Suchergebnisse

IntroductionLamivudine (3TC) and emtricitabine (FTC) are considered interchangeable by HIV‐1 guidelines in first‐line tenofovir/efavirenz (TDF/EFV) and TDF/nevirapine (NVP) combination antiretroviral therapy (cART). Data from trials on equivalence of 3TC and FTC are inconsistent. We examined the effectiveness of 3TC and FTC in the national HIV cohort in the Netherlands.Material and MethodsObservational cohort study on cART naïve HIV‐1 patients. Therapy was initiated as 3TC or FTC with TDF/EFV or TDF/NVP between 2002 and 2012. Patients with baseline resistance or prior cART experience were excluded. Main outcomes were Week 48 virological failure (VF) by on treatment analysis, time to HIV‐RNA <400 copies/mL within 48 weeks and VF within 240 weeks after at least one HIV‐RNA <400 copies/mL. Acquired resistance to reverse transcriptase was evaluated. Analyses were done by logistic regression and Cox proportional hazard models. Propensity score adjusted models and intention to treat evaluations were included as sensitivity analysis.ResultsA total of 4836 patients initiated 3TC/TDF/EFV (n=546), FTC/TDF/EFV (n=3391), 3TC/TDF/NVP (n=207) or FTC/TDF/NVP (n=692). Ninety‐six patients were excluded for baseline resistance or prior cART experience. By Week 48, VF proportions were higher for 3TC/TDF/EFV (10.8%) compared to FTC/TDF/EFV (3.6%) and for 3TC/TDF/NVP (27.0%) compared to FTC/TDF/NVP (11.0%). The multivariable adjusted odds ratio (OR) on VF was 1.78 (95% CI 1.11–2.84; p=0.016) with 3TC/TDF/EFV compared to FTC/TDF/EFV and 2.09 (95% CI 1.25–3.52; p=0.005) with 3TC/TDF/NVP compared to FTC/TDF/NVP. Propensity score adjusted models and intention to treat analyses showed comparable results. The time to virological suppression within 48 weeks was not influenced by using 3TC or FTC in cART. If HIV‐RNA <400 copies/mL was achieved on initial cART first, no differences in VF within 240 weeks were observed between 3TC and FTC with TDF/EFV (p=0.090) or TDF/NVP (P=0.255). Patients failing 3TC‐containing cART had higher median HIV‐RNA at VF compared to FTC containing cART (p<0.001) and 89.8% had acquired resistance on 3TC compared to 81.2% on FTC.ConclusionsIncluding FTC in cART is associated with better virological responses compared to 3TC. As cost constraints may call for the use of generic 3TC, a well‐powered randomized trial to confirm the presumed equivalence of 3TC and FTC is needed.

AbstractIntroductionIn France, oral pre‐exposure prophylaxis (PrEP) for HIV prevention has been publicly available since 2016, mainly targeting at men who have sex with men (MSM). Reliable and robust estimations of the actual PrEP uptake among MSM on a localized level can provide additional insights to identify and better reach marginalized MSM within current HIV prevention service provision. This study used national pharmaco‐epidemiology surveillance data and regional MSM population estimations to model the spatio‐temporal distribution of PrEP uptake among MSM in France 2016–2021 to identify marginalized MSM at risk for HIV and increase their PrEP uptake.MethodsWe first applied Bayesian spatial analyses with survey‐surveillance‐based HIV incidence data as a spatial proxy to estimate the size of (1) regional HIV‐negative MSM populations and (2) MSM who could be eligible for PrEP use according to French PrEP guidelines. We then applied Bayesian spatio‐temporal ecological regression modelling to estimate the regional prevalence and relative probability of the overall‐ and new‐PrEP uptake from 2016 to 2021 across France.ResultsHIV‐negative and PrEP‐eligible MSM populations vary regionally across France. Île‐de‐France was estimated to have the highest MSM density compared to other French regions. According to the final spatio‐temporal model, the relative probability of overall PrEP uptake was heterogeneous across France but remained stable over time. Urban areas have higher‐than‐average probabilities of PrEP uptake. The prevalence of PrEP use increased steadily (ranging from 8.8% [95% credible interval 8.5%;9.0%] in Nouvelle‐Aquitaine to 38.2% [36.5%;39.9%] in Centre‐Val‐de‐Loire in 2021).ConclusionsOur results show that using Bayesian spatial analysis as a novel methodology to estimate the localized HIV‐negative MSM population is feasible and applicable. Spatio‐temporal models showed that despite the increasing prevalence of PrEP use in all regions, geographical disparities and inequalities of PrEP uptake continued to exist over time. We identified regions that would benefit from greater tailoring and delivery efforts. Based on our findings, public health policies and HIV prevention strategies could be adjusted to better combat HIV infections and to accelerate ending the HIV epidemic.

