Safety and Efficacy of Long-Acting Injectable Agents for HIV-1: Systematic Review and Meta-Analysis
BackgroundHIV-1 infection continues to affect global health. Although antiretrovirals can reduce the viral load or prevent HIV-1 infection, current drugs require daily oral use with a high adherence level. Long-acting antiretrovirals (LA-ARVs) significantly improve medication...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
JMIR Publications
2023-07-01
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| Series: | JMIR Public Health and Surveillance |
| Online Access: | https://publichealth.jmir.org/2023/1/e46767 |
| _version_ | 1797733966576353280 |
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| author | Wenjing Wang Shengnan Zhao Yaxin Wu Wenshan Duan Sibo Li Zhen Li Caiping Guo Wen Wang Tong Zhang Hao Wu Xiaojie Huang |
| author_facet | Wenjing Wang Shengnan Zhao Yaxin Wu Wenshan Duan Sibo Li Zhen Li Caiping Guo Wen Wang Tong Zhang Hao Wu Xiaojie Huang |
| author_sort | Wenjing Wang |
| collection | DOAJ |
| description |
BackgroundHIV-1 infection continues to affect global health. Although antiretrovirals can reduce the viral load or prevent HIV-1 infection, current drugs require daily oral use with a high adherence level. Long-acting antiretrovirals (LA-ARVs) significantly improve medication adherence and are essential for HIV-1 prophylaxis and therapy.
ObjectiveThis study aimed to investigate the safety and efficacy of long-acting cabotegravir (CAB-LA) and long-acting rilpivirine (RPV-LA) in the prevention and treatment of HIV-1 infection.
MethodsPubMed, Embase, and the Cochrane Library were searched for studies from database inception to November 12, 2022. We included studies that reported efficacy and safety data on LA-ARV intervention in people living with HIV and excluded reviews, animal studies, and articles with missing or duplicate data. Virological suppression was defined as plasma viral load <50 copies/mL 6 months after antiviral therapy initiation. We extracted outcomes for analysis and expressed dichotomous data as risk ratios (RRs) and continuous data as mean differences. Depending on the heterogeneity assessment, a fixed- or random-effects model was used for data synthesis. We performed subgroup analyses of the partial safety and efficacy outcomes of CAB-LA+RPV-LA. The protocol was registered with the Open Science Framework.
ResultsWe included 12 trials comprising 10,957 individuals, of which 7 were prevention trials and 5 were treatment trials. CAB-LA and RPV-LA demonstrated safety profiles comparable with those of the placebo in terms of adverse event–related withdrawal. Moreover, the efficacy data showed that CAB-LA had a better effect on HIV-1 prevention than tenofovir disoproxil fumarate–emtricitabine (17/5161, 0.33% vs 75/5129, 1.46%; RR 0.21, 95% CI 0.07-0.61; I2=70%). Although CAB-LA+RPV-LA had more drug-related adverse events (556/681, 81.6% vs 37/598, 6.2%; RR 12.50, 95% CI 3.98-39.23; I2=85%), a mild or moderate injection site reaction was the most common reaction, and its frequency decreased over time. The efficacy of CAB-LA+RPV-LA was comparable with that of daily oral drugs at 48 and 96 weeks (1302/1424, 91.43% vs 915/993, 92.2%; RR 0.99, 95% CI 0.97-1.02; I2=0%), and a high level of virological suppression of 80.9% (186/230) was maintained even after 5 years of LA-ARV use. Similar efficacy outcomes were observed in both treatment-naive and treatment-experienced patients (849/911, 93.2% vs 615/654, 94%; RR 0.99, 95% CI 0.96-1.02; I2=0%). According to the questionnaires, more than 85% of people living with HIV favored LA-ARVs.
