Weight, anthropometric and metabolic changes after discontinuing antiretroviral therapy containing tenofovir alafenamide (TAF) in people with HIV.

BACKGROUND: Antiretroviral therapy (ART)-related weight gain is of particular concern in people with HIV (PWH). While weight gain was observed among PWH receiving tenofovir alafenamide (TAF), little is known about the potential reversibility after TAF discontinuation. We evaluated weight and metabolic changes 12 months after TAF discontinuation in the Swiss HIV Cohort Study. METHODS: We included participants who received at least six months of TAF-containing ART between January 2016 and March 2023. Using multivariable mixed-effect models, changes in weight and lipid levels were compared between individuals who continued TAF and those who switched to one of the following TAF-free regimens: TDF-based ART, dolutegravir/lamivudine (DTG/3TC), or long-acting cabotegravir/rilpivirine (CAB/RPV). RESULTS: Of 6555 participants (median age 54 years, 24.3% female, 13% Black), 5485 (83.7%) continued and 1070 (16.3%) stopped TAF. Overall, discontinuing TAF was associated with an adjusted mean weight change of -0.54 kg (95% CI -0.98 to -0.11) after 12 months. In stratified analyses, switching from TAF to TDF led to an adjusted mean weight decrease of -1.84 kg (CI -2.72 to -0.97), and to a decrease in mean total cholesterol (-0.44 mmol/L) and triglycerides (-0.38 mmol/L) after 12 months. Switching from TAF-based ART to DTG/3TC (-0.17 kg, CI -0.82 to 0.48) or long-acting CAB/RPV (-0.64 kg, CI -2.16 to 0.89) did not lead to reductions in weight. CONCLUSIONS: Replacing TAF with TDF in PWH led to a decrease in body weight and an improved lipid profile within one year. Weight changes were not observed among individuals who switched to DTG/3TC or long-acting CAB/RPV.

Trends in preterm birth in women living with HIV in Switzerland over the last three decades: A multicentric, prospective, cohort study.

BACKGROUND: HIV infection and its management during pregnancy to reduce perinatal transmission has been associated with preterm birth (PTB). This management has drastically changed. We aimed to evaluate changes in rates of PTB over 34 years in women living with HIV (WLWH) in Switzerland, and to identify factors and interventions associated with these changes. METHODS: We analysed data from 1238 singleton pregnancies, prospectively collected by the Swiss Mother and Child HIV Cohort Study (MoCHiV) and the Swiss HIV Cohort Study (SHCS) between 1986 and 2020. Rates of PTB in this cohort were compared with that of the general Swiss population for three time periods according to changing treatment strategies recommended at the time. We evaluated the association of PTB with sociodemographic, HIV infection and obstetric variables in uni- and multivariate logistic regression. RESULTS: Rate of PTB in WLWH was highest prior to 2010 (mean 20.4%), and progressively decreased since then (mean 11.3%), but always remained higher than in the general population (5%). Older maternal age, lower CD4 count and detectable viraemia at third trimester (T3), drug consumption and mode of delivery were all significantly associated with both PTB and period of study in univariate analysis. There was no association between PTB and type of antiretroviral regimen. No difference was found in the rate of spontaneous labor between PTB and term delivery groups. Only higher CD4 count at T3 and vaginal delivery were significantly associated with a decrease in PTB over time in multivariate analysis. CONCLUSIONS: Preterm birth in WLWH in Switzerland has drastically decreased over the last three decades, but remains twice the rate of that in the general population. Improved viral control and changes in mode of delivery (vaginal birth recommended if viral loads are low near birth) have led to this progress.

Incidence of sexually transmitted infections and association with behavioural factors: Time-to-event analysis of a large pre-exposure prophylaxis (PrEP) cohort.

