Search

Background: Rapid diagnosis of tuberculosis (TB) and detection of drug resistance are very important for timely and appropriate management of patients. Xpert MTB/RIF assay is approved for use in TB and rifampicin-resistance diagnosis. However, data are limited on the impact of Xpert MTB/RIF assay under routine clinical settings with a heterogeneous group of patients and sample types in Ethiopia., Methods: A retrospective study was carried out in 2220 presumptive TB cases at Jimma University Medical Center. Data were gathered from the registration logbook using formatted data extraction tools and double entered to epidata version 3.1 and further transported to SPSS version 20 for analysis. Associations were determined using the Chi-square test and P-value <0.05 was considered statistically significant., Results: Of 2220 cases enrolled, 1665 (75%) were adults and the remaining 555 (25%) were children aged less than 14 years. The majority, 1964 (88.46%), had pulmonary manifestation and 256 (11.54%) had extrapulmonary involvements. The overall, frequency of Mycobacterium tuberculosis (MTB) was 9.3% (206/2220), among this 10.27% (171/1665) and 6.3% (35/555) were adults and children, respectively. M. tuberculosis was detected from 171 (8.75%) of pulmonary patients and 35 (13.28%) of extrapulmonary manifested patients. Out of 206 M. tuberculosis positive cases, 7(3.4%) were rifampicin-resistant: four from pulmonary tuberculosis (PTB) patients and three from EPTB patients. In the Chi-square test, the age group of 15-24 years, previous history of TB, pus/lymph node sample, and being HIV positive were significantly associated with TB positivity by Xpert MTB/RIF (P-value <0.001)., Conclusion: These data suggest that the overall frequency of M. tuberculosis and rifampicin resistance was found to be relatively low compared to the previous reports in Ethiopia. Nevertheless, better diagnostic tools and approaches are still vital to halt the burden of TB and drug-resistant TB in the country., Competing Interests: The authors have declared that no competing interests exist.

Background: Gay, bisexual and other men who have sex with men (gbMSM) who attend STI clinics represent an easily accessible population for promoting HIV prevention interventions. We examined characteristics of gbMSM STI clinic attendees to identify those who could most benefit from pre-exposure prophylaxis (PrEP)., Setting: GbMSM STI clinic attendees in British Columbia (BC), Canada., Methods: A clinical electronic charting system of STI clinics in BC was used to identify gbMSM from 2004 to 2017. Incident HIV cases were defined as testers who had at least one HIV-negative test and a subsequent HIV-positive test. Seroconversion rates were calculated by risk factor variables and by year. Cox proportional hazards regression was used to identify independent predictors of HIV seroconversion., Results: There were 9,038 gbMSM included, of whom 257 HIV seroconverted over the study period and 8,781 remained negative HIV testers, contributing 650.8 and 29,591.0 person-years to the analysis, respectively. The overall rate of seroconversion was 0.85 per 100 person-years (95% CI: 0.75-0.96). Incidence rates were higher among patients reporting >5 partners in the previous six months, inconsistent condom use, or having a partner living with HIV and who had a previous or concurrent diagnosis of rectal gonorrhea or rectal chlamydia. gbMSM presenting with two STIs such as rectal gonorrhea and syphilis (3.59/100 person-years [95%CI: 2.33-5.22]) or rectal chlamydia and syphilis (3.01/100 person-years [95%CI: 2.00-4.29]) had the highest incidence rates., Conclusion: gbMSM with preceding or concurrent rectal STI diagnoses or syphilis had higher rates of HIV seroconversion. The data support the inclusion of specific STI diagnoses as an indication for PrEP., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Several methods have been proposed to estimate the time of HIV seroconversion, including those based on CD4 cell depletion models. However, previous models have failed to consider the heterogeneity that exists in CD4 trajectories among different sub-populations. Our objective was to estimate the time from HIV seroconversion relative to the HIV diagnosis date in a population-based cohort of people living with HIV (PLWH) in the province of British Columbia, Canada., Methods: We used linked administrative and clinical data from the British Columbia Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) cohort, which contains longitudinal individual-level data on all PLWH ever diagnosed in the province. Eligible participants were aged ≥18 years and diagnosed with HIV between 1989 and 2013. The outcome was pre-antiretroviral treatment CD4 cell count measurements assessed every six months. Models were stratified by age and stage of HIV infection at diagnosis. Several explanatory variables were considered including longitudinal viral load measurements. Longitudinal CD4, square root transformed, was modeled via a non-linear mixed effects model; time was modeled using an exponential decay function. We assumed a Gaussian distribution (identity link), an AR(1) correlation structure, and a random intercept and slope for the longitudinal viral load measurements. Due to the population variation in CD4 count among uninfected individuals, we assumed 500 to 1500 cells/mm3 as the normal range when estimating the time of HIV seroconversion., Results: Longitudinal data on 1,253 individuals were analysed: 80% male, 33% White, and the median age at diagnosis was 38 years (25th-75th percentile [Q1-Q3], 31 to 45). CD4 decay differed by stage of infection at diagnosis and age, with those ≥50 years in Stages 1 and 2 experiencing a faster decline in CD4 over time. The median duration of infection from seroconversion until HIV diagnosis was 6.9 (Q1-Q3, 3.9 to 10.1) years., Conclusions: Considering the heterogeneity that exists in individual CD4 cell trajectories in a population, we presented a methodology that only relies on routinely collected HIV-related data, which can be further extended to estimate other epidemic measures., Competing Interests: Institutional grants have been provided to JSGM by Gilead, J&J, Merck, ViiV Healthcare. The remaining authors do not have conflicts to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

There are no studies on time to test since notification among identified sexual contacts of HIV-positive index clients using program data in Siaya County and Kenya. We sought to understand time to HIV testing by contact characteristics after identification to inform targeted testing interventions. We retrospectively analyzed data from adult (aged ≥18 years) sexual contacts identified by HIV-positive index clients from 117 health facilities in Siaya County (June 2017-August 2018). We used Chi-square tests to assess for differences in characteristics of contacts by HIV testing. We performed Cox proportional hazards analysis and time to HIV testing of contacts analysis including time-varying covariates (cluster-adjusted by facility) to assess characteristics (age, sex, and relationship to index client) associated with time to HIV-testing since notification. Sexual contacts not tested were right censored at last follow-up date. We calculated hazard ratios with 95% confidence intervals to evaluate characteristics associated with time to testing. Of the 6,845 contacts included in this analysis, 3,858 (56.4%) were men. Most were aged 25-34 years (3,209 [46.9%]). Median time to contact testing was 14.5 days (interquartile range, 2.5-62). On multivariable analysis, contacts aged 18-24 years (aHR, 1.32 [95% CI: 1.01-1.73], p = 0.040) and 25-34 years (aHR, 1.18 [95% CI: 1.01-1.39], p = 0.038) had shorter time to HIV testing than those aged 35-44 years. Married polygamous (aHR, 1.12 [95% CI: 1.01-1.25], p = 0.039) and single contacts (aHR, 1.17 [95% CI: 1.08-1.27], p <0.001) had shorter time to HIV testing than married monogamous contacts. Non-spouse sexual contacts had shorter time to HIV testing than spouses, (aHR, 1.23 [95% CI: 1.15-1.32], p <0.001). We recommend enhanced differentiated partner services targeting older adults, married monogamous, and spouse sexual contacts to facilitate early diagnosis, same day treatment, and prevention in Western Kenya and sub-Saharan Africa at large., Competing Interests: The authors have declared that no competing interests exist.