ConclusionsLA-ARVs showed favorable safety profiles for both the prevention and treatment of HIV-1 infection and were well tolerated. CAB-LA has more satisfactory efficacy than tenofovir disoproxil fumarate–emtricitabine, significantly reducing the rate of HIV-1 infection. CAB-LA+RPV-LA maintains virological suppression for a long time and may be a viable switching strategy with enhanced public health benefits by reducing transmission. However, further trials are required to confirm the efficacy of these drugs. |
| first_indexed | 2024-03-12T12:36:17Z |
| format | Article |
| id | doaj.art-6e3706787983430590d3cc3845796146 |
| institution | Directory Open Access Journal |
| issn | 2369-2960 |
| language | English |
| last_indexed | 2024-03-12T12:36:17Z |
| publishDate | 2023-07-01 |
| publisher | JMIR Publications |
| record_format | Article |
| series | JMIR Public Health and Surveillance |
| spelling | doaj.art-6e3706787983430590d3cc38457961462023-08-29T00:08:08ZengJMIR PublicationsJMIR Public Health and Surveillance2369-29602023-07-019e4676710.2196/46767Safety and Efficacy of Long-Acting Injectable Agents for HIV-1: Systematic Review and Meta-AnalysisWenjing Wanghttps://orcid.org/0000-0002-4690-1766Shengnan Zhaohttps://orcid.org/0000-0002-1387-4685Yaxin Wuhttps://orcid.org/0000-0003-1193-926XWenshan Duanhttps://orcid.org/0009-0000-5362-7024Sibo Lihttps://orcid.org/0009-0005-6951-2957Zhen Lihttps://orcid.org/0000-0003-0298-1677Caiping Guohttps://orcid.org/0009-0002-5325-2247Wen Wanghttps://orcid.org/0000-0003-3039-9297Tong Zhanghttps://orcid.org/0000-0003-2534-4785Hao Wuhttps://orcid.org/0000-0001-7096-2027Xiaojie Huanghttps://orcid.org/0000-0002-5045-9202 BackgroundHIV-1 infection continues to affect global health. Although antiretrovirals can reduce the viral load or prevent HIV-1 infection, current drugs require daily oral use with a high adherence level. Long-acting antiretrovirals (LA-ARVs) significantly improve medication adherence and are essential for HIV-1 prophylaxis and therapy. ObjectiveThis study aimed to investigate the safety and efficacy of long-acting cabotegravir (CAB-LA) and long-acting rilpivirine (RPV-LA) in the prevention and treatment of HIV-1 infection. MethodsPubMed, Embase, and the Cochrane Library were searched for studies from database inception to November 12, 2022. We included studies that reported efficacy and safety data on LA-ARV intervention in people living with HIV and excluded reviews, animal studies, and articles with missing or duplicate data. Virological suppression was defined as plasma viral load <50 copies/mL 6 months after antiviral therapy initiation. We extracted outcomes for analysis and expressed dichotomous data as risk ratios (RRs) and continuous data as mean differences. Depending on the heterogeneity assessment, a fixed- or random-effects model was used for data synthesis. We performed subgroup analyses of the partial safety and efficacy outcomes of CAB-LA+RPV-LA. The protocol was registered with the Open Science Framework. ResultsWe included 12 trials comprising 10,957 individuals, of which 7 were prevention trials and 5 were treatment trials. CAB-LA and RPV-LA demonstrated safety profiles comparable with those of the placebo in terms of adverse event–related withdrawal. Moreover, the efficacy data showed that CAB-LA had a better effect on HIV-1 prevention than tenofovir disoproxil fumarate–emtricitabine (17/5161, 0.33% vs 75/5129, 1.46%; RR 0.21, 95% CI 0.07-0.61; I2=70%). Although CAB-LA+RPV-LA had more drug-related adverse events (556/681, 81.6% vs 37/598, 6.2%; RR 12.50, 95% CI 3.98-39.23; I2=85%), a mild or moderate injection site reaction was the most common reaction, and its frequency decreased over time. The efficacy of CAB-LA+RPV-LA was comparable with that of daily oral drugs at 48 and 96 weeks (1302/1424, 91.43% vs 915/993, 92.2%; RR 0.99, 95% CI 0.97-1.02; I2=0%), and a high level of virological suppression of 80.9% (186/230) was maintained even after 5 years of LA-ARV use. Similar efficacy outcomes were observed in both treatment-naive and treatment-experienced patients (849/911, 93.2% vs 615/654, 94%; RR 0.99, 95% CI 0.96-1.02; I2=0%). According to the questionnaires, more than 85% of people living with HIV favored LA-ARVs. ConclusionsLA-ARVs showed favorable safety profiles for both the prevention and treatment of HIV-1 infection and were well tolerated. CAB-LA has more satisfactory efficacy than tenofovir disoproxil fumarate–emtricitabine, significantly reducing the rate of HIV-1 infection. CAB-LA+RPV-LA maintains virological suppression for a long time and may be a viable switching strategy with enhanced public health benefits by reducing transmission. However, further trials are required to confirm the efficacy of these drugs.https://publichealth.jmir.org/2023/1/e46767 |
| spellingShingle | Wenjing Wang Shengnan Zhao Yaxin Wu Wenshan Duan Sibo Li Zhen Li Caiping Guo Wen Wang Tong Zhang Hao Wu Xiaojie Huang Safety and Efficacy of Long-Acting Injectable Agents for HIV-1: Systematic Review and Meta-Analysis JMIR Public Health and Surveillance |
| title | Safety and Efficacy of Long-Acting Injectable Agents for HIV-1: Systematic Review and Meta-Analysis |
| title_full | Safety and Efficacy of Long-Acting Injectable Agents for HIV-1: Systematic Review and Meta-Analysis |
| title_fullStr | Safety and Efficacy of Long-Acting Injectable Agents for HIV-1: Systematic Review and Meta-Analysis |
| title_full_unstemmed | Safety and Efficacy of Long-Acting Injectable Agents for HIV-1: Systematic Review and Meta-Analysis |
| title_short | Safety and Efficacy of Long-Acting Injectable Agents for HIV-1: Systematic Review and Meta-Analysis |
| title_sort | safety and efficacy of long acting injectable agents for hiv 1 systematic review and meta analysis |
| url | https://publichealth.jmir.org/2023/1/e46767 |
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