HIV Seronegative Research Articles

Genetic Polymorphisms in the Open Reading Frame of the CCR5 gene From HIV-1 Seronegative and Seropositive Individuals From National Capital Regions of India

C-C chemokine receptor type 5 (CCR5) serves as a co-receptor for Human immunodeficiency virus (HIV), enabling the virus to enter human CD4 T cells and macrophages. In the absence of CCR5, HIV strains that require CCR5 (R5 or M-tropic HIV) fail to successfully initiate infection. Various natural mutations of the CCR5 gene have been reported to interfere with the HIV-CCR5 interaction, which influences the rate of AIDS progression. Genetic characterization of the CCR5 gene in individuals from the National Capital Regions (NCRs) of India revealed several natural point mutations in HIV seropositive/negative individuals. Furthermore, we identified novel frame-shifts mutations in the CCR5 gene in HIV seronegative individuals, as well as the well reported CCR5Δ32 mutation. Additionally, we observed a number of mutations present only in HIV seropositive individuals. This is the first report to describe the genetic variations of CCR5 in individuals from the NCRs of India and demonstrates the utility of investigating understudied populations to identify novel CCR5 polymorphisms.

Where have I heard that before? A validity study of source memory indices from the California Verbal Learning Test – Second edition

Objective: We investigated the construct and criterion validity of the source memory (SM) indices within the California Verbal Learning Test-II (CVLT-II).Method: Participants included 77 individuals with HIV-associated neurocognitive disorders (HAND+), 287 HIV + neurocognitively normal individuals (HAND−) and 203 seronegative HIV comparisons (HIV−). CVLT-II SM impairment status (normative scores ≤1 standard deviation) was determined using Total Across-List Intrusions and Source Recognition Discriminability (d′). Participants also completed a comprehensive neuropsychological battery, assessments of everyday functioning and experimental measures of SM.Results: CVLT-II SM impairment was significantly associated with increased errors on experimental SM measures and lower scores on measures of passage recall and executive functions, but not visuospatial skills. In a logistic regression controlling for clinicodemographic factors, CVLT-II SM impairment was a significant independent predictor of HAND, with the HAND + group showing higher rates of SM impairment than both the HAND − and HIV − groups. Finally, CVLT-II SM impairment was significantly related to a composite measure of everyday functioning, but this effect disappeared after adjusting for covariates. Note that, the overall pattern of findings across this study also held when CVLT-3 normative standards were applied to the SM indices.Conclusions: Results provide initial support for the construct and criterion validity of a CVLT-II SM index in the setting of HIV disease. Future studies should examine the validity of CVLT-II SM variables in other neuropsychological populations.

Inflammatory and Nutritional Biomarkers in the Plasma of Women in Zambia Reflect Low DHA and HIV Status

Docosahexanenoic Acid (DHA) is a fatty acid that is abundant in the brain, retina, and cerebral cortex. It is critical in fetal brain development and is implicated in resolution of inflammation. In recent years, there has been a growing concern that low dietary levels of DHA in pregnancy may lead to poor birth outcomes and delayed or reduced cognitive function in children after birth. Uncontrolled HIV infection may lead to cognitive impairments as well as reduced immune function. Therefore, for pregnant women living with food insecurity and HIV infection, these problems may be compounded and health risks to their infants high. To evaluate these concerns, a pre‐clinical trial was conducted in pregnant women in Zambia, a country where malnutrition and HIV are endemic. The study participants included 91 women in the second trimester of pregnancy, 46 of which were HIV seropositive and 45 HIV seronegative. Among the HIV positive participants 11 had high viral load. The overarching study goal was to determine if plasma DHA levels were low relative to global averages and if they correlated with inflammation and HIV status. Hematological assessment included measurement of biomarkers for nutritional status, HIV status and viral load, as well as inflammation. Plasma lipids were assessed using the Folch extraction method, fatty acid methyl esters were prepared and analyzed by gas chromatography/mass spectrometry. Protein biomarkers data were measured using commercial ELISA kits. Overall, DHA levels were low at 2.16±0.75 mass percent of total fatty acids but did not vary significantly with HIV status. Averages of the nutritional biomarkers insulin and leptin were low and high, respectively, compared to global averages when comparing all participants. Insulin was not significantly different based on HIV status. Leptin was reduced in HIV seropositive participants compared to those who were seronegative and this correlated, as expected, with pre‐pregnancy BMI. For the inflammatory markers CRP and LCN2, only LCN2 was significantly different dependent on HIV status, and levels were on average lower in seropositive individuals. Within the HIV positive participants, the 11 with high vial load did not have levels of insulin, leptin, CRP or LCN2 that were significantly different from those with low viral load. These data demonstrate that select protein biomarkers for inflammation and nutrition are variably affected by HIV and nutritional status. Currently, these studies are being expanded to understand the role of dietary fatty acids in contributing to health outcomes in pregnancy and dependent upon HIV status.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