OBJECTIVES: Our objective was to obtain long-term data on the incidence of sexually transmitted infections (STIs) and their association with behavioural factors after widespread pre-exposure prophylaxis (PrEP) implementation. METHODS: This was a time-to-event analysis of a national PrEP cohort in Switzerland (SwissPrEPared study). Participants were people without HIV interested in taking PrEP with at least two STI screening visits. Primary outcomes were incidence rate of gonorrhoea, chlamydia, and syphilis. The association between behavioural factors and STI diagnosis was expressed using hazard ratios. We adjusted for testing frequency and calendar year. RESULTS: This analysis included 3907 participants enrolled between April 2019 and April 2022, yielding 3815.7 person-years of follow-up for gonorrhoea (15 134 screenings), 3802.5 for chlamydia (15 141 screenings), and 3858.6 for syphilis (15 001 screenings). The median age was 39 years (interquartile range [IQR] 32-47), 93.8% (n = 3664) identified as men who have sex with men (MSM). The incidence was 22.8 (95% confidence interval [CI] 21.3-24.4) per 100 person-years for gonorrhoea, 26.3 (95% CI 24.7-28.0) for chlamydia, and 4.4 (95% CI 3.8-5.1) for syphilis. Yearly incidence rates decreased between 2019 (all bacterial STIs: 81.6; 95% CI 59.1-109.9) and 2022 (all bacterial STIs: 49.8; 95% CI 44.6-55.3). Participants reporting chemsex substance use were at higher risk of incident STIs, as were those reporting multiple sexual partners. Younger age was associated with a higher risk of gonorrhoea and chlamydia. CONCLUSIONS: Incidence rates of bacterial STIs decreased over time. Young MSM, those with multiple partners, and those using chemsex substances were at increased risk of STIs.

Triggers of Change in Sexual Behavior Among People With HIV: The Swiss U U Statement and COVID-19 Compared.

We assessed changes in sexual behavior among people with human immunodeficiency virus (HIV) over 20 years. Condom use with stable partners steadily declined from over 90 to 29 since the Swiss U U statement, with similar trajectories between men who have sex with men (MSM) and heterosexuals. Occasional partnership remained higher among MSM compared to heterosexuals even during coronavirus disease 2019 (COVID-19) social distancing.

One for all, all for one: neuro-HIV multidisciplinary platform for the assessment and management of neurocognitive complaints in people living with HIV.

BACKGROUND: With ageing, comorbidities such as neurocognitive impairment increase among people living with HIV (PLWH). However, addressing its multifactorial nature is time-consuming and logistically demanding. We developed a neuro-HIV clinic able to assess these complaints in 8 h using a multidisciplinary approach. METHODS: People living with HIV with neurocognitive complaints were referred from outpatient clinics to Lausanne University Hospital. Over 8 h participants underwent formal infectious disease, neurological, neuropsychological and psychiatric evaluations, with opt-out magnetic resonance imaging (MRI) and lumbar puncture. A multidisciplinary panel discussion was performed afterwards, with a final report weighing all findings being produced. RESULTS: Between 2011 and 2019, a total of 185 PLWH (median age 54 years) were evaluated. Of these, 37 (27%) had HIV-associated neurocognitive impairment, but they were mainly asymptomatic (24/37, 64.9%). Most participants had non-HIV-associated neurocognitive impairment (NHNCI), and depression was prevalent across all participants (102/185, 79.5%). Executive function was the principal neurocognitive domain affected among both groups (75.5% and 83.8% of participants impaired, respectively). Polyneuropathy was found in 29 (15.7%) participants. Abnormalities in MRI were found in 45/167 participants (26.9%), being more common among NHNCI (35, 77.8%), and HIV-1 RNA viral escape was detected in 16/142 participants (11.2%). Plasma HIV-RNA was detectable in 18.4% out of 185 participants. CONCLUSIONS: Cognitive complaints remain an important problem among PLWH. Individual assessment from a general practitioner or HIV specialist is not enough. Our observations show the many layers of HIV management and suggest that a multidisciplinary approach could be helpful in determining non-HIV causes of NCI. A 1-day evaluation system is beneficial for both participants and referring physicians.

Diagnosis of latent tuberculosis infection is associated with reduced HIV viral load and lower risk for opportunistic infections in people living with HIV.

