HIV Epidemiology Research Articles

HIV-2 Antibody Detection after Indeterminate or Negative HIV-1 Western Blot in Cuba, 2005–2008

INTRODUCTION Differentiating between HIV-1 and HIV-2 infection is the first step to understanding HIV transmission, epidemiology and pathogenesis in geographical areas where both viruses circulate. In Cuba, positive results in mixed HIV-1/2 screening assays are confirmed by HIV-1 Western blot. Indeterminate results constitute the main limitation of this test and HIV-2 infection is among their possible causes; hence the importance of second-stage screening and confirmatory tests for HIV-2 infection. OBJECTIVE Investigate the contribution of HIV-2 antibodies to negative or indeterminate HIV-1 Western blot results in serum samples from 2005 through 2008 in Cuba. METHODS HIV-2 reactivity was studied using the ELISA DAVIH-VIH-2 diagnostic kit (Cuba) in 1723 serum samples with negative or indeterminate results for HIV-1 Western blot from January 2005 through December 2008. Duplicate sera reactive by ELISA were confirmed by HIV-2 Western blot, results interpreted according to WHO criteria. The epidemiological interview established by Cuba's National Program for Prevention and Control Sexually-Transmitted Diseases and HIV/AIDS was applied to HIV-2 Western blot-positive patients. RESULTS Among all sera studied, HIV-2 ELISA identified 12 reactive serum samples (0.70%) and 1711 non-reactive (99.30%). Western blot analysis of the 12 ELISA-reactive samples confirmed two positive samples (16.67%), 4 negative (33.33%) and 6 indeterminate (50%). Positive samples reacted against the p16, p26, gp36, p53, p56, p68 and gp105 proteins. All 12 ELISA-reactive samples belonged to the HIV-1 Western blot indeterminate group. The two HIV-2-positive samples showed well defined reactivity to gp160, p53, p55 and p34 of HIV-1. HIV-1 seroconversion was observed in all 10 remaining samples during serological followup. CONCLUSIONS Two new HIV-2 seropositive cases were diagnosed using DAVIH-VIH-2 and HIV-2 Western blot in indeterminate HIV-1 Western blot samples. Results support the recommendation that HIV-2 Western blot be included in the diagnostic algorithm for HIV-1/2 to followup negative or indeterminate HIV-1 Western blot results. KEYWORDS Diagnosis, laboratory techniques and procedures, antibodies, HIV-2, Western blot, enzyme-linked immunosorbent assay, algorithm, Cuba.

HIV-2 antibody detection after indeterminate or negative HIV-1 Western blot in Cuba, 2005-2008

INTRODUCTION Differentiating between HIV-1 and HIV-2 infection is the first step to understanding HIV transmission, epidemiology and pathogenesis in geographical areas where both viruses circulate. In Cuba, positive results in mixed HIV-1/2 screening assays are confirmed by HIV-1 Western blot. Indeterminate results constitute the main limitation of this test and HIV-2 infection is among their possible causes; hence the importance of second-stage screening and confirmatory tests for HIV-2 infection. OBJECTIVE Investigate the contribution of HIV-2 antibodies to negative or indeterminate HIV-1 Western blot results in serum samples from 2005 through 2008 in Cuba. METHODS HIV-2 reactivity was studied using the ELISA DAVIH-VIH-2 diagnostic kit (Cuba) in 1723 serum samples with negative or indeterminate results for HIV-1 Western blot from January 2005 through December 2008. Duplicate sera reactive by ELISA were confirmed by HIV-2 Western blot, results interpreted according to WHO criteria. The epidemiological interview established by Cuba's National Program for Prevention and Control Sexually-Transmitted Diseases and HIV/AIDS was applied to HIV-2 Western blot-positive patients. RESULTS Among all sera studied, HIV-2 ELISA identified 12 reactive serum samples (0.70%) and 1711 non-reactive (99.30%). Western blot analysis of the 12 ELISA-reactive samples confirmed two positive samples (16.67%), 4 negative (33.33%) and 6 indeterminate (50%). Positive samples reacted against the p16, p26, gp36, p53, p56, p68 and gp105 proteins. All 12 ELISA-reactive samples belonged to the HIV-1 Western blot indeterminate group. The two HIV-2-positive samples showed well defined reactivity to gp160, p53, p55 and p34 of HIV-1. HIV-1 seroconversion was observed in all 10 remaining samples during serological followup. CONCLUSIONS Two new HIV-2 seropositive cases were diagnosed using DAVIH-VIH-2 and HIV-2 Western blot in indeterminate HIV-1 Western blot samples. Results support the recommendation that HIV-2 Western blot be included in the diagnostic algorithm for HIV-1/2 to followup negative or indeterminate HIV-1 Western blot results.

