Steven Callens

HIV testing in Europe: Mapping policies

OBJECTIVES In the absence of treatment and in the context of discrimination, HIV testing was embedded within exceptional procedures. With increasing treatment effectiveness, early HIV diagnosis became important, calling for the normalization of testing. National HIV testing policies were mapped to explore the characteristics and variations across European countries. METHODS Key informants within the health authorities of all EU/EEA countries were questioned on HIV testing policies, which were assessed within a conceptual framework and the level of exceptionalism and normalization was scored based on defined attributes. RESULTS Twenty-four out of 31 countries participated in the survey. Policies tended to support confidential voluntary testing, informed consent, and counselling. In the majority of countries, specific groups were targeted for provider-initiated testing. Taking together all attributes of HIV testing, 14 countries obtained a high score for exceptionalism, while only 3 achieved a high score on normalization. Italy, Lithuania and Romania had primarily exceptional procedures; Norway leant more towards normalization; Netherlands, the United Kingdom, and Denmark scored high in both. CONCLUSIONS In most EU/EEA countries, policies are integrating HIV testing in health care settings, through voluntary and targeted testing strategies. Current HIV testing policies exhibited a high level of exceptionalism with varying degrees of normalization. Further research should compare HIV testing policies with practices.

Risk of Misinterpretation of Ebola Virus PCR Results After rVSV ZEBOV–GP Vaccination

TO THE EDITOR—We would like to report on a recent false-positive Ebola polymerase chain reaction (PCR) result after postexposure prophylaxis (PEP) with the recombinant vesicular stomatitis virus (rVSV) Zaire Ebola virus–glycoprotein (ZEBOV–GP) vaccine. We believe this observation is important in light of ongoing vaccine and diagnostic developments sparked by the recent Ebola virus disease (EVD) epidemic. A physician working for Médecins Sans Frontières (MSF) was evacuated from Monrovia, Liberia, to Belgium on 4 December 2014. Two days earlier, she had accidentally pricked herself with an unused needle through 2 gloves that had been in contact with the skin of a patient confirmedwithEVD.Upon arrival inBrussels, she was asymptomatic but nonetheless immediately hospitalized at the SaintPierre University Hospital. The MSFOperational Center Brussels occupational physicians and the Belgian clinical Ebola expert team performed a risk assessment. Considering the limited options available for PEP in humans, the experience with post-exposure vaccination using a live-attenuated rVSV ZEBOV–GP in nonhuman primates [1], and a single report of PEP with this vaccine in a human [2], it was decided that a single dose (titer ≥1 × 10 pfu/mL) of the rVSV ZEBOV–GP vaccine (NewLink Genetics, Canada) would be administered. The next morning, the patient developed fever. Although the fever was likely attributable to an adverse reaction to the vaccine, the expert group agreed to immediately performmolecular testing for EVD. Blood samples collected immediately prior to and 16 hours after vaccination were sent to the Belgian National Reference Laboratory for Infectious and Tropical Diseases (Institute of Tropical Medicine, Antwerp) for analysis using 2 real-time (RT)-PCRs targeting different EBOV genes, according to the European guidelines [3]. An in-house RT-PCR (adapted from [4]), targeting EBOV–GP, and the commercially available RealStar filovirus RT-PCR (Altona Diagnostics GmbH, Hamburg, Germany), targeting the large polymerase gene, were used [5].The commercial PCR test was negative in both samples, while the in-house test was positive in the sample after vaccination (Figure 1A). Based on these results, the patient was considered as not infected. The patient fully recovered the following day. Subsequent PCR testing revealed that the in-house RT-PCR remained positive for up to 5 days after vaccination, which is longer than the 2 days previously reported [2] and most likely the result of the higher vaccine dose given. At day 6

HIV-1 RNA and HIV-1 DNA persistence during suppressive ART with PI-based or nevirapine-based regimens

