Recent Human Immunodeficiency Virus Research Articles

Testing and Treatment Interventions in Community Settings Key to Controlling a Recent Human Immunodeficiency Virus Outbreak Among People Who Inject Drugs in Glasgow: A Modeling Study.

A human immunodeficiency virus (HIV) outbreak was identified among people who inject drugs (PWID) in Glasgow in 2015, with >150 diagnoses by the end of 2019. The outbreak response involved scaling up HIV testing and improving HIV treatment initiation and retention. We parameterized and calibrated a dynamic, deterministic model of HIV transmission among PWID in Glasgow to epidemiological data. We use this model to evaluate HIV testing and treatment interventions. We present results in terms of relative changes in HIV prevalence, incidence, and cases averted. If the improvements in both testing and treatment had not occurred, we predict that HIV prevalence would have reached 17.8% (95% credible interval [CrI], 14.1%-22.6%) by the beginning of 2020, compared to 5.9% (95% CrI, 4.7%-7.4%) with the improvements. If the improvements had been made on detection of the outbreak in 2015, we predict that peak incidence would have been 26.2% (95% CrI, 8.8%-49.3%) lower and 62.7% (95% CrI, 43.6%-76.6%) of the outbreak cases could have been averted. The outbreak could have been avoided if the improvements had already been in place. Our modeling suggests that the HIV testing and treatment interventions successfully brought the HIV outbreak in Glasgow under control by the beginning of 2020.

Trends and associated factors of HIV, HCV and syphilis infection among different drug users in the China–Vietnam border area: an 11-year cross-sectional study (2010–2020)

BackgroundData on recent human immunodeficiency virus (HIV), hepatitis C virus (HCV) and syphilis prevalence among drug users in the Southwest China are sparse despite the high burden of drug use. This study aims at assessing the prevalence trends and related factors of HIV, HCV and syphilis infection among different drug users in the China–Vietnam border area.MethodsA continuous cross-sectional survey was conducted among drug users from 2010 to 2020 in the China–Vietnam border area. Chi-square trend tests were used to assess the trend of HIV, HCV and syphilis prevalence and the proportion for drug type used by drug users. Multivariate logistic regression was used to identify associated factors of HIV, HCV and syphilis infection in different drug users.ResultsIn this study, a total of 28,951 drug users were included, of which 27,893 (96.45%) male, 15,660 (54.09%) aged 13–34 years, 24,543 (84.77%) heroin-only users, 2062 (7.12%) synthetic drug-only (SD-only) users and 2346 (8.10%) poly-drug users. From 2010 to 2020, the proportion of heroin-only users decreased from 87.79% to 75.46%, whereas SD-only users and poly-drug users increased from 5.16% to 16.03%, and from 7.05% to 8.52%, respectively. The prevalence of HIV, HCV, and syphilis during the study period declined from 12.76%, 60.37% and 5.72% to 4.35%, 53.29% and 4.53%, respectively, among heroin-only users and declined from 18.30%, 66.67% and 15.69% to 6.95%, 27.81% and 5.35%, respectively, among poly-drug users; however, the prevalence of HIV and HCV among SD-only users increased from 0.89% and 8.93% to 2.84% and 18.75%, respectively. Having ever injected drugs and needle sharing were common associated factors for both HIV and HCV infection among poly-drug users and heroin-only users. Aged ≥ 35 years old was an associated factor for HIV, HCV and syphilis infection among the SD-only users. Female drug users were at high risk of contracting syphilis among three different drug users.ConclusionsThe prevalence of HIV, HCV and syphilis among heroin-only users and poly-drug users decreased during the study period. However, the prevalence of HIV and HCV among SD-only users increased. Comprehensive intervention strategies, particularly focusing on the SD-only users are needed in order to bring down the disease burden in this population in the China–Vietnam border areas.

