Frequency and Spectrum of Unexpected Clinical Manifestations of Primary HIV-1 Infection

We studied the clinical manifestations among 290 patients with documented primary human immunodeficiency virus type 1 infection (PHI) of whom 30% presented with unexpected patterns of signs and symptoms or occurrence of opportunistic diseases. Morbidity associated with PHI was substantia

Incidence of hypertension in people with HIV who are treated with integrase inhibitors versus other antiretroviral regimens in the RESPOND cohort consortium

OBJECTIVE To compare the incidence of hypertension in people living with HIV receiving integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) versus non-nucleoside reverse transcriptase inhibitors (NNRTIs) or boosted protease inhibitors (PIs) in the RESPOND consortium of HIV cohorts. METHODS Eligible people with HIV were aged ≥18 years who initiated a new three-drug ART regimen for the first time (baseline), did not have hypertension, and had at least two follow-up blood pressure (BP) measurements. Hypertension was defined as two consecutive systolic BP measurements ≥140 mmHg and/or diastolic BP ≥90 mmHg or initiation of antihypertensives. Multivariable Poisson regression was used to determine adjusted incidence rate ratios (aIRRs) of hypertension, overall and in those who were ART naïve or experienced at baseline. RESULTS Overall, 4606 people living with HIV were eligible (INSTIs 3164, NNRTIs 807, PIs 635). The median baseline systolic BP, diastolic BP, and age were 120 (interquartile range [IQR] 113-130) mmHg, 78 (70-82) mmHg, and 43 (34-50) years, respectively. Over 8380.4 person-years (median follow-up 1.5 [IQR 1.0-2.7] years), 1058 (23.0%) participants developed hypertension (incidence rate 126.2/1000 person-years, 95% confidence interval [CI] 118.9-134.1). Participants receiving INSTIs had a higher incidence of hypertension than those receiving NNRTIs (aIRR 1.76; 95% CI 1.47-2.11), whereas the incidence was no different in those receiving PIs (aIRR 1.07; 95% CI 0.89-1.29). The results were similar when the analysis was stratified by ART status at baseline. CONCLUSION Although unmeasured confounding and channelling bias cannot be excluded, INSTIs were associated with a higher incidence of hypertension than were NNRTIs, but rates were similar to those of PIs overall, in ART-naïve and ART-experienced participants within RESPOND

Effect of SLCO1B1 c.521T>C polymorphism on the lipid response to statins in people living with HIV on a boosted protease inhibitor-containing regimen

AIMS: We previously observed that some individuals on HIV boosted protease inhibitor-containing regimen do not achieve their lipid targets despite elevated statin concentrations. This study evaluated whether the common single polymorphism c.521T>C in SLCO1B1, associated with reduced statin uptake in the liver, could explain this observation. METHODS: People living with HIV in the Swiss HIV Cohort Study were eligible if they were on a boosted protease inhibitor concomitantly with a statin for at least 6 months and if their SLCO1B1 genotype was available. Furthermore, their lipids had to be documented before and after the introduction of the statin. The statin efficacy was defined as % change in total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and triglycerides levels after statin initiation compared to pretreatment levels. Lipid response was adjusted for differences in potency and dose between statins. RESULTS: In total, 88 people living with HIV were included, of whom 58, 28 and 2 carried the SLCO1B1 TT, TC and CC genotypes, respectively. The change in lipid levels after statin initiation tended to be lower in carriers of the polymorphism although the difference was not statistically significant (TT vs. TC/CC: total cholesterol: -11.7 vs. -4.8%; low-density lipoprotein- cholesterol: -20.6 vs. -7.4%; high-density lipoprotein-cholesterol: 1.6 vs. 0%; triglycerides: -11.5 vs. -7.9%). In the multiple linear regression, change in total cholesterol was inversely correlated with the total cholesterol level prestatin treatment (coefficient -6.60, 95% confidence interval: -9.63 to -3.56, P < .001). CONCLUSION: The lipid-lowering effect of statins tended to be attenuated by SLCO1B1 polymorphism and progressively declined as total cholesterol under the boosted protease inhibitor treatment decreased

Female Genital Mutilation/Cutting in the Swiss HIV Cohort Study: A Cross-Sectional Study.

FGM/C is a harmful practice that involves injury of the external female genitalia without medical purpose. It is mainly practiced in Africa, Asia, and the Middle East. However, with the migratory flows, women and girls with FGM/C and its consequences live all over the world. The lack of knowledge on how to care for women and girls living with FGM/C extends among all categories of health professionals involved in women's health, including infectious disease specialists. This is a national, exploratory descriptive cross-sectional study aimed to generate descriptive statistics about FGM/C among HIV-infected migrant women included in the Swiss HIV Cohort Study (SHCS). Among the 387 women interviewed about FGM/C and who provided an answer, 80 (20.7%) reported to have undergone FGM/C. Fifty-six of the 80 women (70.0%) who reported having undergone FGM/C, also reported that they had never discussed their cutting with a health professional before. Our study demonstrates how common female genital mutilation is in women living with HIV and who have migrated to Switzerland and suggest how care and prevention could be improved significantly