Highlights from the 2012 International Symposium on HIV & Emerging Infectious Diseases (ISHEID): from cART management to the search of an HIV cure.

The 2012 International Symposium on HIV and Emerging Infectious Diseases (ISHEID) provided a forum for investigators to hear the latest research developments in the clinical management of HIV and HCV infections as well as HIV-1 reservoirs and cure research. Combined anti-retroviral therapy (c-ART) has had a profound impact on the disease prognosis of individuals living with HIV-1 infection. However, although these anti-retroviral regimens are able to reduce plasma viremia to below the limits of detection for sustained periods of time, there is a rapid recrudescence in plasma viremia if treatment is interrupted. Therefore, despite this potent anti-retroviral suppression, HIV-1 is able to persist within the infected individual. The main 2012 ISHEID theme was, hence “searching for an HIV cure”. In this report we not only give details on this main topic of the 2012 ISHEID but also summarize what has been discussed in the areas of HIV epidemiology, access to care, antiretroviral therapy management and recent progress in the therapy of HCV infection in patients with HIV.

Application of Estimation and Projection Package and Spectrum to the Context of Australia’s HIV Epidemic

Objectives: Understanding and monitoring the HIV epidemic is essential for developing and evaluating public health responses. The Joint United Nations Programme on AIDS (UNAIDS) Estimation and Projection Package (EPP) and Spectrum have become a standard tool to interpret HIV surveillance systems in many settings, particularly in low- and middle-income countries where surveillance data is often based on serial cross-sectional prevalence studies and not on notifications. EPP has not previously been used to evaluate the HIV epidemic in Australia. We derived best HIV estimates using EPP and assumptions that reflect the current understanding of HIV epidemiology in Australia and compared derived estimates with independent estimates and estimates from mathematical models using backprojections method. Methods: The epidemic curves for different population groups (i.e., men who have sex with men, injecting drug users, and low-risk population) generated by EPP were combined with antiretroviral therapy (ART) data into a demographic projection model, Spectrum to determine the consequences of the HIV epidemic in Australia. Results: The overall pattern of the HIV epidemic was consistent with both independent estimates and backprojection modelling estimates. However, the number of HIV-infected females, AIDS-related deaths, and the number in need of ART estimated by EPP were approximately 3.7 times, 20 times, and 6.3 times, respectively higher than independent estimates based on our current surveillance system. EPP estimates of new HIV infections were, however, half the number of independent and back-projection estimates. Conclusions: These findings suggest that customized tools that are tailored to the unique epidemiology and surveillance mechanisms in each setting are required to enable effective programmatic response and policy.

Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa

There is paucity of data on the genetic landscape of HIV-1 viruses circulating in the Limpopo Province of northeastern South Africa. Here, we examine the genetic diversity of viruses from Bela-Bela and Musina, two towns with high HIV prevalence. Between June 2007 and March 2008, blood samples were collected from antiretroviral-drug-naïve individuals. Viruses were analyzed for genetic subtypes and drug resistance mutations. All of the viruses in these samples were shown by phylogenetic analysis based on gag p17, gag p24, reverse transcriptase, protease and envelope C2-C3 gene regions to belong to HIV-1 subtype C. Two of 44 reverse transcriptase sequences (4.5%) contained N rather than the consensus K at position 103. The K103N mutation is normally associated with resistance to NNRTIs. No major mutations were observed in the protease gene. However, several polymorphisms and amino acid changes normally considered to be minor drug resistance mutations were observed in the protease sequences. These results suggest that HIV-1 subtype C remains the predominant variant responsible for the epidemic in northeastern South Africa and that the prevalence of drug-resistant viruses among the naïve population is low.

The future of HIV care in the USA

BackgroundThe number of people living with HIV in the USA increased by 50% to 1.115 million persons from 1996 to 2006 and may exceed 1.5 million by 2015. The rising...