Application of the Multi-Omics Liquid Biopsy Method M2P-HCC in Early Liver Cancer Screening for High-Risk Individuals with Hepatitis B-Related Liver Cancer.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with low rates of early diagnosis and surgical resection. In recent years, with the rapid development of liquid biopsy technology, circulating tumor DNA (ctDNA) has emerged as a research hotspot in the field of precision medicine for liver cancer. Existing studies have demonstrated the suitability of ctDNA for combined detection with other liver cancer diagnostic markers, enabling a multi-index analysis. In recent years, a novel prediction model has been developed for early liver cancer screening based on ctDNA liquid biopsy, M2P-HCC (methylation, mutation, and protein-HCC), mainly incorporating methylation changes, gene mutations, and protein markers associated with liver cancer. Preliminary validation in the HCCscreenTM Investigational (HIT, ChiCTR1800020233) study, which focused on screening early liver cancer in communities with Hepatitis B surface antigen (HBsAg) positivity, yielded promising results with 100% sensitivity and 94% specificity. However, it remains uncertain whether M2P-HCC can be effectively applied in high-risk populations for Hepatitis B-associated liver cancer, warranting further research. Patients who were under long-term follow-up at the outpatient clinic of the Infectious Diseases Center of West China Hospital of Sichuan University from December 2020 to January 2023 were recruited in this prospective observational study and underwent the M2P-HCC test. The study population consisted of high-risk patients with Hepatitis B-related liver cancer who met the inclusion criteria. Patients with a history of previous malignancy, recent blood transfusion, autoimmune diseases, and human immunodeficiency virus (HIV) infection were excluded. Clinical data were collected at a baseline, and all patients underwent the M2P-HCC blood test. Based on the test results, they were categorized into positive, early-warning, and negative groups. Prospective cohort observation and regular follow-ups were performed for 6-8 months. 313 patients met the inclusion criteria and were included in the study. After 6-8 months of follow-up, HCC occurred in 41(13.1%) participants. The M2P-HCC test demonstrated good predictive performance with an area under the curve (AUC) of 0.88 (95% CI: 0.81-0.95, p < 0.001) and a cutoff value of 83 points (sensitivity 82.9% and specificity 85.7%). In contrast, the combination of alpha-fetoprotein (AFP) and ultrasound (US) yielded an inferior predictive performance (AUC 0.76 (95% CI: 0.69-0.84, p < 0.001), sensitivity 58.5%, and specificity 94.1%). Multivariate analyses revealed that M2P-HCC was an independent predictor of increased risk of HCC (OR = 1.16 [1.09-1.22], p < 0.001). M2P-HCC liquid biopsy demonstrated good performance for early liver cancer screening in high-risk populations of Hepatitis B-related liver cancer, exhibiting better sensitivity than the combination of AFP and US.

HIV Incidence, Recent HIV Infection, and Associated Factors, Kenya, 2007-2018.

Nationally representative surveys provide an opportunity to assess trends in recent human immunodeficiency virus (HIV) infection based on assays for recent HIV infection. We assessed HIV incidence in Kenya in 2018 and trends in recent HIV infection among adolescents and adults in Kenya using nationally representative household surveys conducted in 2007, 2012, and 2018. To assess trends, we defined a recent HIV infection testing algorithm (RITA) that classified as recently infected (<12 months) those HIV-positive participants that were recent on the HIV-1 limiting antigen (LAg)-avidity assay without evidence of antiretroviral use. We assessed factors associated with recent and long-term (≥12 months) HIV infection versus no infection using a multinomial logit model while accounting for complex survey design. Of 1,523 HIV-positive participants in 2018, 11 were classified as recent. Annual HIV incidence was 0.14% in 2018 [95% confidence interval (CI) 0.057-0.23], representing 35,900 (95% CI 16,300-55,600) new infections per year in Kenya among persons aged 15-64 years. The percentage of HIV infections that were determined to be recent was similar in 2007 and 2012 but fell significantly from 2012 to 2018 [adjusted odds ratio (aOR) = 0.31, p < .001]. Compared to no HIV infection, being aged 25-34 versus 35-64 years (aOR = 4.2, 95% CI 1.4-13), having more lifetime sex partners (aOR = 5.2, 95% CI 1.6-17 for 2-3 partners and aOR = 8.6, 95% CI 2.8-26 for ≥4 partners vs. 0-1 partners), and never having tested for HIV (aOR = 4.1, 95% CI 1.5-11) were independently associated with recent HIV infection. Although HIV remains a public health priority in Kenya, HIV incidence estimates and trends in recent HIV infection support a significant decrease in new HIV infections from 2012 to 2018, a period of rapid expansion in HIV diagnosis, prevention, and treatment.

Increase in recreational drug use between 2008 and 2018: results from a prospective cohort study among HIV-negative men who have sex with men.