Approximately 28% of the human population have been exposed to Mycobacterium tuberculosis (MTB), with the overwhelming majority of infected individuals not developing disease (latent TB infection (LTBI)). While it is known that uncontrolled HIV infection is a major risk factor for the development of TB, the effect of underlying LTBI on HIV disease progression is less well characterized, in part because longitudinal data are lacking. We sorted all participants of the Swiss HIV Cohort Study (SHCS) with at least 1 documented MTB test into one of the 3 groups: MTB uninfected, LTBI, or active TB. To detect differences in the HIV set point viral load (SPVL), linear regression was used; the frequency of the most common opportunistic infections (OIs) in the SHCS between MTB uninfected patients, patients with LTBI, and patients with active TB were compared using logistic regression and time-to-event analyses. In adjusted models, we corrected for baseline demographic characteristics, i.e., HIV transmission risk group and gender, geographic region, year of HIV diagnosis, and CD4 nadir. A total of 13,943 SHCS patients had at least 1 MTB test documented, of whom 840 (6.0%) had LTBI and 770 (5.5%) developed active TB. Compared to MTB uninfected patients, LTBI was associated with a 0.24 decreased log HIV SPVL in the adjusted model (p < 0.0001). Patients with LTBI had lower odds of having candida stomatitis (adjusted odds ratio (OR) = 0.68, p = 0.0035) and oral hairy leukoplakia (adjusted OR = 0.67, p = 0.033) when compared to MTB uninfected patients. The association of LTBI with a reduced HIV set point virus load and fewer unrelated infections in HIV/TB coinfected patients suggests a more complex interaction between LTBI and HIV than previously assumed.

Unsupervised machine learning predicts future sexual behaviour and sexually transmitted infections among HIV-positive men who have sex with men.

Machine learning is increasingly introduced into medical fields, yet there is limited evidence for its benefit over more commonly used statistical methods in epidemiological studies. We introduce an unsupervised machine learning framework for longitudinal features and evaluate it using sexual behaviour data from the last 20 years from over 3'700 participants in the Swiss HIV Cohort Study (SHCS). We use hierarchical clustering to find subgroups of men who have sex with men in the SHCS with similar sexual behaviour up to May 2017, and apply regression to test whether these clusters enhance predictions of sexual behaviour or sexually transmitted diseases (STIs) after May 2017 beyond what can be predicted with conventional parameters. We find that behavioural clusters enhance model performance according to likelihood ratio test, Akaike information criterion and area under the receiver operator characteristic curve for all outcomes studied, and according to Bayesian information criterion for five out of ten outcomes, with particularly good performance for predicting future sexual behaviour and recurrent STIs. We thus assess a methodology that can be used as an alternative means for creating exposure categories from longitudinal data in epidemiological models, and can contribute to the understanding of time-varying risk factors.

Women with HIV transitioning through menopause: Insights from the Swiss HIV Cohort Study (SHCS).

OBJECTIVES: We aimed to assess prevalence and age at menopause, identify factors associated with early menopause and explore the provision and utilization of healthcare in women living with HIV in Switzerland. METHODS: This was a retrospective Swiss HIV Cohort Study analysis from January 2010 to December 2018. Descriptive statistics to characterise the population and menopause onset. Logistic regression analysis to identify risk factors for early menopause. RESULTS: Of all women in the SHCS, the proportion of postmenopausal women tripled from 11.5% (n = 274) in 2010 to 36.1% (n = 961) in 2018. The median age at menopause was 50 years. Early menopause (< 45 years) occurred in 115 (10.2%) women and premature ovarian insufficiency (POI) (< 40 years) in 23 (2%) women. Early menopause was associated with black ethnicity (52.2% vs. 21.6%, p < 0.001), but not with HIV acquisition mode, CDC stage, viral suppression, CD4 cell count, hepatitis C, smoking or active drug use. While 92% of the postmenopausal women underwent a gynaecological examination during the 36 months before menopause documentation, only 27% received a bone mineral density measurement within 36 months after the last bleed and 11% were on hormone replacement therapy at the time of menopause documentation. CONCLUSIONS: The median age of women living with HIV at menopause is around 2 years lower than that reported for HIV-negative women in Switzerland. HIV care providers need to adapt their services to the requirements of the increasing number of women living with HIV transitioning through menopause. They should be able to recognize menopause-associated symptoms and improve access to bone mineral density measurement as well as hormone replacement therapy.