Tuberculosis among Children in Kenya: Epidemiology and Impact of HIV in Two Provinces

We collected clinical register data on children in two provinces of Kenya and conducted bivariate and multivariate analyses to assess characteristics associated with death. Among 987 children with tuberculosis (TB), pulmonary disease was diagnosed in 689 (70%) children. Final outcomes were known for 830 children, 40 (5%) of whom died during TB treatment. HIV test results were available for 670 (68%) children; 371 (55%) of whom tested positive. Only 63 of 134 (47%) of children <1 year were tested for HIV. There were no data on CD4 or anti-retroviral use. The relative risk for death for HIV-infected children compared to HIV-uninfected children was 9.3 for children <1 year [95% confidence interval (CI) 1.2-69.2], 3.9 for children aged 1-4 (95% CI 0.9-17.7) and 0.9 for children aged 5-14 (95% CI 0.3-2.6). In Kenya, HIV infection in children with TB is common, and our data suggest that HIV is particularly deadly in TB patients <1 year, the group with the lowest rate of testing. Poor data recording and reporting limit our understanding of TB in this age group. Expansion of HIV testing may improve survival, and more complete data recording and reporting will enhance our understanding of pediatric TB.

A Paradigm Shift in the Epidemiology of HIV in Pregnancy at ICTC of a Medical College.

To study the present status and effect of paradigm shift in the epidemiology of HIV amongst pregnant women in urban set up. The purpose of the study is to evaluate the paradigm shift in overall screening and management strategy of HIV in antenatal women for last four and half years in an urban medical college. The study was conducted from 1st January 2004 to 30th June 2008 and all registered and unregistered pregnant women who attended ICTC clinic and also for emergency admission (unregistered) were counseled and blood samples were tested as per NACO guidelines with cafeteria choice of opt in and opt out strategy. Reactive women in antenatal period were counseled and discussed about anti-retroviral therapy (ART) and universal treatment regime. Seroprevalent women were counseled about their spouse, personal habits and demographic status. Marked improvement was seen in the use of contraceptive and drug abuse. During labor mother and baby were given nevirapine as per NACO guidelines. The seroprevalence of HIV reactive women in our Centre was 0.23, 0.19, 0.14 and 0.12% in the year 2004, 2005, 2006, 2007 and zero prevalence in 2008 till date. Spouse positivity was noted in 80, 58.33, 72.72 and 70% in the set period from 2004 to 2008. Marked improvement was noticed in all the strategic points from registration, counseling, screening and availability of improved diagnostic kits for screening HIV 1 and HIV 2.

The Association Between Trichomonas Infection and Incarceration in HIV-Seropositive and At-Risk HIV-Seronegative Women

The prevalence of Trichomonas vaginalis is higher among incarcerated women than in the general community. We sought to determine whether a history of incarceration itself was independently associated with trichomoniasis. The HIV Epidemiology Research Study is a prospective cohort study of 871 HIV-seropositive and 439 high-risk seronegative women in 4 urban centers (Bronx, NY; Detroit, MI; Providence, RI; Baltimore, MD). All participants enrolled between April 1993 and January 1995, with interviews and physical examinations conducted at baseline and at follow-up visits every 6 months up to 7 years. Of 1310 subjects, 427 (33%) reported being incarcerated on at least one occasion. In addition, 724 (55%) were found to have a sexually transmitted infection on at least one occasion during the study; baseline rates were 21% for T. vaginalis, 4.3% for Chlamydia trachomatis, 0.6% for N. gonorrhea, and 8% for syphilis. Incarceration was associated with the detection of trichomonas infection (between-subject, odds ratio, 2.4; 95% confidence interval: 1.85-3.14; P < 0.01 and within-subject, odds ratio, 1.56; 95% confidence interval: 1.26-1.92; P < 0.01). The association with incarceration remained significant after adjusting for age, race, HIV status, enrollment risk group, number of sexual partners, marital status, education, bacterial vaginosis, vaginal candidiasis, drug use (crack, cocaine, heroin), alcohol use, health insurance, receipt of public assistance, employment status, visit number, and study site. A history of incarceration was independently associated with the detection of trichomonas infection in a cohort of high-risk women. These data have implications for increased sexually transmitted infection prevention, screening, and treatment upon entry to jail as well as in the communities most affected by incarceration.