128. Sexually Transmitted Infections Among Adolescent Girls in Thika, Kenya

BackgroundGlobally, the rates of sexually transmitted infections (STIs) are highest among 15- to 24-year-old girls, especially in Sub-Saharan African countries where the adolescent sexual health is poor. Recruiting girls presexual debut could identify risk factors for STI acquisition.MethodsWe recruited a prospective cohort of “low-risk” adolescent girls aged 16–20 in Kenya. To be eligible, girls were HIV and HSV-2 seronegative and reported no history of sexual intercourse or reported having sex with only one partner. Demographic data were collected, and girls had nucleic acid testing of vaginal swabs for Neisseria gonorrhea, Chlamydia trachomatis, and Trichomonas vaginalis, and vaginal gram stains for bacterial vaginosis (BV).ResultsWe enrolled 400 girls, with a median age of 18.6 years. In this cohort, 322 (80.5%) girls reported never having had sex, while 78 (19.5%) reported prior sex with 1 partner. Of those reporting prior sex, only 20 (25.6%) reported contraception use in the last 3 months, with 60% using only emergency contraceptive pills. The median age of sexual partners was 22 (IQR 19–25). Of the 373 participants with an STI swab result, 49 participants (13.1%) tested positive for STIs at entry into the study, with 41 chlamydia, 5 gonorrhea, and 3 trichomonas cases. Of these 49 participants, 33 (67.3%) had denied prior sexual intercourse. Testing positive for STIs was, however, significantly different among those reporting prior sexual intercourse vs. reporting never having had sex, 21.1% vs. 11.1% (P = 0.02). BV was rare (5.6%) in the cohort, with 90% of participants with a normal Nugent score of 0–3.ConclusionIn the initial testing of a sexually inexperienced cohort of girls, we found unexpectedly high numbers of prevalent STIs, especially chlamydia which is not routinely screened for in Kenyan settings. Additionally, lack of sexual activity appeared overreported. BV was rare, with much lower prevalence than in adult women in Africa. Our data suggest that prior to initiation of sexual activity, most girls in this Kenyan cohort have vaginal microflora that is dominated by Lactobacillus. Interventions to address STIs, including pre-exposure prophylaxis for HIV, should be targeted at girls at a young age, presexual debut, and in nonmedical settings where girls can be reached who do not selfidentify as at risk for STI.Disclosures All authors: No reported disclosures.

Pulmonary Tuberculosis and Associated Factors Among Diabetic Patients Attending Hawassa Adare Hospital, Southern Ethiopia.

Background:Developing countries have a high burden of Tuberculosis (TB); although it is considered as a disease of the past in most developed countries. The end TB strategy was predicted to stabilize or drop the incidence of TB. However, the rising of the prevalence of immune-related diseases like Diabetes Mellitus (DM) are challenging the TB control strategy in high TB burden region. The objective of this study was to determine the prevalence and associated factors of pulmonary tuberculosis in DM patients attending Adare Hospital, south Ethiopia.Methods:A cross-sectional study was carried out on 207 randomly selected diabetic patients at the Adare hospital. A structured pre-tested questionnaire was used during the data collection from participants. Sputum concentration technique followed by Ziehl-Neelsen staining method was used to examine pulmonary tuberculosis. Logistic regression analysis was used to assess the association between various variables and pulmonary tuberculosis. Odds ratios and 95% CI were computed to determine the strength and presence of the association.Results:The prevalence of pulmonary tuberculosis among diabetics was 5.3% [95% CI: (2.2, 8.4)]. Diabetic patients who were underweight [AOR = 9.94, 95% CI: (1.51-80.89)], had more than 10 years duration with DM [AOR = 7.03 95% CI: (1.357, 73.6)], Alcohol drinking habit [AOR = 12.49, 95% CI: (3.28, 77.94)], and history of contact with TB [AOR = 5.35, 95% CI: (1.1-39.12)] were the factors positively associated with pulmonary TB infection while being HIV seronegative had a negative association with pulmonary TB infection [AOR =0.074, 95% CI: (0.001-0.29)].Conclusion:High proportion of pulmonary TB was observed in diabetic patients as compared to the national estimated prevalence of TB in the total population. Duration of patient with DM, being underweight, alcohol consumption habit, and contact history with TB were positively associated with pulmonary TB infection while being HIV seronegative had a negative association with the infection in diabetic patients.