Background: Mother to child transmission (MTCT) of HIV remains a challenge in resource-limited settings. Central to elimination of MTCT is effective Provider Initiated HIV Counseling and Testing (PICT). Research has shown that conducting PICT only at the initial antenatal care (ANC) visit fails to benefit pregnant women who seroconvert later in their pregnancy. This study aimed to determine the most cost effective time to perform repeat HIV testing during ANC and perinatal care (PNC)., Methods: We studied the repeat HIV testing results of pregnant women ≥ 18 and adolescent girls aged 15-17 in the Sauri, Kenya Millennium Villages Project (MVP) site. Nurses provided HIV screening to 1,403 expectant women and 256 adolescent girls following the 1st, 2nd, 3rd and 4th ANC visits, at birth and 6 and 14 weeks postpartum., Results: Five women seroconverted during the study period (incidence proportion 0.41%). One woman seroconverted at the 2nd ANC visit, another one at the 3rd, two at the 4th and one at 6 weeks post-partum. Of all the women who seroconverted, four reported an HIV negative primary partner, while one reported an unknown partner status. None of the participants reported condom use during pregnancy. Two of the seroconverters vertically transmitted HIV to their babies. The results did not suggest a clear pattern of seroconversion during ANC and PNC., Conclusions: The low rates of seroconversion suggest that testing pregnant women multiple times during ANC and PNC may not be cost effective, but a follow-up test during birth may be protective of the newborn., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Cryptococcus causes 15% of AIDS-related deaths and in South Africa, with its high HIV burden, is the dominant cause of adult meningitis. Cryptococcal meningitis (CM) mortality is high, partly because patients enter care with advanced HIV disease and because of failure of integrated care following CM diagnosis. We evaluated pathways to hospital care, missed opportunities for HIV testing and initiation of care., Methods: We performed a cross-sectional study at five public-sector urban hospitals. We enrolled adults admitted with a first or recurrent episode of cryptococcal meningitis. Study nurses conducted interviews, supplemented by a prospective review of medical charts and laboratory records., Results: From May to October 2015, 102 participants were enrolled; median age was 40 years (interquartile range [IQR] 33.9-46.7) and 56 (55%) were male. In the six weeks prior to admission, 2/102 participants were asymptomatic, 72/100 participants sought care at a public-sector facility, 16/100 paid for private health care. The median time from seeking care to admission was 4 days (IQR, 0-27 days). Of 94 HIV-seropositive participants, only 62 (66%) knew their status and 41/62 (66%) had ever taken antiretroviral treatment. Among 13 participants with a known previous CM episode, none were taking fluconazole maintenance therapy. In-hospital management was mostly amphotericin B; in-hospital mortality was high (28/92, 30%). Sixty-four participants were discharged, 92% (59/64) on maintenance fluconazole, 4% (3/64) not on fluconazole and 3% (2/64) unknown. Twelve weeks post-discharge, 31/64 (48%) participants were lost to follow up. By 12 weeks post discharge 7/33 (21%) had died. Interviewed patients were asked if they were still on fluconazole, 11% (2/18) were not., Conclusions: Among hospitalised participants with CM, there were many missed opportunities for HIV care and linkage to ART prior to admission. Universal reflex CrAg screening may prompt earlier diagnosis of cryptococcal meningitis but there is a wider problem of timely linkage to care for HIV-seropositive people., Competing Interests: The authors have declared that no competing interests exist.

Finding new HIV-positive cases remains a priority to achieve the UNAIDS goals. An enhanced peer outreach approach (EPOA) was implemented to expand the delivery of HIV services to female sex workers (FSWs) and men who have sex with men (MSM) in three countries in West and Central Africa. The aim of EPOA is to identify new HIV-positive cases. EPOA was implemented in Burundi among FSWs, and in Cote d'Ivoire and Democratic Republic of the Congo (DRC) among both FSWs and MSM. Implementation ranged from five to nine weeks and was nested within a three-month reporting period. Standard outreach was suspended for the duration of EPOA implementation but was resumed thereafter. Summary service statistics were used to compare HIV seropositivity during standard outreach and EPOA. Trends were analyzed during the quarter in which EPOA was implemented, and these were compared with the two preceding quarters. Differences in proportions of HIV seropositivity were tested using Pearson's chi-square test; p-values of less than 0.05 were considered statistically significant. Overall, EPOA resulted in a higher proportion of new HIV-positive cases being found, both within and between quarters. In Burundi, HIV seropositivity among FSWs was significantly higher during EPOA than during standard outreach (10.8% vs. 4.1%, p<0.001). In Cote d'Ivoire, HIV seropositivity was significantly higher during EPOA among both populations (FSWs: 5.6% vs. 1.81%, p<0.01; MSM: 15.4% vs. 5.9%; p<0.01). In DRC, HIV seropositivity was significantly higher during EPOA among MSM (6.9% vs. 1.6%; p<0.001), but not among FSWs (5.2% vs. 4.3%; p = 0.08). Trends in HIV seropositivity during routine outreach for both populations were constant during three successive quarters but increased with the introduction of EPOA. EPOA is a public health approach with great potential for reaching new populations and ensuring that they are aware of their HIV status., Competing Interests: The authors have declared that no competing interests exist.

Background: Given the great efforts put into the strategic objective of reducing the proportion of HIV-infected patients that are undiagnosed, the aim of the present study was to review the temporal trends between 1997 and 2016 for median estimates of infection duration and median CD4 count at diagnosis for the main patient origins in French Guiana., Methods: CD4 cell count at HIV sero-conversion and square root of CD4 cell decline were obtained using the CD4 decline in a cohort of HIV-infected persons in the UK, fitting random effect (slope and intercept) multilevel linear regression models. Multivariate analysis used robust regression for modeling the delay between estimated HIV seroconversion and diagnosis and quantile regression for CD4 at HIV diagnosis., Results: The median interval between the estimated HIV seroconversion and HIV diagnosis was 8 years for patients fromBrazil, 4.5 years for those from Haiti, 6.6 years for those from Suriname, 3.3 years for patients from Guyana, and 3.1 years for French patients. A simple robust regression model with French patients as reference group adjusting for sex and age at the time of diagnosis showed that the interval was significantly longer for Brazilian (β = +3.7 years, P = 0.001), Surinamese (β = +4.2 years, P<0.0001), Haitian origins (β = +1.5 years, P = 0.049) but not for those originating from Guyana (β = -0.03 years, P = 0.9); Men independently had a longer interval than women (β = +3.5 years, P<0.0001)., Conclusions: Despite great efforts in French Guiana regarding HIV testing both in terms of diversification and intensification we still need to tailor the offer to better reach the communities in need. These results should help authorities scale up and optimize initiatives to reduce the proportion of patients who are unaware of their infection. They also raise the question of the role of stigma and discrimination as a barrier to HIV testing in small communities, and further emphasize the importance of reducing it., Competing Interests: The authors have declared that no competing interests exist.

Background: Pregnancy incidence rates among women living with HIV (WLWH) have increased over time due to longer life expectancy, improved health status, and improved access to and HIV prevention benefits of combination antiretroviral therapy (cART). However, it is unclear whether intended or unintended pregnancies are contributing to observed increases., Methods: We analyzed retrospective data from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS). Kaplan-Meier methods and GEE Poisson models were used to measure cumulative incidence and incidence rate of pregnancy after HIV diagnosis overall, and by pregnancy intention. We used multivariable logistic regression models to examine independent correlates of unintended pregnancy among the most recent/current pregnancy., Results: Of 1,165 WLWH included in this analysis, 278 (23.9%) women reported 492 pregnancies after HIV diagnosis, 60.8% of which were unintended. Unintended pregnancy incidence (24.6 per 1,000 Women-Years (WYs); 95% CI: 21.0, 28.7) was higher than intended pregnancy incidence (16.6 per 1,000 WYs; 95% CI: 13.8, 20.1) (Rate Ratio: 1.5, 95% CI: 1.2-1.8). Pregnancy incidence among WLWH who initiated cART before or during pregnancy (29.1 per 1000 WYs with 95% CI: 25.1, 33.8) was higher than among WLWH not on cART during pregnancy (11.9 per 1000 WYs; 95% CI: 9.5, 14.9) (Rate Ratio: 2.4, 95% CI: 2.0-3.0). Women with current or recent unintended pregnancy (vs. intended pregnancy) had higher adjusted odds of being single (AOR: 1.94; 95% CI: 1.10, 3.42), younger at time of conception (AOR: 0.95 per year increase, 95% CI: 0.90, 0.99), and being born in Canada (AOR: 2.76, 95% CI: 1.55, 4.92)., Conclusion: Nearly one-quarter of women reported pregnancy after HIV diagnosis, with 61% of all pregnancies reported as unintended. Integrated HIV and reproductive health care programming is required to better support WLWH to optimize pregnancy planning and outcomes and to prevent unintended pregnancy.

Background: An enabling environment is believed to have significant and critical effects on HIV and AIDS program implementation and desired outcomes. This paper estimates the paths, directionality, and direct and indirect associations between critical enablers with antiretroviral treatment (ART) coverage and to AIDS-related mortality., Methods: Frameworks that consider the role of enablers in HIV and AIDS programs were systematically reviewed to develop a conceptual model of interaction. Measurements for constructs of the model were pooled from the latest publicly available data. A hypothetical model, including latent/unobserved factors and interaction of enablers, program activities and outcomes, was analyzed cross-sectionally with structural equation modeling. Coefficients of the model were used to estimate the indirect associations of enablers to treatment coverage and the subsequent associated impact on AIDS related mortality., Findings: The model's fit was adequate (RMSEA = 0·084, 90% CI [0·062, 0·104]) and the indirect effects of enablers on outcomes were measured. Enablers having significant associations with increased ART coverage were social/financial protection, governance, anti-discrimination, gender equality, domestic AIDS spending, testing service delivery, and logistics., Interpretation: Critical enablers are significantly correlated to outcomes like ART coverage and AIDS related mortality. Even while this model does not allow inference on causality, it provides directionality and magnitude of the significant associations.