HIV and hepatitis C coinfection

aThe Kirby Institute (formerly National Centre in HIV Epidemiology and Clinical Research), University of New South Wales, Darlinghurst, Sydney, New South Wales, Australia bUniversity of Bonn, Bonn, Germany Correspondence to Gail V. Matthews, The Kirby Institute, The CFI Building Corner Boundary and West Streets, Darlinghurst, Sydney, NSW 2010, Australia E-mail: [email protected]

Management of HIV and hepatitis C virus infections in resource-limited settings

To provide an update on the epidemiology and management of HIV and hepatitis C virus (HCV) in resource-limited settings (RLSs). The global prevalence of HIV is 33.3 million people of whom 22.5 million live in sub-Saharan Africa. Hepatitis C affects 170 million people globally with majority of the infected persons living in sub-Saharan Africa and other RLSs. Transmission of these viruses varies greatly even within the RLSs. In the RLSs in Europe, Asia and Central/South America, most transmissions occur through injection drug use, whereas in Africa use of needles for medical treatment and blood transfusion may be the main modes of transmission. However, generally there is a rise in injection drug use even in RLSs. Hepatitis C and HIV are common infections and are more prevalent in RLSs, but there are regional differences in transmission even in RLSs. Treatment is difficult in some of the RLSs and prevention by screening donor blood as well and use of sterile instruments in treatment of patients will be important in curbing transmission in some of these settings.

Diversity and molecular epidemiology of HIV-1 in Cape Town; 1984 to 2010

HIV-1 is a major health problem in South Africa with more than 6 million people infected. One of the features of the virus is the extreme genetic diversity, resulting in an uneven distribution of the different viral subtypes. This diversity may also impact on diagnostic assays, antiretroviral treatment, prevention and vaccine development. We investigated the diversity and molecular epidemiology of HIV-1 in the CapeTown area between 1984 and 2010. Materials and methods Patient samples were collected from the Cape Town area between 1984 and 2010. HIV-1 RNA was extracted, amplified by RT-PCR and sequenced. High resolution phylogenetic analysis was used to investigate the molecular epidemiology and introduction of HIV-1 into

Recent Increase in HIV Rate by Age, Cohort, Period Analysis of Surveillance Data Suggests Changes in HIV Epidemiology in Poland

To interpret the gradual increase in HIV detection rate in Poland during 1993-2007, separating effects due to epidemic maturation from effects possibly due to new outbreaks or implemented measures. Data from routine HIV/AIDS case-based surveillance reported until the end of 2007 (HIV cases) or 2008 (AIDS cases) was used. Cases aged 15 or above at the time of report of HIV infection were included. Age, cohort and period effects were analyzed using Poisson based model with intrinsic estimator, adjusting for sex and late presentation. We showed no calendar period effect from 1996 until 2005-2007, when a 21% significant increase over the average level occurred. Cohorts born in 1965-1980 are the most affected and the risk is above average for ages 18-47. Until recently the increase in HIV detection rate was due to maturation of epidemic, with HIV affected cohorts replacing older unaffected ones (no calendar period effect). The recent increase coincided with increased testing in general population and increased prevalence in diagnostic testing of men who have sex with men, suggesting important changes in HIV epidemic in Poland.

An economic case for providing free access to antiretroviral therapy for HIV-positive people in South Australia

As financial constraints can be a barrier to accessing HIV antiretroviral therapy (ART), we argue for the removal of copayment requirements from HIV medications in South Australia. Using a simple mathematical model informed by available behavioural and biological data and reflecting the HIV epidemiology in South Australia, we calculated the expected number of new HIV transmissions caused by persons who are not currently on ART compared with transmissions for people on ART. The extra financial investment required to cover the copayments to prevent an HIV infection was compared with the treatment costs saved due to averting HIV infections. It was estimated that one HIV infection is prevented per year for every 31.4 persons (median, 24.0-42.7 interquartile range (IQR)) who receive treatment. By considering the incremental change in costs and outcomes of a change in program from the current status quo, it would cost the health sector $17860 per infection averted (median, $13651-24287 IQR) if ART is provided as a three-dose, three-drug combination without requirements for user-pay copayments. The costs of removing copayment fees for ART are less than the costs of treating extra HIV infections that would result under current conditions. Removing the copayment requirement for HIV medication would be cost-effective from a governmental perspective.