Inefficient HIV-1 trans Infection of CD4+ T Cells by Macrophages from HIV-1 Nonprogressors Is Associated with Altered Membrane Cholesterol and DC-SIGN.

ABSTRACTProfessional antigen-presenting cells (APC; myeloid dendritic cells [DC] and macrophages [MΦ]; B lymphocytes) mediate highly efficient HIV-1 infection of CD4+ T cells, termed trans infection, that could contribute to HIV-1 pathogenesis. We have previously shown that lower cholesterol content in DC and B lymphocytes is associated with a lack of HIV-1 trans infection in HIV-1-infected nonprogressors (NP). Here, we assessed whether HIV-1 trans infection mediated by another major APC, MΦ, is deficient in NP due to altered cholesterol metabolism. When comparing healthy HIV-1 seronegatives (SN), rapid progressors (PR), and NP, we found that monocyte-derived MΦ from NP did not mediate HIV-1 trans infection of autologous CD4+ T cells, in contrast to efficient trans infection mediated by SN and PR MΦ. MΦ trans infection efficiency was directly associated with the number of DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)-expressing MΦ. Significantly fewer NP MΦ expressed DC-SIGN. Unesterified (free) cholesterol in MΦ cell membranes and lipid rafting was significantly lower in NP than PR, as was virus internalization in early endosomes. Furthermore, simvastatin (SIMV) decreased the subpopulation of DC-SIGN+ MΦ as well as cis and trans infection. Notably, SIMV decreased cell membrane cholesterol and led to lipid raft dissociation, effectively mimicking the incompetent APC trans infection environment characteristic of NP. Our data support that DC-SIGN and membrane cholesterol are central to MΦ trans infection, and a lack of these limits HIV-1 disease progression. Targeting the ability of MΦ to drive HIV-1 dissemination in trans could enhance HIV-1 therapeutic strategies.IMPORTANCE Despite the success of combination antiretroviral therapy, neither a vaccine nor a cure for HIV infection has been developed, demonstrating a need for novel prophylactic and therapeutic strategies. Here, we show that efficiency of MΦ-mediated HIV trans infection of CD4+ T cells is a unique characteristic associated with control of disease progression, and it is impaired in HIV-infected NP. In vitro treatment of MΦ from healthy donors with SIMV lowers their cholesterol content, which results in a strongly reduced trans infection ability, similar to the levels of MΦ from NP. Taken together, our data support the hypothesis that MΦ-mediated HIV-1 trans infection plays a role in HIV infection and disease progression and demonstrate that the use of SIMV to decrease this mechanism of virus transfer should be considered for future HIV therapeutic development.

Enteric viruses in HIV-1 seropositive and HIV-1 seronegative children with diarrheal diseases in Brazil.

Diarrheal diseases (DD) have distinct etiological profiles in immune-deficient and immune-competent patients. This study compares detection rates, genotype distribution and viral loads of different enteric viral agents in HIV-1 seropositive (n = 200) and HIV-1 seronegative (n = 125) children hospitalized with DD in Rio de Janeiro, Brazil. Except for group A rotavirus (RVA), which were detected through enzyme immunoassay, the other enteric viruses (norovirus [NoV], astrovirus [HAstV], adenovirus [HAdV] and bocavirus [HBoV]) were detected through PCR or RT-PCR. A quantitative PCR was performed for RVA, NoV, HAstV, HAdV and HBoV. Infections with NoV (19% vs. 9.6%; p<0.001), HBoV (14% vs. 7.2%; p = 0.042) and HAdV (30.5% vs. 14.4%; p<0.001) were significantly more frequent among HIV-1 seropositive children. RVA was significantly less frequent among HIV-1 seropositive patients (6.5% vs. 20%; p<0.001). Similarly, frequency of infection with HAstV was lower among HIV-1 seropositive children (5.5% vs. 12.8%; p = 0.018). Among HIV-1 seropositive children 33 (16.5%) had co-infections, including three enteric viruses, such as NoV, HBoV and HAdV (n = 2) and NoV, HAstV and HAdV (n = 2). The frequency of infection with more than one virus was 17 (13.6%) in the HIV-1 negative group, triple infection (NoV + HAstV + HBoV) being observed in only one patient. The median viral load of HAstV in feces was significantly higher among HIV-1 positive children compared to HIV-1 negative children. Concerning children infected with RVA, NoV, HBoV and HAdV, no statistically significant differences were observed in the medians of viral loads in feces, comparing HIV-1 seropositive and HIV-1 seronegative children. Similar detection rates were observed for RVA, HAstV and HAdV, whilst NoV and HBoV were significantly more prevalent among children with CD4+ T lymphocyte count below 200 cells/mm3. Enteric viruses should be considered an important cause of DD in HIV-1 seropositive children, along with pathogens more classically associated with intestinal infections in immunocompromised hosts.