Female Genital Mutilation/Cutting in the Swiss HIV Cohort Study: A Cross-Sectional Study

FGM/C is a harmful practice that involves injury of the external female genitalia without medical purpose. It is mainly practiced in Africa, Asia, and the Middle East. However, with the migratory flows, women and girls with FGM/C and its consequences live all over the world. The lack of knowledge on how to care for women and girls living with FGM/C extends among all categories of health professionals involved in women's health, including infectious disease specialists. This is a national, exploratory descriptive cross-sectional study aimed to generate descriptive statistics about FGM/C among HIV-infected migrant women included in the Swiss HIV Cohort Study (SHCS). Among the 387 women interviewed about FGM/C and who provided an answer, 80 (20.7%) reported to have undergone FGM/C. Fifty-six of the 80 women (70.0%) who reported having undergone FGM/C, also reported that they had never discussed their cutting with a health professional before. Our study demonstrates how common female genital mutilation is in women living with HIV and who have migrated to Switzerland and suggest how care and prevention could be improved significantly

High Rates of Asymptomatic Mycoplasma genitalium Infections With High Proportion of Genotypic Resistance to First-Line Macrolide Treatment Among Men Who Have Sex With Men Enrolled in the Zurich Primary HIV Infection Study

Background Mycoplasma genitalium (Mg) is an emerging sexually transmitted pathogen among men who have sex with men (MSM). Resistance to recommended antimicrobial agents are of public health concern. Few data exist on Mg infections in MSM diagnosed with human immunodeficiency virus (HIV) during primary HIV infection. Methods Participants of the Zurich Primary HIV Study (ClinicalTrials.gov Identifier NCT00537966) were systematically offered screening for sexually transmitted infections (STIs) between April 2019 and September 2020. Screening was performed using an in-house polymerase chain reaction panel comprising Mg including genotypic resistance testing for macrolides and quinolones, Chlamydia trachomatis including serovars L1-L3, Neisseria gonorrhoeae, Treponema pallidum, and Hemophilus ducreyi. Results We screened 148 of 266 (55.6%) participants, with an overall total of 415 follow-up visits. Ninety-one percent were MSM. The incidence rate for all STIs was 47.0 (95% confidence interval [CI], 32.2-68.6) per 100 person-years. Mycoplasma genitalium was the most frequently detected pathogen: 30 participants (20%) presented with at least 1 Mg infection, corresponding to a period prevalence of 20.3% and incidence rate of 19.5 Mg infections (95% CI, 11.8-32.4). Most Mg infections (93%) were asymptomatic, and 9 (30%) participants showed spontaneous clearance. We detected high rates of antibiotic resistance: 73.3% to macrolides, 3.3% to quinolones, and 13.3% resistance to both antibiotics. Conclusions The high prevalence of mostly asymptomatic Mg infections and high rate of spontaneous clearance support cautious initiation for treatment. The high proportion of macrolide-resistant strains suggests that a genotypic determination of resistance should be standard of care. Moxifloxacin should be the preferred treatment option for symptomatic Mg infections among MSM if resistance testing is unavailable

Long-term trends in hepatitis C prevalence, treatment uptake and liver-related events in the Swiss HIV Cohort Study

BACKGROUND AND AIMS: Treatment for chronic hepatitis C virus (HCV) infections changed dramatically in the last decade. We assessed changes in the prevalence of replicating HCV infection, treatment uptake and liver-related morbidity and mortality in persons with HIV (PWH) and hepatitis C in the Swiss HIV cohort study. METHODS: We included all cohort participants between 2002 and 2021. We assessed yearly prevalence of replicating HCV infection, overall and liver-related mortality, as well as the yearly incidence of liver-related events in persons with at least one documented positive HCV-RNA. RESULTS: Of 14 652 participants under follow-up, 2294 had at least one positive HCV-RNA measurement. Of those, 1316 (57%) ever received an HCV treatment. Treatment uptake increased from 8.1% in 2002 to a maximum of 32.6% in 2016. Overall, prevalence of replicating HCV infection declined from 16.5% in 2004 to 1.3% in 2021. HCV prevalence declined from 63.2% to 7.1% in persons who inject drugs, and from 4.1% to 0.6% in men who have sex with men. Among the 2294 persons with replicating HCV infection, overall mortality declined from a maximum of 3.3 per 100 patient-years (PY) to 1.1 per 100 PY, and incidence of liver-related events decreased from 1.4/100 PY to 0.2/100 PY. CONCLUSIONS: The introduction of DAA therapy was associated with a more than 10-fold reduction in prevalence of replicating HCV infection in PWH, approaching the estimates in the general population. Overall mortality and liver-related events declined substantially in persons living with HIV and hepatitis C

Long-term trends in hepatitis C prevalence, treatment uptake and liver-related events in the Swiss HIV Cohort Study.

