This report updates and combines earlier versions of guidelines for the prevention and treatment of opportunistic infections (OIs) in HIV-infected adults (i.e., persons aged >/=18 years) and adolescents (i.e., persons aged 13--17 years), last published in 2002 and 2004, respectively. It has been prepared by the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by clinicians and other health-care providers, HIV-infected patients, and policy makers in the United States. These guidelines address several OIs that occur in the United States and five OIs that might be acquired during international travel. Topic areas covered for each OI include epidemiology, clinical manifestations, diagnosis, prevention of exposure; prevention of disease by chemoprophylaxis and vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; discontinuation of secondary prophylaxis after immune reconstitution; and special considerations during pregnancy. These guidelines were developed by a panel of specialists from the United States government and academic institutions. For each OI, a small group of specialists with content-matter expertise reviewed the literature for new information since the guidelines were last published; they then proposed revised recommendations at a meeting held at NIH in June 2007. After these presentations and discussion, the revised guidelines were further reviewed by the co-editors; by the Office of AIDS Research, NIH; by specialists at CDC; and by HIVMA of IDSA before final approval and publication. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy for the prevention and treatment of OIs, especially those OIs for which no specific therapy exists; 2) information regarding the diagnosis and management of immune reconstitution inflammatory syndromes; 3) information regarding the use of interferon-gamma release assays for the diagnosis of latent Mycobacterium tuberculosis (TB) infection; 4) updated information concerning drug interactions that affect the use of rifamycin drugs for prevention and treatment of TB; 5) the addition of a section on hepatitis B virus infection; and 6) the addition of malaria to the list of OIs that might be acquired during international travel. This report includes eleven tables pertinent to the prevention and treatment of OIs, a figure that pertains to the diagnois of tuberculosis, a figure that describes immunization recommendations, and an appendix that summarizes recommendations for prevention of exposure to opportunistic pathogens.

Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.

Bias in questionnaires is an important issue in public health research. To collect the most accurate data from respondents, investigators must understand and be able to prevent or at least minimize bias in the design of their questionnaires. This paper identifies and categorizes 48 types of bias in questionnaires based on a review of the literature and offers an example of each type. The types are categorized according to three main sources of bias: the way a question is designed, the way the questionnaire as a whole is designed, and how the questionnaire is administered. This paper is intended to help investigators in public health understand the mechanism and dynamics of problems in questionnaire design and to provide a checklist for identifying potential bias in a questionnaire before it is administered.

A catalog of biases in questionnaires.

ContextEvidence suggests that since highly active antiretroviral therapy (HAART)
became available, the prevalence of unprotected sex and the incidence of sexually
transmitted infections (STIs) have increased.ObjectiveTo conduct 3 meta-analyses to determine whether (1) being treated with
HAART, (2) having an undetectable viral load, or (3) holding specific beliefs
about HAART and viral load are associated with increased likelihood of engaging
in unprotected sex.Data SourcesA comprehensive search included electronic bibliographic databases,
including AIDSLINE, MEDLINE, PubMed, CINHAL, PsycInfo, ERIC, EMBASE, and Sociofile,
from January 1996 to August 2003, conference proceedings, hand searches of
journals, reference lists of articles, and contacts with researchers.Study SelectionTwenty-five English-language studies (some contributing >1 finding)
met the selection criteria and examined the association of unprotected sexual
intercourse or STIs with receiving HAART (21 findings), having an undetectable
viral load (13 findings), or beliefs about HAART and viral load (18 findings).Data ExtractionReports were screened and information from eligible studies was abstracted
independently by pairs of reviewers using a standardized spreadsheet.Data SynthesisRandom-effects models were used to aggregate data. The prevalence of
unprotected sex was not higher among persons with the human immunodeficiency
virus (HIV) receiving HAART (prevalence range, 9%-56%; median, 33%) vs those
not receiving HAART (range, 11%-77%; median, 44%; odds ratio [OR], 0.92; 95%
confidence interval [CI], 0.65-1.31) or among HIV-positive persons with an
undetectable viral load (range, 10%-68%; median, 39%) vs those with a detectable
viral load (range, 14%-70%; median, 42%; OR, 0.99; 95% CI, 0.82-1.21). The
prevalence of unprotected sex was elevated (OR, 1.82; 95% CI, 1.52-2.17) in
HIV-positive, HIV-negative, and unknown serostatus persons who believed that
receiving HAART or having an undetectable viral load protects against transmitting
HIV or who had reduced concerns about engaging in unsafe sex given the availability
of HAART (range, 17%-81% [median, 49%] vs 9%-68% [median, 38%] for counterparts).ConclusionsIn the studies reviewed, HIV-positive patients receiving HAART did not
exhibit increased sexual risk behavior, even when therapy achieved an undetectable
viral load. However, people's beliefs about HAART and viral load may promote
unprotected sex and may be amenable to change through prevention messages.