Association between Apolipoprotein B mRNA-editing Enzyme Catalytic Polypeptide-Like 3B (APOBEC3B) Deletion with HIV-1 Acquisition and AIDS among North Indian Population

Objective: Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-Like 3B (APOBEC3B) is involved in innate immune response, exhibiting insertion–deletion polymorphism across the world in human population. A naturally occurring 29.5 kb deletion removes complete APOBEC3B gene. Human APOBEC3B family of proteins restricts HIV- 1 replication. Very few studies have been conducted on this subject and the deductions regarding the effects of APOBEC3B deletion on HIV-1 susceptibility and pathogenesis have been largely inconsistent. Therefore, we studied the association of APOBEC3B deletion with HIV-1 in the North Indian population. Methods: Insertion (I)/Deletion (D) APOBEC3B polymorphism was analyzed using Polymerase chain reaction. Infection rates as wells as stages of HIV were compared among the three genotypes: deletion-homozygous (D/D), Insertionhomozygous (I/I) and hemizygous (I/D) in 150 HIV-1 seropositive (HSP) and 250 HIV-1 seronegative (HSN) subjects. Results and discussion: The genotypic analysis revealed insignificant associations among homozygous deletion (D/D) genotype (P=0.130, OR=1.93, 95% CI=0.95–4.30) and moderate associations among hemizygous (I/D) genotypes (P=0.057, OR=1.56, 95% CI-1.03–2.44) with HIV-1 susceptibility and also the single copy of variant allele was more susceptible to HIV-1 infection. The severity of HIV-1 infection on the basis of CD4 count was not associated significantly with the disease progression to AIDS. Conclusion: In conclusion, we found that the deletion genotype of APOBEC3B gene polymorphism does not play any significant role on HIV-1 susceptibility. Hence, further studies with the expansion of sample size are needed to validate the results.

Liver dysfunction as the presenting feature of disseminated cryptococcosis

Disseminated cryptococcosis is rare in immunocompetent individuals with central nervous and respiratory systems being the most common initial sites of involvement. Liver dysfunction as a presenting feature of disseminated cryptococcosis has been reported rarely, with the majority of patients being HIV negative and immunocompetent. We report a case of disseminated cryptococcosis in a three-year-old HIV seronegative, immunocompetent male child presenting with obstructive jaundice and lymphadenopathy. Initial diagnosis was made on liver and lymph node biopsy. Lung, skin, central nervous system (CNS) and urinary tract involvement occurred later in the course of disease. Diagnosis was confirmed by serology and culture.

Liver dysfunction as the presenting feature of disseminated cryptococcosis

Disseminated cryptococcosis is rare in immunocompetent individuals with central nervous and respiratory systems being the most common initial sites of involvement. Liver dysfunction as a presenting feature of disseminated cryptococcosis has been reported rarely, with the majority of patients being HIV negative and immunocompetent. We report a case of disseminated cryptococcosis in a three-year-old HIV seronegative, immunocompetent male child presenting with obstructive jaundice and lymphadenopathy. Initial diagnosis was made on liver and lymph node biopsy. Lung, skin, central nervous system (CNS) and urinary tract involvement occurred later in the course of disease. Diagnosis was confirmed by serology and culture.

