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The availability of reliable laboratory methods for determining recent HIV infection is vital for accurate estimation of population-based incidence. The mean duration of recent infection (MDRI) and false recent rate (FRR) are critical parameters for HIV incidence assays, as they impact HIV incidence estimates and provide a measure of assay performance. The HIV-1 Multiplex assay is an in-house developed, magnetic bead-based assay that measures virus-specific antibody levels and avidity to multiple analytes. To ensure quality control and to facilitate transfer of the assay to external laboratories or testing facilities, the in-house assay has been adapted and produced in kit form. Here, we describe the performance characteristics of the multiplex kit and demonstrate the stability of the kit components over a one-year period. Two statistical methods were employed to estimate the MDRI of the individual analytes and five different algorithms, combining multiple analyte values. The MDRI estimates for the individual analytes and five algorithms were all between 200 and 300 days post-seroconversion, with no notable difference between the two statistical approaches. All five algorithms exhibited a 0% FRR with specimens from long-term, subtype B HIV-1-infected individuals. The assay parameters described in this study provide the necessary tools to implement the HIV-1 multiplex assay and improves the utility of the assay for field use. [ABSTRACT FROM AUTHOR]

Background. Understanding the period of time between an exposure resulting in infection with human immunodeficiency virus (HIV) and when a test can reliably detect the presence of that infection, that is, the test window period, may benefit testing programs and clinicians in counseling patients about when the clinician and the patient can be confident a suspected exposure did not result in HIV infection. Methods. We evaluated the intervals between reactivity of the Aptima HIV-1 RNA test (Aptima) and 20 US Food and Drug Administration-approved HIV immunoassays using 222 longitudinally collected plasma specimens from HIV-1 seroconverters from the United States. Using interval-censored survival and binomial regression approaches a multi-model framework was implemented to estimate the relative emergence of test reactivity, referred to here as an inter-test reactivity interval (ITRI).We then combined ITRI results with simulated data for the eclipse period, the time between exposure and detection of HIV virus by Aptima, to estimate the window period for each test. Results. The estimated ITRIs were shorter with each new class of HIV tests, ranging from 5.9 to 24.8 days. The 99th percentiles of the window period probability distribution ranged from 44 days for laboratory screening tests that detect both antigen and antibody to 65 days for the Western blot test. Conclusions. Our directly comparable estimates of the emergence of reactivity for 20 immunoassays are valuable to testing providers for interpreting negative HIV test results obtained shortly after exposure, and for counseling individuals on when to retest after an exposure. [ABSTRACT FROM AUTHOR]

HIV incidence estimates are used to monitor HIV-1 infection in the United States. Use of laboratory biomarkers that distinguish recent from longstanding infection to quantify HIV incidence rely on having accurate knowledge of the average time that individuals spend in a transient state of recent infection between seroconversion and reaching a specified biomarker cutoff value. This paper describes five estimation procedures from two general statistical approaches, a survival time approach and an approach that fits binomial models of the probability of being classified as recently infected, as a function of time since seroconversion. We compare these procedures for estimating the mean duration of recent infection (MDRI) for two biomarkers used by the U.S. National HIV Surveillance System for determination of HIV incidence, the Aware BED EIA HIV-1 incidence test (BED) and the avidity-based, modified Bio-Rad HIV-1/HIV-2 plus O ELISA (BRAI) assay. Collectively, 953 specimens from 220 HIV-1 subtype B seroconverters, taken from 5 cohorts, were tested with a biomarker assay. Estimates of MDRI using the non-parametric survival approach were 198.4 days (SD 13.0) for BED and 239.6 days (SD 13.9) for BRAI using cutoff values of 0.8 normalized optical density and 30%, respectively. The probability of remaining in the recent state as a function of time since seroconversion, based upon this revised statistical approach, can be applied in the calculation of annual incidence in the United States. [ABSTRACT FROM AUTHOR]

