Resurgence of HIV infection among men who have sex with men in Switzerland : mathematical modelling study

New HIV infections in men who have sex with men (MSM) have increased in Switzerland since 2000 despite combination antiretroviral therapy (cART). The objectives of this mathematical modelling study were: to describe the dynamics of the HIV epidemic in MSM in Switzerland using national data; to explore the effects of hypothetical prevention scenarios; and to conduct a multivariate sensitivity analysis. METHODOLOGY/PRINCIPAL FINDINGS: The model describes HIV transmission, progression and the effects of cART using differential equations. The model was fitted to Swiss HIV and AIDS surveillance data and twelve unknown parameters were estimated. Predicted numbers of diagnosed HIV infections and AIDS cases fitted the observed data well. By the end of 2010, an estimated 13.5% (95% CI 12.5, 14.6%) of all HIV-infected MSM were undiagnosed and accounted for 81.8% (95% CI 81.1, 82.4%) of new HIV infections. The transmission rate was at its lowest from 1995-1999, with a nadir of 46 incident HIV infections in 1999, but increased from 2000. The estimated number of new infections continued to increase to more than 250 in 2010, although the reproduction number was still below the epidemic threshold. Prevention scenarios included temporary reductions in risk behaviour, annual test and treat, and reduction in risk behaviour to levels observed earlier in the epidemic. These led to predicted reductions in new infections from 2 to 26% by 2020. Parameters related to disease progression and relative infectiousness at different HIV stages had the greatest influence on estimates of the net transmission rate. CONCLUSIONS/SIGNIFICANCE: The model outputs suggest that the increase in HIV transmission amongst MSM in Switzerland is the result of continuing risky sexual behaviour, particularly by those unaware of their infection status. Long term reductions in the incidence of HIV infection in MSM in Switzerland will require increased and sustained uptake of effective interventions

"If it is left, it becomes easy for me to get tested": use of oral self-tests and community health workers to maximize the potential of home-based HIV testing among adolescents in Lesoth

Home-based HIV testing fails to reach high coverage among adolescents and young adults (AYA), mainly because they are often absent during the day of home-based testing. ADORE (ADolescent ORal tEsting) is a mixed-method nested study among AYA in rural Lesotho, measuring the effect of home-based secondary distribution of oral HIV self-tests (HIVST) on coverage, as well as exploring how AYA perceive this HIV self-testing model.; ADORE study was nested in a cluster-randomized trial. In intervention village-clusters, oral HIVST were left for household members who were absent or declined testing during a testing campaign. One present household member was trained on HIVST use. Distributed HIVST were followed up by village health workers (VHW). In control clusters no self-tests were distributed. The quantitative outcome was testing coverage among AYA (age 12 to 24) within 120 days, defined as a confirmed HIV test result or known status, using adjusted random-effects logistic regression on the intention-to-treat population. Qualitatively, we conducted in-depth interviews among both AYA who used and did not use the distributed HIVST.; From July 2018 to December 2018, 49 and 57 villages with 1471 and 1620 consenting households and 1236 and 1445 AYA in the control and intervention arm, respectively, were enrolled. On the day of the home-visit, a testing coverage of 37% (461/1236) and 41% (596/1445) in the control and the intervention arm, respectively, were achieved. During the 120 days follow-up period, an additional 23 and 490 AYA in control and intervention clusters, respectively, knew their status. This resulted in a testing coverage of 484/1236 (39%) in the control versus 1086/1445 (75%) in the intervention arm (aOR 8.80 [95% CI 5.81 to 13.32]; p < 0.001). 21 interviews were performed. Personal assistance after the secondary distribution emerged as a key theme and VHWs were generally seen as a trusted cadre.; Secondary distribution of HIVST for AYA absent or refusing to test during home-based testing in Lesotho resulted in an absolute 36% increase in coverage. Distribution should, however, go along with clear instructions on the use of the HIVST and a possibility to easily access more personal support

Rationing of nursing care and its relationship to patient outcomes: the Swiss extension of the International Hospital Outcomes Study