Introduction: Fourth generation (Ag/Ab combination) point of care HIV tests like the FDA-approved Determine HIV1/2 Ag/Ab Combo test offer the promise of timely detection of acute HIV infection, relevant in the context of HIV control. However, a synthesis of their performance has not yet been done. In this meta-analysis we not only assessed device performance but also evaluated the role of study quality on diagnostic accuracy., Methods: Two independent reviewers searched seven databases, including conferences and bibliographies, and independently extracted data from 17 studies. Study quality was assessed with QUADAS-2. Data on sensitivity and specificity (overall, antigen, and antibody) were pooled using a Bayesian hierarchical random effects meta-analysis model. Subgroups were analyzed by blood samples (serum/plasma vs. whole blood) and study designs (case-control vs. cross-sectional)., Results: The overall specificity of the Determine Combo test was 99.1%, 95% credible interval (CrI) [97.3-99.8]. The overall pooled sensitivity for the device was at 88.5%, 95% [80.1-93.4]. When the components of the test were analyzed separately, the pooled specificities were 99.7%, 95% CrI [96.8-100] and 99.6%, 95% CrI [99.0-99.8], for the antigen and antibody components, respectively. Pooled sensitivity of the antibody component was 97.3%, 95% CrI [60.7-99.9], and pooled sensitivity for the antigen component was found to be 12.3%, 95% (CrI) [1.1-44.2]. No significant differences were found between subgroups by blood sample or study design. However, it was noted that many studies restricted their study sample to p24 antigen or RNA positive specimens, which may have led to underestimation of overall test performance. Detection bias, selection (spectrum) bias, incorporation bias, and verification bias impaired study quality., Conclusions: Although the specificity of all test components was high, antigenic sensitivity will merit from an improvement. Besides the accuracy of the device itself, study quality, also impacts the performance of the test. These factors must be kept in mind in future evaluations of an improved device, relevant for global scale up and implementation.

Introduction: Female sex workers (FSWs) are the second most affected population by HIV in Iran. However, their HIV testing practices are poorly understood. The aim of this study was to investigate testing and its associated factors among HIV negative FSWs., Materials and Methods: Using facility based sampling, 1005 FSWs were recruited in 14 cities of Iran in 2010. Biological and survey data were collected through dried blood spot testing and standardized risk assessment questionnaire, respectively. In this paper, the prevalence of HIV testing and its correlates were explored among 714 HIV-negative FSWs using descriptive statistics and logistic regression models., Results: Overall 65.4% had not tested in the past year. Only 27.5% had tested in the past year and received their results. FSWs who perceived themselves at risk of HIV (Adjusted Odds Ratio (AOR) = 8.35, 95% CI: 1.46, 47.6), had received free condom during past year (AOR = 3.90, 95% CI: 1.67, 9.14), started sex work at an older age (AOR18-24 = 2.83, 95% CI: 1.14, 7.0; AOR >24 = 2.76, 95% CI: 1.11, 6.84), and knew an HIV testing site (AOR = 5.67, 95% CI: 2.60, 12.4) had a significantly higher chance of having a recent HIV test result., Conclusions: Less than one third of FSWs in Iran knew their recent HIV status. Interventions to help FSWs evaluate their potential risk for HIV and integrate HIV testing services in condom distribution programs, could be viable strategies in increasing HIV testing uptake among FSWs. Health policy makers should also try to de-stigmatize HIV testing, identify the barriers to HIV testing, and make HIV testing sites more visible to FSWs.

Background: We assessed the integration of early infant HIV diagnosis with the expanded programme for immunization in a rural Zambian setting with the aim of determining whether infant and postpartum maternal HIV testing rates would increase without harming immunization uptake., Methods: In an unblinded, location stratified, cluster randomised controlled trial, 60 facilities in Zambia's Southern Province were equally allocated to a control group, Simple Intervention group that received a sensitization meeting and the resupply of HIV testing commodities in the event of a stock-out, and a Comprehensive Intervention group that received the Simple Intervention as well as on-site operational support to facilitate the integration of HIV testing services with EPI., Findings: The average change in number of first dose diphtheria, pertussis, and tetanus vaccine (DPT1) provided per month, per facility was approximately 0.86 doses higher [90% confidence interval (CI) -1.40, 3.12] in Comprehensive Intervention facilities compared to the combined average change in the Simple Intervention and control facilities. The interventions resulted in a 16.6% [90% CI: -7%, 46%, P-value = 0.26] and 10% [90% CI: -10%, 36%, P-value = 0.43] greater change in average monthly infant DBS testing compared to control for the Simple and Comprehensive facilities respectively. We also found 15.76 (90% CI: 7.12, 24.41, P-value < 0.01) and 10.93 (90% CI: 1.52, 20.33, P-value = 0.06) additional total maternal re-tests over baseline for the Simple and Comprehensive Facilities respectively., Conclusions: This study provides strong evidence to support Zambia's policy of integration of HIV testing and EPI services. Actions in line with the interventions, including HIV testing material supply reinforcement, can increase HIV testing rates without harming immunization uptake. In response, Zambia's Ministry of Health issued a memo to remind health facilities to provide HIV testing at under-five clinics and to include under-five HIV testing as part of district performance assessments., Trial Registration: ClinicalTrials.gov, Registration Number: NCT02479659.

Introduction: Analysis of data from HIV testing and counseling (HTC) services provides an opportunity to identify important populations for targeting of HIV prevention efforts. Our primary aim was to describe the demographics of clients presenting to HTC in Bangladesh, a low HIV prevalence country. Our secondary aim was to determine the risk factors for HIV positivity among returning migrant workers who were tested., Methods: We performed a cross-sectional study of data collected between 2002 and 2010 from the first HTC service established in Bangladesh, located in three large cities., Results: 8973 individuals attended HTC services, with 558 (6.2%) of clients testing positive for HIV, including 33 children. The majority of those who tested positive were aged 25-44 (71%), male (70%), and married (68%). Key populations considered at increased risk of HIV, such as female sex workers, people who inject drugs, and males who have sex with males accounted for only 11% of adults who tested positive. Notably, 75% of adults testing positive had a history of migrant work or was the spouse of a migrant worker. In multivariable logistic regression of those with a migrant work history presenting for HTC, we found rural residence, working in the Middle East, and longer duration of migrant work to be independently associated with testing positive, and female gender and higher level of education to be negatively associated., Conclusions: These data suggest that in Bangladesh, in addition to targeting traditional key populations, HIV prevention efforts should also focus on migrant workers and their spouses.

Background: Routine HIV testing is an essential approach to identifying undiagnosed infections, linking people to care and treatment, and preventing new infections. In Washington, DC, where HIV prevalence is 2.4%, a combination of routine and targeted testing approaches has been implemented since 2006., Methods: We sought to evaluate the cost effectiveness of the District of Columbia (DC) Department of Health's routine and targeted HIV testing implementation strategies. We collected HIV testing data from 3 types of DC Department of Health-funded testing sites (clinics, hospitals, and community-based organizations); collected testing and labor costs; and calculated effectiveness measures including cost per new diagnosis and cost per averted transmission., Results: Compared to routine testing, targeted testing resulted in higher positivity rates (1.33% vs. 0.44%). Routine testing averted 34.30 transmissions per year compared to targeted testing at 17.78. The cost per new diagnosis was lower for targeted testing ($2,467 vs. $7,753 per new diagnosis) as was the cost per transmission averted ($33,160 vs. $104,205). When stratified by testing site, both testing approaches were most cost effective in averting new transmissions when conducted by community based organizations ($25,037 routine; $33,123 targeted) compared to hospitals or clinics., Conclusions: While routine testing identified more newly diagnosed infections and averted more infections than targeted testing, targeted testing is more cost effective per diagnosis and per transmission averted overall. Given the high HIV prevalence in DC, the DC Department of Health's implementation strategy should continue to encourage routine testing implementation with emphasis on a combined testing strategy among community-based organizations.

Background: Mean duration of recent infection (MDRI) and misclassification of long-term HIV-1 infections, as proportion false recent (PFR), are critical parameters for laboratory-based assays for estimating HIV-1 incidence. Recent review of the data by us and others indicated that MDRI of LAg-Avidity EIA estimated previously required recalibration. We present here results of recalibration efforts using >250 seroconversion panels and multiple statistical methods to ensure accuracy and consensus., Methods: A total of 2737 longitudinal specimens collected from 259 seroconverting individuals infected with diverse HIV-1 subtypes were tested with the LAg-Avidity EIA as previously described. Data were analyzed for determination of MDRI at ODn cutoffs of 1.0 to 2.0 using 7 statistical approaches and sub-analyzed by HIV-1 subtypes. In addition, 3740 specimens from individuals with infection >1 year, including 488 from patients with AIDS, were tested for PFR at varying cutoffs., Results: Using different statistical methods, MDRI values ranged from 88-94 days at cutoff ODn = 1.0 to 177-183 days at ODn = 2.0. The MDRI values were similar by different methods suggesting coherence of different approaches. Testing for misclassification among long-term infections indicated that overall PFRs were 0.6% to 2.5% at increasing cutoffs of 1.0 to 2.0, respectively. Balancing the need for a longer MDRI and smaller PFR (<2.0%) suggests that a cutoff ODn = 1.5, corresponding to an MDRI of 130 days should be used for cross-sectional application. The MDRI varied among subtypes from 109 days (subtype A&D) to 152 days (subtype C)., Conclusions: Based on the new data and revised analysis, we recommend an ODn cutoff = 1.5 to classify recent and long-term infections, corresponding to an MDRI of 130 days (118-142). Determination of revised parameters for estimation of HIV-1 incidence should facilitate application of the LAg-Avidity EIA for worldwide use.