AimsTo test whether recreational drug use (RDU) and sexualized drug use (SDU) changed in the Amsterdam area between 2008 and 2018 and quantify associations of SDU with condomless anal sex (CAS), recent human immunodeficiency virus (HIV) or sexually transmitted infections (STI) among human immunodeficiency virus (HIV)‐negative men who have sex with men (MSM).DesignOpen prospective cohort study.SettingPublic Health Service of Amsterdam, the Netherlands.ParticipantsA total of 976 HIV‐negative MSM, aged ≥ 18 years.MeasurementsSelf‐reported RDU and sexual behaviour in the past 6 months. Laboratory‐confirmed HIV and STI (chlamydia, gonorrhoea and syphilis). We studied: any RDU; any SDU (i.e. any RDU during sex); specific SDU (i.e. use of mephedrone, methamphetamine, gamma‐hydroxybutyric acid/gamma‐butyrolactone, ketamine, amphetamine, cocaine and/or ecstasy during sex); use of individual drugs; and use of individual drugs during sex. We evaluated changes over calendar years in the proportion of individuals with these end‐points [using logistic regression with generalized estimating equations (GEE)] and number of drugs (using negative binomial regression with GEE), adjusted for current age, country of birth and education level.FindingsMedian age of participants in 2008 was 33.2 years (interquartile range = 27.8–40.1); 83.1% were born in the Netherlands. The proportion of any RDU increased from 67.2% in 2008 to 69.5% in 2018 [adjusted odds ratio (aOR) = 1.25; 95% confidence interval (CI) = 1.03–1.51]. Any SDU increased from 53.8% in 2008 to 59.8% in 2013 (aOR = 1.23; 95% CI = 1.07–1.42) and remained stable afterwards. Specific SDU increased from 25.0% in 2008 to 36.1% in 2018 (aOR = 2.10; 95% CI = 1.71–2.58). The average number of drugs used increased for those reporting any RDU, any SDU and specific SDU (all P < 0.05. Among those engaging in sex, any SDU was associated with CAS (aOR = 1.36; 95% CI = 1.19–1.55), HIV (aOR = 5.86; 95% CI = 2.39–14.4) and STI (aOR = 2.31; 95% CI = 1.95–2.73). Specific SDU was associated with CAS (aOR = 1.58; 95% CI = 1.37–1.81), HIV (aOR = 6.30; 95% CI = 3.28–12.1) and STI (aOR = 2.15; 95% CI = 1.81–2.55).ConclusionsAmong human immunodeficiency virus (HIV)‐negative men who have sex with men in Amsterdam, recreational drug use, including sexualized drug use, increased between 2008 and 2018. Sexualized drug use was strongly associated with condomless anal sex, HIV and sexually transmitted infections.

Современные методы выявления случаев недавней инфекции, вызванной вирусом иммунодефицита человека

Современные методы выявления случаев недавней инфекции, вызванной вирусом иммунодефицита человека

Near Real-Time Identification of Recent Human Immunodeficiency Virus Transmissions, Transmitted Drug Resistance Mutations, and Transmission Networks by Multiplexed Primer ID-Next-Generation Sequencing in North Carolina.

The identification of recent human immunodeficiency virus (HIV) 1 infections among people with new HIV diagnoses is important to both tailoring and assessing the impact of HIV-1 prevention strategies. We developed a multiplexed Primer ID-next-generation sequencing approach to identify recent infections by measuring the intrahost viral diversity over multiple regions of the HIV-1 genome, in addition to detecting drug resistance mutations (DRMs) and phylogenetically linked clusters. We summarize the field implementation of this all-in-one platform among persons with newly diagnosed HIV-1 by the North Carolina State Laboratory of Public Health in 2018. Overall, recent infection was identified in 94 (35%) of 268 patients with new HIV diagnoses. People <30 years old, and people who inject drugs were more likely to have diagnoses of recent infection. The reverse-transcriptase region K103N was the most commonly detected DRM (prevalence, approximately 15%). We found a total of 28 clusters, and persons with recent infection were more likely to be cluster members than were those with chronic infections (P = .03). We demonstrate the rapid identification of recent infection and pretreatment DRMs coupled with cluster analysis that will allow prioritization of linkage to care, treatment, and prevention interventions to those at highest risk of onward transmission.