BACKGROUND AND AIMS Treatment for chronic hepatitis C virus (HCV) infections changed dramatically in the last decade. We assessed changes in the prevalence of replicating HCV infection, treatment uptake and liver-related morbidity and mortality in persons with HIV (PWH) and hepatitis C in the Swiss HIV cohort study. METHODS We included all cohort participants between 2002 and 2021. We assessed yearly prevalence of replicating HCV infection, overall and liver-related mortality, as well as the yearly incidence of liver-related events in persons with at least one documented positive HCV-RNA. RESULTS Of 14 652 participants under follow-up, 2294 had at least one positive HCV-RNA measurement. Of those, 1316 (57%) ever received an HCV treatment. Treatment uptake increased from 8.1% in 2002 to a maximum of 32.6% in 2016. Overall, prevalence of replicating HCV infection declined from 16.5% in 2004 to 1.3% in 2021. HCV prevalence declined from 63.2% to 7.1% in persons who inject drugs, and from 4.1% to 0.6% in men who have sex with men. Among the 2294 persons with replicating HCV infection, overall mortality declined from a maximum of 3.3 per 100 patient-years (PY) to 1.1 per 100 PY, and incidence of liver-related events decreased from 1.4/100 PY to 0.2/100 PY. CONCLUSIONS The introduction of DAA therapy was associated with a more than 10-fold reduction in prevalence of replicating HCV infection in PWH, approaching the estimates in the general population. Overall mortality and liver-related events declined substantially in persons living with HIV and hepatitis C

Sustained Viral Suppression With Dolutegravir Monotherapy Over 192 Weeks in Patients Starting Combination Antiretroviral Therapy During Primary Human Immunodeficiency Virus Infection (EARLY-SIMPLIFIED): A Randomized, Controlled, Multi-site, Noninferiority Trial

BACKGROUND: Starting combination antiretroviral therapy (cART) during primary human immunodeficiency virus type 1 (HIV-1) infection results in a smaller HIV-1 latent reservoir, reduced immune activation, and less viral diversity compared to starting cART during chronic infection. We report results of a 4-year study designed to determine whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir (DTG) monotherapy. METHODS: EARLY-SIMPLIFIED is a randomized, open-label, noninferiority trial. People with HIV (PWH) who started cART <180 days after a documented primary HIV-1 infection with suppressed viral load were randomized (2:1) to DTG monotherapy with 50 mg daily or continuation of cART. The primary endpoints were the proportion of PWH with viral failure at 48, 96, 144, and 192 weeks; noninferiority margin was 10%. After 96 weeks, randomization was lifted and patients were permitted to switch treatment groups as desired. RESULTS: Of 101 PWH randomized, 68 were assigned to DTG monotherapy and 33 to cART. At week 96 in the per-protocol population, 64/64 (100%) showed virological response in the DTG monotherapy group versus 30/30 (100%) in the cART group (difference, 0.00%; upper bound of 95% confidence interval 6.22%). This demonstrated noninferiority of DTG monotherapy at the prespecified level. At week 192, the study end, no virological failure occurred in either group during 13 308 and 4897 person weeks of follow-up for the DTG monotherapy (n = 80) and cART groups, respectively. CONCLUSIONS: This trial suggests that early cART initiation during primary HIV infection allows sustained virological suppression after switching to DTG monotherapy

Dolutegravir Monotherapy as Maintenance Strategy: A Meta-Analysis of Individual Participant Data From Randomized Controlled Trials

Background Dolutegravir monotherapy (DTG-m) results in virological failure (VF) in some people with human immunodeficiency virus (PWH). We sought to identify the independent factors associated with the risk of VF and to explore the effect size heterogeneity between subgroups of PWH enrolled in DTG-m trials. Methods We searched for randomized clinical trials (RCTs) evaluating DTG-m versus combined antiretroviral therapy (cART) among PWH virologically controlled for at least 6 months on cART. We performed an individual participant data meta-analysis of VF risk factors and quantified their explained heterogeneity in random-effect models. Definition of VF was a confirmed plasma human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) >50 copies/mL by week 48. Results Among 416 PWH from 4 RCTs, DTG-m significantly increased the risk of VF (16 of 227 [7%] versus 0 of 189 for cART; risk difference 7%; 95% confidence interval [CI], 1%-2%; P = .02; I$^{2}$ = 51%). Among 272 participants exposed to DTG-m, VF were more likely in participants with the following: first cART initiated ≥90 days from HIV acute infection (adjusted hazard ratio [aHR], 5.16; 95% 95% CI, 1.60-16.65), CD4 T cells nadir <350/mm$^{3}$ (aHR, 12.10; 95% CI, 3.92-37.40), HIV RNA signal at baseline (aHR, 4.84; 95% CI, 3.68-6.38), and HIV-deoxyribonucleic acid (DNA) copy number at baseline ≥2.7 log/10$^{6}$ peripheral blood mononuclear cells (aHR, 3.81; 95% CI, 1.99-7.30). Among these independent risk factors, the largest effect size heterogeneity was found between HIV DNA subgroups (I$^{2}$ = 80.2%; P for interaction = .02). Conclusions Our study supports the importance of a large viral reservoir size for explaining DTG-m simplification strategy failure. Further studies are needed to link size and genetic diversity of the HIV-1 reservoir