OBJECTIVES Whether ART regimens differ in their propensity to allow persistent HIV-1 detection remains unclear. To investigate this, we performed a cross-sectional study to characterize HIV-1 persistence in peripheral blood during suppressive therapy with NRTIs plus a PI or nevirapine. METHODS Residual plasma HIV-1 RNA was quantified by real-time PCR. Cell-associated proviral total HIV-1 DNA, unspliced and multiply spliced HIV-1 RNA and 2-long terminal repeat (2-LTR) circles were quantified by digital PCR. RESULTS Comparing PI with nevirapine recipients, residual plasma HIV-1 RNA detection rates were 47/80 (58.8%) versus 37/81 (45.7%), with median (IQR) levels of 4 (3-8) versus 4 (3-7) copies/mL (P = 0.207); detection was less likely with longer duration of suppressive ART (P = 0.020), independently of treatment. HIV-1 DNA was detected in all patients, with median levels of 2.3 (IQR 2.0-2.7) versus 2.5 (IQR 2.1-2.7) log10 copies/10(6) PBMCs, respectively; HIV-1 DNA levels were associated with pre-ART viral load (P = 0.004) and with residual HIV-1 RNA (P = 0.034), unspliced HIV-1 RNA (P = 0.001) and 2-LTR circles (P = 0.005), independently of treatment. CONCLUSIONS No significant differences were revealed in levels of residual plasma HIV-1 RNA, total HIV-1 DNA or intracellular markers of ongoing virus replication (unspliced and multiply spliced HIV-1 RNA and 2-LTR circles) between treatment groups.

Identifying factors associated with the uptake of prevention of mother to child HIV transmission programme in Tigray region, Ethiopia: a multilevel modeling approach

BackgroundPrevention of mother to child HIV transmission (PMTCT) remains a challenge in low and middle-income countries. Determinants of utilization occur – and often interact - at both individual and community levels, but most studies do not address how determinants interact across levels. Multilevel models allow for the importance of both groups and individuals in understanding health outcomes and provide one way to link the traditionally distinct ecological- and individual-level studies. This study examined individual and community level determinants of mother and child receiving PMTCT services in Tigray region, Ethiopia.MethodsA multistage probability sampling method was used for this 2011 cross-sectional study of 220 HIV positive post-partum women attending child immunization services at 50 health facilities in 46 districts. In view of the nested nature of the data, we used multilevel modeling methods and assessed macro level random effects.ResultsSeventy nine percent of mothers and 55.7% of their children had received PMTCT services. Multivariate multilevel modeling found that mothers who delivered at a health facility were 18 times (AOR = 18.21; 95% CI 4.37,75.91) and children born at a health facility were 5 times (AOR = 4.77; 95% CI 1.21,18.83) more likely to receive PMTCT services, compared to mothers delivering at home. For every addition of one nurse per 1500 people, the likelihood of getting PMTCT services for a mother increases by 7.22 fold (AOR = 7.22; 95% CI 1.02,51.26), when other individual and community level factors were controlled simultaneously. In addition, district-level variation was low for mothers receiving PMTCT services (0.6% between districts) but higher for children (27.2% variation between districts).ConclusionsThis study, using a multilevel modeling approach, was able to identify factors operating at both individual and community levels that affect mothers and children getting PMTCT services. This may allow differentiating and accentuating approaches for different settings in Ethiopia. Increasing health facility delivery and HCT coverage could increase mother-child pairs who are getting PMTCT. Reducing the distance to health facility and increasing the number of nurses and laboratory technicians are also important variables to be considered by the government.

Comparison of methods for in-house screening of HLA-B∗57:01 to prevent abacavir hypersensitivity in HIV-1 care