A Recent Human Immunodeficiency Virus Outbreak Among People Who Inject Drugs in Munich, Germany, Is Associated With Consumption of Synthetic Cathinones.

BackgroundNeedle and syringe sharing among people who inject drugs (PWID) can result in a rapid regional spread of a human immunodeficiency virus (HIV) variant. Such outbreaks have been identified recently in several countries and have raised public health attention because of an association with new psychoactive substances (NPS).MethodsDried serum spots from approximately 60% of newly diagnosed HIV cases in Germany in 2013–2018 were received together with statutory notification data. Samples were sequenced in the pol-region, genotyped, and viral phylogenies were analyzed. For selected samples, the hepatitis C virus (HCV) status and the presence of NPS were determined.ResultsAn outbreak of closely related 27 subtype C infections with a core of 11 cases with almost identical sequences was identified using phylogenetic analyses. The first case of the outbreak was diagnosed in 2015, and the last one was in 2018. With exception of 3 infections, all were reported from Munich, the capital of the federal state of Bavaria. Of 26 analyzed outbreak members, 24 (92.3%) had a resolved or viremic HCV coinfection. In 8 of 18 (44%) cases, α-pyrrolidinopentiothiophenone and/or the related substance α-pyrrolidinoheptiophenone was identified.ConclusionsDespite harm reduction services in place, HIV outbreaks of considerable size can occur in PWID. The establishment of a real-time molecular surveillance is advised to rapidly identify outbreaks and target prevention measures.

Peripheral Th17 cells expressing β7 intestinal homing receptor in recent and chronic HIV infections.

The objective of this study was to conduct an analysis of peripheral blood Th17 cells with the ability to home to gut mucosa (CD4+ Th17+ β7+ ) during recent or chronic human immunodeficiency virus (HIV) infections. The relationship between HIV load and systemic inflammation markers was studied. Twenty-five patients with recent (n=10) or chronic (n=15) untreated HIV infections; 30 treated HIV-infected patients with undetectable HIV load at the time of inclusion and 30 healthy controls were included. Bacterial translocation markers (16S rDNA), soluble CD14 (sCD14) and interleukin (IL)-6 monocyte activation parameters, CD4/CD8 ratio and T helper type 17 (Th17) subpopulations [CD4+ Th17+ expressing the IL-23 receptor (IL-23R) or β7] were analysed at baseline and after 6 and 12months of anti-retroviral therapy (ART). 16S rDNA was detected in all patients. Significantly increased serum levels of sCD14 and IL-6 and a decreased CD4/CD8 ratio were observed in patients. Similar percentages of CD4+ IL-23R+ and CD4+ Th17+ β7+ cells were observed in healthy controls and patients at baseline. After 12months of therapy, patients with a recent HIV infection showed significant increases of CD4+ IL-23R+ and CD4+ Th17+ β7+ cell percentages and a decrease in IL-6 levels, although 16S rDNA continued to be detectable in all patients. No significant differences were observed in Th17 subpopulations in patients with chronic HIV infection after therapy. Early initiation of ART helps to increase the number of Th17 cells with the ability to home to the intestinal mucosa and to partially restore gut mucosal homeostasis. These results provide a rationale for initiating ART during the acute phase of HIV infection.

Using Primer-ID Deep Sequencing to Detect Recent Human Immunodeficiency Virus Type 1 Infection.

Intrahost viral sequence diversity can be evaluated over multiple genomic regions using next-generation sequencing (NGS) and scaled to population-level diversity to identify recent human immunodeficiency virus type 1 infection. Using Primer-ID NGS, we sequenced the reverse transcriptase (RT) and env V1-V3 regions from persons with known infection dates, and assessed the mean (π) and first quintile of pairwise diversity distributions over time. The receiver operating characteristic area under the curve (AUC) of RT and V1-V3 combined showed excellent discrimination of recent infection <9 months: using π (only single transmitted variants: AUC, 0.98; threshold <1.03%; sensitivity, 97%; specificity, 89%) and the first quintile (including all variants: AUC, 0.90; threshold <0.60%; sensitivity, 91%; specificity, 92%).