Mutation in AIDS restriction gene affecting HIV infection and disease progression in a high risk group from Northeastern India

BackgroundHIV estimates for 2009 released by National AIDS Control Organization (NACO) reveals that 2.4 million people in India were living with HIV, 39% being female, 4.4% children and 82.4% adult males between the age group of 15 and 49 years. Persons with host genetic polymorphism CCR5Δ32 mutation are known to be partially or fully resistant to HIV infection. Persons with mutation affecting both the alleles (homozygous) are resistant to HIV infection whereas single allele (heterozygous) polymorphism leads to slower progression to AIDS. CCR5Δ32 mutation is commoner in Caucasians but less prevalent amongst Africans and Asians thereby rendering them susceptible to HIV infection. Method571 HIV serologically naive subjects from a young and homogenous male population hailing from the seven northeastern states; West Bengal and Gorkha people were selected. All the subjects belonged to a special high risk group, sexually active and typically working in difficult and uncongenial terrain involved in frequent moves including overseas missions. Their family lives are severely disrupted. 181 HIV seropositive cases of which 92 cases that were admitted in a large tertiary care hospital were also included. The distribution of CCR5Δ32 polymorphism amongst both HIV seronegative (HSN) and HIV seropositive study cohorts (HSP) using molecular methods was studied. Results and conclusionThere was failure to detect any CCR5Δ32 amongst this study group suggesting that this population from the northeastern India, West Bengal and Gorkha people are not protected by this specific host polymorphism in respect of acquisition of HIV infection as well as progression to AIDS.

Impact of Interleukin 16 (IL-16) Gene Polymorphism among Seropositive Stages in HIV-1 Infected Patients in North India

Objective: Cytokines have a major role in host immune defense system, and proinflammatory cytokines acts in both innate and immune systems. IL-16 is a pleiotropic cytokine, plays a role in inflammatory diseases and is involved in expression of several proinflammatory cytokines i.e., TNF-α and IL-1β. Previous studies reached inconclusive results regarding the role of IL-16 polymorphism on HIV-1 disease and progression. Hence, we studied its effects on HIV-1 infection and disease susceptibility. Aim: This study aims to deduce the association of host genetic factors, IL-16 (rs 11556218, rs 4072111, rs 47778889) polymorphism on HIV-1 seropositive subjects in North Indian population. Methods: 100 HIV-1 seropositive (HSP) subjects differentiated on the basis of disease severity (Stage I, II and III) and 150 HIV-1 seronegative (HSN) as control subjects were genotyped for IL 16 (rs 11556218 T/G, rs 4072111 C/T, rs 4778889 T/C using Polymerase chain reaction-reaction fragment length polymorphism (PCR-RFLP) methods. Statistical analysis was done using SPSS software. Results: IL 16 rs 11556218 TG, GG genotypes (P=0.003 for both) and G allele was highly significantly associated (P<0.01) with risk estimated to 2.5, 4.4 and 2.59 folds. For IL 16 rs 407211 T allele was seen highly protective (P<0.01) for HIV-1.

Implementation and Operational Research: Age Distribution and Determinants of Invasive Cervical Cancer in a "Screen-and-Treat" Program Integrated With HIV/AIDS Care in Zambia.

Cervical cancer screening efforts linked to HIV/AIDS care programs are being expanded across sub-Saharan Africa. Evidence on the age distribution and determinants of invasive cervical cancer (ICC) cases detected in such programs is limited. We analyzed program operations data from the Cervical Cancer Prevention Program in Zambia, the largest public sector programs of its kind in sub-Saharan Africa. We examined age distribution patterns by HIV serostatus of histologically confirmed ICC cases and used multivariable logistic regression to evaluate independent risk factors for ICC among younger (≤35 years) and older (>35 years) women. Between January 2006 and April 2010, of 48,626 women undergoing screening, 571 (1.2%) were diagnosed with ICC, including 262 (46%) HIV seropositive (median age: 35 years), 131 (23%) HIV seronegative (median age: 40 years), and 178 (31%) of unknown HIV serostatus (median age: 38 years). Among younger (≤35 years) women, being HIV seropositive was associated with a 4-fold higher risk of ICC [adjusted odds ratio = 4.1 (95% confidence interval: 2.8, 5.9)] than being HIV seronegative. The risk of ICC increased with increasing age among HIV-seronegative women and women with unknown HIV serostatus, but among HIV-seropositive women, the risk peaked around age 35 and nonsignificantly declined with increasing ages. Other factors related to ICC included being married (vs. being unmarried/widowed) in both younger and older women, and with having 2+ (vs. ≤1) lifetime sexual partners among younger women. HIV infection seems to have increased the risk of cervical cancer among younger women in Zambia, pointing to the urgent need for expanding targeted screening interventions.