Introduction: Prevention of acute HIV infections in pregnancy is required to achieve elimination of pediatric HIV. Identification and support for HIV negative pregnant women and their partners, particularly serodiscordant couples, are critical. A mixed method study done in Southern Mozambique estimated HIV incidence during pregnancy, associated risk factors and factors influencing partner's HIV testing., Methods: Between April 2008 and November 2011, a prospective cohort of 1230 HIV negative pregnant women was followed during pregnancy. A structured questionnaire, HIV testing, and collection of dried blood spots were done at 2-3 scheduled visits. HIV incidence rates were calculated by repeat HIV testing and risk factors assessed by Poisson regression. A qualitative study including 37 individual interviews with men, women, and nurses and 11 focus group discussions (n = 94) with men, women and grandmothers explored motivators and barriers to uptake of male HIV testing., Results: HIV incidence rate was estimated at 4.28/100 women-years (95%CI: 2.33-7.16). Significant risk factors for HIV acquisition were early sexual debut (RR 3.79, 95%CI: 1.04-13.78, p = 0.04) and living in Maputo Province (RR 4.35, 95%CI: 0.97-19.45, p = 0.05). Nineteen percent of women reported that their partner had tested for HIV (93% knew the result with 8/213 indicating an HIV positive partner), 56% said their partner had not tested and 19% did not know their partner test status. Of the 14 seroconversions, only one reported being in a serodiscordant relationship. Fear of discrimination or stigma was reported as a key barrier to male HIV testing, while knowing the importance of getting tested and receiving care was the main motivator., Conclusions: HIV incidence during pregnancy is high in Southern Mozambique, but knowledge of partners' HIV status remains low. Knowledge of both partners' HIV status is critical for maximal effectiveness of prevention and treatment services to reach elimination of pediatric HIV/AIDS.

Background: CD4 T cell enumeration is the most widely used prognostic marker for management of HIV disease. Internal quality control and external quality assessment (EQA) programs are critical to ensure reliability of clinical measurements. The utility of stabilized whole blood products (SWBP) as a test reagent for EQA programs such as Quality Assessment and Standardization for Immunological measures relevant to HIV/AIDS (QASI) program have been demonstrated previously. Since then, several new commercial SWBPs and alternative CD4 enumeration technologies have become available. Seven SWBPs were evaluated on seven different enumeration platforms to determine which product(s) are most suitable for EQA programs that support multiple analytical technologies., Method: Assessment of SWBPs was based on two criteria: (1) accuracy of CD4 T cell measurements and; (2) stability under sub optimal storage conditions., Results: Three SWBPs (Multi-Check, StatusFlow and CD4 Count) showed accurate CD4 T-cell absolute count and percentage values across six of the enumeration platforms. All products retain stability up to 18 days at 21-23°C with the exception of Multi-Check-high on FacsCount and Multi-Check-Low and StatusFlow-Low on Pima. One of the products (CD4 Count) retained stability for three days on all platforms tested when stored at 37°C., Conclusion: This study demonstrated that the characteristics of commercially available SWBPs vary across multiple CD4 platforms. The compatibility of testing panels for EQA programs with multiple analytical platforms needs to be carefully considered, especially in large multiplatform CD4 EQA programs. The selection of a suitable cross-platform SWBP is an increasing challenge as more reagents and platforms are introduced for CD4 T-cell enumeration.

Background: The coverage of HIV testing among Chinese men who have sex with men (MSM) remains low after the scale-up of free HIV testing at government-sponsored testing sites. We evaluated the feasibility of home-based HIV self-testing and the willingness to be HIV tested at community-based organizations (CBO)., Methods: We recruited MSM via on-line advertisement, where they completed an on-line informed consent and subsequent questionnaire survey. Eligible MSM received HIV rapid testing kits by mail, performed the test themselves and reported the result remotely., Results: Of the 220 men taking a home-based HIV self-testing, 33 MSM (15%) were seropositive. Nearly 65% of the men reported that they were willing to take HIV testing at CBO, while 28% preferred receiving free HIV testing in the government programs at local Centers for Disease Control and Prevention (CDC). Older and lower-income MSM, those who self-reported homosexual orientation, men with no history of sexually transmitted diseases and a lower number of sexual partners in the past six months were associated with preference for taking HIV testing at CBOs. The top three self-reported existing barriers for HIV testing were: no perception of HIV risk (56%), fear of an HIV positive result being reported to the government (41%), and fear of a positive HIV test result (36%)., Conclusion: Home-based HIV self-testing is an alternative approach for increasing the coverage of HIV testing among Chinese MSM. CBO-based HIV testing is a potential alternative, but further studies are needed to evaluate its feasibility.

Background: The variety and limitations of current laboratory methods for estimating HIV-incidence has driven attempts to improve and standardize the performance of serological 'Tests for Recent HIV-Infections' (TRI). Primary and follow-up HIV-1 positive plasma samples from individuals with well-defined dates of infection collected as part of the German Seroconverter Cohort provided specimens highly suitable for use in comparing the performance of three TRIs: the AWARE™ BED™ EIA HIV-1 Incidence test (BED-CEIA), Genetic systems HIV-1/HIV-2 Plus O EIA antibody avidity-based assay (BioRad Avidity) and Sedia™ HIV-1 LAg Avidity EIA (LAg Avidity)., Methods: The evaluation panel included 180 specimens: 44 from antiretroviral (ARV)-naïve individuals with recently acquired HIV-infection (≤ 130 days; 25 B and 19 non-B subtypes) and 136 from long-term (>12 months) infected individuals [101 ARV-naïve subtype B, 16 non-B subtypes, 14 ARV-treated individuals, 5 slow progressors (SLP)]., Results: For long-term infected, ARV-naïve individuals the false recent rates (FRR) of both the BioRad and LAg Avidity assays were 2% (2/101 for subtype B) and 6% (1/16 for subtype 'non-B'), while the FRR of the BED-CEIA was 7% (7/101 for subtype B) and 25% (4/16 for subtype 'non-B') (all p>0.05). Misclassification of ARV-treated individuals and SLP was rare by LAg (1/14, 0/5) and BioRad Avidity assays (2/14, 1/5) but more frequent by BED-CEIA (5/14, 3/5). Among recently-infected individuals (subtype B), 60% (15/25) were correctly classified by BED-CEIA, 88% (22/25) by BioRad Avidity and significantly fewer by LAg (48%, 12/25) compared to BioRad Avidity (p = 0.005) with a higher true-recency rate among non-B infections for all assays., Conclusions: This study using well-characterized specimens demonstrated lower FRRs for both avidity methods than with the BED-CEIA. For recently infected individuals the BioRad Avidity assay was shown to give the most accurate results.

Background: Early diagnosis of HIV and treatment initiation at higher CD4 counts improves outcomes and reduces transmission. However, Lesotho is not realizing the full benefits of ART because of the low proportion of men tested (40%). Public sector VMMC services, which were launched in district hospitals in February 2012 by the Lesotho MOH supported by USAID/MCHIP, include HIV testing with referral to care and treatment. The objective of this study was to better understand the contribution of VMMC services to HIV diagnosis and treatment., Methods: VMMC clients diagnosed with HIV were traced after 6 months to ascertain whether they: (1) presented to the referral HIV center, (2) had a CD4 count done and (3) were enrolled on ART. Linkages between VMMC and HIV services were assessed by comparing the proportion of HIV-infected males referred from VMMC services with those from other hospital departments., Results: Between March and September 2012, 72 men presenting for VMMC services tested positive for HIV, representing 65% of the total male tests at the hospital; 45 of these men (62.5%) received an immediate CD4 count and went to the HIV referral site; 40 (89%) were eligible for treatment and initiated ART. 27 clients did not have a CD4 count due to stock-out of reagents. Individuals who did not receive a CD4 count on the same day did not return to the HIV center., Conclusion: All VMMC clients testing positive for HIV and receiving a CD4 count on the testing day began ART. Providing VMMC services in a district hospital offering the continuum of care could increase diagnoses and treatment uptake among men, but requires an investment in communication between VMMC and ART clinics. In high HIV prevalence settings, investing in PIMA CD4 devices at integrated VMMC clinics is likely to increase male ART enrolment.

