Evidence for a "Founder Effect" among HIV-infected injection drug users (IDUs) in Pakistan.
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ABSTRACT: Background
We have previously reported a HIV-1 subtype A infection in a community of injection drug users (IDUs) in Karachi, Pakistan. We now show that this infection among the IDUs may have originated from a single source.Methods
Phylogenetic analysis was performed of partial gag sequences, generated using PCR, from 26 HIV-positive IDU samples.Results
Our results showed formation of a tight monophyletic group with an intra-sequence identity of < 98% indicating a "founder effect". Our data indicate that the HIV-1 epidemic in this community of IDUs may have been transmitted by an HIV positive overseas contract worker who admitted to having contact with commercial sex workers during stay abroad.Conclusion
Specific measures need to implemented to control transmission of HIV infection in Pakistan through infected migrant workers.
SUBMITTER: Rai MA
PROVIDER: S-EPMC2820481 | biostudies-literature | 2010 Jan
REPOSITORIES: biostudies-literature
Publications
Evidence for a "Founder Effect" among HIV-infected injection drug users (IDUs) in Pakistan.
Rai Mohammad A MA Nerurkar Vivek R VR Khoja Suhail S Khan Saeed S Yanagihara Richard R Rehman Arish A Kazmi Shahana U SU Ali Syed H SH
BMC infectious diseases 20100112
<h4>Background</h4>We have previously reported a HIV-1 subtype A infection in a community of injection drug users (IDUs) in Karachi, Pakistan. We now show that this infection among the IDUs may have originated from a single source.<h4>Methods</h4>Phylogenetic analysis was performed of partial gag sequences, generated using PCR, from 26 HIV-positive IDU samples.<h4>Results</h4>Our results showed formation of a tight monophyletic group with an intra-sequence identity of < 98% indicating a "founder ...[more]
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Project description:BackgroundMucosally acquired human immunodeficiency virus type 1 (HIV-1) infection results from a limited number of variants, and these infecting strains potentially have unique properties, such as increased susceptibility to entry blockers, relative interferon-alpha (IFN-α) resistance, and replication differences in some primary cells. There is no data about the phenotypic properties of HIV-1 envelope variants found early after acquisition among subjects infected through injection drug use (IDU). For the first time, we compared the characteristics of virus envelopes among injection drug users sampled prior to seroconversion (HIV RNA+/Ab-), within 1 year (early), and more than 2 years (chronic) after estimated acquisition.ResultsVirus envelopes from 7 HIV RNA+/Ab- subjects possessed lower genetic diversity and divergence compared to 7 unrelated individuals sampled during the chronic phase of disease. Replication competent recombinant viruses incorporating the HIV RNA+/Ab- as compared to the chronic phase envelopes were significantly more sensitive to a CCR5 receptor inhibitor and IFN-α and showed a statistical trend toward greater sensitivity to a fusion blocker. The early as compared to chronic infection envelopes also demonstrated a statistical trend or significantly greater sensitivity to CCR5 and fusion inhibitor and IFN- α. The HIV RNA+/Ab- as compared to chronic envelope viruses replicated to a lower extent in mature monocyte derived dendritic cells - CD4+ T cell co-cultures, but there were no significant replication differences in other primary cells among the viruses with envelopes from the 3 different stages of infection.ConclusionsSimilar to mucosal acquisition, HIV-1 envelope quasispecies present in injection drug users prior to seroconversion have unique phenotypic properties compared to those circulating during the chronic phase of disease.
| S-EPMC4253609 | biostudies-literature
Project description:IntroductionVitamin D deficiency is highly prevalent and is associated with bone disease, cardiovascular disease, metabolic syndrome and malignancy. Injection drug users (IDUs), with or without HIV infection, are at risk for these conditions; however, limited data on vitamin D deficiency exist in this population. We determined the prevalence and correlates of vitamin D deficiency among urban IDUs in the AIDS Linked to the IntraVenous Experience (ALIVE) Study cohort.MethodsFor this cross-sectional sub-study, vitamin D deficiency was defined as a serum 25(OH)-vitamin D level <20 ng/mL. Multivariable logistic regression was used to identify factors independently associated with vitamin D deficiency.ResultsOf 950 individuals analyzed, 29% were HIV-infected. The median age was 49 years; 65% were male, and 91% were black. The median vitamin D level was 13.5 ng/mL (IQR, 9.0-20.3); 74% were deficient (68% in HIV-infected vs. 76% in HIV-uninfected, p?=?0.01). Non-black race, fall/winter season, multivitamin intake, higher serum albumin, HCV seropositivity and HIV-infection were associated with significantly lower odds of vitamin D deficiency.ConclusionsVitamin D deficiency is prevalent among IDUs. Notably, HIV-infected IDUs were less likely to be vitamin D deficient. Higher vitamin D levels were associated with multivitamin intake and with higher albumin levels, suggesting that nutritional status contributes substantially to deficiency. The association between HCV serostatus and vitamin D level remains unclear. Further investigation is needed to define the clinical implications of the heavy burden of vitamin D deficiency in this high-risk, aging population with significant co-morbidities.