AbstractIntroductionAlthough pre‐exposure prophylaxis (PrEP.) is an efficacious HIV prevention strategy, its preventive benefit has not been shown among young women in sub‐Saharan Africa, likely due to non‐adherence. Adherence may be improved with the use of injectable long‐acting PrEP methods currently being developed. We hypothesize that providing long‐acting PrEP to women using injectable contraceptives, the most frequently used contraceptive method in South Africa, could improve adherence to PrEP, result in a reduction of new HIV infections, and be a relatively easy‐to‐reach target population. In this modelling study, we assessed the epidemiological impact and cost‐effectiveness of providing long‐acting PrEP to injectable contraceptive users in Limpopo, South Africa.MethodsWe developed a deterministic mathematical model calibrated to the HIV epidemic in Limpopo. Long‐acting PrEP was provided to 50% of HIV negative injectable contraceptive users in 2018 and scaled‐up over two years. We estimated the number of HIV infections that could be averted by 2030 and the drug price of long‐acting PrEP for which this intervention would be cost‐effective over a time horizon of 40 years, from a healthcare payer perspective. In the base‐case scenario we assumed long‐acting PrEP is 75% effective in preventing HIV infections and 85% of infected individuals are on antiretroviral drug therapy (ART) by 2030. In sensitivity analyses we adjusted PrEP effectiveness and ART coverage. Costs between $519 and $1119 per disability‐adjusted life‐year (DALY) averted were considered potentially cost‐effective, and <$519 as cost‐effective.ResultsWithout long‐acting injectable PrEP, 224,000 (interquartile range 176,000 to 271,000) new infections will occur by 2030; use of long‐acting injectable PrEP could prevent 21,000 (17,000 to 26,000) or 9.8% (8.9% to 10.6%) new HIV infections by 2030 (including 6000 (4000 to 7000) in men). Long‐acting PrEP would prevent 34,000 (29,000 to 39,000) or 12,000 (8000 to 15,000) at 75% and 95% ART coverage by 2030 respectively. To be considered potentially cost‐effective the annual long‐acting PrEP drug price should be <$16, and/or ART coverage remains at <85% in 2030.ConclusionsProviding long‐acting PrEP to injectable contraceptive users in Limpopo is only potentially cost‐effective when long‐acting PrEP drug prices are low. If low prices are not feasible, providing long‐acting PrEP only to women at high risk of HIV infection will become important.

IntroductionEarlier antiretroviral therapy (ART) initiation reduces HIV‐1 incidence. This benefit may be offset by increased transmitted drug resistance (TDR), which could limit future HIV treatment options. We analyze the epidemiological impact and cost‐effectiveness of strategies to reduce TDR.MethodsWe develop a deterministic mathematical model representing Kampala, Uganda, to predict the prevalence of TDR over a 10‐year period. We then compare the impact on TDR and cost‐effectiveness of: (1) introduction of pre‐therapy genotyping; (2) doubling use of second‐line treatment to 80% (50–90%) of patients with confirmed virological failure on first‐line ART; and (3) increasing viral load monitoring from yearly to twice yearly. An intervention can be considered cost‐effective if it costs less than three times the gross domestic product per capita per quality adjusted life year (QALY) gained, or less than $3420 in Uganda.ResultsThe prevalence of TDR is predicted to rise from 6.7% (interquartile range [IQR] 6.2–7.2%) in 2014, to 6.8% (IQR 6.1–7.6%), 10.0% (IQR 8.9–11.5%) and 11.1% (IQR 9.7–13.0%) in 2024 if treatment is initiated at a CD4 <350, <500, or immediately, respectively. The absolute number of TDR cases is predicted to decrease 4.4–8.1% when treating earlier compared to treating at CD4 <350 due to the preventative effects of earlier treatment. Most cases of TDR can be averted by increasing second‐line treatment (additional 7.1–10.2% reduction), followed by increased viral load monitoring (<2.7%) and pre‐therapy genotyping (<1.0%). Only increasing second‐line treatment is cost‐effective, ranging from $1612 to $2234 (IQR $450‐dominated) per QALY gained.ConclusionsWhile earlier treatment initiation will result in a predicted increase in the proportion of patients infected with drug‐resistant HIV, the absolute numbers of patients infected with drug‐resistant HIV is predicted to decrease. Increasing use of second‐line treatment to all patients with confirmed failure on first‐line therapy is a cost‐effective approach to reduce TDR. Improving access to second‐line ART is therefore a major priority.