Objectives To explore the association between implicit rationing of nursing care and selected patient outcomes in Swiss hospitals, adjusting for major organizational variables, including the quality of the nurse practice environment and the level of nurse staffing. Rationing was measured using the newly developed Basel Extent of Rationing of Nursing Care (BERNCA) instrument. Additional data were collected using an adapted version of the International Hospital Outcomes Study questionnaire. Design Multi-hospital cross-sectional surveys of patients and nurses. Setting Eight Swiss acute care hospitals Participants Nurses (1338) and patients (779) on 118 medical, surgical and gynecological units. Main outcome measures Patient satisfaction, nurse-reported medication errors, patient falls, nosocomial infections, pressure ulcers and critical incidents involving patients over the previous year. Results Generally, nurses reported rarely having omitted any of the 20 nursing tasks listed in the BERNCA over their last 7 working days. However, despite relatively low levels, implicit rationing of nursing care was a significant predictor of all six patient outcomes studied. Although the adequacy of nursing resources was a significant predictor for most of the patient outcomes in unadjusted models, it was not an independent predictor in the adjusted models. Low nursing resource adequacy ratings were a significant predictor for five of the six patient outcomes in the unadjusted models, but not in the adjusted ones. Conclusion As a system factor in acute general hospitals, implicit rationing of nursing care is an important new predictor of patient outcomes and merits further stud

A Bundle of Services Increased Ascertainment of Tuberculosis among HIV-Infected Individuals Enrolled in a HIV Cohort in Rural Sub-Saharan Africa

OBJECTIVES: To report on trends of tuberculosis ascertainment among HIV patients in a rural HIV cohort in Tanzania, and assessing the impact of a bundle of services implemented in December 2012, consisting of three components:(i)integration of HIV and tuberculosis services; (ii)GeneXpert for tuberculosis diagnosis; and (iii)electronic data collection. DESIGN: Retrospective cohort study of patients enrolled in the Kilombero Ulanga Antiretroviral Cohort (KIULARCO), Tanzania.). METHODS: HIV patients without prior history of tuberculosis enrolled in the KIULARCO cohort between 2005 and 2013 were included.Cox proportional hazard models were used to estimate rates and predictors of tuberculosis ascertainment. RESULTS: Of 7114 HIV positive patients enrolled, 5123(72%) had no history of tuberculosis. Of these, 66% were female, median age was 38 years, median baseline CD4+ cell count was 243 cells/microl, and 43% had WHO clinical stage 3 or 4. During follow-up, 421 incident tuberculosis cases were notified with an estimated incidence of 3.6 per 100 person-years(p-y)[95% confidence interval(CI)3.26-3.97]. The incidence rate varied over time and increased significantly from 2.96 to 43.98 cases per 100 p-y after the introduction of the bundle of services in December 2012. Four independent predictors of tuberculosis ascertainment were identified:poor clinical condition at baseline (Hazard Ratio (HR) 3.89, 95% CI 2.87-5.28), WHO clinical stage 3 or 4 (HR 2.48, 95% CI 1.88-3.26), being antiretroviralnaive (HR 2.97, 95% CI 2.25-3.94), and registration in 2013(HR 6.07, 95% CI 4.39-8.38). CONCLUSION: The integration of tuberculosis and HIV services together with comprehensive electronic data collection and use of GeneXpert increased dramatically the ascertainment of tuberculosis in this rural African HIV cohort

Cryptococcal Antigenemia in Immunocompromised Human Immunodeficiency Virus Patients in Rural Tanzania: A Preventable Cause of Early Mortality

Background. Cryptococcal meningitis is a leading cause of death in people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome. The World Health Organizations recommends pre-antiretroviral treatment (ART) cryptococcal antigen (CRAG) screening in persons with CD4 below 100 cells/microL. We assessed the prevalence and outcome of cryptococcal antigenemia in rural southern Tanzania. Methods. We conducted a retrospective study including all ART-naive adults with CD4 <150 cells/microL prospectively enrolled in the Kilombero and Ulanga Antiretroviral Cohort between 2008 and 2012. Cryptococcal antigen was assessed in cryopreserved pre-ART plasma. Cox regression estimated the composite outcome of death or loss to follow-up (LFU) by CRAG status and fluconazole use. Results. Of 750 ART-naive adults, 28 (3.7%) were CRAG-positive, corresponding to a prevalence of 4.4% (23 of 520) in CD4 <100 and 2.2% (5 of 230) in CD4 100-150 cells/microL. Within 1 year, 75% (21 of 28) of CRAG-positive and 42% (302 of 722) of CRAG-negative patients were dead or LFU (P<.001), with no differences across CD4 strata. Cryptococcal antigen positivity was an independent predictor of death or LFU after adjusting for relevant confounders (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.29-4.83; P = .006). Cryptococcal meningitis occurred in 39% (11 of 28) of CRAG-positive patients, with similar retention-in-care regardless of meningitis diagnosis (P = .8). Cryptococcal antigen titer >1:160 was associated with meningitis development (odds ratio, 4.83; 95% CI, 1.24-8.41; P = .008). Fluconazole receipt decreased death or LFU in CRAG-positive patients (HR, 0.18; 95% CI, .04-.78; P = .022). Conclusions. Cryptococcal antigenemia predicted mortality or LFU among ART-naive HIV-infected persons with CD4 <150 cells/microL, and fluconazole increased survival or retention-in-care, suggesting that targeted pre-ART CRAG screening may decrease early mortality or LFU. A CRAG screening threshold of CD4 <100 cells/microL missed 18% of CRAG-positive patients, suggesting guidelines should consider a higher threshold