Abacavir is a nucleoside reverse transcriptase inhibitor used as part of combination antiretroviral therapy in HIV-1-infected patients. Because this drug can cause a hypersensitivity reaction that is correlated with the presence of the HLA-B*57:01 allotype, screening for the presence of HLA-B*57:01 is recommended before abacavir initiation. Different genetic assays have been developed for HLA-B*57:01 screening, each with specific sensitivity, turnaround time and assay costs. Here, a new real-time PCR (qPCR) based analysis is described and compared to sequence specific primer PCR with capillary electrophoresis (SSP PCR CE) on 149 patient-derived samples, using sequence specific oligonucleotide hybridization combined with high resolution SSP PCR as gold standard. In addition to these PCR based methods, a complementary approach was developed using flow cytometry with an HLA-B17 specific monoclonal antibody as a pre-screening assay to diminish the number of samples for genetic testing. All three assays had a maximum sensitivity of >99. However, differences in specificity were recorded, i.e. 84.3%, 97.2% and >99% for flow cytometry, qPCR and SSP PCR CE respectively. Our data indicate that the most specific and sensitive of the compared methods is the SSP PCR CE. Flow cytometry pre-screening can substantially decrease the number of genetic tests for HLA-B*57:01 typing in a clinical setting.

HIV testing practices as reported by HIV-infected patients in four European countries

HIV testing constitutes an important strategy to control the HIV epidemic, which therefore merits an observation of HIV testing practices to help improve testing effectiveness. In 2008, a cross-sectional survey among recently diagnosed (≤ 3 years) HIV-infected patients was conducted in Belgium, Estonia, Finland and Portugal. Participants were questioned about reasons for HIV testing, testing place and testing conditions. Univariate and multivariate analyses were performed. Out of 1460 eligible participants, 629 (43%) were included. Forty-one per cent were diagnosed late and 55% had never undergone a previous HIV test with perceived low risk being the primary reason for not having been tested earlier. Heterogeneity in HIV testing practices was observed across countries. Overall, tests were most frequently conducted in primary care (38%) and specialised clinics (21%), primarily on the initiative of the health care provider (65%). Sixty-one per cent were tested with informed consent, 31% received pretest counselling, 78% received post-test counselling, 71% were involved in partner notification and 92% were in care three months after diagnosis. The results showed that HIV testing is done in a variety of settings suggesting that multiple pathways to HIV testing are provided. HIV testing practice is being normalised, with less focus on pretest counselling, yet with emphasis on post-test follow-up. Major barriers to testing are centred on the denial of risk. Efforts are needed to concurrently promote public awareness about HIV risk and benefits of HIV testing and train clinicians to be more proactive in offering HIV testing.

Helicobacter pylori eradication in the Swedish population

Abstract Objectives: Helicobacter pylori is associated with peptic ulcers and gastric cancer and its eradication aims to prevent these conditions. The recommended eradication regimen is triple therapy, consisting of a proton-pump inhibitor in combination with clarithromycin and amoxicillin or metronidazole for 7 days. Yet, other antibiotic regimens are sometimes prescribed. We aimed to assess the use of eradication therapy for H. pylori in the Swedish population during the last decade. Materials and methods: This population-based study used data from the Swedish Prescribed Drug Register. From July 2005 until December 2014, all regimens that can eradicate H. pylori were identified and evaluated according to patients’ age and sex and calendar year of eradication. Results: We identified 157,915 eradication episodes in 140,391 individuals (53.8% women, 42.6% older than 60 years), who correspond to 1.5% of the Swedish population. The absolute number and incidence of eradications decreased over the study period. Overall, 91.0% had one eradication and 0.1% had more than three. Of all eradications, 95.4% followed the recommended regimen, while 4.7% did not. The latter group was overrepresented among individuals aged ≥80 years (7.8%). Amoxicillin and clarithromycin were most frequently prescribed, while metronidazole was rarely used (0.01%). Other prescribed antibiotics were ciprofloxacin (2.4%), doxycycline (1.4%), nitrofurantoin (0.7%), norfloxacin (0.5%) and erythromycin (0.3%). Conclusions: During the last decade in Sweden H. pylori eradication has been frequently prescribed, but the incidence of eradication has slowly declined. Most eradications followed the recommended regimen, including those occurring after a previous eradication.

Pediatric HIV: new opportunities to treat children.