HIV testing in termination of pregnancy and colposcopy services: a scoping review.

BACKGROUND: Women and girls are relatively under-represented across the HIV treatment cascade. Two conditions unique to women, pregnancy and cervical cancer/dysplasia, share a common acquisition mode with HIV. This scoping review aimed to explore HIV testing practices in voluntary termination of pregnancy (TOP) and colposcopy services. METHODS: The scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. We searched articles published up to 20 December 2020 using three electronic databases (PubMed/Medline, Embase, Google Scholar) and including the keywords "HIV Testing", "Abortion, Induced", "Colposcopy", "HIV screen*" and "termination of pregnancy". RESULTS: A total of 1496 articles were identified, of which 55 met the inclusion criteria. We included studies providing background HIV prevalence in addition to prevalence in the study population and studies of women seeking TOP rather than presenting with TOP complications. This limited our review to high-income, low HIV prevalence settings. We observed two study phases: studies pre-antiretroviral therapy (ART) using unlinked anonymous testing data and examining HIV risk factors associated with positive HIV tests and studies post-ART using routine testing data and exploring HIV testing uptake. HIV prevalence was estimated at >0.2% in most TOP settings and >1% (range 1.7%-11.4%) in colposcopy services. Many TOP providers did not have local HIV testing policies and HIV testing was not mentioned in many specialist guidelines. Testing uptake was 49%-96% in TOP and 23%-75% in colposcopy services. CONCLUSION: Given the estimated HIV prevalence of >0.1% among women attending TOP and colposcopy services, HIV testing would be economically feasible to perform in high-income settings. Explicit testing policies are frequently lacking in these two settings, both at the local level and in specialist guidelines. Offering HIV testing regardless of risk factors could normalise testing, reduce late HIV presentation and create an opportunity for preventive counselling.

Telomere Length, Traditional Risk Factors, Factors Related to Human Immunodeficiency Virus (HIV) and Coronary Artery Disease Events in Swiss Persons Living With HIV.

BACKGROUND: Leukocyte telomere length (TL) shortens with age and is associated with coronary artery disease (CAD) events in the general population. Persons living with human immunodeficiency virus (HIV; PLWH) may have accelerated atherosclerosis and shorter TL than the general population. It is unknown whether TL is associated with CAD in PLWH. METHODS: We measured TL by quantitative polymerase chain reaction (PCR) in white Swiss HIV Cohort Study participants. Cases had a first CAD event during 1 January 2000 to 31 December 2017. We matched 1-3 PLWH controls without CAD events on sex, age, and observation time. We obtained univariable and multivariable odds ratios (OR) for CAD from conditional logistic regression analyses. RESULTS: We included 333 cases (median age 54 years; 14% women; 83% with suppressed HIV RNA) and 745 controls. Median time (interquartile range) of TL measurement was 9.4 (5.9-13.8) years prior to CAD event. Compared to the 1st (shortest) TL quintile, participants in the 5th (longest) TL quintile had univariable and multivariable CAD event OR = 0.56 (95% confidence interval [CI], .35-.91) and OR = 0.54 (95% CI, .31-.96). Multivariable OR for current smoking was 1.93 (95% CI, 1.27-2.92), dyslipidemia OR = 1.92 (95% CI, 1.41-2.63), and for recent abacavir, cumulative lopinavir, indinavir, and darunavir exposure was OR = 1.82 (95% CI, 1.27-2.59), OR = 2.02 (95% CI, 1.34-3.04), OR = 3.42 (95% CI, 2.14-5.45), and OR = 1.66 (95% CI, 1.00-2.74), respectively. The TL-CAD association remained significant when adjusting only for Framingham risk score, when excluding TL outliers, and when adjusting for CMV-seropositivity, HCV-seropositivity, time spent with detectable HIV viremia, and injection drug use. CONCLUSIONS: In PLWH, TL measured >9 years before, is independently associated with CAD events after adjusting for multiple traditional and HIV-related factors.