Background: Determine HIV Combo (DHC) is the first point of care assay designed to increase sensitivity in early infection by detecting both HIV antibody and antigen. We conducted a large multi-centre evaluation of DHC performance in Sydney sexual health clinics., Methods: We compared DHC performance (overall, by test component and in early infection) with conventional laboratory HIV serology (fourth generation screening immunoassay, supplementary HIV antibody, p24 antigen and Western blot tests) when testing gay and bisexual men attending four clinic sites. Early infection was defined as either acute or recent HIV infection acquired within the last six months., Results: Of 3,190 evaluation specimens, 39 were confirmed as HIV-positive (12 with early infection) and 3,133 were HIV-negative by reference testing. DHC sensitivity was 87.2% overall and 94.4% and 0% for the antibody and antigen components, respectively. Sensitivity in early infection was 66.7% (all DHC antibody reactive) and the DHC antigen component detected none of nine HIV p24 antigen positive specimens. Median HIV RNA was higher in false negative than true positive cases (238,025 vs. 37,591 copies/ml; p = 0.022). Specificity overall was 99.4% with the antigen component contributing to 33% of false positives., Conclusions: The DHC antibody component detected two thirds of those with early infection, while the DHC antigen component did not enhance performance during point of care HIV testing in a high risk clinic-based population.

We report on a method to improve in vitro diagnostic assays that detect immune response, with specific application to HIV-1. The inherent polyclonal diversity of the humoral immune response was addressed by using sequential in situ click chemistry to develop a cocktail of peptide-based capture agents, the components of which were raised against different, representative anti-HIV antibodies that bind to a conserved epitope of the HIV-1 envelope protein gp41. The cocktail was used to detect anti-HIV-1 antibodies from a panel of sera collected from HIV-positive patients, with improved signal-to-noise ratio relative to the gold standard commercial recombinant protein antigen. The capture agents were stable when stored as a powder for two months at temperatures close to 60(o)C.

Background: In the absence of stand-alone infrastructures for delivering cervical cancer screening services, efforts are underway in sub-Saharan Africa to dovetail screening with ongoing vertical health initiatives like HIV/AIDS care programs. Yet, evidence demonstrating the utilization of cervical cancer prevention services in such integrated programs by women of the general population is lacking., Methods: We analyzed program operations data from the Cervical Cancer Prevention Program in Zambia (CCPPZ), the largest public sector programs of its kind in sub-Saharan Africa. We evaluated patterns of utilization of screening services by HIV serostatus, examined contemporaneous trends in screening outcomes, and used multivariable modeling to identify factors associated with screening test positivity., Results: Between January 2006 and April 2011, CCPPZ services were utilized by 56,247 women who underwent cervical cancer screening with visual inspection with acetic acid (VIA), aided by digital cervicography. The proportion of women accessing these services who were HIV-seropositive declined from 54% to 23% between 2006-2010, which coincided with increasing proportions of HIV-seronegative women (from 22% to 38%) and women whose HIV serostatus was unknown (from 24% to 39%) (all p-for trend<0.001). The rates of VIA screening positivity declined from 47% to 17% during the same period (p-for trend <0.001), and this decline was consistent across all HIV serostatus categories. After adjusting for demographic and sexual/reproductive factors, HIV-seropositive women were more than twice as likely (Odds ratio 2.62, 95% CI 2.49, 2.76) to screen VIA-positive than HIV-seronegative women., Conclusions: This is the first 'real world' demonstration in a public sector implementation program in a sub-Saharan African setting that with successful program scale-up efforts, nurse-led cervical cancer screening programs targeting women with HIV can expand and serve all women, regardless of HIV serostatus. Screening program performance can improve with adequate emphasis on training, quality control, and telemedicine-support for nurse-providers in clinical decision making.

Background: Routine screening for HIV infection leads to early detection and treatment. We examined patient characteristics associated with repeated screening in a high prevalence country., Methods: We analyzed data from a cohort of 5,229 adults presenting for rapid HIV testing in the outpatient departments of 2 South African hospitals from November 2006 to August 2010. Patients were eligible if they were ≥18 years, reported no previous diagnosis with HIV infection, and not pregnant. Before testing, participants completed a questionnaire including gender, age, HIV testing history, health status, and knowledge about HIV and acquaintances with HIV. Enrollment HIV test results and CD4 counts were abstracted from the medical record. We present prevalence of HIV infection and median CD4 counts by HIV testing history (first-time vs. repeat). We estimated adjusted relative risks (ARR's) for repeat testing by demographics, health status, and knowledge of HIV and others with HIV in a generalized linear model., Results: Of 4,877 participants with HIV test results available, 26% (N = 1258) were repeat testers. Repeat testers were less likely than first-time testers to be HIV-infected (34% vs. 54%, p<0.001). Median CD4 count was higher among repeat than first-time testers (201/uL vs. 147/uL, p<0.001). Among those HIV negative at enrollment (N = 2,499), repeat testing was more common among those with family or friends living with HIV (ARR 1.50, 95% CI: 1.33-1.68), women (ARR: 1.24, 95% CI: 1.11-1.40), and those self-reporting very good health (ARR: 1.28, 95% CI: 1.12-1.45)., Conclusions: In this high prevalence setting, repeat testing was common among those undergoing HIV screening, and was associated with female sex, lower prevalence of HIV infection, and higher CD4 counts at diagnosis.

Background: A major concern with using antiretroviral (ARV)-based products for HIV prevention is the potential spread of drug resistance, particularly from individuals who are HIV-infected but unaware of their status. Limited data exist on the prevalence of HIV infection or drug resistance among potential users of ARV-based prevention products., Methods: A cross-sectional study of reproductive-aged women who presented to screen for an HIV prevention trial was conducted at 7 clinical sites in Durban, South Africa. CD4+T cell counts, HIV-1 RNA levels and population sequencing of the protease and reverse transcriptase genes were performed for all women with 2 positive HIV rapid tests. Resistance mutations were identified using the Stanford Calibrated Population Resistance Tool., Results: Of the 1073 evaluable women, 400(37%) were confirmed as HIV-infected. Of those, plasma HIV-1 RNA was detectable in 365/400(91%) and undetectable(<40 copies/ml) in 35/400(9%) women. 156 women(39%) were eligible for antiretroviral therapy (CD4+T cell counts<350 cells/mm(3)) and 50(13%) met criteria for AIDS(CD4<200 cells/mm(3)). Of 352 plasma samples(>200 copies/ml) analyzed for drug resistance, 26(7.4%) had nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) drug resistance mutations. Among those with resistance, 18/26 participants(62%) had single-class NNRTI resistance and 5/26(19%) had dual-class NRTI/NNRTI. Major mutations in reverse transcriptase included K65R(n = 1), L74I(n = 1), K103N(n = 19), V106M(n = 4), Y181C(n = 2), M184V(n = 4), and K219E/R(n = 2). Major PI-resistance mutations were rare: M46L(n = 1) and I85V(n = 1). All participants were infected with subtype C virus, except one infected with subtype A., Conclusions: In women from Durban, South Africa screening for an HIV prevention trial, the HIV prevalence was high (37%) and HIV drug resistance prevalence was above 5%. This study highlights the potential challenges faced when implementing an ARV-based prevention product that overlaps with first-line antiretroviral therapy. Effective screening to exclude HIV infection among women interested in uptake of ARV-based HIV prevention will be essential in limiting the spread of ARV resistance.

Improved methods for targeting HIV testing among patients most likely to be infected are required; HIDES I aimed to define the methodology of a European wide study of HIV prevalence in individuals presenting with one of eight indicator conditions/diseases (ID); sexually transmitted infection, lymphoma, cervical or anal cancer/dysplasia, herpes zoster, hepatitis B/C, mononucleosis-like illness, unexplained leukocytopenia/thrombocytopenia and seborrheic dermatitis/exanthema, and to identify those with an HIV prevalence of >0.1%, a level determined to be cost effective. A staff questionnaire was performed. From October 2009- February 2011, individuals, not known to be HIV positive, presenting with one of the ID were offered an HIV test; additional information was collected on previous HIV testing behaviour and recent medical history. A total of 3588 individuals from 16 centres were included. Sixty-six tested positive for HIV, giving an HIV prevalence of 1.8% [95% CI: 1.42-2.34]; all eight ID exceeded 0.1% prevalence. Of those testing HIV positive, 83% were male, 58% identified as MSM and 9% were injecting drug users. Twenty percent reported previously having potentially HIV-related symptoms and 52% had previously tested HIV negative (median time since last test: 1.58 years); which together with the median CD4 count at diagnosis (400 cell/uL) adds weight to this strategy being effective in diagnosing HIV at an earlier stage. A positive test was more likely for non-white individuals, MSM, injecting drug users and those testing in non-Northern regions. HIDES I describes an effective strategy to detect undiagnosed HIV infection. All eight ID fulfilled the >0.1% criterion for cost effectiveness. All individuals presenting to any health care setting with one of these ID should be strongly recommended an HIV test. A strategy is being developed in collaboration with ECDC and WHO Europe to guide the implementation of this novel public health initiative across Europe.

