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Mathematical modeling of HIV-1 transmission risk from condomless anal intercourse in HIV-infected MSM by the type of initial ART.

ABSTRACT: BACKGROUND:Initiation of antiretroviral therapy (ART) for HIV infection using regimens that include integrase strand transfer inhibitors (INSTIs) is associated with a faster decline in HIV-1 RNA than what is observed with regimens that are anchored by other ART drug classes. We compared the impact of ART regimens that include dolutegravir (DTG), raltegravir (RAL), efavirenz (EFV), or darunavir/ritonavir (DRV/r), in treatment naïve men who have sex with men (MSM) on the probability of HIV-1 sexual transmission events (HIV-TE). SETTING:Mathematical model. METHODS:We used discrete event simulation modeling to estimate HIV-TE during the first 8 weeks after initiation of ART. HIV-1 RNA decay in men was modeled from the databases of three clinical trials: Single (DTG vs. EFV), Spring-2 (DTG vs. RAL) and Flamingo (DTG vs. DRV/r). RESULTS:All regimens substantially reduced the number of HIV-TE compared to no treatment. DTG led to fewer HIV-TE than its comparator in each of the three trials: 22.72% fewer transmissions than EFV; 0.52% fewer transmissions than RAL; and 38.67% fewer transmissions than DRV/r. The number of patients needed to treat with DTG to prevent one transmission event instead of comparator was 48 vs EFV, 2,194 vs RAL, and 31 vs DRV/r. CONCLUSION:Unsurprisingly, this mathematical model showed that all regimens reduced HIV-TE compared to no treatment. The results also suggest that that initial use of INSTIs, by virtue of their superior viral decay kinetics, have the potential to reduce HIV-1 horizontal transmission following initiation of ART in naïve MSM. TRIAL REGISTRATION:ClinicalTrials.gov NCT03183154.

SUBMITTER: Berenguer J

PROVIDER: S-EPMC6641501 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Mathematical modeling of HIV-1 transmission risk from condomless anal intercourse in HIV-infected MSM by the type of initial ART.

Berenguer Juan J Parrondo Javier J Landovitz Raphael J RJ

PloS one 20190719 7

<h4>Background</h4>Initiation of antiretroviral therapy (ART) for HIV infection using regimens that include integrase strand transfer inhibitors (INSTIs) is associated with a faster decline in HIV-1 RNA than what is observed with regimens that are anchored by other ART drug classes. We compared the impact of ART regimens that include dolutegravir (DTG), raltegravir (RAL), efavirenz (EFV), or darunavir/ritonavir (DRV/r), in treatment naïve men who have sex with men (MSM) on the probability of HIV ...[more]

PMID: 31323075

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Project description:BackgroundThe human immunodeficiency virus (HIV) infectiousness of anal intercourse (AI) has not been systematically reviewed, despite its role driving HIV epidemics among men who have sex with men (MSM) and its potential contribution to heterosexual spread. We assessed the per-act and per-partner HIV transmission risk from AI exposure for heterosexuals and MSM and its implications for HIV prevention.MethodsSystematic review and meta-analysis of the literature on HIV-1 infectiousness through AI was conducted. PubMed was searched to September 2008. A binomial model explored the individual risk of HIV infection with and without highly active antiretroviral therapy (HAART).ResultsA total of 62,643 titles were searched; four publications reporting per-act and 12 reporting per-partner transmission estimates were included. Overall, random effects model summary estimates were 1.4% [95% confidence interval (CI) 0.2-2.5)] and 40.4% (95% CI 6.0-74.9) for per-act and per-partner unprotected receptive AI (URAI), respectively. There was no significant difference between per-act risks of URAI for heterosexuals and MSM. Per-partner unprotected insertive AI (UIAI) and combined URAI-UIAI risk were 21.7% (95% CI 0.2-43.3) and 39.9% (95% CI 22.5-57.4), respectively, with no available per-act estimates. Per-partner combined URAI-UIAI summary estimates, which adjusted for additional exposures other than AI with a 'main' partner [7.9% (95% CI 1.2-14.5)], were lower than crude (unadjusted) estimates [48.1% (95% CI 35.3-60.8)]. Our modelling demonstrated that it would require unreasonably low numbers of AI HIV exposures per partnership to reconcile the summary per-act and per-partner estimates, suggesting considerable variability in AI infectiousness between and within partnerships over time. AI may substantially increase HIV transmission risk even if the infected partner is receiving HAART; however, predictions are highly sensitive to infectiousness assumptions based on viral load.ConclusionsUnprotected AI is a high-risk practice for HIV transmission, probably with substantial variation in infectiousness. The significant heterogeneity between infectiousness estimates means that pooled AI HIV transmission probabilities should be used with caution. Recent reported rises in AI among heterosexuals suggest a greater understanding of the role AI plays in heterosexual sex lives may be increasingly important for HIV prevention.

Dataset Information

Mathematical modeling of HIV-1 transmission risk from condomless anal intercourse in HIV-infected MSM by the type of initial ART.

Publications

Mathematical modeling of HIV-1 transmission risk from condomless anal intercourse in HIV-infected MSM by the type of initial ART.

Similar Datasets

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