| S-EPMC3995810 | biostudies-literature
Project description:Research needs to build evidence for the roles that HIV status of injection partners may or may not play in injection risk behaviors of injection drug users (IDUs). Using baseline data collected from a randomized controlled study (INSPIRE) conducted in four cities (Baltimore, Miami, New York, and San Francisco) from 2001 to 2005, we categorized 759 primarily heterosexual HIV-positive IDUs into four groups based on HIV serostatus of drug injection partners. Thirty-two percent of the sample injected exclusively with HIV-positive partners in the past 3 months and more than 60% had risky injection behavior with these partners. Eight percent injected exclusively with HIV-negative partners and 49% injected with any unknown status partners. The remaining 11% reported having both HIV-positive and -negative injection partners, but no partners of unknown HIV status. Riskier injection behavior was found among the group with mixed status partners. The risk among the group with any unknown status partners appeared to be driven by the greater number of injection partners. No major group differences were observed in socio-demographic and psychosocial factors. Our analysis suggests that serosorting appeared to be occurring among some, but not an overwhelming majority of HIV-positive IDUs, and knowledge of HIV status of all injection partners per se did not appear to be as important as knowledge of sexual partner's HIV status in its association with risk behavior.
| S-EPMC3232423 | biostudies-literature
Project description:Information about HBV sero-markers, infection stages and genotypes in HIV-1 infected and uninfected injection and non-injection drug users (IDUs) in Kenya remains elusive.A cross-sectional study examining HBV sero-marker, infection stages and genotypes was conducted among HIV-1 infected and uninfected, respectively, IDUs (n?=?157 and n?=?214) and non-IDUs (n?=?139 and n?=?48), and HIV-1 uninfected non-drug using controls (n?=?194) from coastal, Kenya. HBV sero-marker and infection stages were based on HBV 5-panel rapid test plasma sero-reactivity. DNA was extracted from acute and chronic plasma samples and genotypes established by nested-PCR and direct sequencing.HBsAg positivity was higher in HIV-1 infected IDUs (9.6%) relative to HIV-1 uninfected IDUs (2.3%), HIV-1 infected non-IDUs (3.6%), HIV-1 uninfected non-IDUs (0.0%) and non-drug users (2.6%; P?=?0.002). Contrastingly, HBsAb positivity was higher in HIV-1 uninfected IDUs (14.6%) and non-IDUs (16.8) in comparison to HIV-1 infected IDUs (8.3%), and non-IDUs (8.6%), and non-drug users (8.2%; P?=?0.023). HBcAb positivity was higher in HIV-1 infected IDUs (10.2%) compared to HIV-1 uninfected IDUs (3.3%), HIV-1 infected non-IDUs (6.5%), HIV-1 uninfected non-IDUs (2.1%) and non-drug users (4.6%; P?=?0.038). Acute (5.7%, 1.4%, 0.0%, 0.0% and 1.5%) and chronic (5.1%, 0.9%, 3.6%, 0.0% and 1.5%) stages were higher in HIV-1 infected IDUs, compared to HIV-1 uninfected IDUs, HIV-1 infected and uninfected non-IDUs and non-drug users, respectively. However, vaccine type response stage was higher in HIV-1 uninfected IDUs (15.4%) relative to HIV-1 infected IDUs (6.4%), and HIV-1 infected (6.5%), and uninfected (10.4%) non-IDUs, and non-drug users (5.7%; P?=?0.003). Higher resolved infection rates were also recorded in HIV-1 uninfected IDUs (11.2%) compared to HIV-1 infected IDUs (8.3%), and HIV-1 infected (7.2%), uninfected (6.3%) non-IDUs, and non-drug users (6.7%; P?=?0.479), respectively. Only A1 genotype showing minimal diversity was detected among the study participants.HBV sero-markers and infection staging are valuable in diagnosis and genotyping of HBV infections. Among IDUs, higher HBsAg and HBcAb positivity in HIV-1 infected and higher HBsAb positivity in HIV-1 negative IDUs suggests frequent exposure. Additionally, HBV genotype A is the dominant circulating genotype in both high and low risk populations of Kenya.