Clusters of Sexual Behavior in Human Immunodeficiency Virus-positive Men Who Have Sex With Men Reveal Highly Dissimilar Time Trends.

BACKGROUND: Separately addressing specific groups of people who share patterns of behavioral change might increase the impact of behavioral interventions to prevent transmission of sexually transmitted infections. We propose a method based on machine learning to assist the identification of such groups among men who have sex with men (MSM). METHODS: By means of unsupervised learning, we inferred "behavioral clusters" based on the recognition of similarities and differences in longitudinal patterns of condomless anal intercourse with nonsteady partners (nsCAI) in the HIV Cohort Study over the last 18 years. We then used supervised learning to investigate whether sociodemographic variables could predict cluster membership. RESULTS: We identified 4 behavioral clusters. The largest behavioral cluster (cluster 1) contained 53% of the study population and displayed the most stable behavior. Cluster 3 (17% of the study population) displayed consistently increasing nsCAI. Sociodemographic variables were predictive for both of these clusters. The other 2 clusters displayed more drastic changes: nsCAI frequency in cluster 2 (20% of the study population) was initially similar to that in cluster 3 but accelerated in 2010. Cluster 4 (10% of the study population) had significantly lower estimates of nsCAI than all other clusters until 2017, when it increased drastically, reaching 85% by the end of the study period. CONCLUSIONS: We identified highly dissimilar behavioral patterns across behavioral clusters, including drastic, atypical changes. The patterns suggest that the overall increase in the frequency of nsCAI is largely attributable to 2 clusters, accounting for a third of the population.

Antibodies against HPV16E6 oncoprotein in the Swiss HIV cohort study: Kinetics and anal cancer risk prediction.

Our aim was to describe HPV16E6 antibody kinetics prior to anal cancer in people living with HIV/AIDS (PLWHA) and evaluate the possible contribution of HPV16E6 serology to anal cancer risk prediction. For 91 persons diagnosed with anal cancer in the Swiss HIV Cohort Study (1989-2017), serial serum/plasma samples were tested for HPV16E6 antibodies using multiplex serology, supplemented with samples from 1,356 participants without anal cancer. Anal cancer incidence was estimated for PLWHA from 40 years-old in the cART era, stratified by HPV16E6 serostatus. HPV16E6 seroprevalence was 23.3% in samples <2 years prior to anal cancer diagnosis and decreased with increasing time prior to cancer: 16.7% at 2-4 years, 4.4% at 5-9, and 7.0% at ≥10 years. Of 25 individuals with anal cancer who were HPV16E6-seropositive at any time during follow-up, the majority (n = 18) remained seropositive in all samples after seroconversion, whereas for seven cases, seropositivity was transitory. Among individuals with anal cancer, HPV16E6 seroprevalence was marginally higher in women vs. men who have sex with men (adjusted OR = 4.3, 95% CI: 1.1, 17.2) and in older participants (adjusted OR = 6.2, 95% CI: 1.1, 34.8 for cases diagnosed at ≥55 vs. <45 years). Anal cancer incidence was 402/100,000 person-years in HPV16E6-positive vs. 82/100,000 in HPV16E6-negative PLWHA (incidence rate ratio = 4.9, 95% CI: 1.3, 13.1). In conclusion, HPV16E6 serology, despite its low sensitivity, allows characterization of a group of individuals with very high anal cancer incidence and may have a place in secondary prevention in groups at high risk for anal cancer such as PLWHA.

[Stigma and HIV: relevant for everyone]. / Stigmatisation et VIH : tous concernés.

Medical advances in the treatment of HIV over the last 35 years mean that people living with HIV (PLHIV) now have a life expectancy close to that of the general population. Further, when successfully treated, PLHIV cannot transmit the virus. Despite this, HIV-related stigma remains widespread, including within healthcare settings. Stigma is not a vague sociological notion but represents a real threat to public health, with repercussions for both PLHIV and HIV-negative individuals. Stigma has been shown to have a negative impact on HIV prevention, testing, access to health services, and on the healthcare management of PLHIV. Taking stigma into consideration is essential, both in meeting the medical and psycho-social needs of PLHIV and in order to effectively combat HIV/AIDS.