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) ; Human immunodeficiency virus type 1 (HIV-1) was discovered in the early 1980s when the virus had already established a pandemic. For at least three decades the epidemic in the Western World has been dominated by subtype B infections, as part of a sub-epidemic that traveled from Africa through Haiti to United States. However, the pattern of the subsequent spread still remains poorly understood. Here we analyze a large dataset of globally representative HIV-1 subtype B strains to map their spread around the world over the last 50years and describe significant spread patterns. We show that subtype B travelled from North America to Western Europe in different occasions, while Central/Eastern Europe remained isolated for the most part of the early epidemic. Looking with more detail in European countries we see that the United Kingdom, France and Switzerland exchanged viral isolates with non-European countries than with European ones. The observed pattern is likely to mirror geopolitical landmarks in the post-World War II era, namely the rise and the fall of the Iron Curtain and the European colonialism. In conclusion, HIV-1 spread through specific migration routes which are consistent with geopolitical factors that affected human activities during the last 50 years, such as migration, tourism and trade. Our findings support the argument that epidemic control policies should be global and incorporate political and socioeconomic factors. ; info:eu-repo/semantics/publishedVersion

Human immunodeficiency virus type 1 (HIV-1) was discovered in the early 1980s when the virus had already established a pandemic. For at least three decades the epidemic in the Western World has been dominated by subtype B infections, as part of a sub-epidemic that traveled from Africa through Haiti to United States. However, the pattern of the subsequent spread still remains poorly understood. Here we analyze a large dataset of globally representative HIV-1 subtype B strains to map their spread around the world over the last 50 years and describe significant spread patterns. We show that subtype B travelled from North America to Western Europe in different occasions, while Central/Eastern Europe remained isolated for the most part of the early epidemic. Looking with more detail in European countries we see that the United Kingdom, France and Switzerland exchanged viral isolates with non-European countries than with European ones. The observed pattern is likely to mirror geopolitical landmarks in the post-World War II era, namely the rise and the fall of the Iron Curtain and the European colonialism. In conclusion, HIV-1 spread through specific migration routes which are consistent with geopolitical factors that affected human activities during the last 50 years, such as migration, tourism and trade. Our findings support the argument that epidemic control policies should be global and incorporate political and socioeconomic factors.

Human immunodeficiency virus type 1 (HIV-1) was discovered in the early 1980s when the virus had already established a pandemic. For at least three decades the epidemic in the Western World has been dominated by subtype B infections, as part of a sub-epidemic that traveled from Africa through Haiti to United States. However, the pattern of the subsequent spread still remains poorly understood. Here we analyze a large dataset of globally representative HIV-1 subtype B strains to map their spread around the world over the last 50 years and describe significant spread patterns. We show that subtype B travelled from North America to Western Europe in different occasions, while Central/Eastern Europe remained isolated for the most part of the early epidemic. Looking with more detail in European countries we see that the United Kingdom, France and Switzerland exchanged viral isolates with non-European countries than with European ones. The observed pattern is likely to mirror geopolitical landmarks in the post-World War II era, namely the rise and the fall of the Iron Curtain and the European colonialism. In conclusion, HIV-1 spread through specific migration routes which are consistent with geopolitical factors that affected human activities during the last 50 years, such as migration, tourism and trade. Our findings support the argument that epidemic control policies should be global and incorporate political and socioeconomic factors.