Are HIV Epidemics among Men Who Have Sex with Men Emerging in the Middle East and North Africa?: A Systematic Review and Data Synthesis

Men who have sex with men (MSM) bear a disproportionately higher burden of HIV infection than the general population. MSM in the Middle East and North Africa (MENA) are a largely hidden population because of a prevailing stigma towards this type of sexual behavior, thereby limiting the ability to assess infection transmission patterns among them. It is widely perceived that data are virtually nonexistent on MSM and HIV in this region. The objective of this review was to delineate, for the first time, the evidence on the epidemiology of HIV among MSM in MENA. This was a systematic review of all biological, behavioral, and other related data on HIV and MSM in MENA. Sources of data included PubMed (Medline), international organizations' reports and databases, country-level reports and databases including governmental and nongovernmental organization publications, and various other institutional documents. This review showed that onsiderable data are available on MSM and HIV in MENA. While HIV prevalence continues at low levels among different MSM groups, HIV epidemics appear to be emerging in at least few countries, with a prevalence reaching up to 28% among certain MSM groups. By 2008, the contribution of MSM transmission to the total HIV notified cases increased and exceeded 25% in several countries. The high levels of risk behavior (4-14 partners on average in the last six months among different MSM populations) and of biomarkers of risks (such as herpes simplex virus type 2 at 3%-54%), the overall low rate of consistent condom use (generally below 25%), the relative frequency of male sex work (20%-76%), and the substantial overlap with heterosexual risk behavior and injecting drug use suggest potential for further spread. This systematic review and data synthesis indicate that HIV epidemics appear to be emerging among MSM in at least a few MENA countries and could already be in a concentrated state among several MSM groups. There is an urgent need to expand HIV surveillance and access to HIV testing, prevention, and treatment services in a rapidly narrowing window of opportunity to prevent the worst of HIV transmission among MSM in the Middle East and North Africa. Please see later in the article for the Editors' Summary.

HIV‐1 evolution in relation to molecular epidemiology and antiretroviral resistance

HIV/AIDS has become one of the most important infectious diseases with a cumulative number of almost 60 million infections worldwide. The prevalence and epidemiological patterns are unevenly distributed across the globe and also within countries. HIV is one of the fastest evolving organisms known. Several genetically distinct subtypes are present and new circulating recombinant forms are continuously emerging. This review discusses HIV-1 evolution in relation to molecular epidemiology and antiretroviral resistance. Factors and concepts that influence global spread and within-patient evolution of HIV-1 are discussed as well as future perspectives on the use of phylodynamics in HIV epidemiology.

Epidemiologic and clinical characteristics of pregnant women living with HIV/AIDS in a region of Southern Brazil where the subtype C of HIV-1 infection predominates

Southern Brazil has the highest prevalence rate of AIDS in the country and is the only region in the Americas where HIV-1 subtype C prevails. OBJECTIVE: We evaluated the epidemiologic and clinical characteristics of pregnant women living with HIV/AIDS in the South region of Santa Catarina, Brazil. METHODS: All pregnant women with HIV infection attending the obstetric outpatient clinic of Criciúma, State of Santa Catarina, in 2007 (n = 46) were invited to participate. Data of 36 eligible participants were obtained through a standardized questionnaire. RESULTS: The great majority were young, with a steady partner, low family income, low education level and referring early first sexual intercourse. Many reported use of illicit non-injecting drugs (55.5%) and unprotected sex with partners that were HIV-positive (57.7%), injecting drug user (22.2%), male inmate (19.4%), truck driver (13.8%), with history of sexually transmitted disease (11.1%) or men who have sex with men (MSM) (2.8%). Most (66.7%) of the participants had their HIV diagnosis done during the pregnancy, 7 (19.4%) had a previous history of HIV mother-to-child transmission. Therapy based on highly active antiretroviral therapy (94%) was initiated at 19.3 weeks on average and 33% showed irregular antiretroviral adherence. CONCLUSION: These results confirm previous data on HIV epidemiology in Brazil and suggest that the women partners' sexual behavior and unprotected sexual intercourse are important aspects of HIV epidemic. Additional efforts in education, prophylaxis and medication adherence are needed.