Objectives: Accurate methods of estimating HIV-1 incidence are critical for monitoring the status of the epidemic and the impact of prevention strategies. Although several laboratory-based tests have been developed strictly for this purpose, several limitations exist and improved methods or technologies are needed. We sought to further optimize a previously described bead-based, HIV-1-specific multiplex assay with the capability of measuring multiple immune responses for determining recent infection. Methods: We refined the customized HIV-1 Bio-Plex assay by determining cutoffs and mean durations of recency (MDR), based on the reactivity to longitudinal seroconversion specimens (n = 1347) from 311 ART-naïve, HIV-1-infected subjects. False-recent rates (FRRs) were calculated for various long-term cohorts, including AIDS patients, individuals on ART, and subtype C specimens. Incidence was estimated for each individual assay analyte from a simulated population with a known incidence of 1%. For improved incidence estimates, multi-analyte algorithms based on combinations of 3 to 6 analytes were evaluated and compared to the performance of each individual analyte. Results: The MDR for the six analytes varied from 164.2 to 279.4 days, while the multi-analyte algorithm MDRs were less variable with a minimum and maximum value of 228.4 and 277.9 days, respectively. The FRRs for the 7 multi-analyte algorithms evaluated in this study varied from 0.3% to 3.1%, in a population of ART-naïve, long-term individuals. All algorithms yielded improved incidence estimates as compared to the individual analytes, predicting an incidence of 0.95% to 1.02%. Conclusions: The HIV-specific multiplex assay described here measures several distinct immune responses in a single assay, allowing for the consideration of multi-analyte algorithms for improved HIV incidence estimates. [ABSTRACT FROM AUTHOR]

The article discusses the study which examines the host's susceptibility to HIV virus exposure in the development of infection using animal models. It analysis the predisposed plasma cytokines/ chemokines and overall immunology of macaque model in repeated low-dose rectal or vaginal virus exposure. It implies that the macaque model has identified key resistance factors associated with human resistance factors, high plasma interleukin-8, and Eotaxin.

The article discusses a study which examines the impact on hemoglobin of starting zidovudine (AZT)-containing and non-AZT-containing combination antiretroviral therapy (cART) in anemic HIV-infected patients. The study found that most anemic patients starting cART have increases in hemoglobin, especially those with more severe anemia or immunosuppression.

Background: Persons who are HIV-infected may be at higher risk for certain types of cancer than the general population. Objective: To compare cancer incidence among HIV-infected persons with incidence in the general population from 1992 to 2003. Design: Prospective observational cohort studies. Setting: United States. Patients: 54 780 HIV-infected persons in the Adult and Adolescent Spectrum of HIV Disease Project (47 832 patients) and the HIV Outpatient Study (6948 patients), who contributed 157 819 person-years of follow-up from 1992 to 2003, and 334 802 121records from the Surveillance, Epidemiology, and End Results program of 13 geographically defined, population-based, central cancer registries. Measurements: Standardized rate ratios (SRRs) to compare cancer incidence in the HIV-infected population with standardized cancer incidence in the general population. Results: The incidence of the following types of non-AIDS-defining cancer was significantly higher in the HIV-infected population than in the general population: anal (SRR, 42.9 [95% CI, 34.1 to 53.3]), vaginal (21.0 [CI, 11.2 to 35.9]), Hodgkin lymphoma (14.7 [CI, 11.6 to 18.2]), liver (7.7 [CI, 5.7 to 10.1]), lung (3.3 [CI, 2.8 to 3.9]), melanoma (2.6 [CI, 1.9 to 3.6]), oropharyngeal (2.6 [CI, 1.9 to 3.4]), leukemia (2.5 [CI, 1.6 to 3.8]), colorectal (2.3 [CI, 1.8 to 2.9]), and renal (1.8 [CI, 1.1 to 2.7]). The incidence of prostate cancer was significantly lower among HIV-infected persons than the general population (SRR, 0.6 [CI, 0.4 to 0.8]). Only the relative incidence of anal cancer increased over time. Limitations: Lower ascertainment of cancer in the HIV cohorts may result in a potential bias to underestimate rate disparities. Tobacco use as a risk factor and the effect of changes in cancer screening practices could not be evaluated. Conclusion: The incidence of many types of non-AIDS-defining cancer was higher among HIV-infected persons than among the general population from 1992 to 2003. [ABSTRACT FROM AUTHOR]

The article presents information on a study that was conducted to examine reasons behind substantial morbidity among HIV-infected persons despite availability of effective prophylaxis, Pneumocystis jiroveci pneumonia (PCP) in the U.S. A total of 483 episodes of PCP were diagnosed during 7315 person-years. Incidence was lowest among persons prescribed both antiretroviral therapy (ART) and PCP prophylaxis, while persons not prescribed prophylaxis had higher PCP incidence.