Highly active antiretroviral therapy and sexual risk behavior: a meta-analytic review.

Uganda provides the clearest example that human immunodeficiency virus (HIV) is preventable if populations are mobilized to avoid risk. Despite limited resources, Uganda has shown a 70% decline in HIV prevalence since the early 1990s, linked to a 60% reduction in casual sex. The response in Uganda appears to be distinctively associated with communication about acquired immunodeficiency syndrome (AIDS) through social networks. Despite substantial condom use and promotion of biomedical approaches, other African countries have shown neither similar behavioral responses nor HIV prevalence declines of the same scale. The Ugandan success is equivalent to a vaccine of 80% effectiveness. Its replication will require changes in global HIV/AIDS intervention policies and their evaluation.

/pdf/population-level-hiv-declines-and-behavioral-risk-avoidance-30tugjicqj.pdf

Population-Level HIV Declines and Behavioral Risk Avoidance in Uganda

Background The findings from observational studies reviews and meta- analyses supported by biological theories that circumcised men appear less likely to acquire human immunodeficiency virus (HIV) has contributed to the recent ground swell of support for considering male circumcision as a strategy for preventing sexually acquired infection. We sought to elucidate and appraise the global evidence from published and unpublished studies that circumcision can be used as an intervention to prevent HIV infection. Objectives 1) To assess the evidence of an interventional effect of male circumcision for preventing acquisition of HIV-1 and HIV-2 by men through heterosexual intercourse; 2) To examine the feasibility and value of performing individual person data (IPD) meta-analysis. Search strategy We searched online for published and unpublished studies in The Cochrane Library (issue 2 2002) MEDLINE (April 2002) EMBASE (February 2002) and AIDSLINE (August 2001). We also searched databases listing conference abstracts scanned reference lists of articles and contacted authors of included studies. Selection criteria We searched for randomized and quasi- randomized controlled trials of male circumcisions or in their absence observational studies that compare acquisition rates of HIV-1 and HIV-2 infection in circumcised and uncircumcised heterosexual men. Data collection and analysis Independent reviewers selected studies assessed study quality and extracted data. We stratified studies based on study design and on whether they included participants from the general population or high-risk groups (such as patients treated for sexually transmitted infections). We expressed findings as crude and adjusted odds ratios (OR) together with their 95% confidence intervals (CI) and conducted a sensitivity analysis to explore the effect of adjustment on study results. We investigated whether the method of circumcision ascertainment influenced study outcomes. Main results We identified no completed randomized controlled trials. Three randomized controlled trials are currently underway or commencing shortly. We found 35 observational studies: 16 conducted in the general population and 19 in high-risk populations. It seems unlikely that potential confounding factors were completely accounted for in any of the included studies. In particular important risk factors such as religion and sexual practices were not adequately accounted for in many of the included studies. General population study results: The single cohort study (N = 5516) showed a significant difference in HIV transmission rates between circumcised and uncircumcised men [OR = 0.58; 95% CI: 0.36 to 0.96]. Results for the 14 cross-sectional studies were inconsistent with point estimates for unadjusted odds ratios varying between 0.28 and 1.73. Six studies had statistically significant results four in the direction of benefit and two in the direction of harm. The test for heterogeneity between the cross-sectional studies was highly significant (chi-square = 77.59; df = 13; P-value < 0.00001). Nine studies reported adjusted odds ratios with eight in the direction of benefit