Les progrès des 35 dernières années dans la prise en charge médicale du VIH ont permis aux personnes vivant avec ce virus (PVVIH) d'avoir une espérance de vie similaire à celle de la population générale. Avec un traitement efficace, les PVVIH ne peuvent plus transmettre le virus. Cependant, la stigmatisation associée au VIH reste considérable, y compris dans les milieux de soins. La stigmatisation n'est pas une vague notion sociologique, mais un véritable enjeu de santé publique pouvant avoir un impact tant chez les personnes séronégatives que chez les PVVIH. Elle a un impact néfaste sur la prévention de l'infection, le dépistage, l'accès aux soins, et sur la gestion de la santé des PVVIH. Une prise en considération de la stigmatisation est essentielle pour garantir aux PVVIH un accompagnement médical et psychosocial optimal, ainsi que pour lutter contre l'épidémie du VIH/sida.

No Effect of Pegylated Interferon-α on Total HIV-1 DNA Load in HIV-1/HCV Coinfected Patients.

Pegylated interferon-alpha (pIFN-α) is suggested to lower human immunodeficiency virus type-1 (HIV-1) DNA load in antiretroviral therapy (ART)-treated patients. We studied kinetics of HIV-1 DNA levels in 40 HIV-1/hepatitis C virus (HCV) coinfected patients, treated with pIFN-α for HCV and categorized into 3 groups according to start of ART: chronic HIV-1 infection (n = 22), acute HIV-1 infection (n = 8), no-ART (n = 10). Total HIV-1 DNA levels in 247 peripheral blood mononuclear cell samples were stable before, during, and after pIFN-α treatment in all groups. Our results question the benefit of pIFN-α as an immunotherapeutic agent for reducing the HIV-1 reservoir.

Population-based outcome analysis of diffuse large B-cell lymphoma in people living with HIV infection and competent individuals.

The prognostic factors and outcome of 58 acquired immunodeficiency syndrome-related diffuse large B-cell lymphoma (AR-DLBCL) patients from the Swiss HIV Cohort Study, diagnosed from 2004 to 2011, were compared with those of 326 immunocompetent (IC)-DLBCL from the Hematology Division of the Amedeo Avogadro University (Italy) and the Oncology Institute of Southern Switzerland. Median follow-up was 6 years; 5-year overall survival (OS) was 68% (95% CI: 63%-73%) in IC-DLBCL and 63% (95% CI: 49%-75%) in AR-DLBCL (P = .220). The acquired immunodeficiency syndrome-related lymphoma international prognostic index predicted OS in AR-DLBCL. Among 148 patients younger than 61 years (40 AR-DLBCL and 108 IC-DLBCL) treated with RCHOP/RCHOP-like regimens, 20 IC-DLBCL and 9 AR-DLBCL patients died and OS was not significantly different. A higher proportion of early deaths occurred in the AR-DLBCL: indeed, 1-year OS was 94% (95% CI: 87%-97%) in IC-DLBCL and 82% (95% CI: 66%-91%) in AR-DLBCL patients. After rituximab and active antiretroviral therapy introduction, AR-DLBCL and IC-DLBCL patients treated with curative intent have similar long-term survival.

Hepatitis C virus transmission among human immunodeficiency virus-infected men who have sex with men: Modeling the effect of behavioral and treatment interventions.