0BJECTIVE: To describe factors associated with pregnancy and trends in pregnancy rates among women with human immunodeficiency virus (H]V) before and after the release of U.S. Public Health Service Guidelines for the Use of Zidovudine and the Increased Availability of Highly Active Antiretroviral Therapy. METHODS: Human immunodeficiency virus (HIV)-infected women aged 15 to 44 years who were enrolled in the Adult/Adolescent Spectrum Of HIV Disease Project, a medical records cohort study of HIV-infected persons conducted in more than 100 U.S. health care facilities. RESULTS: Among 8,857 women, there were 1,185 incident pregnancies during 21,617 person-years of follow-up from 1992 through 2001. Pregnancy rate at enrollment was 16%; thereafter, an average of 5.5% of women became pregnant annually. Pregnancies were more likely to occur in women aged 15 to 24 years (adjusted rate ratio [RR] 9.2; 95% confidence interval [CI] 7.4, 11.3) and 25 to 34 years (adjusted RR 4.0; 95% CI 3.3, 4.9) than in women aged 35 to 44 years. Pregnancies were less likely to occur in women with a history of acquired immunodeficiency syndrome (AIDS)-opportunistic illness (adjusted RR 0.4; 95% CI 0.3, 0.5) or a CD4 count below 200 cells/μL and no opportunistic illness (adjusted RR 0.6; 95% CI 0.5, 0.7) than in women with HIV but not AIDS. Higher rates of pregnancy were observed for women prescribed highly active antiretroviral therapy (adjusted RR 1.3; 95% CI 1.0, 1.6) than women prescribed other regimens of antiretroviral therapy. There were significantly higher rates of pregnancy during 1997 through 2001. CONCLUSION: The increase in pregnancy rates during the era of widespread use of highly active antiretroviral therapy illustrates the continued need for comprehensive prevention and treatment services. [ABSTRACT FROM AUTHOR]

Assesses the risk of AIDS-related opportunistic illness or death among persons first prescribed highly active antiretroviral therapy in the U.S. Increase of HIV plasma RNA levels; Improvement of the quality of life of HIV-infected persons; Cause of the decrease of CD4[sup +] lymphocyte counts.

We determined incidence and risk factors for acute and chronic hepatitis B virus (HBV) infection and HBV vaccination rates among human immunodeficiency virus (HIV)-infected subjects from the Adult/Adolescent Spectrum of HIV Disease Project, during 1998-2001. Among 16,248 HIV-infected patients receiving care, the incidence of acute HBV was 12.2 cases/1000 person-years (316 cases), was higher among black subjects (rate ratio [RR], 1.4; 95% confidence interval [CI], 1.0-2.0), subjects with alcoholism (RR, 1.7; 95% CI, 1.2-2.3), subjects who had recently injected drugs (RR, 1.6; 95% CI, 1.1-2.4), and subjects with a history of AIDS-defining conditions (RR, 1.5; 95% CI, 1.2-1.9) and was lower in those taking either antiretroviral therapy (ART) with lamivudine (RR, 0.5; 95% CI, 0.4-0.6), ART without lamivudine (RR, 0.5; 95% CI, 0.3-0.7), or ≥ 1 dose of HBV vaccine (14% of subjects) (RR, 0.6; 95% CI, 0.4-0.9). Prevalence of chronic HBV was 7.6% among unvaccinated subjects. HBV rates in this population were much higher than those in the general population, and vaccination levels were low. HBV remains an important cause of comorbidity in HIV-infected persons, but ART and vaccination are associated with decreased disease. [ABSTRACT FROM AUTHOR]

Determines the factors associated with prescription of highly active antiretroviral therapy (HAART) in the U.S. Eligibility of HIV-infected patients for antiretroviral therapy; Assessment of factors associated with HAART prescription; Difference in HAART prescription by gender, race, exposure mode, alcoholism, and provider type for all patients.

Features a study which evaluated the trend and impact of antiretroviral and antiherpesvirus therapies on the incidence of Kaposi's Sarcoma (KS) in a multicenter HIV/AIDS surveillance system between 1990 and 1998. Risk factors associated with KS among HIV-infected persons; Methodology; Results and discussion.

Examines incidence trends in seven HIV-associated cancers and the effects of antiretroviral therapy on the trends. Occurrence of certain cancers in HIV-infected persons; Risk of cervical cancer among women with AIDS; Improvement in the therapy for HIV.

Surveys the incidence of AIDS-defining opportunistic illnesses (OIs) in the United States. Problems and conditions; Incidence of OIs in the country; Percentage of persons with specific OIs during the course of AIDS; Results of the study; Interpretation of the data.

Studies the association of depletion of circulating CD4+ T lymphocytes among HIV-infected persons with increased risk for development of opportunistic and life-threatening diseases and death in the United States. Background on AIDS; Survey of medical records; Diagnostic procedures.

Presents a study of the occurrence, associations and effect on survival of thrombocytopenia in HIV-infected persons. Analysis of data abstracted from medical records of persons enrolled in a project that provides surveillance for opportunistic illnesses, other clinical conditions, drugs prescribed and laboratory data of HIV-infected persons.