ranging from 0.26 to 0.80. Use of adjusted results tended to show stronger evidence of an association although they remained heterogeneous (chi-square = 75.2; df = 13; P-value < 0.00001). Only one case-control study was found (N = 51) which had a non-significant result [OR = 1.90; 95% CI: 0.50 to 7.20]. High- risk group study results: The four cohort studies identified found a protective effect from circumcision with point estimates for unadjusted odds ratios varying from 0.10 to 0.39. Two of these studies had statistically significant results. Two studies reported adjusted odds ratios both protective with one being significant. The chi-square test for between-study heterogeneity was not significant (chi-square = 5.21; df = 3; P-value = 0.16). All eleven cross- sectional studies reporting unadjusted results found benefit from circumcision eight of which had statistically significant results. Estimates of effect varied from an unadjusted odds ratio of 0.10 to 0.66. Between-study heterogeneity was significant with the chi-square = 29.77; df = 10; P-value = 0.0009. Four of these studies reported adjusted odds ratios ranging from 0.20 to 0.59 and all were significant. One additional cross-sectional study only reported an adjusted odds ratio ranging from 0.20 to 0.59 and all were significant. All three case- control studies found a protective effect of circumcision on HIV status two being statistically significant. Point estimates varied from unadjusted odds ratios of 0.37 to 0.88. One reported an adjusted odds ratio showing a significant protective effect. Adverse effects: No studies reported on the adverse effects of circumcision. In most studies circumcision had taken place during childhood or adolescence before the studies commenced. Authors conclusions We found insufficient evidence to support an interventional effect of male circumcision on HIV acquisition in heterosexual men. The results from existing observational studies show a strong epidemiological association between male circumcision and prevention of HIV especially among high-risk groups. However observational studies are inherently limited by confounding which is unlikely to be fully adjusted for. In the light of forthcoming results from RCTs the value of IPD analysis of the included studies is doubtful. The results of these trials will need to be carefully considered before circumcision is implemented as a public health intervention for prevention of sexually transmitted HIV. (authors)

Male circumcision for prevention of heterosexual acquisition of HIV in men

Objectives: We investigated if a rise in rectal gonorrhoea and early syphilis among men who have sex with men (MSM) in Amsterdam coincided with the introduction of highly active antiretroviral therapies (HAART) in July 1996 and determined risk factors for these sexually transmitted infections (STI). 

Methods: Subjects were patients of the STI clinic of the municipal health service in Amsterdam. Surveillance data (1994–9) represented consultations (n=11 240) of MSM (n=6103). For analyses we used logistic regression. 

Results: Comparing the periods before and after the introduction of HAART, the infection rate for rectal gonorrhoea increased from 4% to 5.4% (p=.001) and for syphilis, from 0.5% to 0.8% (p = 0.050). Independent risk factors for rectal gonorrhoea (younger age, western nationality, and concurrent infection with another STI) and for early syphilis (non-western nationality and concurrent infection with rectal gonorrhoea) did not change after HAART became available. For rectal gonorrhoea, however, the infection rate increased only among men who had exclusively homosexual contacts (OR 1.38, p<0.01), compared with bisexual men. For early syphilis, the infection rate increased only among men of western nationality (OR 3.38, p<0.01) compared to men of non-western nationality. 

Conclusions: Infection rates of rectal gonorrhoea and early syphilis increased, indicating a change in sexual behaviour, possibly as a result of the introduction of HAART. For now, it is important to find out how sexual behaviour is changing and to keep monitoring trends in STIs (including HIV) among MSM in Amsterdam. 