The incidence of hepatitis C virus (HCV) infections among human immunodeficiency virus (HIV)-infected men who have sex with men has increased in recent years and is associated with high-risk sexual behavior. Behavioral interventions that target high-risk behavior associated with HCV transmission and treatment with direct-acting antivirals may prevent further HCV infections. We predicted the effect of behavioral and treatment interventions on HCV incidence and prevalence among HIV-infected men who have sex with men up to 2030 using a HCV transmission model parameterized with data from the Swiss HIV Cohort Study. We assessed behavioral interventions associated with further increase, stabilization, and decrease in the size of the population with high-risk behavior. Treatment interventions included increase in treatment uptake and use of direct-acting antivirals. If we assumed that without behavioral interventions high-risk behavior spread further according to the trends observed over the last decade and that the treatment practice did not change, HCV incidence converged to 10.7/100 person-years. All assessed behavioral interventions alone resulted in reduced HCV transmissions. Stabilization of high-risk behavior combined with increased treatment uptake and the use of direct-acting antivirals reduced incidence by 77% (from 2.2 in 2015 to 0.5/100 person-years) and prevalence by 81% (from 4.8% in 2015 to 0.9%) over the next 15 years. Increasing treatment uptake was more effective than increasing treatment efficacy to reduce HCV incidence and prevalence. A decrease in high-risk behavior led to a rapid decline in HCV incidence, independent of treatment interventions. CONCLUSION: Treatment interventions to curb the HCV epidemic among HIV-infected men who have sex with men are effective if high-risk behavior does not increase as it has during the last decade; reducing high-risk behavior associated with HCV transmission would be the most effective intervention for controlling the HCV epidemic, even if this was not accompanied by an increase in treatment uptake or efficacy. (Hepatology 2016;64:1856-1869).

Dually Active HIV/HBV Antiretrovirals as Protection Against Incident Hepatitis B Infections: Potential for Prophylaxis.

BACKGROUND: Hepatitis B virus (HBV) has a detrimental effect on human immunodeficiency virus (HIV) natural course, and HBV vaccination is less effective in the HIV infected. We examine the protective effect of dually active antiretroviral therapy (DAART) for HIV/HBV (tenofovir, lamivudine, and emtricitabine) in a large cohort encompassing heterosexuals, men who have sex with men, and intravenous drug users who are HIV infected yet susceptible to HBV, with comprehensive follow-up data about risky behavior and immunological profiles. METHODS: We defined an incident HBV infection as the presence of any of HBV serological markers (hepatitis B surface antigen, anti-hepatitis B core antibodies, or HBV DNA) after a negative baseline test result for anti-hepatitis B core antibodies. Patients with positive anti-hepatitis B surface antigen serology were excluded. Cox proportional hazards models were used, with an incident case of HBV infection as the outcome variable. RESULTS: We analyzed 1716 eligible patients from the Swiss HIV Cohort Study with 177 incident HBV cases. DAART was negatively associated with incident HBV infection (hazard ratio [HR], 0.4; 95% confidence interval [CI], .2-.6). This protective association was robust to adjustment (HR, 0.3; 95% CI, .2-.5) for condomless sex, square-root-transformed CD4 cell count, drug use, and patient demographics. Condomless sex (HR, 1.9; 95% CI, 1.4-2.6), being a man who has sex with men (2.7; 1.7-4.2), and being an intravenous drug user (3.8; 2.4-6.1) were all associated with a higher hazard of contracting HBV. CONCLUSIONS: Our study suggests that DAART, independently of CD4 cell count and risky behavior, has a potentially strong public health impact, including pre-exposure prophylaxis of HBV coinfection in the HIV infected.

Trends in Incidences and Risk Factors for Hepatocellular Carcinoma and Other Liver Events in HIV and Hepatitis C Virus-coinfected Individuals From 2001 to 2014: A Multicohort Study.

BACKGROUND: While liver-related deaths in human immunodeficiency virus (HIV) and hepatitis C virus (HCV)-coinfected individuals have declined over the last decade, hepatocellular carcinoma (HCC) may have increased. We describe the epidemiology of HCC and other liver events in a multicohort collaboration of HIV/HCV-coinfected individuals. METHODS: We studied HCV antibody-positive adults with HIV in the EuroSIDA study, the Southern Alberta Clinic Cohort, the Canadian Co-infection Cohort, and the Swiss HIV Cohort study from 2001 to 2014. We calculated the incidence of HCC and other liver events (defined as liver-related deaths or decompensations, excluding HCC) and used Poisson regression to estimate incidence rate ratios. RESULTS: Our study comprised 7229 HIV/HCV-coinfected individuals (68% male, 90% white). During follow-up, 72 cases of HCC and 375 other liver events occurred, yielding incidence rates of 1.6 (95% confidence interval [CI], 1.3, 2.0) and 8.6 (95% CI, 7.8, 9.5) cases per 1000 person-years of follow-up, respectively. The rate of HCC increased 11% per calendar year (95% CI, 4%, 19%) and decreased 4% for other liver events (95% CI, 2%, 7%), but only the latter remained statistically significant after adjustment for potential confounders. Older age, cirrhosis, and low current CD4 cell count were associated with a higher incidence of both HCC and other liver events. CONCLUSIONS: In HIV/HCV-coinfected individuals, the crude incidence of HCC increased from 2001 to 2014, while other liver events declined. Individuals with cirrhosis or low current CD4 cell count are at highest risk of developing HCC or other liver events.