Objective. This study was undertaken to assess the completeness of vital statistics and case reports of acquired immunodeficiency syndrome (AIDS) in measuring human immunodeficiency virus (HIV)- related mortality in women 15 through 44 years of age. Methods. We used vital records to determine the number of deaths attributed to HIV infection and excess deaths due to causes that have increased in tandem with the HIV epidemic. Results. In 1988, among women 15 through 44 years of age, there were 1365 deaths with HIV infection listed as the underlying cause, 202 deaths with HIV infection listed as an associated cause, and 149 excess deaths due to conditions highly associated with HIV infection (subtotal = 1716). In addition, there were 780 excess deaths due to causes that may be related to HIV infection or illicit drug use (maximum estimate of HIV-related deaths = 2496). Of the deaths that occurred in 1988, 1532 were reported through AIDS surveillance (1668 deaths when adjusted for reporting delays). Conclusions. Underlying-cause-of-death vital records and AIDS surveillance identified 55% to 80% and 67% to 97%, respectively, of HIV-related deaths in women 15 through 44 years of age in 1988. the wide ranges of these estimates reflect the potential role of both HIV infection and drug use in contributing to excess mortality. [ABSTRACT FROM AUTHOR]

Presents a study which examined the survival of AIDS patients diagnosed with Pneumocystis carinii pneumonia in the United States. Methodology; Results; Discussion.

Supplemental Digital Content is Available in the Text. Background: Laboratory assays for determining recent HIV-1 infection are an important public health tool for aiding in the estimation of HIV incidence. Some incidence assay analytes are remarkably predictive of time since seroconversion and may be useful for additional applications, such as predicting recent transmission events during HIV outbreaks and informing prevention strategies. Methods: Plasma samples (n = 154) from a recent HIV-1 outbreak in a rural community in Indiana were tested with the customized HIV-1 Multiplex assay, based on the Bio-Rad Bio-Plex platform, which measures antibody response to HIV envelope antigens, gp120, gp160, and gp41. Assay cutoffs for each analyte were established to determine whether an individual seroconverted within 30, 60, or 90 days of the sample collection date. In addition, a novel bioinformatics method was implemented to infer infection dates of persons newly diagnosed with HIV during the outbreak. Results: Sensitivity/specificity of the HIV-1 Multiplex assay for predicting seroconversion within 30, 60, and 90 days, based on a training data set, was 90.5%/95.4%, 94.1%/90%, and 89.4%/82.9%, respectively. Of 154 new diagnoses in Indiana between December 2014 and August 2016, the majority (71%) of recent infections (≤3 months since seroconversion) were identified between February and May 2016. The epidemiologic curve derived from the bioinformatics analysis indicated HIV transmission began as early as 2010, grew exponentially in 2014, and leveled off in April 2015. Conclusions: The HIV-1 Multiplex assay has the potential to identify and monitor trends in recent infection during an epidemic to assess the efficacy of programmatic or treatment interventions. [ABSTRACT FROM AUTHOR]

Examines the risk for preventable opportunistic infections (Pneumocystis carinii pneumonia and Mycobacterium avium for persons with AIDS. Analysis on the effect of antiretroviral therapy for AIDS patients; Application of the counting-process formulation of the Cox model; Considerations for the discontinuation of prophylaxis.

Abstract: Background: Quantification of HIV-1 RNA remains difficult to implement in Africa. Simple and inexpensive tests for antiretroviral treatment (ART) monitoring are needed. Objective: To evaluate an HIV-1 p24 ELISA, which combines efficient virus disruption, heat-denaturation and signal amplification, in a West African setting. Study design: Eighty-six HIV-1 infected patients from Abidjan, Côte d’Ivoire, were tested for p24, HIV-1 RNA, and CD4+ count at baseline, and twice within 8 months after ART initiation. Results: All patients responded to ART with a minimal HIV-1 RNA drop of 0.5log10 at first follow-up. Forty-one (47.7%) then rebounded >0.5log10 or persisted above 1000copies/mL by week 24. The predicted baseline concentration of p24 corresponding to 100,000copies/mL of HIV-1 RNA, above which ART is recommended, was 4546fg/mL (95% confidence interval 3148–6566). A prediction model of virologic failure, occurring after an initial response to ART, correctly classified 84% of patients using baseline p24, p24 change on therapy, and achievement of undetectable p24 as explanatory variables. The model and further bootstrap evaluation suggested a good ability to discriminate between sustained or failing virologic response to ART. Conclusion: HIV-1 p24 and RNA based-ART monitoring in a low-resource country dominated by HIV-1 CRF02 AG appeared comparable. [Copyright &y& Elsevier]

In a large, diverse cohort of human immunodeficiency virus (HIV)-infected persons receiving routine care, the proportion of eligible persons who discontinued primary prophylaxis against Mycobacterium avium complex (MAC) infection, according to guidelines of the US Public Health Service and the Infectious Diseases Society of America, increased from 16.7% (in 1996) to 84.9% (in 2002). The discontinuation of primary prophylaxis was not associated with an increased risk of disseminated MAC infection. [ABSTRACT FROM AUTHOR]

Presents information on a study which investigated the risk factors and the impact of vaccination on pneumococcal disease in HIV-infected patients. Methodology; Results of the study; Discussion.