Key Words: rectal gonorrhoea; syphilis; HAART; high risk sexual behaviour; MSM

https://sti.bmj.com/content/sextrans/77/3/184.full.pdf

Increase in sexually transmitted infections among homosexual men in Amsterdam in relation to HAART

Buts: determiner si les jeunes et les recents usagers de drogue par injection (UDI) sont plus a risque d'infection VIH, et comparer les tendances au niveau des comportements a risque ainsi que l'incidence VIH parmi les sous-groupes d'UDI. Projet: les associations de l'âge et du debut d'injection avec la prevalence et les comportements a risques lies a l'injection ont ete determinees parmi les UDI actuels entres dans une cohorte d'Amsterdam entre 1989 et 1995, et comparees aux UDI actuels recrutes dans deux enquetes de rue en 1990 et 1993. Dans la cohorte, les tendances de 1986 jusqu'en 1995 au niveau du comportement a risque lie a l'injection (tel que rapporte a l'entree) et au niveau de la seroconversion (parmi les UDI actuels au cours du suivi) ont ete determinees a l'aide de la regression logistique et la distribution de Poisson. Resultats: les tranches d'UDI les plus grandes etaient jeunes (< 25 ans:14-30%) ou avaient recemment commence les injections (au cours des trois dernieres annees:17-21%). Entre 37 et 50% des jeunes UDI avaient commence recemment a s'injecter. La prevalence VIH allait de 12 a 24% parmi les jeunes UDI, et de 5 a 12% parmi les recents UDI. Les jeunes UDI rapportaient plus souvent un comportement de partage des aiguilles que les UDI plus âges. L'emprunt diminuait significativement dans tous les sous-groupes, excepte parmi les jeunes UDI. L'incidence VIH brute diminuait de 18/100 personnes-annees (PA) en 1986 a 5/100 PA en 1995. Les tendances au niveau de l'incidence VIH n'etaient pas significativement differentes pour les sous-groupes d'âge ou le debut de l'injection. Dans une analyse multivariee, le debut recent de l'injection etait un indice de prediction independant (p = 0,04) pour la seroconversion VIH, mais l'âge ne l'etait pas (p = 0,68). Conclusions: les proportions importantes d'usagers de drogue sont jeunes ou ont recemment commence les injections. La prevalence VIH est relativement elevee parmi les jeunes et les recents UDI. Le debut recent des injections est un indice de prediction independant pour la seroconversion VIH. Ces observations peuvent etre expliquees par les modeles non-randomises d'emprunt de seringues et/ou d'aiguilles usagees. Les UDI recents devraient etre abordes de maniere plus active au niveau des conseils et des tests VIH.

Young and recent-onset injecting drug users are at higher risk for HIV

To the Editor: An outbreak of rectal lymphogranuloma venereum (LGV) has been detected in the Netherlands among men who have sex with men (1–4). More cases of LGV in other European countries such as Belgium, France, and the United Kingdom have been reported, and the first cases have been detected in the United States as well. This infection is encountered not only by clinicians who treat sexually transmitted diseases but also by gastroenterologists. Both the European Surveillance of Sexually Transmitted Infections (http://www.essti.org) and the Centers for Disease Control and Prevention (http://www.cdc.gov) are working on outbreak warning and response systems to increase the awareness and the direct management of the LGV outbreak (5,6).

Different approaches have been described to diagnose LGV infections (Figure). The first 3 approaches have serious disadvantages: cell culture is rarely available in routine diagnostic settings, polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) analysis (usually nested PCR approaches are used) needs post-PCR restriction enzyme profiling, and sequencing requires additional analyses of sequence data to identify the Chlamydia trachomatis serovar responsible for infection. In addition, all 3 techniques are time consuming (at least 1–4 days to get a result), laborious, and require specially trained personnel in a sophisticated laboratory setting. Therefore, we developed a real-time PCR approach (TaqMan and Rotorgene) that can easily identify LGV strains in 2 hours with equipment that is available in almost all diagnostic settings.