Background: HIV infection remains a major US public health concern. While HIV-infected individuals now benefit from earlier diagnosis and improved treatment options, progress is tempered by large numbers of newly diagnosed patients who are lost to follow-up prior to disease confirmation and linkage to care., Methodology: In the randomized, controlled USHER trial, we offered rapid HIV tests to patients presenting to a Boston, MA emergency department. Separate written informed consent was required for confirmatory testing. In a secondary analysis, we compared participants with reactive results who did and did not complete confirmatory testing to identify factors associated with refusal to complete the confirmation protocol., Principal Findings: Thirteen of 62 (21.0%, 95% CI (11.7%, 33.2%)) participants with reactive rapid HIV tests refused confirmation; women, younger participants, African Americans, and those with fewer HIV risks, with lower income, and without primary care doctors were more likely to refuse. We projected that up to four true HIV cases were lost at the confirmation stage., Conclusions: These findings underscore the need to better understand the factors associated with refusal to confirm reactive HIV testing and to identify interventions that will facilitate confirmatory testing and linkage to care among these populations., Trial Registration: ClinicalTrials.gov NCT00502944; NCT01258582.

Objective: To explore the feasibility of using Internet outreach to encourage men who have sex with men (MSM) to get tested for HIV at voluntary counseling and testing (VCT) clinics in Beijing and Urumqi, China., Methods: From June to August 2007, two volunteers contacted MSM using instant messaging, online chat rooms, mobile phone, and e-mail (active recruitment). Banners with study information were put at the front pages of three major Chinese gay websites (passive recruitment). Those contacted were offered a modest financial incentive to seek HIV testing at existing VCT clinics. Those who subsequently sought HIV testing services at VCT clinics and provided informed consent completed a questionnaire and a blood draw to test for HIV and syphilis., Results: A total of 3,332 MSM were contacted and 429 attended VCT clinics. One out of every 4 men that were recruited through instant messaging actually went for HIV testing, while the recruitment yields for online gay chat rooms, mobile phone contact, and email were 1∶6, 1∶10, and 1∶140, respectively. The majority of participants (80%, 317/399) reported being motivated to seek HIV testing out of concern for their health, and only 3% (11/399) reported being motivated by the financial incentive. Active recruitment tend to recruit MSM who are younger (X(2) = 11.400, P = 0.001), never tested for HIV (X(2) = 4.281, P = 0.039), tested less often (X(2) = 5.638, P = 0.018)., Conclusion: Internet outreach is a promising way to encourage MSM to seek HIV testing at existing VCT clinics. Active recruitment can target MSM who are younger, never tested for HIV and tested less often.

Objective: We assessed changes in sexual behavior among men who have sex with men (MSM), before and for several years after HIV diagnosis, accounting for adoption of a variety of seroadaptive practices., Methods: We collected self-reported sexual behavior data every 3 months from HIV-positive MSM at various stages of HIV infection. To establish population level trends in sexual behavior, we used negative binomial regression to model the relationship between time since diagnosis and several sexual behavior variables: numbers of (a) total partners, (b) potentially discordant partners (PDP; i.e., HIV-negative or unknown-status partners), (c) PDPs with whom unprotected anal intercourse (UAI) occurred, and (d) PDPs with whom unprotected insertive anal intercourse (uIAI) occurred., Results: A total of 237 HIV-positive MSM contributed 502 interviews. UAI with PDPs occurred with a mean of 4.2 partners in the 3 months before diagnosis. This declined to 0.9 partners/3 months at 12 months after diagnosis, and subsequently rose to 1.7 partners/3 months at 48 months, before falling again to 1.0 partners/3 months at 60 months. The number of PDPs with whom uIAI occurred dropped from 2.4 in the pre-diagnosis period to 0.3 partners/3 months (an 87.5% reduction) by 12 months after enrollment, and continued to decline over time., Conclusion: Within months after being diagnosed with HIV, MSM adopted seroadaptive practices, especially seropositioning, where the HIV-positive partner was not in the insertive position during UAI, resulting in a sustained decline in the sexual activity associated with the highest risk of HIV transmission.

Background: We evaluated willingness to participate in CVCT and associated factors among MSM in the United States., Methods: 5,980 MSM in the US, recruited through MySpace.com, completed an online survey March-April, 2009. A multivariable logistic regression model was built using being "willing" or "unwilling" to participate in CVCT in the next 12 months as the outcome., Results: Overall, 81.5% of respondents expressed willingness to participate in CVCT in the next year. Factors positively associated with willingness were: being of non-Hispanic Black (adjusted odds ratio [aOR]: 1.5, 95% confidence interval [CI]: 1.2-1.8), Hispanic (aOR: 1.3, CI: 1.1-1.6), or other (aOR: 1.4, CI: 1.1-1.8) race/ethnicity compared to non-Hispanic White; being aged 18-24 (aOR: 2.5, CI: 1.7-3.8), 25-29 (aOR: 2.3, CI: 1.5-3.6), 30-34 (aOR: 1.9, CI: 1.2-3.1), and 35-45 (aOR: 2.3, CI: 1.4-3.7) years, all compared to those over 45 years of age; and having had a main male sex partner in the last 12 months (aOR: 1.9, CI: 1.6-2.2). Factors negatively associated with willingness were: not knowing most recent male sex partner's HIV status (aOR: 0.81, CI: 0.69-0.95) compared to knowing that the partner was HIV-negative; having had 4-7 (aOR: 0.75, CI: 0.61-0.92) or >7 male sex partners in the last 12 months (aOR: 0.62, CI: 0.50-0.78) compared to 1 partner; and never testing for HIV (aOR: 0.38, CI: 0.31-0.46), having been tested over 12 months ago (aOR: 0.63, CI: 0.50-0.79), or not knowing when last HIV tested (aOR: 0.67, CI: 0.51-0.89), all compared to having tested 0-6 months previously., Conclusions: Young MSM, men of color, and those with main sex partners expressed a high level of willingness to participate in couples HIV counseling and testing with a male partner in the next year. Given this willingness, it is likely feasible to scale up and evaluate CVCT interventions for US MSM.

Background: Nontuberculous mycobacterial (NTM) infections cause morbidity worldwide. They are difficult to diagnose in resource-limited regions, and most patients receive empiric treatment for tuberculosis (TB). Our objective here is to evaluate the potential impact of NTM diseases among patients treated presumptively for tuberculosis in Mali., Methods: We re-evaluated sputum specimens among patients newly diagnosed with TB (naïve) and those previously treated for TB disease (chronic cases). Sputum microscopy, culture and Mycobacterium tuberculosis drug susceptibility testing were performed. Identification of strains was performed using molecular probes or sequencing of secA1 and/or 16S rRNA genes., Results: Of 142 patients enrolled, 61 (43%) were clinically classified as chronic cases and 17 (12%) were infected with NTM. Eleven of the 142 (8%) patients had NTM disease alone (8 M. avium, 2 M. simiae and 1 M. palustre). All these 11 were from the chronic TB group, comprising 11/61 (18%) of that group and all were identified as candidates for second line treatment. The remaining 6/17 (35.30%) NTM infected patients had coinfection with M. tuberculosis and all 6 were from the TB treatment naïve group. These 6 were candidates for the standard first line treatment regimen of TB. M. avium was identified in 11 of the 142 (8%) patients, only 3/11 (27.27%) of whom were HIV positive., Conclusions: NTM infections should be considered a cause of morbidity in TB endemic environments especially when managing chronic TB cases to limit morbidity and provide appropriate treatment.

Background: The United States FDA approved an over-the-counter HIV self-test, to facilitate increased HIV testing and earlier linkage to care. We assessed the accuracy of self-testing by untrained participants compared to healthcare worker (HCW) testing, participants' ability to interpret sample results and user-acceptability of self-tests in Singapore., Methodology/principal Findings: A cross-sectional study, involving 200 known HIV-positive patients and 794 unknown HIV status at-risk participants was conducted. Participants (all without prior self-test experience) performed self-testing guided solely by visual instructions, followed by HCW testing, both using the OraQuick ADVANCE Rapid HIV 1/2 Antibody Test, with both results interpreted by the HCW. To assess ability to interpret results, participants were provided 3 sample results (positive, negative, and invalid) to interpret. Of 192 participants who tested positive on HCW testing, self-testing was positive in 186 (96.9%), negative in 5 (2.6%), and invalid in 1 (0.5%). Of 794 participants who tested negative on HCW testing, self-testing was negative in 791 (99.6%), positive in 1 (0.1%), and invalid in 2 (0.3%). Excluding invalid tests, self-testing had sensitivity of 97.4% (95% CI 95.1% to 99.7%) and specificity of 99.9% (95% CI: 99.6% to 100%). When interpreting results, 96%, 93.1% and 95.2% correctly read the positive, negative and invalid respectively. There were no significant demographic predictors for false negative self-testing or wrongly interpreting positive or invalid sample results as negative. Eighty-seven percent would purchase the kit over-the-counter; 89% preferred to take HIV tests in private. 72.5% and 74.9% felt the need for pre- and post-test counseling respectively. Only 28% would pay at least USD15 for the test., Conclusions/significance: Self-testing was associated with high specificity, and a small but significant number of false negatives. Incorrectly identifying model results as invalid was a major reason for incorrect result interpretation. Survey responses were supportive of making self-testing available.