Frequency and Determinants of Unprotected Sex among HIV-Infected Persons: The Swiss HIV Cohort Study

Background. Access to antiretroviral therapy may have changed condom use behavior. In January 2008, recommendations on condom use for human immunodeficiency virus (HIV)-positive persons were published in Switzerland, which allowed for unprotected sex under well-defined circumstances ("Swiss statement”). We studied the frequency, changes over time, and determinants of unprotected sex among HIV-positive persons. Methods. Self-reported information on sexual preference, sexual partners, and condom use was collected at semi-annual visits in all participants of the prospective Swiss HIV Cohort Study from April 2007 through March 2009. Multivariable logistic regression models were fit using generalized estimating equations to investigate associations between characteristics of cohort participants and condom use. Findings. A total of 7309 participants contributed to 21,978 visits. A total of 4291 persons (80%) reported sexual contacts with stable partners, 1646 (30%) with occasional partners, and 557 (10%) with stable and occasional partners. Of the study participants, 5838 (79.9%) of 7309 were receiving antiretroviral therapy, and of these, 4816 patients (82%) had a suppressed viral load. Condom use varied widely and differed by type of partner (visits with stable partners, 10,368 [80%] of 12,983; visits with occasional partners, 4300 [88%] of 4880) and by serostatus of stable partner (visits with HIV-negative partners, 7105 [89%] of 8174; visits with HIV-positive partners, 1453 [48%] of 2999). Participants were more likely to report unprotected sex with stable partners if they were receiving antiretroviral therapy, if HIV replication was suppressed, and after the publication of the "Swiss statement.” Noninjection drug use and moderate or severe alcohol use were associated with unprotected sex. Conclusions. Antiretroviral treatment and plasma HIV RNA titers influence sexual behavior of HIV-positive persons. Noninjection illicit drug and alcohol use are important risk factors for unprotected sexual contact

Prospective assessment of loss to follow-up: incidence and associated factors in a cohort of HIV-positive adults in rural Tanzania

Lifelong antiretroviral therapy (ART) improves health outcomes for HIV-positive individuals, but is jeopardized by irregular clinic attendance and hence poor adherence. Loss to follow-up (LTFU) is typically defined retrospectively but this may lead to biased inferences. We assessed incidence of and factors associated with LTFU, prospectively and accounting for recurrent LTFU episodes, in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) of HIV-positive persons in rural Tanzania.; We included adults (≥15 years) enrolled in 2005 to 2016, regardless of ART status, with follow-up through April 2017. LTFU was defined as >60 days late for a scheduled appointment. Participants could experience multiple LTFU episodes. We performed analyses based on the first (prospective) and last (retrospective) events observed during follow-up, and accounting for recurrent LTFU episodes. Time to LTFU was estimated using cumulative incidence functions. We assessed factors associated with LTFU using cause-specific proportional hazards, marginal means/rates, and Prentice, Williams and Peterson models.; Among 8087 participants (65% female, 60% aged ≥35 years, 42% WHO stage 3/4, and 47% CD4 count <200 cells/mm; 3; ), there were 8140 LTFU episodes, after which there were 2483 (31%) returns to care. One-year LTFU probabilities were 0.41 (95% confidence interval 0.40, 0.42) and 0.21 (0.20, 0.22) considering the first and last events respectively. Factors associated with LTFU were broadly consistent across different models: being male, younger age, never married, living far from the clinic, not having an HIV-positive partner, lower BMI, advanced WHO stage, not having tuberculosis, and shorter time since ART initiation. Associations between LTFU and pregnancy, CD4 count, and enrolment year depended on the analysis approach.; LTFU episodes were common and prompt tracing efforts are urgently needed. We identified socio-demographic and clinical characteristics associated with LTFU that can be used to target tracing efforts and to help inform the design of appropriate interventions. Incidence of and risk factors for LTFU differed based on the LTFU definition applied, highlighting the importance of appropriately accounting for recurrent LTFU episodes. We recommend using a prospective definition of LTFU combined with recurrent event analyses in cohorts where repeated interruptions in care are common