Describes the incidence of and laboratory and clinical characteristics associated with Entamoeba histolytica or Entamoeba dispar infection diagnosed in HIV-infected persons. Effects of sexual preference on the occurrence of E. histolytica or E. dispar infection; Potential risk factors for the occurrence of the infection.

Examines the factors that affect HIV-infected patients' survival after diagnosis of the neurologic condition, progressive multifocal leukoencephalopathy. Median survival time following diagnosis; Risk factors associated with decreased survival time; Antiretroviral medication that increase patients' survival.

Introduction: Hormonal contraception with depot medroxyprogesterone acetate (DMPA) may increase HIV acquisition risk, but observational human studies are inconclusive, and animal models can help investigate this risk. In this study, we test the impact of a low DMPA dose, designed to resemble human contraceptive use, on Simian-Human Immunodeficiency Virus (SHIV) acquisition risk in pigtail macaques (Macaca nemestrina). Methods: Macaques metabolize DMPA faster than humans. We previously identified a per-weight DMPA dose and administration frequency that achieves long-lasting suppression of ovulation in macaques. Eight macaques were given 1.5-mg/kg DMPA monthly, whereas 11 were untreated controls. For comparison, women receive 150 mg (approximately 2 mg/kg) every 3 months. We exposed monkeys to 20 suboptimal SHIV challenges, designed to slowly infect half of controls and allow increased infection in the DMPA group. Results: It took a median 5.5 viral challenges to infect DMPAtreated macaques and 9 challenges for controls (P = 0.27; exact conditional logistic regression). The exact odds ratio was 2.2 (CI: 0.6 to 8.3). Ovulation was suppressed, and the vaginal epithelium was thinned after DMPA treatment in all animals (mean, 30 and 219 mm in DMPA-treated and control macaques, respectively, P = 0.03, t test using the Satterthwaite degrees-of-freedom approximation). Conclusions: SHIV infections in DMPA-treated macaques were 2.2 times those of controls, but this was not statistically significant. The result is remarkably similar to studies of human DMPA use, which have shown HIV risk increases of a similar magnitude and of variable significance. Taken together with previous studies of higher DMPA doses in macaques, the results suggest a dose-dependent effect of DMPA on Simian Immunodeficiency Virus (SIV) or SHIV acquisition. [ABSTRACT FROM AUTHOR]

Background: Topically delivered tenofovir (TFV) from intravaginal rings, tablets, or gels is being evaluated for HIV prevention. We previously demonstrated that TFV delivered vaginally by gel protected macaques from vaginal infection with SHIV. Here we investigated efficacy of the TFV gel against vaginal transmission of a TFV-resistant SHIV containing the K65R mutation (SHIV162P3K65R) and its relationship to drug levels in vaginal tissues. Results: SHIV162P3K65R shows approximately a 5-fold reduction in susceptibility to TFV compared to wild-type SHIV. Efficacy was evaluated in pig-tailed macaques exposed vaginally twice-weekly (up to 10 weeks) to SHIV162P3K65R 30 min after receiving placebo (n = 6) or 1% TFV (n = 6) gel. Four of the six controls were infected after a median of 5 exposures. In contrast, five of six macaques that received TFV gel remained uninfected after 20 vaginal SHIV162P3K65R exposures, resulting in an estimated efficacy of 75%. The mean intracellular TFV-diphosphate (TFV-DP) concentrations in vaginal lymphocytes 4 h after a single gel dose were found to be high (1,631 fmol/106 cells, range 492-3,847) and within the in vitro IC75 range (1,206 fmol/106 cells) for SHIV162P3K65R. Conclusion: Both the modest resistance conferred by K65R and the high TFV-DP exposure in vaginal lymphocytes, likely explain the observed protection. The findings in this model do not predict complete loss of protection by topical TFV against vaginal exposure to HIV-1K65R viruses and provide a tissue drug target for high efficacy. These data will facilitate the development of TFV delivery platforms that have high activity on both wild-type and TFV-resistant viruses. [ABSTRACT FROM AUTHOR]