Human immunodeficiency virus has similar effects on brain volumetrics and cognition in males and females.

Most studies that have examined neuropsychological impairments associated with human immunodeficiency virus (HIV) have focused on males, yet females represent one of the largest groups of newly infected patients. Further, few studies have examined neuropsychological performance and neuroimaging outcomes among females compared to males in the modern era of highly active anti-retroviral therapy (HAART). The present study investigated neuropsychological performance and brain volumetrics among HIV+ males (n = 93) and females (n = 44) on stable HAART compared to HIV seronegative (HIV-) males (n = 42) and females (n = 49). Results revealed a significant effect of HIV on neuropsychological performance and neuroimaging measures. An effect of gender, independent of HIV status, was also observed for neuroimaging measures but not neuropsychological performance. Additionally, no significant differences in neuropsychological performance or brain volumetrics were seen between HIV+ males and females. No significant interaction was observed between HIV and gender on either neuropsychological or neuroimaging indices. Our results suggest that both HIV+ males and females treated with HAART experience similar outcomes in terms of brain integrity.

Reactivity of routine HIV antibody tests in children who initiated antiretroviral therapy in early infancy as part of the Children with HIV Early Antiretroviral Therapy (CHER) trial: a retrospective analysis

Early antiretroviral therapy (ART) and virological suppression can affect evolving antibody responses to HIV infection. We aimed to assess frequency and predictors of seronegativity in infants starting early ART. We compared HIV antibody results between two of three treatment groups of the Children with HIV Early Antiretroviral Therapy (CHER) trial, done from July, 2005, until July, 2011, in which infants with HIV infection aged 5·7-12·0 weeks with a percentage of CD4-positive T lymphocytes of at least 25% were randomly assigned to immediate ART for 96 weeks (ART-96W) or deferred ART until clinical or immunological progression (ART-Def). We measured antibody from all available stored samples for ART-96W and ART-Def at trial week 84 using three assays: fourth-generation enzyme immunoassay HIV antigen-antibody combination, HIV-1 and HIV-2 rapid antibody test, and quantitative anti-gp120 IgG ELISA. We also assessed odds of seropositivity with respect to age of ART initiation and cumulative viral load. The CHER trial was registered with ClinicalTrials.gov, number NCT00102960. The median age of the infants from when samples were taken (184 samples from 268 infants) was 92 weeks (IQR 90·6-93·4). More specimens from the ART-96W group were seronegative than from the ART-Def group by enzyme immunoassay (ART-96W 49 [46%] of 107 vs ART-Def eight [11%] of 75; p<0·0001) and rapid antibody test (54 [53%] of 101 vs eight [11%] of 74; p<0·0001). Median anti-gp120 IgG concentration was lower in the ART-96W group (230 μg/μL [IQR 133-13 129]) than in the ART-Def group (6870 μg/μL [1706-53 645]; p<0·0001). If ART was started between 12 and 24 weeks of age, odds of seropositivity were increased 13·7 times (95% CI 3·1-60·2; p=0·001) compared with starting it between 0 and 12 weeks. All children starting ART aged older than 24 weeks were seropositive. Cumulative viral load to week 84 correlated with anti-gp120 IgG concentrations (coefficient 0·54; p<0·0001) and increased odds of seropositivity (odds ratio 1·59 [95% CI 1·1-2·3]) adjusted for ART initiation age. About half of children starting ART before 12 weeks of age were HIV seronegative by almost 2 years of age. HIV antibody tests cannot be used to reconfirm HIV diagnosis in children starting early ART. Long-term effects of seronegativity need further study. Clear guidelines are needed for retesting alongside improved diagnostic tests. Wellcome Trust, Medical Research Council, and National Institutes of Health.

Factors associated with loss-to-follow-up during behavioral interventions and HIV testing cohort among men who have sex with men in Nanjing, China.