Figure

Diagnosis of lymphogranuloma venereum. MIF, microimmunofluorescence; STI, sexually transmitted infection; PCR, polymerase chain reaction; RFLP, restriction fragment length polymorphism; PAA, poly acrylamide; BLAST, basic local alignment search tool.



We used the polymorphic membrane protein H gene (pmp gene) as a PCR target because it has a unique gap in LGV strains of C. trachomatis, compared to other serovars, which makes it highly specific. The following primers and probes were selected: LGV-F 5´ CTG TGC CAA CCT CAT CAT CAA 3´, LGV-R 5´ AGA CCC TTT CCG AGC ATC ACT 3´, and LGV MGB-probe 6-FAM-CCT GCT CCA ACA GT. Real-time PCR conditions (20-μL format) for TaqMan were as follows: 2× TaqMan Universal Mastermix (Applied Biosystems, Foster City, CA, USA), 18 pmol each primer, 0.2 μmol/L probe, and 2 μL (LGV L2) DNA or clinical sample; 2 min at 50°C, 10 min at 95°C, and 40 cycles of 15 sec at 95°C and 1 min at 60°C. Conditions for Rotorgene were as follows: 10× buffer (Hoffman-La Roche Ltd, Basel, Switzerland), 10 pmol each primer, 0.04 μmol/L probe, 2 μL (LGV L2) DNA or clinical sample; 2 min at 50°C, 10 min at 95°C, and 45 cycles of 15 sec at 95°C and 1 min at 60°C. By using a previously described serial dilution of LGV L2 (7), sensitivity was assessed as 0.01 inclusion-forming units for both real-time PCR assays.

To determine specificity, we tested different C. trachomatis serovars and serovariants A, B, Ba, C, D, Da, D-, E, F, G, Ga, H, I, Ia, I-, J, Jv, K, L1, L2, L2b, L3, C. muridarum (MoPn), C. pneumoniae, C. pecorum, C. psittaci, and 32 other microorganisms that normally reside in the human perianal and urogenital region and in the oropharynx. These organisms included gram-positive and gram-negative bacteria and yeast: Acinetobacter baumannii, Campylobacter jejuni, Candida albicans, other yeast, Enterobacter agglomerans, Enterococcus faecalis, Escherichia coli, Streptococcus spp., Haemophilus influenzae, Klebsiella pneumoniae, Mycoplasma spp., Neisseria meningitidis, Pasteurella spp., Pseudomonas aeruginosa, Salmonella enteritidis, Shigella sonnei, Staphylococcus aureus, and others. Only LGV strains L1, L2, L2b, and L3 tested positive in both the TaqMan and Rotorgene assays, which shows the analytical specificity of real-time PCR.

Subsequently, we determined in a blinded setting the presence of LGV in a selected group of patients (clinical spectrum and epidemiology described elsewhere [8]) according to C. trachomatis–positive rectal swab (Chlamydia 2SP Collection & Transport Kit [Quelab] by commercially available PCR (COBAS AMPLICOR, Hoffman-La Roche Ltd). By using the 2 reference standard techniques to type C. trachomatis serovars (PCR-based RFLP of the omp1 gene or sequencing the variable segment 2 [VS-2] of the omp1 gene) (9,10) with DNA isolated from rectal swab specimens (standard isopropanol DNA isolation method), we identified 28 of 125 men as LGV-positive. These 28 samples were also positive in both the TaqMan and Rotorgene assays. We also identified 2 additional LGV infections, which were initially typed and then retested as single-strain infections with serovars E and D by both PCR-based RFLP analysis and VS-2 sequencing. This discrepancy is most likely due to a double infection, which will, in most cases, result in the preferential amplification of 1 strain in the omp1 PCR and PCR-based sequencing methods; in the TaqMan and Rotorgene assays, only LGV strains can be amplified. Whether this outbreak is partially technically driven must be assessed in the future by retrospectively investigating the presence of these LGV infections in men who have sex with men and the presence of the L2b strain in the past, since at present only LGV infections from 2003 to 2005 have been investigated.