Background: Topically delivered tenofovir (TFV) from intravaginal rings, tablets, or gels is being evaluated for HIV prevention. We previously demonstrated that TFV delivered vaginally by gel protected macaques from vaginal infection with SHIV. Here we investigated efficacy of the TFV gel against vaginal transmission of a TFV-resistant SHIV containing the K65R mutation (SHIV162P3K65R) and its relationship to drug levels in vaginal tissues. Results: SHIV162P3K65R shows approximately a 5-fold reduction in susceptibility to TFV compared to wild-type SHIV. Efficacy was evaluated in pig-tailed macaques exposed vaginally twice-weekly (up to 10 weeks) to SHIV162P3K65R 30 min after receiving placebo (n = 6) or 1% TFV (n = 6) gel. Four of the six controls were infected after a median of 5 exposures. In contrast, five of six macaques that received TFV gel remained uninfected after 20 vaginal SHIV162P3K65R exposures, resulting in an estimated efficacy of 75%. The mean intracellular TFV-diphosphate (TFV-DP) concentrations in vaginal lymphocytes 4 h after a single gel dose were found to be high (1,631 fmol/106 cells, range 492–3,847) and within the in vitro IC75 range (1,206 fmol/106 cells) for SHIV162P3K65R. Conclusion: Both the modest resistance conferred by K65R and the high TFV-DP exposure in vaginal lymphocytes, likely explain the observed protection. The findings in this model do not predict complete loss of protection by topical TFV against vaginal exposure to HIV-1K65R viruses and provide a tissue drug target for high efficacy. These data will facilitate the development of TFV delivery platforms that have high activity on both wild-type and TFV-resistant viruses. [ABSTRACT FROM AUTHOR]

Daily preexposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) is a novel strategy for preventing human immunodeficiency virus infection. We investigated in macaques whether FTC/TDF prevents transmission of a tenofovir-resistant simian/human immunodeficiency virus (SHIV) containing the K65R mutation. Six macaques received weekly a dose of FTC/TDF 3 days before rectal SHIV exposures and a second dose 2 hours after. Six untreated animals were controls. Animals were exposed rectally to escalating virus doses weekly for up to 28 weeks. PrEP significantly delayed infection with SHIVK65R (P = .028), although 4 of 6 FTC/TDF-treated macaques were infected at the end of the challenges. These findings highlight the need to closely monitor PrEP efficacy in areas with prevalent K65R. [ABSTRACT FROM AUTHOR]

Limited information is available to describe the molecular epidemiology of HIV-1 in Bulgaria. To better understand the genetic diversity and the epidemiologic dynamics of HIV-1 we analyzed 125 new polymerase (pol) sequences from Bulgarians diagnosed through 2009 and 77 pol sequences available from our previous study from persons infected prior to 2007. Epidemiologic and demographic information was obtained from each participant and phylogenetic analysis was used to infer HIV-1 evolutionary histories. 120 (59.5%) persons were infected with one of five different HIV-1 subtypes (A1, B, C, F1 and H) and 63 (31.2%) persons were infected with one of six different circulating recombinant forms (CRFs; 01_AE, 02_AG, 04_cpx, 05_DF, 14_BG, and 36_cpx). We also for the first time identified infection with two different clusters of unique A-like and F-like sub-subtype variants in 12 persons (5.9%) and seven unique recombinant forms (3.5%), including a novel J/C recombinant. While subtype B was the major genotype identified and was more prevalent in MSM and increased between 2000–2005, most non-B subtypes were present in persons ≥45 years old. CRF01_AE was the most common non-B subtype and was higher in women and IDUs relative to other risk groups combined. Our results show that HIV-1 infection in Bulgaria reflects the shifting distribution of genotypes coincident with the changing epidemiology of the HIV-1 epidemic among different risk groups. Our data support increased public health interventions targeting IDUs and MSM. Furthermore, the substantial and increasing HIV-1 genetic heterogeneity, combined with fluctuating infection dynamics, highlights the importance of sustained and expanded surveillance to prevent and control HIV-1 infection in Bulgaria. [ABSTRACT FROM AUTHOR]

