS), a paradoxical response to successful ART. Integrase inhibitors lead to significantly more rapid declines in HIV viral load (VL) than all other ART classes. We hypothesised that intensifying standard triple-drug ART with the integrase inhibitor, raltegravir, would reduce HIV VL faster and hence reduce early mortality, although this strategy could also risk more IRIS events. In a 2×2×2 factorial open-label parallel-group trial, treatment-naive adults, adolescents, and children >5 years old infected with HIV, with cluster of differentiation 4 (CD4) 0.7) and despite significantly greater VL suppression with raltegravir-intensified ART at 4 weeks (343/836 [41.0%] versus 113/841 [13.4%] with standard ART, p < 0.001) and 12 weeks (567/789 [71.9%] versus 415/803 [51.7%] with standard ART, p < 0.001). Through 48 weeks, there was no evidence of differences in mortality (aHR = 0.98 [95% CI 0.76-1.28], p = 0.91); in serious (aHR = 0.99 [0.81-1.21], p = 0.88), grade-4 (aHR = 0.88 [0.71-1.09], p = 0.29), or ART-modifying (aHR = 0.90 [0.63-1.27], p = 0.54) adverse events (the latter occurring in 59 [6.5%] participants with raltegravir-intensified ART versus 66 [7.3%] with standard ART); in events judged compatible with IRIS (occurring in 89 [9.9
ISSN:1549-1676
1549-1277
1549-1676
DOI:10.1371/journal.pmed.1002706