Immunodeficiency and the risk of cervical intraepithelial neoplasia 2/3 and cervical cancer: A nested case-control study in the Swiss HIV cohort study.

HIV-infected women are at increased risk of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening and immunodeficiency. A case-control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985-2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir [odds ratio (OR) per 100-cell/µL decrease = 1.15, 95% CI: 1.08, 1.22], or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200-349 versus ≥350 cells/µL (OR = 1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2-year cART use was seen against CIN2/3 (OR versus never cART use = 0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 vs. >350 cells/µL= 11.10, 95% CI: 1.24, 100). HPV16-L1 antibodies were significantly associated with CIN2/3, but HPV16-E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts, is a significant risk factor for CIN2/3 and cervical cancer.

Investigating Barriers in HIV-Testing Oncology Patients: The IBITOP Study, Phase I.

BACKGROUND: Although the prevalence of non-AIDS-defining cancers (non-ADCs) among people living with HIV is rising, we observed HIV testing rates below 5% at our oncology center, against a regional HIV prevalence of 0.2%-0.4%. We performed the Investigating Barriers in HIV-Testing Oncology Patients (IBITOP) study among oncology physicians and patients. METHODS: Between July 1 and October 31, 2013, patients of unknown HIV status newly diagnosed with solid-organ non-ADCs referred to Lausanne University Hospital Oncology Service, Switzerland, were offered free HIV testing as part of their oncology work-up. The primary endpoints were (a) physician willingness to offer and patient acceptance of HIV testing and (b) physicians' reasons for not offering testing. RESULTS: Of 239 patients of unknown HIV status with a new non-ADC diagnosis, 43 (18%) were offered HIV testing, of whom 4 declined (acceptance rate: 39 of 43; 91%). Except for 21 patients tested prior to oncology consultation, 175 patients (of 239; 73%) were not offered testing. Testing rate declined among patients who were >70 years old (12% versus 30%; p = .04); no non-European patients were tested. Physicians gave reasons for not testing in 16% of cases, the main reason being patient follow-up elsewhere (10 patients; 5.7%). HIV testing during the IBITOP study increased the HIV testing rate to 18%. CONCLUSION: Although the IBITOP study increased HIV testing rates, most patients were not tested. Testing was low or nonexistent among individuals at risk of late HIV presentation (older patients and migrants). Barriers to testing appear to be physician-led, because patient acceptance of testing offered was very high (91%). In November 2013, the Swiss HIV testing recommendations were updated to propose testing in cancer patients. Phase II of the IBITOP study is examining the effect of these recommendations on HIV testing rates and focusing on physician-led testing barriers. IMPLICATIONS FOR PRACTICE: Patients of unknown HIV status newly diagnosed with solid-organ non-AIDS-defining cancers were offered free HIV testing. Physician and patient barriers to HIV testing were examined. Most patients (82%) were not offered testing, and testing of individuals at risk of late HIV presentation (older patients and migrants) was low or nonexistent. Conversely, patient acceptance of testing offered was very high (91%), suggesting that testing barriers in this setting are physician-led. Since this study, the Swiss HIV testing recommendations now advise testing cancer patients before chemotherapy. Phase II of the Investigating Barriers in HIV-Testing Oncology Patients study is examining the effect of these recommendations on testing rates and physician barriers.