Background: Zoonotic transmission of simian retroviruses in Central Africa is ongoing and can result in pandemic human infection. While simian foamy virus (SFV) infection was reported in primate hunters in Cameroon and Gabon, little is known about the distribution of SFV in Africa and whether human-to-human transmission and disease occur. We screened 3,334 plasmas from persons living in rural villages in central Democratic Republic of Congo (DRC) using SFV-specific EIA and Western blot (WB) tests. PCR amplification of SFV polymerase sequences from DNA extracted from buffy coats was used to measure proviral loads. Phylogenetic analysis was used to define the NHP species origin of SFV. Participants completed questionnaires to capture NHP exposure information. Results: Sixteen (0.5%) samples were WB-positive; 12 of 16 were from women (75%, 95% confidence limits 47.6%, 92.7%). Sequence analysis detected SFV in three women originating from Angolan colobus or red-tailed monkeys; both monkeys are hunted frequently in DRC. NHP exposure varied and infected women lived in distant villages suggesting a wide and potentially diverse distribution of SFV infections across DRC. Plasmas from 22 contacts of 8 WB-positive participants were all WB negative suggesting no secondary viral transmission. Proviral loads in the three women ranged from 14 - 1,755 copies/105 cells. Conclusions: Our study documents SFV infection in rural DRC for the first time and identifies infections with novel SFV variants from Colobus and red-tailed monkeys. Unlike previous studies, women were not at lower risk for SFV infection in our population, providing opportunities for spread of SFV both horizontally and vertically. However, limited testing of close contacts of WB-positive persons did not identify human-to-human transmission. Combined with the broad behavioral risk and distribution of NHPs across DRC, our results suggest that SFV infection may have a wider geographic distribution within DRC. These results also reinforce the potential for an increased SFV prevalence throughout the forested regions of Africa where humans and simians co-exist. Our finding of endemic foci of SFV infection in DRC will facilitate longitudinal studies to determine the potential for person-to-person transmissibility and pathogenicity of these zoonotic retroviral infections. [ABSTRACT FROM AUTHOR]

Background: Persons who are HIV-infected may be at higher risk for certain types of cancer than the general population.Objective: To compare cancer incidence among HIV-infected persons with incidence in the general population from 1992 to 2003.Design: Prospective observational cohort studies.Setting: United States.Patients: 54,780 HIV-infected persons in the Adult and Adolescent Spectrum of HIV Disease Project (47,832 patients) and the HIV Outpatient Study (6948 patients), who contributed 157,819 person-years of follow-up from 1992 to 2003, and 334,802,121 records from the Surveillance, Epidemiology, and End Results program of 13 geographically defined, population-based, central cancer registries.Measurements: Standardized rate ratios (SRRs) to compare cancer incidence in the HIV-infected population with standardized cancer incidence in the general population.Results: The incidence of the following types of non-AIDS-defining cancer was significantly higher in the HIV-infected population than in the general population: anal (SRR, 42.9 [95% CI, 34.1 to 53.3]), vaginal (21.0 [CI, 11.2 to 35.9]), Hodgkin lymphoma (14.7 [CI, 11.6 to 18.2]), liver (7.7 [CI, 5.7 to 10.1]), lung (3.3 [CI, 2.8 to 3.9]), melanoma (2.6 [CI, 1.9 to 3.6]), oropharyngeal (2.6 [CI, 1.9 to 3.4]), leukemia (2.5 [CI, 1.6 to 3.8]), colorectal (2.3 [CI, 1.8 to 2.9]), and renal (1.8 [CI, 1.1 to 2.7]). The incidence of prostate cancer was significantly lower among HIV-infected persons than the general population (SRR, 0.6 [CI, 0.4 to 0.8]). Only the relative incidence of anal cancer increased over time.Limitations: Lower ascertainment of cancer in the HIV cohorts may result in a potential bias to underestimate rate disparities. Tobacco use as a risk factor and the effect of changes in cancer screening practices could not be evaluated.Conclusion: The incidence of many types of non-AIDS-defining cancer was higher among HIV-infected persons than among the general population from 1992 to 2003. [ABSTRACT FROM AUTHOR]

Pneumocystis pneumonia (PCP) has historically been one of the leading causes of disease among persons with AIDS. The introduction of highly active antiretroviral therapy in industrialized nations has brought about dramatic declines in the incidence of AIDS-associated complications, including PCP. In the adult population, the incidence of PCP has significantly decreased, but it remains among the most common AIDS-defining infections. Similar declines have been documented in the pediatric population. In much of the developing world, PCP remains a significant health problem, although its incidence among adults in sub-Saharan Africa has been debated. This review discusses the epidemiology of PCP during the current era of the AIDS epidemic. Although fewer cases of PCP occur in industrialized countries, increasing drug-resistant HIV infections, possible drug-resistant PCP, and the tremendous number of AIDS cases in developing countries make this disease of continued public health importance. [ABSTRACT FROM AUTHOR]

Presents a study on the incidence of aspergillosis among HIV-infected people and survival after aspergillosis diagnosis by use of national HIV surveillance database. Information on aspergillosis; Methods; Results and discussion.