BackgroundBehavioral interventions (BIs) remained the cornerstone of HIV prevention in resource-limited settings. One of the major concerns for such efforts is the loss-to-follow-up (LTFU) that threatens almost every HIV control program involving high-risk population groups.MethodsTo evaluate the factors associated with LTFU during BIs and HIV testing among men who have sex with men (MSM), 410 HIV sero-negatives MSM were recruited using respondent driven sampling (RDS) in Nanjing, China during 2008, they were further followed for 18 months. At baseline and each follow-up visits, each participant was counseled about various HIV risk-reductions BIs at a designated sexually transmitted infection (STI) clinic.ResultsAmong 410 participants recruited at baseline, altogether 221 (53.9%) were LTFU at the 18-month follow-up visit. Overall, 46 participants were found to be positive for syphilis infection at baseline while 13 participants were HIV sero-converted during the follow-up period. Increasing age was less (Adjusted Odds Ratio(aOR) of 0.90, 95% confidence Interval (CI) 0.86–0.94) and official residency of provinces other than Nanjing (AOR of 2.49, 95%CI 1.32–4.71), lower level of education (AOR of 2.01, 95%CI 1.10–3.66) and small social network size (AOR of 1.75, 95%CI 1.09–2.80) were more likely to be associated with higher odds of LTFU.ConclusionTo improve retention in the programs for HIV control, counseling and testing among MSM in Nanjing, focused intensified intervention targeting those who were more likely to be LTFU, especially the young, less educated, unofficial residents of Nanjing who had smaller social network size, might be helpful.

Praziquantel efficacy against Schistosoma mansoni among HIV-1 infected and uninfected adults living in fishing villages along Lake Victoria, Northwest Tanzania.

BackgroundAnimal studies have demonstrated that functional immune responses, as determined by the levels of CD4+ cell counts and anti-schistosome antibodies responses, determine the efficacy of praziquantel. Based on this evidence, it has been hypothesised that the immunodeficiency effects of the human immunodeficiency virus (HIV)-1 infection may affect the efficacy of praziquantel in co-infected human hosts. Thus, the present study assessed the efficacy of praziquantel by comparing parasitological cure rates and the reduction in infection intensity in HIV-1 seronegative individuals infected with S. mansoni and HIV-1 seropositive individuals co-infected with S. mansoni, following treatment with a single oral dose of praziquantel.MethodsThis was a prospective longitudinal study which included, at baseline, 555 S. mansoni infected adults aged 21–55 years, who were either co-infected or not with HIV-1 and who lived in fishing villages along Lake Victoria in Northwest Tanzania. These individuals were treated with a single oral dose of praziquantel (40 mg/kg) and, at 12 weeks, single stool samples were obtained and examined for S. mansoni eggs using the Kato-Katz technique. Finger prick and venous blood samples were collected for HIV-1 screening and CD4+ cell quantification.ResultsThe parasitological cure rate did not differ significantly from the HIV-1 serostatus (P = 0.12): among the co-infected individuals, the cure rate was 48.3% (14/29), and among the individuals infected only with S. mansoni, the cure rate was 62.6% (329/526). The egg reduction rate did not vary with the HIV-1 serostatus (P = 0.22): 77.22% for HIV-1 seronegative and 75% for HIV-1 seropositive individuals. The level of CD4+ cell counts (median 228 cells/μL: range 202–380 cells) did not influence the cure rate (P = 0.23) or the reduction in the intensity of the infection (P = 0.37).ConclusionThe HIV-1 infection per se or its moderate immunodeficiency effects, demonstrated by the range of CD4+ cell counts observed in co-infected individuals, did not affect praziquantel efficacy, as measured by the parasitological cure rate and the reduction in intensity of infection in the present study cohort.Electronic supplementary materialThe online version of this article (doi:10.1186/2049-9957-3-47) contains supplementary material, which is available to authorized users.

Bacterial and parasitic etiological agents in HIV seropositive diarrhoea cases.