Molecular Surveillance of HIV-1 in Madrid, Spain: a Phylogeographic Analysis

The molecular epidemiology of HIV-1 is constantly changing, mainly as a result of human migratory flows and the high adaptive ability of the virus. In recent years, Spain has become one of Europe's main destinations for immigrants and one of the western European countries with the highest rates of HIV-positive patients. Using a phylogeographic approach, we have analyzed the relationship between HIV-1 variants detected in immigrant and native populations of the urban area of Madrid. Our project was based on two coincidental facts. First, resistance tests were extended to naïve and newly diagnosed patients, and second, the Spanish government legislated the provision of legal status to many immigrants. This allowed us to obtain a large data set (n = 2,792) from 11 Madrid hospitals of viral pol sequences from the two populations, and with this unique material, we explored the impact of immigration in the epidemiological trends of HIV-1 variants circulating in the largest Spanish city. The prevalence of infections by non-B HIV-1 variants in the studied cohort was 9%, rising to 25% among native Spanish patients. Multiple transmission events involving different lineages and subsubtypes were observed in all the subtypes and recombinant forms studied. Our results also revealed strong social clustering among the most recent immigrant groups, such as Russians and Romanians, but not in those groups who have lived in Madrid for many years. Additionally, we document for the first time the presence of CRF47_BF and CRF38_BF in Europe, and a new BG recombinant form found in Spaniards and Africans is tentatively proposed. These results suggest that the HIV-1 epidemic will evolve toward a more complex epidemiological landscape.

Epidemiologic and clinical characteristics of pregnant women living with HIV/AIDS in a region of Southern Brazil where the subtype C of HIV-1 infection predominates

Southern Brazil has the highest prevalence rate of AIDS in the country and is the only region in the Americas where HIV-1 subtype C prevails. ObjectiveWe evaluated the epidemiologic and clinical characteristics of pregnant women living with HIV/AIDS in the South region of Santa Catarina, Brazil. MethodsAll pregnant women with HIV infection attending the obstetric outpatient clinic of Criciúma, State of Santa Catarina, in 2007 (n=46) were invited to participate. Data of 36 eligible participants were obtained through a standardized questionnaire. ResultsThe great majority were young, with a steady partner, low family income, low education level and referring early first sexual intercourse. Many reported use of illicit non-injecting drugs (55.5%) and unprotected sex with partners that were HIV-positive (57.7%), injecting drug user (22.2%), male inmate (19.4%), truck driver (13.8%), with history of sexually transmitted disease (11.1%) or men who have sex with men (MSM) (2.8%). Most (66.7%) of the participants had their HIV diagnosis done during the pregnancy, 7 (19.4%) had a previous history of HIV mother-to-child transmission. Therapy based on highly active antiretroviral therapy (94%) was initiated at 19.3 weeks on average and 33% showed irregular antiretroviral adherence. ConclusionThese results confirm previous data on HIV epidemiology in Brazil and suggest that the women partners’ sexual behavior and unprotected sexual intercourse are important aspects of HIV epidemic. Additional efforts in education, prophylaxis and medication adherence are needed.

Validation Data-based Adjustments for Outcome Misclassification in Logistic Regression

Misclassification of binary outcome variables is a known source of potentially serious bias when estimating adjusted odds ratios. Although researchers have described frequentist and Bayesian methods for dealing with the problem, these methods have seldom fully bridged the gap between statistical research and epidemiologic practice. In particular, there have been few real-world applications of readily grasped and computationally accessible methods that make direct use of internal validation data to adjust for differential outcome misclassification in logistic regression. In this paper, we illustrate likelihood-based methods for this purpose that can be implemented using standard statistical software. Using main study and internal validation data from the HIV Epidemiology Research Study, we demonstrate how misclassification rates can depend on the values of subject-specific covariates, and we illustrate the importance of accounting for this dependence. Simulation studies confirm the effectiveness of the maximum likelihood approach. We emphasize clear exposition of the likelihood function itself, to permit the reader to easily assimilate appended computer code that facilitates sensitivity analyses as well as the efficient handling of main/external and main/internal validation-study data. These methods are readily applicable under random cross-sectional sampling, and we discuss the extent to which the main/internal analysis remains appropriate under outcome-dependent (case-control) sampling.