Preexposure prophylaxis (PrEP) with antiretroviral drugs is a novel human immunodeficiency virus (HIV) prevention strategy. It is generally thought that high systemic and mucosal drug levels are sufficient for protection. We investigated whether GS7340, a next-generation tenofovir (TFV) prodrug that effectively delivers tenofovir diphosphate (TFV-DP) to lymphoid cells and tissues, could protect macaques against repeated weekly rectal simian-human immunodeficiency virus (SHIV) exposures. Macaques received prophylactic GS7340 treatment 3 days prior to each virus exposure. At 3 days postdosing, TFV-DP concentrations in peripheral blood mononuclear cells (PBMCs) were about 50-fold higher than those seen with TFV disoproxil fumarate (TDF), and they remained above 1,000 fmol/106 cells for as long as 7 days. TFV-DP accumulated in lymphoid and rectal tissues, with concentrations at 3 days exceeding 500 fmol/106 mononuclear cells. Despite high mucosal and systemic TFV levels, GS7340 was not protective. Since TFV-DP blocks reverse transcription by competing with the natural dATP substrate, we measured dATP contents in peripheral lymphocytes, lymphoid tissue, and rectal mononuclear cells. Compared to those in circulating lymphocytes and lymphoid tissue, rectal lymphocytes had 100-fold higher dATP concentrations and dATP/TFV-DP ratios, likely reflecting the activated status of the cells and suggesting that TFV-DP may be less active at the rectal mucosa. Our results identify dATP/TFV-DP ratios as a possible correlate of protection by TFV and suggest that natural substrate concentrations at the mucosa will likely modulate the prophylactic efficacy of nucleotide reverse transcriptase inhibitors. [ABSTRACT FROM AUTHOR]

An abstract of the study "Durable Protection from Vaginal Simian-Human Immunodeficiency Virus Infection in Macaques by Tenofovir Gel and Its Relationship to Drug Levels in Tissue," by Charles Dobard and colleagues is presented.

New-generation gels that deliver potent antiretroviral drugs against human immunodeficiency virus type 1 have renewed hopes for topical prophylaxis as a prevention strategy. Previous preclinical research with monkey models suggested that high concentrations and drug combinations are needed for high efficacy. We evaluated two long-acting reverse transcriptase inhibitors, tenofovir (TFV) and emtricitabine (FTC), by using a twice-weekly repeat challenge macaque model and showed that a preexposure vaginal application of gel with 1% TFV alone or in combination with 5% FTC fully protected macaques from a total of 20 exposures to simian-human immunodeficiency virus SF162p3. FTC and TFV were detected in plasma 30 min after vaginal application, suggesting rapid absorption. FTC was detected more frequently than TFV and showed higher levels, reflecting the fivefold-higher concentration of this drug than of TFV. Two of 12 repeatedly exposed but protected macaques showed limited T-cell priming, which did not induce resistance to infection when macaques were rechallenged. Thus, single drugs with durable antiviral activity can provide highly effective topical prophylaxis and overcome the need for noncoital use or for drug combinations which are more complex and costly to formulate and approve. [ABSTRACT FROM AUTHOR]

Abstract: Background: New injection drug users (IDUs) are at high risk for blood-borne viral infections. Given U.S. policy to only fund proven-effective HIV prevention interventions, insights into conducting intervention trials among young IDUs are provided here by describing methods and participants’ characteristics in the CIDUS III/DUIT study. Methods: In 2002–2004, 15–30-year-old IDUs in Baltimore, Chicago, Los Angeles, New York, and Seattle were recruited through community outreach, advertising and coupon-based participant referrals. Baseline interviews assessed sociodemographics, injection, and sexual behaviors. Antibody tests for HIV and hepatitis A, B, and C viruses (HAV, HBV, and HCV) were conducted. IDUs who were HIV and HCV antibody negative at baseline were eligible to participate in a randomized controlled HIV/HCV prevention trial. Follow-up assessments were conducted 3 and 6 months post-intervention. Data were analyzed to identify participant differences at baseline by city, trial enrollment, and trial retention. Results: Baseline assessments were completed by 3285 IDUs. Participants were mean age 23.8 years, 69% male, 64% White, 17% Hispanic, and 8% Black. Seroprevalence of HIV, HCV, HBV, and HAV antibodies were 2.9, 34.4, 22.4, and 19.3%, respectively. Of the 2062 (62.7%) baseline participants who were HIV and HCV antibody negative, 859 (41.7%) were randomized. At least one follow-up assessment was completed by 712 (83%) randomized participants. Contextual factors, primarily homelessness, were associated with lower enrollment and retention. Conclusions: Recruitment and retention of young-adult IDUs for complex intervention trials is complicated, yet feasible. Risk behaviors among participants enrolling in and completing the trial reflected those eligible to enroll. [Copyright &y& Elsevier]