Factors Associated with HIV-Testing among African Americans: Analysis of the 2016 National Health Interview Survey

African-Americans represent 12% of the total United States population, but account for more recent human immunodeficiency virus (HIV) diagnoses (44%), people estimated to be living with HIV disease (40%), and HIV-related deaths (44%) than any other racial/ethnic group in the United States. This paper examines the prevalence of HIV testing and its correlates among African Americans during the pre-exposure HIV prophylaxis era. Secondary analysis of the 2016 National Health Interview Survey (NHIS) data was carried out using descriptive and logistic regression analyses to determine the prevalence of recent HIV testing and factors associated with HIV testing. Of the 33,028 individuals included in the Sample Adult Core, 3,777 (11.43%) were African Americans, the sample for this study. Among them, an estimated 2,050 respondents (54.3%) reported to have ever tested for HIV. Respondents aged 25 to 34 years of age were more likely to have ever tested for HIV compared to individuals aged 25 years or younger (OR: 2.47, P<0.001). Respondents who had a paid employment were more likely to have ever tested for HIV compared to those who were unemployed (OR: 1.74, P<0.05). There was no difference in HIV testing among the marital status categories. Since HIV testing is critical to improve prevention efforts, more research is needed to understand the characteristics of individuals who get tested for HIV to inform the design of innovative interventions to motivate younger adults and individuals from different marital status categories to seek HIV testing.

Nutritional status and quality of life in HIV-infected patients.

Nutritional status and the progression of the human immunodeficiency virus (HIV) are interlinked; though some studies have looked at the impact nutritional status has on quality of life (QoL) in patients with chronic diseases, few have studied this in HIV-infected individuals. To investigate the relationship between nutritional status and QoL in adults with a recent HIV diagnosis. Individuals with an HIV diagnosis performed in the fourteen months prior to a medical visit to one of Lisbon's central hospitals were eligible. Nutritional status was assessed by anthropometry, body composition analysis, and dietary intake. QoL was assessed using the WHOQOLHIV-BREF questionnaire. Sociodemographic and clinical data were also considered. Fifty-one subjects were eligible for enrolment; the majority were male, Caucasian, employed, single, and under highly active antiretroviral therapy (HAART). Lower QoL scores were observed in subjects with inadequate energy intakes, reported weight loss, and a high waist circumference in bivariate analysis (p < 0.05); the same variables influenced QoL negatively after adjusting for confounders in multivariate analysis (p < 0.05). Various sociodemographic characteristics such as level of education, age, gender, and current health problems also predicted QoL significantly (p < 0.05). Various aspects of nutritional status were responsible for the variations observed in QoL, suggesting a potential for nutritional intervention in improving QoL in this population.

Timing of antiretroviral therapy initiation after diagnosis of recent human immunodeficiency virus infection and CD4+ T-cell recovery

We retrospectively examined the timing of antiretroviral therapy (ART) initiation and CD4+ T-cell recovery over 36 months among recent human immunodeficiency virus (HIV) infections using BED (HIV-1 subtypes B, E and D) immunoglobulin G capture enzyme immunoassay (BED-CEIA). Regardless of baseline CD4+ counts, individuals (n = 393) who initiated ART >2 months after diagnosis had significantly decreased probability and rate of achieving CD4+ counts ≥900 cells/μL or ≥600 cells/μL than those individuals (n = 135) who started ART earlier (≤2 months). But the mean CD4+ counts in two groups converged after 30 months of treatment. Early ART initiation leads to accelerated CD4+ recovery, but does not offer a long-term advantage in CD4+ counts.

HIV-1 Transmission During Recent Infection and During Treatment Interruptions as Major Drivers of New Infections in the Swiss HIV Cohort Study.

Reducing the fraction of transmissions during recent human immunodeficiency virus (HIV) infection is essential for the population-level success of "treatment as prevention". A phylogenetic tree was constructed with 19 604 Swiss sequences and 90 994 non-Swiss background sequences. Swiss transmission pairs were identified using 104 combinations of genetic distance (1%-2.5%) and bootstrap (50%-100%) thresholds, to examine the effect of those criteria. Monophyletic pairs were classified as recent or chronic transmission based on the time interval between estimated seroconversion dates. Logistic regression with adjustment for clinical and demographic characteristics was used to identify risk factors associated with transmission during recent or chronic infection. Seroconversion dates were estimated for 4079 patients on the phylogeny, and comprised between 71 (distance, 1%; bootstrap, 100%) to 378 transmission pairs (distance, 2.5%; bootstrap, 50%). We found that 43.7% (range, 41%-56%) of the transmissions occurred during the first year of infection. Stricter phylogenetic definition of transmission pairs was associated with higher recent-phase transmission fraction. Chronic-phase viral load area under the curve (adjusted odds ratio, 3; 95% confidence interval, 1.64-5.48) and time to antiretroviral therapy (ART) start (adjusted odds ratio 1.4/y; 1.11-1.77) were associated with chronic-phase transmission as opposed to recent transmission. Importantly, at least 14% of the chronic-phase transmission events occurred after the transmitter had interrupted ART. We demonstrate a high fraction of transmission during recent HIV infection but also chronic transmissions after interruption of ART in Switzerland. Both represent key issues for treatment as prevention and underline the importance of early diagnosis and of early and continuous treatment.