/pdf/real-time-polymerase-chain-reaction-to-diagnose-11ceqtu09n.pdf

Real-time polymerase chain reaction to diagnose lymphogranuloma venereum.

Objective To evaluate the effectiveness of register based, yearly chlamydia screening. Design Controlled trial with randomised stepped wedge implementation in three blocks. Setting Three regions of the Netherlands: Amsterdam, Rotterdam, and South Limburg. Participants 317 304 women and men aged 16-29 years listed on municipal registers at start of trial. Intervention From March 2008 to February 2011, the Chlamydia Screening Implementation programme offered yearly chlamydia screening tests. Postal invitations asked people to use an internet site to request a kit for self collection of samples, which would then be sent to regional laboratories for testing. Treatment and partner notification were done by the general practitioner or at a sexually transmitted infection clinic. Main outcome measures Primary outcomes were the percentage of chlamydia tests positive (positivity), percentage of invitees returning a specimen (uptake), and estimated chlamydia prevalence. Secondary outcomes were positivity according to sex, age, region, and sociodemographic factors; adherence to screening invitations; and incidence of self reported pelvic inflammatory disease. Results The participation rate was 16.1% (43 358/269 273) after the first invitation, 10.8% after the second, and 9.5% after the third, compared with 13.0% (6223/48 031) in the control block invited at the end of round two of the intervention. Chlamydia positivity in the intervention blocks at the first invitation was the same as in the control block (4.3%) and 0.2% lower at the third invitation (odds ratio 0.96 (95% confidence interval 0.83 to 1.10)). No substantial decreases in positivity were seen after three screening rounds in any region or sociodemographic group. Among the people who participated three times (2.8% of all invitees), positivity fell from 5.9% to 2.9% (odds ratio 0.49 (0.47 to 0.50)). Conclusions There was no statistical evidence of an impact on chlamydia positivity rates or estimated population prevalence from the Chlamydia Screening Implementation programme after three years at the participation levels obtained. The current evidence does not support a national roll out of this register based chlamydia screening programme. Trial registration NTR 3071 (Netherlands Trial Register, www.trialregister.nl).

https://www.bmj.com/content/bmj/345/bmj.e4316.full.pdf

Effectiveness of yearly, register based screening for chlamydia in the Netherlands: controlled trial with randomised stepped wedge implementation.

Lymphogranuloma venereum (LGV) is a systemic, sexually transmitted disease (STD) caused by a variety of the bacterium Chlamydia trachomatis that rarely occurs in the United States and other industrialized countries; the prevalence of LGV is greatest in Africa, Southeast Asia, Central and South America, and Caribbean countries However, in the Netherlands, which typically has fewer than five cases a year, as of September 2004, a total of 92 cases of LGV had been confirmed during the preceding 17 months among men who have sex with men (MSM) The first 13 cases, diagnosed during April-November 2003, were reported by local health authorities in Rotterdam in December 2003 An alert was sent to the Early Warning and Reporting System of the European Union and to the European Surveillance of Sexually Transmitted Infections Network (ESSTI) In April 2004, a report was made to CDC, and state and local health departments were alerted Of the 92 cases confirmed in the Netherlands, 30 occurred during 2003 and 62 during 2004 This report describes the ongoing investigation of the LGV outbreak Health-care providers should be vigilant for LGV, especially among MSM exposed to persons from Europe, and prepared to diagnose the disease and provide appropriate treatment to patients and their exposed sex partners

/pdf/lymphogranuloma-venereum-among-men-who-have-sex-with-men-56vtenf5vt.pdf

J. S. A. Fennema

Papers

Increase in sexually transmitted infections among homosexual men in Amsterdam in relation to HAART

Young and recent-onset injecting drug users are at higher risk for HIV

Real-time polymerase chain reaction to diagnose lymphogranuloma venereum.

Effectiveness of yearly, register based screening for chlamydia in the Netherlands: controlled trial with randomised stepped wedge implementation.

Lymphogranuloma Venereum Among Men Who Have Sex with Men --- Netherlands, 2003--2004