High failure rates of protease inhibitor-based antiretroviral treatment in rural Tanzania - a prospective cohort study

Poor adherence to antiretroviral drugs and viral resistance are the main drivers of treatment failure in HIV-infected patients. In sub-Saharan Africa, avoidance of treatment failure on second-line protease inhibitor therapy is critical as treatment options are limited.; In the prospective observational study of the Kilombero & Ulanga Antiretroviral Cohort in rural Tanzania, we assessed virologic failure (viral load ≥1,000 copies/mL) and drug resistance mutations in bio-banked plasma samples 6-12 months after initiation of a protease inhibitor-based treatment regimen. Additionally, viral load was measured before start of protease inhibitor, a second time between 1-5 years after start, and at suspected treatment failure in patients with available bio-banked samples. We performed resistance testing if viral load was ≥1000 copies/ml. Risk factors for virologic failure were analyzed using logistic regression.; In total, 252 patients were included; of those 56% were female and 21% children. Virologic failure occurred 6-12 months after the start of a protease inhibitor in 26/199 (13.1%) of adults and 7/53 of children (13.2%). The prevalence of virologic failure did not change over time. Nucleoside reverse transcriptase inhibitors drug resistance mutation testing performed at 6-12 months showed a positive signal in only 9/16 adults. No cases of resistance mutations for protease inhibitors were seen at this time. In samples taken between 1-5 years protease inhibitor resistance was demonstrated in 2/7 adults. In adult samples before protease inhibitor start, resistance to nucleoside reverse transcriptase inhibitors was detected in 30/41, and to non-nucleoside reverse-transcriptase inhibitors in 35/41 patients. In 15/16 pediatric samples, resistance to both drug classes but not for protease inhibitors was present.; Our study confirms high early failure rates in adults and children treated with protease inhibitors, even in the absence of protease inhibitors resistance mutations, suggesting an urgent need for adherence support in this setting

Absence of hepatitis delta infection in a large rural HIV cohort in Tanzania

OBJECTIVES: The epidemiological and clinical determinants of hepatitis delta virus (HDV) infection in Sub-Saharan Africa are ill-defined. The prevalence of HDV infection was determined in HIV/hepatitis B virus (HBV) co-infected individuals in rural Tanzania. METHODS: All hepatitis B virus (HBV)-infected adults under active follow-up in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) were screened for anti-HDV antibodies. For positive samples, a second serological test and nucleic acid amplification were performed. Demographic and clinical characteristics at initiation of antiretroviral therapy (ART) were compared between anti-HDV-negative and positive patients. RESULTS: Among 222 HIV/HBV co-infected patients on ART, 219 (98.6%) had a stored serum sample available and were included in the study. Median age was 37 years, 55% were female, 46% had World Health Organization stage III/IV HIV disease, and the median CD4 count was 179 cells/mul. The prevalence of anti-HDV positivity was 5.0% (95% confidence interval 2.8-8.9%). There was no significant predictor of anti-HDV positivity. HDV could not be amplified in any of the anti-HDV-positive patients and the second serological test was negative in all of them. CONCLUSIONS: No confirmed case of HDV infection was found among over 200 HIV/HBV co-infected patients in Tanzania. As false-positive serology results are common, screening results should be confirmed with a second test

Pregnancy and delivery outcomes of HIV infected women in Switzerland 2003-2008

Objective: Rates of vertical HIV transmission between mother and child are low, allowing many HIV positive women to have children with near impunity. In this study, data from the Swiss Mother and Child HIV Cohort Study were used to describe maternal characteristics and their association with pregnancy outcomes in HIV positive women. Study design: HIV positive women were followed prospectively during their pregnancies and deliveries by anonymous questionnaires between January 2003 and October 2008. Adverse pregnancy outcomes included preterm delivery, preeclampsia and gestational diabetes mellitus. Results: This study included 266 HIV positive women, of which 67 (25.2%) were first diagnosed with HIV during pregnancy. Thirty percent (n=80) of the women had pregnancy complications after 24weeks of gestation. Preterm delivery was noted in 72 (27%) patients. Other complications included preeclampsia (n=7; 2.6%) and gestational diabetes (n=7; 2.6%). Older maternal age was the only risk factor associated with adverse pregnancy outcomes (adjusted odds ratio: 1.06, 95% confidence interval 1.01-1.12, P=0.02). Conclusions: HIV positive women, especially with advanced maternal age, have high-risk pregnancies and should be monitored as in an interdisciplinary setting. The preponderance of initial HIV diagnosis during pregnancy confirms the importance of HIV screening in pregnant wome