Relationship between Western blot band profile of human immunodeficiency virus antibody and recent human immunodeficiency virus infection

Objective To investigate the relationship between Western blot (WB)band profile of human immunodeficiency virus (HIV) antibody and recent HIV infection. Methods A total of 294 newly reported HIV-infected patients who were confirmed by WB were included and their serum samples were tested by BED HIV incidence capture enzyme immunoassay (BED-CEIA). The differences of WB band profile were compared between patients of recent infection and established infection, which were compared with 95 acquired immunodeficiency syndrome (AIDS) patients. LSD test and chi square test were used for statistical analysis. Results The mean antibody intensities in patients with recent infection were lower than those of established infection. The mean intensity of p31 in recent infection was the most different compared to established infection and AIDS, which were 1.32, 2.80 and 2.19, respectively (F=127.25, P=0.000). The lack ratios of p66, p55, p51, gp41 and p31 in recent infection were higher than those of established infection and AIDS. The lack of p31 was found in 28 of the recent infections, 0 of established infections and 1 of AIDS, which were statistically different (χ2=54.70, P=0.000). Reactivity with all the bands was the most commonly observed WB pattern, which occurred in 49.1% (191/389) patients. The gp160+ gp120+ p24 WB pattern was the most frequently observed in recent infection (6 cases), and was not observed in established infection. Conclusion The changes of WB band profile of HIV antibody is related to recent HIV infection. Key words: HIV; Blotting, Western; Recent infection

Evaluation of an antibody avidity index method for detecting recent human immunodeficiency virus type 1 infection using an automated chemiluminescence immunoassay

BackgroundRecent infection testing algorithms (RITAs) are used in public health surveillance to estimate the incidence of recently acquired HIV-1 infection. ObjectivesOur aims were (i) to evaluate the precision of the VITROS® Anti-HIV 1+2 automated antibody avidity assay for qualitative detection of antibodies to HIV 1+2 virus; (ii) to validate the accuracy of an automated guanidine-based antibody avidity assay to discriminate between recent and long standing infections using the VITROS 3600 platform; (iii) to compare this method with BED-CEIA assay; and (iv) to evaluate the occurrence of false recent misclassifications by the VITROS antibody avidity assay in patients with a CD4 count <200cells/μL and in patients on combination antiretroviral therapy (cART). ResultsThe VITROS® antibody avidity assay is highly reproducible. The ROC curve analysis of the accuracy of this assay, optimized for sensitivity and specificity, had an AI cut off of ≤0.51, with sensitivity and specificity values of 86.67% (95% CI: 72.51–94.46) and 86.24% (95% CI: 78.00–91.84), respectively. The agreement between VITROS antibody avidity and BED-CEIA assays was good. Misclassifications of long standing infections as recent infection occurred in 8.2% of patients with CD4 <200cell/μL and 8.7% in patients on combination antiretroviral therapy. ConclusionsThe VITROS antibody avidity assay is a reliable serological method to detect recent HIV-1 infections and it could be incorporated into a RITA to estimate HIV incidence.

Nonneutralizing functional antibodies: a new "old" paradigm for HIV vaccines.