Background: Treating HIV-infected children remains a challenge due to a lack of treatment options, appropriate drug formulations and, in countries with limited resources, insufficient access to diagnostic tests and treatment. Objective: To summarize current data concerning new opportunities to improve the treatment of HIV-infected children. Methods: This review includes data from the most recently published peer-reviewed publications, guidelines or presentations at international meetings concerning new ways to treat HIV-infected children. Results/conclusions: New WHO guidelines recommend starting combination antiretroviral treatment in all infants aged < 1 year. Although this is common practice in some high-income countries, implementation of these recommendations in countries with limited resources is still a challenge. There is still an important gap between the availability of licensed drugs in children compared with adults. There remains a need for further pharmacokinetic studies, and for more pediatric formulations of antiretroviral drugs with improved palatability.

Epidemiology of HPV Genotypes among HIV Positive Women in Kenya: A Systematic Review and Meta-Analysis

Background There is a scarcity of data on the distribution of human papillomavirus (HPV) genotypes in the HIV positive population and in invasive cervical cancer (ICC) in Kenya. This may be different from genotypes found in abnormal cytology. Yet, with the advent of preventive HPV vaccines that target HPV 16 and 18, and the nonavalent vaccine targeting 90% of all ICC cases, such HPV genotype distribution data are indispensable for predicting the impact of vaccination and HPV screening on prevention. Even with a successful vaccination program, vaccinated women will still require screening to detect those who will develop ICC from other High risk (HR) HPV genotypes not prevented by current vaccines. The aim of this review is to report on the prevalence of pHR/HR HPV types and multiple pHR/HR HPV genotypes in Kenya among HIV positive women with normal, abnormal cytology and ICC. Methods PUBMED, EMBASE, SCOPUS, and PROQUEST were searched for articles on HPV infection up to August 2nd 2016. Search terms were HIV, HPV, Cervical Cancer, Incidence or Prevalence, and Kenya. Results The 13 studies included yielded a total of 2116 HIV-infected women, of which 89 had ICC. The overall prevalence of pHR/HR HPV genotypes among HIV-infected women was 64% (95%CI: 50%-77%). There was a borderline significant difference in the prevalence of pHR/HR HPV genotypes between Female Sex workers (FSW) compared to non-FSW in women with both normal and abnormal cytology. Multiple pHR/HR HPV genotypes were highly prominent in both normal cytology/HSIL and ICC. The most prevalent HR HPV genotypes in women with abnormal cytology were HPV 16 with 26%, (95%CI: 23.0%-30.0%) followed by HPV 35 and 52, with 21% (95%CI: 18%-25%) and 18% (95%CI: 15%-21%), respectively. In women with ICC, the most prevalent HPV genotypes were HPV 16 (37%; 95%CI: 28%-47%) and HPV 18 (24%; 95%CI: 16%-33%). Conclusion HPV 16/18 gains prominence as the severity of cervical disease increases, with HPV 16/18 accounting for 61% (95%CI: 50.0%-70.0%) of all ICC cases. A secondary prevention program will be necessary as this population harbors multiple pHR/HR HPV co-infections, which may not be covered by current vaccines. A triage based on FSW as an indicator may be warranted.

Pediatric HIV infection: the state of antiretroviral therapy.

Pediatric HIV/AIDS has become less of a problem in resource-rich countries as the number of perinatal infections has reduced dramatically since the advent of antiretrovirals, resulting in the effective prevention of mother-to-child transmission. In resource-limited settings, however, pediatric HIV infection remains a colossal problem; a separate review in this same issue of Expert Review of Anti-Infective Therapy examines the international aspects of pediatric HIV/AIDS. Treatment of HIV infection in children differs from that in adults in the use of immunologic markers and owing to drug pharmacokinetics and age-related adherence issues. This review, geared for the general pediatrician or family practitioner who may see the HIV-positive child in the clinic or the hospital, summarizes the most recent pediatric data and guidelines for the testing and treatment of HIV, including the US NIH guidelines released in February 2008. Treatment-experienced patients, who should be cared for by pediatric HIV specialists, are not addressed here specifically. Adolescents, infected either perinatally or sexually, with their own unique issues, deserve a separate review.