Objectives: To determine 1) HIV testing practices in a 1400-bed university hospital where local HIV prevalence is 0.4% and 2) the effect on testing practices of national HIV testing guidelines, revised in March 2010, recommending Physician-Initiated Counselling and Testing (PICT)., Methods: Using 2 hospital databases, we determined the number of HIV tests performed by selected clinical services, and the number of patients tested as a percentage of the number seen per service ('testing rate'). To explore the effect of the revised national guidelines, we examined testing rates for two years pre- and two years post-PICT guideline publication., Results: Combining the clinical services, 253,178 patients were seen and 9,183 tests were performed (of which 80 tested positive, 0.9%) in the four-year study period. The emergency department (ED) performed the second highest number of tests, but had the lowest testing rates (0.9-1.1%). Of inpatient services, neurology and psychiatry had higher testing rates than internal medicine (19.7% and 9.6% versus 8%, respectively). There was no significant increase in testing rates, either globally or in the majority of the clinical services examined, and no increase in new HIV diagnoses post-PICT recommendations., Conclusions: Using a simple two-database tool, we observe no global improvement in HIV testing rates in our hospital following new national guidelines but do identify services where testing practices merit improvement. This study may show the limit of PICT strategies based on physician risk assessment, compared to the opt-out approach.

Background and Objectives: Access to antiretroviral treatment among adolescents living with HIV (ALH) is increasing. Health-related quality of life (HRQOL) is relevant for monitoring the impact of the disease on both well-being and treatment outcomes. However, adequate screening tools to assess HRQOL in low-resource settings are scarce. This study aims to fill this research gap, by 1) assessing the psychometric properties and reliability of an Eastern African English version of a European HRQOL scale for adolescents (KIDSCREEN) and 2) determining which version of the KIDSCREEN (52-, 27- and 10-item version) is most suitable for low-resource settings., Methods: The KIDSCREEN was translated into Eastern African English, Luganda (Uganda) and Dholuo (Kenya) according to standard procedures. The reconciled version was administered in 2011 to ALH aged 13-17 in Kenya (n = 283) and Uganda (n = 299). All three KIDSCREEN versions were fitted to the data with confirmatory factor analysis (CFA). After comparison, the most suitable version was adapted based on the CFA outcomes utilizing the results of previous formative research. In order to develop a general HRQOL factor, a second-order measurement model was fitted to the data., Results: The CFA results showed that without adjustments, the KIDSCREEN cannot be used for measuring the HRQOL of HIV-positive adolescents. After comparison, the most suitable version for low-resource settings--the 27-item version--was adapted further. The introduction of a negative wording factor was required for the Dholuo model. The Dholuo (CFI: 0.93; RMSEA: 0.039) and the Luganda model (CFI: 0.90; RMSEA: 0.052) showed a good fit. All cronbach's alphas of the factors were 0.70 or above. The alpha value of the Dholuo and Lugandan HRQOL second-order factor was respectively 0.84 and 0.87., Conclusions: The study showed that the adapted KIDSCREEN-27 is an adequate tool for measuring HRQOL in low-resource settings with high HIV prevalence.

Introduction: Since 2008, the Singapore Ministry of Health (MOH) has expanded HIV testing by increasing anonymous HIV test sites, as well as issuing a directive to hospitals to offer routine voluntary opt out inpatient HIV testing. We reviewed this program implemented at the end of 2008 at Tan Tock Seng Hospital (TTSH), the second largest acute care general hospital in Singapore., Methods and Findings: From January 2009 to December 2010, all inpatients aged greater or equal than 21 years were screened for HIV unless they declined or were not eligible for screening. We reviewed the implementation of the Opt Out testing policy. There were a total of 93,211 admissions; 41,543 patients were included based on HIV screening program eligibility criteria. Among those included, 79% (n = 32,675) opted out of HIV screening. The overall acceptance rate was 21%. Majority of eligible patients who were tested (63%) were men. The mean age of tested patients was 52 years. The opt out rate was significantly higher among females (OR: 1.5, 95%CI: 1.4-1.6), aged >60 years (OR: 2.3, 95%CI: 2.2-2.4) and Chinese ethnicity (OR: 1.7, 95%CI:1.6-1.8). The false positive rate of the HIV screening test is 0.56%. The proportion of patients with HIV infection among those who underwent HIV screening is 0.18%. All 16 confirmed HIV patients were linked to care., Conclusion: The default opt-in rate of inpatient HIV testing was low at Tan Tock Seng Hospital, Singapore. Efforts to address individual HIV risk perception and campaigns against HIV stigma are needed to encourage more individuals to be tested for HIV.

Background: Accurate and reliable laboratory methods are needed for estimation of HIV-1 incidence to identify the high-risk populations and target and monitor prevention efforts. We previously described a single-well limiting-antigen avidity enzyme immunoassay (LAg-Avidity EIA) to detect recent HIV-1 infection., Methods: We describe here further optimization and characterization of LAg-Avidity EIA, comparing it to the BED assay and a two-well avidity-index (AI) EIA. Specimen sets included longitudinal sera (n = 393), collected from 89 seroconverting individuals from 4 cohorts representing 4 HIV-1 subtypes, and sera from AIDS patients (n = 488) with or without TB co-infections from 3 different cohorts. Ninety seven HIV-1 positive specimens were purchased commercially. The BED assay, LAg-Avidity EIA, AI-EIA and HIV serology were performed, as needed., Results: Monitoring quality control specimens indicated high reproducibility of the LAg-Avidity EIA with coefficient of variation of <10% in the dynamic range. The LAg-Avidity EIA has an overall mean duration of recency (ω) of 141 days (95% CI 119-160) at normalized optical density (ODn) cutoff of 1.0, with similar ω in different HIV-1 subtypes and populations (132 to 143 days). Antibody avidity kinetics were similar among individuals and subtypes by both the LAg-Avidity EIA and AI-EIA compared to the HIV-IgG levels measured by the BED assay. The false recent rate among individuals with AIDS was 0.2% with the LAg-Avidity EIA, compared to 2.9% with the BED assay. Western blot profiles of specimens with increasing avidity confirm accurate detection of recent HIV-1 infections., Conclusions: These data demonstrate that the LAg-Avidity EIA is a promising assay with consistent ω in different populations and subtypes. The assay should be very useful for 1) estimating HIV-1 incidence in cross-sectional specimens as part of HIV surveillance, 2) identifying risk factors for recent infections, 3) measuring impact of prevention programs, and 4) studying avidity maturation during vaccine trials.

Background: Late diagnosis of HIV infection is a major challenge to the scale-up of HIV prevention and treatment. In 2005 Uganda adopted provider-initiated HIV testing in the health care setting to ensure earlier HIV diagnosis and linkage to care. We provided HIV testing to patients at Mulago hospital in Uganda, and performed CD4 tests to assess disease stage at diagnosis., Methods: Patients who had never tested for HIV or tested negative over one year prior to recruitment were enrolled between May 2008 and March 2010. Participants who tested HIV positive had a blood draw for CD4. Late HIV diagnosis was defined as CD4≤250 cells/mm. Predictors of late HIV diagnosis were analyzed using multi-variable logistic regression., Results: Of 1966 participants, 616 (31.3%) were HIV infected; 47.6% of these (291) had CD4 counts ≤250. Overall, 66.7% (408) of the HIV infected participants had never received care in a medical clinic. Receiving care in a non-medical setting (home, traditional healer and drug stores) had a threefold increase in the odds of late diagnosis (OR = 3.2; 95%CI: 2.1-4.9) compared to receiving no health care., Conclusions: Late HIV diagnosis remains prevalent five years after introducing provider-initiated HIV testing in Uganda. Many individuals diagnosed with advanced HIV did not have prior exposure to medical clinics and could not have benefitted from the expansion of provider initiated HIV testing within health facilities. In addition to provider-initiated testing, approaches that reach individuals using non-hospital based encounters should be expanded to ensure early HIV diagnosis.