Animal and human data from various viral infections and vaccine studies suggest that nonneutralizing antibodies (nNAb) without neutralizing activity in vitro may play an important role in protection against viral infection in vivo. This was illustrated by the recent human immunodeficiency virus (HIV) RV144 vaccine efficacy trial, which demonstrated that HIV-specific IgG-mediated nNAb directed against the V2 loop of HIV type 1 envelope (Env) were inversely correlated with risk for HIV acquisition, while Env-specific plasma IgA-mediated antibodies were directly correlated with risk. However, tier 1 NAb in the subset of responders with a low level of plasma Env-specific IgA correlated with decreased risk. Nonhuman primate simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) challenge studies suggest that Env-mediated antibodies are essential and sufficient for protection. A comparison of immune responses generated in human efficacy trials reveals subtle differences in the fine specificities of the antibody responses, in particular in HIV-specific IgG subclasses. The underlying mechanisms that may have contributed to protection against HIV acquisition in humans, although not fully understood, are possibly mediated by antibody-dependent cell-mediated cytotoxicity (ADCC) and/or other nonneutralizing humoral effector functions, such as antibody-mediated phagocytosis. The presence of such functional nNAb in mucosal tissues and cervico-vaginal and rectal secretions challenges the paradigm that NAb are the predominant immune response conferring protection, although this does not negate the desirability of evoking neutralizing antibodies through vaccination. Instead, NAb and nNAb should be looked upon as complementary or synergistic humoral effector functions. Several HIV vaccine clinical trials to study these antibody responses in various prime-boost modalities in the systemic and mucosal compartments are ongoing. The induction of high-frequency HIV-specific functional nNAb at high titers may represent an attractive hypothesis-testing strategy in future HIV vaccine efficacy trials.

Mixture models for calibrating the BED for HIV incidence testing.

A number of antibody biomarkers have been developed to distinguish between recent and established Human Immunodeficiency Virus (HIV) infection and used for HIV incidence estimation from cross-sectional specimens. In general, a cut-off value is specified, and estimates of the following parameters are needed: (i) the mean time interval .w/ between seroconversion and reaching that cut-off; (ii) the probability of correctly identifying individuals who became infected in the last w years (sensitivity); and (iii) the probability of correctly identifying individuals who have been infected for more than w years (specificity). We develop two statistical methods to study the distribution of a biomarker and derive a formula for estimating HIV incidence from a cross-sectional survey. Both methods allow handling interval censored data and basically consist of using a generalized mixture model to model the growth of the biomarker as a function of time since infection. The first uses data from all followed-up individuals and allows incidence estimation in the cohort, whereas the second only uses data from seroconverters. We illustrate our methods using repeated measures of the IgG capture BED enzyme immunoassay. Estimates of calibration parameters, that is, mean window period, mean recency period, sensitivity, and specificities obtained from both models are comparable. The formula derived for incidence estimation gives the maximum likelihood estimate of incidence which, for a given window period, depends only on sensitivity and specificity. The optimal choice of the window period is discussed. Numerical simulations suggest that data from seroconverters can provide reasonable estimates of the calibration parameters.

Incidence of Recent Human Immunodeficiency Virus Infection at Two Voluntary Counseling Testing Centers in Pernambuco, Brazil, from 2006 to 2009

This study shows HIV-1 incidence in the northeastern region of Brazil, where the HIV epidemic has spread recently. Incidence was higher among men (1.34%; 95% confidence interval [CI], 1.00% to 1.69%) than among women (0.55%; 95% CI, 0.43% to 0.68%) (P < 0.0001), and there was an association between younger age and recent HIV infection (P < 0.004).

Prevalence of Human Immunodeficiency Virus (HIV), Risk Behavior, and Recent Substance Use in a Sample of Urban Drug Users: Findings by Race and Sex

The aim of the current study was to examine the prevalence of HIV, past six-month illicit drug use, and risk behaviors among a population of heavy drug users living in an urban setting. Although many studies investigate substance use, sex-risk behavior, and HIV by race and gender, no studies have examined these variables simultaneously. The current study seeks to fill this gap in the literature by exploring HIV prevalence among a predominantly heterosexual sample of recent substance users by injection drug use (IDU) status, race, and sex. Baseline data from the Baltimore site of the NEURO-HIV epidemiologic study was used in this study. This study examines neuropsychological and social-behavioral risk factors of HIV, hepatitis A, hepatitis B, and hepatitis C among both injection and non-injection drug users. Descriptive statistics and chi-square statistics were used in data analyses. Blood and urine samples were obtained to test for the presence of recent drug use, viral hepatitis, HIV, and other sexually transmitted diseases (STDs). Findings presented here have several important implications for HIV prevention and care among substance users. Intervention programs that incorporate substance use treatment in addition to HIV education, particularly with respect to substance use and sex risk behavior are imperative.