Introduction: Studies in India indicated that diarrhoea has been the third common clinical presentation in AIDS patients. It is a second leading cause of hospital visit in developing nations and makes its place top ten worldwide. A diagnostic spectrum of enteric pathogen causing diarrhoea includes bacteria, parasites, fungi & viruses. Some pathogen tend to occur more frequently to cause more severe disease in person infected with HIV than in HIV uninfected persons with diarrhoea. These include Salmonella spp., Isospora spp., Crytptosporidium spp., Microsporidia spp., Cytomegalovirus. Aims & Objectives: Present study was undertaken to find out which etiological agents are most commonly responsible for causing diarrhoea in HIV seropositive patients. Material Methods: Total 181 cases were included in study out which 150 were HIV seropositive and 31 were HIV seronegative. Diagnosis of HIV infection was done as per NACO guidelines and CD4 count estimation was done. Isolation of bacterial pathogen was done using standard bacteriological procedures and parasite detection was done by direct examination after formal ether concentration technique, using staining as: modified Kinyouns acid fast staining and modified acid fast trichrome staining. Results: In this study, most common bacterial pathogen detected was Escherichia coli ( 57.6%), followed by Proteus spp (9.4%), % klebsiella spp ( 7.7%). Most common protozoal parasite was Cryptosporidium (53.6%), & Microsporidium (2.9%) and most common helminthic parasite was S. stercoralis (1.6%). All the enteric pathogens were predominantly detected with CD4+ count < 200 cells/ul. Conclusion: Cryptosporidium was the most common 53.6% parasitic enteropathogen detected while diarrheogenic E. coli 18.2% was the most common bacterial enteropathogens isolated. Majority of cases were with <200 CD4+ count had more than one pathogen.

HIV acquisition is associated with increased antimicrobial peptides and reduced HIV neutralizing IgA in the foreskin prepuce of uncircumcised men.

BackgroundThe foreskin is the site of most HIV acquisition in uncircumcised heterosexual men. Although HIV-exposed, seronegative (HESN) uncircumcised men demonstrate HIV-neutralizing IgA and increased antimicrobial peptides (AMPs) in the foreskin prepuce, no prospective studies have examined the mucosal immune correlates of HIV acquisition.MethodsTo assess the association of foreskin immune parameters with HIV acquisition, antimicrobial peptides and IgA with the capacity to neutralize a primary clade C HIV strain were quantified by blinded investigators, using sub-preputial swabs collected longitudinally during a randomized trial of male circumcision for HIV prevention in Rakai, Uganda.ResultsParticipants were 99 men who acquired HIV (cases) and 109 randomly selected controls who remained HIV seronegative. At enrollment, 44.4% of cases vs. 69.7% of controls demonstrated IgA neutralization (adjusted OR = 0.31; 95% CI, 0.16–0.61). IgA neutralization was detected in 38.7% of cases and 70.7% of controls at the last seronegative case visit prior to HIV acquisition and the comparable control visit (adjusted OR 0.21; 95% CI, 0.11–0.39). Levels of the α-defensins and secretory leukocyte protease inhibitor (SLPI) were over ten-fold higher in the foreskin prepuce of cases who acquired HIV, both at enrollment (mean 4.43 vs. 3.03 and 5.98 vs. 4.61 logn pg/mL, P = 0.005 and 0.009, respectively), and at the last seronegative visit (mean 4.81 vs. 3.15 and 6.46 vs. 5.20 logn pg/mL, P = 0.0002 and 0.013).ConclusionsThis prospective, blinded analysis is the first to assess the immune correlates of HIV acquisition in the foreskin. HIV-neutralizing IgA, previously associated with the HESN phenotype, was a biomarker of HIV protection, but other HESN associations correlated with increased HIV acquisition. This emphasizes the importance of prospective epidemiological studies or in vitro tissue studies to define the impact of mucosal parameters on HIV risk.

Influence of education on HIV infection among pregnant women attending their antenatal care in Sekondi-Takoradi metropolis, Ghana.

This study investigated the influence of the level of education on HIV infection among pregnant women attending antenatal care in Sekondi-Takoradi, Ghana. A cross-sectional study was conducted at four hospitals in the Sekondi-Takoradi metropolis. The study group comprised 885 consenting pregnant women attending antenatal care clinics. Questionnaires were administered and venous blood samples were screened for HIV and other parameters. Multivariable logistic regression analyses were performed to determine the association between the level of education attained by the pregnant women and their HIV statuses. The data showed that 9.83% (87/885) of the pregnant women were HIV seropositive while 90.17% (798/885) were HIV seronegative. There were significant differences in mean age (years) between the HIV seropositive women (27.45 ± 5.5) and their HIV seronegative (26.02 ± 5.6) counterparts (p = .026) but the inference disappeared after adjustment (p = .22). Multivariable logistic regression analysis revealed that pregnant women with secondary/tertiary education were less likely to have HIV infection compared with those with none/primary education (adjusted OR, 0.53; 95% CI, 0.30-0.91; p = .022). Our data showed an association with higher level of education and HIV statuses of the pregnant women. It is imperative to encourage formal education among pregnant women in this region.