Background: Although many men who have sex with men (MSM) in Peru are unaware of their HIV status, they are frequent users of the Internet, and can be approached by that medium for promotion of HIV testing., Methods: We conducted an online randomized controlled trial to compare the effect of HIV-testing motivational videos versus standard public health text, both offered through a gay website. The videos were customized for two audiences based on self-identification: either gay or non-gay men. The outcomes evaluated were 'intention to get tested' and 'HIV testing at the clinic.', Findings: In the non-gay identified group, 97 men were randomly assigned to the video-based intervention and 90 to the text-based intervention. Non-gay identified participants randomized to the video-based intervention were more likely to report their intention of getting tested for HIV within the next 30 days (62.5% vs. 15.4%, Relative Risk (RR): 2.77, 95% Confidence Interval (CI): 1.42-5.39). After a mean of 125.5 days of observation (range 42-209 days), 11 participants randomized to the video and none of the participants randomized to text attended our clinic requesting HIV testing (p = 0.001). In the gay-identified group, 142 men were randomized to the video-based intervention and 130 to the text-based intervention. Gay-identified participants randomized to the video were more likely to report intentions of getting an HIV test within 30 days, although not significantly (50% vs. 21.6%, RR: 1.54, 95% CI: 0.74-3.20). At the end of follow up, 8 participants who watched the video and 10 who read the text visited our clinic for HIV testing (Hazard Ratio: 1.07, 95% CI: 0.40-2.85)., Conclusion: This study provides some evidence of the efficacy of a video-based online intervention in improving HIV testing among non-gay-identified MSM in Peru. This intervention may be adopted by institutions with websites oriented to motivate HIV testing among similar MSM populations., Trial Registration: Clinicaltrials.gov NCT00751192.

Background: The acceptability and feasibility of provider-initiated HIV testing and counseling (PITC) in many settings across Asia with concentrated HIV epidemics is not known. A pilot study of the PITC policy undertaken within the public health care systems in two districts in India offered the opportunity to understand patient's perspectives on the process of referral for HIV testing and linking to HIV treatment and care., Methods: We conducted a cross-sectional study of randomly selected TB patients registered by the TB control program between July and November 2007 in two districts in south India. Trained interviewers met patients shortly after TB diagnosis and administered a structured questionnaire. Patients were assessed regarding their experience with HIV status assessment, referral for counseling and testing, and for HIV-infected patients the counseling itself and subsequent referral for HIV treatment and care., Results: Of the 568 interviewed TB patients, 455 (80%) reported being referred for HIV testing after they presented to the health facility for investigations or treatment for TB. Over half the respondents reported having to travel long distances and incurred financial difficulties in reaching the Integrated Counselling and Testing Centre (ICTC) and two-thirds had to make more than two visits. Only 48% reported having been counseled before the test. Of the 110 HIV-infected patients interviewed, (including 43 with previously-known positive HIV status and 67 detected by PITC), 89 (81%) reported being referred for anti-retroviral treatment (ART); 82 patients reached the ART centre but only 44 had been initiated on ART., Conclusions: This study provides the first evidence from India that routine, provider-initiated voluntary HIV testing of TB patients is acceptable, feasible and can be achieved with very high efficiency under programmatic conditions. While PITC is useful in identifying new HIV-infected patients so that they can be successfully linked to ART, the convenience and proximity of testing centres, quality of HIV counseling, and efficiency of ART services need attention.

Background: Because a recent cluster of false positive results on the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test occurred in San Francisco on test kits close to their expiration date, we decided to assess the relationship between time to expiration and rate of false positive results from tests used with oral fluid., Methodology/principal Findings: We analyzed results of 20,904 tests with either an initial HIV-negative result (n = 20,828) or a preliminary positive result that was then negative on confirmatory tests (n = 76). We computed specificity for kits with time to expiration from < or = 1 to > or = 6 months, with exact binomial confidence intervals, then used logistic regression to estimate the independent association of time to expiration with false positive results, adjusting for site and technician effects. For 1,108 kits used in the last month before expiration, specificity was 98.83% (95% exact binomial confidence interval (CI) 98.00%-99.37%); the upper bound is below the claimed specificity of 99.60%. After adjustment using regression standardization for the effects of site, test lot, and technician factors, adjusted specificity in the last month before expiration was 99.18% (95% bootstrap confidence interval 98.60-99.57%)., Conclusions/significance: We found that specificity of the OraQuick ADVANCE with oral fluid declined significantly with < or = 1 month remaining to expiration, leaving little margin for error from other sources.

Background: Rapid testing of pregnant women aims to increase uptake of HIV testing and results and thus optimize care. We report on the acceptability of HIV counselling and testing, and uptake of results, before and after the introduction of rapid testing in this area., Methods and Principal Findings: HIV counsellors offered counselling and testing to women attending 8 antenatal clinics, prior to enrolment into a study examining infant feeding and postnatal HIV transmission. From August 2001 to April 2003, blood was sent for HIV ELISA testing in line with the Prevention of Mother-to-Child Transmission (PMTCT) programme in the district. From May 2003 to September 2004 women were offered a rapid HIV test as part of the PMTCT programme, but also continued to have ELISA testing for study purposes. Of 12,323 women counselled, 5,879 attended clinic prior to May 2003, and 6,444 after May 2003 when rapid testing was introduced; of whom 4,324 (74.6%) and 4,810 (74.6%) agreed to have an HIV test respectively. Of the 4,810 women who had a rapid HIV test, only 166 (3.4%) requested to receive their results on the same day as testing, the remainder opted to return for results at a later appointment. Women with secondary school education were less likely to agree to testing than those with no education (AOR 0.648, p<0.001), as were women aged 21-35 (AOR 0.762, p<0.001) and >35 years (AOR 0.756, p<0.01) compared to those <20 years., Conclusions: Contrary to other reports, few women who had rapid tests accepted their HIV results the same day. Finding strategies to increase the proportion of pregnant women knowing their HIV results is critical so that appropriate care can be given.

Background: It is commonly assumed that sexual risk factors for heterosexual HIV transmission in sub-Saharan Africa, such as multi-partner sex, paid sex and co-infections, become less important as HIV epidemics mature and prevalence increases., Methods and Findings: We conducted a systematic review of 68 African epidemiological studies from 1986 to 2006 involving 17,000 HIV positive adults and 73,000 controls. We used random-effects methods and stratified results by gender, time, background HIV prevalence rates and other variables. The number of sex partners, history of paid sex, and infection with herpes simplex virus (HSV-2) or other sexually-transmitted infections (STIs) each showed significant associations with HIV infection. Among the general population, the odds ratio (OR) of HIV infection for women reporting 3+ sex partners versus 0-2 was 3.64 (95%CI [2.87-4.62]), with similar risks for men. About 9% of infected women reported ever having been paid for sex, versus 4% of control women (OR = 2.29, [1.45-3.62]). About 31% of infected men reported ever paying for sex versus 18% of uninfected men (OR = 1.75, [1.30-2.36]). HSV-2 infection carried the largest risk of HIV infection: OR = 4.62, [2.85-7.47] in women, and OR = 6.97, [4.68-10.38] in men. These risks changed little over time and stratification by lower and higher HIV background prevalence showed that risk ratios for most variables were larger in high prevalence settings. Among uninfected controls, the male-female differences in the number of sex partners and in paid sex were more extreme in the higher HIV prevalence settings than in the lower prevalence settings., Significance: Multi-partner sex, paid sex, STIs and HSV-2 infection are as important to HIV transmission in advanced as in early HIV epidemics. Even in high prevalence settings, prevention among people with high rates of partner change, such as female sex workers and their male clients, is likely to reduce transmission overall.

Background: In March 2004, the OraQuick rapid HIV antibody test became the first rapid HIV test approved by the US Food and Drug Administration for use on oral fluid specimens. Test results are available in 20 minutes, and the oral fluid test is non-invasive. From August 2004-June 2005, we investigated a sudden increase in false-positive results occurring in a performance study of OraQuick oral-fluid rapid HIV tests in Minnesota., Methodology/principal Findings: In a field investigation, we reviewed performance study data on oral-fluid and whole-blood OraQuick rapid HIV test device lots and expiration dates and assessed test performance and interpretation with oral-fluid and whole-blood specimens by operators who reported false-positive results. We used multivariate logistic regression to evaluate client demographic and risk characteristics associated with false-positive results. Next, we conducted an incidence study of false-positive OraQuick rapid HIV tests in nine US cities and tested both oral-fluid and finger-stick whole-blood specimens from clients; reactive tests were confirmed with Western blot. Sixteen (4.1%) false-positive oral-fluid results occurred in the performance study from April 15, 2004 through August 31, 2004 with unexpired devices from six test lots among 388 HIV-uninfected clients (specificity, 95.9%; 95% CI: 93.4-97.6). Three test operators who had reported false-positive results performed and interpreted the test according to package-insert instructions. In multivariate analysis, only older age was significantly associated with false-positive results (adjusted odds ratio = 4.5, 95% CI: 1.2-25.7). In the incidence study, all valid oral-fluid and whole-blood results from 2,268 clients were concordant and no false-positive results occurred (100% specificity)., Conclusions/significance: The field investigation did not identify a cause for the increase in false-positive oral-fluid results, and the incidence study detected no false-positive results. The findings suggest this was an isolated cluster; the test's overall performance was as specified by the manufacturer.