| S-EPMC4520198 | biostudies-literature
Project description:Depression and substance use, the most common comorbidities with HIV, are both associated with poor treatment adherence. Injection drug users comprise a substantial portion of individuals with HIV in the United States and globally. The present study tested cognitive behavioral therapy for adherence and depression (CBT-AD) in patients with HIV and depression in active substance abuse treatment for injection drug use.This is a 2-arm, randomized controlled trial (N = 89) comparing CBT-AD with enhanced treatment as usual (ETAU). Analyses were conducted for two time-frames: (a) baseline to post-treatment and (b) post-treatment to follow-up at 3 and 6 months after intervention discontinuation.At post-treatment, the CBT-AD condition showed significantly greater improvement than ETAU in MEMS (electronic pill cap) based adherence, ?slope = 0.8873, t(86) = 2.38, p = .02; dGMA-raw = 0.64, and depression, assessed by blinded assessor: Mongomery-Asberg Depression Rating Scale, F(1, 79) = 6.52, p < .01, d = 0.55; clinical global impression, F(1, 79) = 14.77, p < .001, d = 0.85. After treatment discontinuation, depression gains were maintained, but adherence gains were not. Viral load did not differ across condition; however, the CBT-AD condition had significant improvements in CD4 cell counts over time compared with ETAU, ?slope = 2.09, t(76) = 2.20, p = .03, dGMA-raw = 0.60.In patients managing multiple challenges including HIV, depression, substance dependence, and adherence, CBT-AD is a useful way to integrate treatment of depression with an adherence intervention. Continued adherence counseling is likely needed, however, to maintain or augment adherence gains in this population.
| S-EPMC3365619 | biostudies-literature
Project description:Although injection drug use drives antiretroviral drug resistance, the prevalence of protease inhibitor (PI) resistance among Kenyan IDUs remains undetermined. We, therefore, explored PI resistance mutations and their association with viral load and CD4+ T cell counts in HIV-1 infected IDUs (ART-naive, n = 32; and -experienced, n = 47) and non-drug users (ART-naive, n = 21; and -experienced, n = 32) naive for PI treatment from coastal Kenya.Only IDUs harboured major PI resistance mutations consisting of L90M, M46I and D30 N among 3 (6.4 %) ART-experienced and 1 (3.1 %) -naive individuals. Minor PI mutations including A71T, G48E, G48R, I13V, K20I, K20R, L10I, L10V, L33F, L63P, T74S, V11I, and V32L were detected among the ART-experienced (36.2 vs. 46.9 %) and -naive (43.8 vs. 66.7 %) IDUs and non-drug users, respectively. All the four IDUs possessing major mutations had high viral load while three presented with CD4+ T cell counts of <500 cells/ml. Among the ART-naive non-drug users, CD4+ T cell counts were significantly lower in carriers of minor mutations compared to non-carriers (P < 0.05).Transmitted drug resistance may occur in IDUs underscoring the need for genotyping resistance before initiating PI treatment.
| S-EPMC4537595 | biostudies-literature
Project description:BACKGROUND: Data on the subtypes of HIV in a population help in predicting the potential foci of epidemic, tracking the routes of infection and following the patterns of the virus' genetic divergence. Globally, the most prevalent HIV infection is the HIV-1 subtype C. In Asia, predominant subtypes of HIV-1 are B, C, and CRF-01AE. During the last few years, HIV prevalence in Pakistan has taken the form of a concentrated epidemic in at least two high risk groups, namely, Intravenous Drug Users (IDUs) and Male Sex Workers (MSWs). Factors that have facilitated the proliferation of HIV infection include transmission through a large number of repatriates and needle-sharing intravenous drug users, unscreened blood transfusions, and sexual illiteracy. The HIV subtypes infecting Pakistani populations have not been explored to date. In this study, we analyzed HIV-1 subtypes from in a high-risk community of IDUs in Karachi, the largest city of Pakistan. METHODS: Samples were collected from 34 IDUs after their informed consent. In addition, the study subjects were administered a questionnaire regarding their sexual behavior and travel history. For HIV analysis, DNA was extracted from the samples and analyzed for HIV types and subtypes using subtype-specific primers in a nested polymerase chain reaction (PCR). The results from this PCR were further confirmed using the Heteroduplex Mobility Assay (HMA). RESULTS: We found HIV-1 subtype A in all the 34 samples analyzed. A few of the study subjects were found to have a history of travel and stay in the United Arab Emirates. The same subjects also admitted to having contact with commercial sex workers during their stay abroad. CONCLUSION: Our study therefore shows clade A HIV-1 to be prevalent among the IDUs in Karachi. As the prevalence of HIV in Pakistan continues to rise, more work needs to be done to track the infection, and to analyze the strains of HIV spreading through the country.
| S-EPMC1654165 | biostudies-literature
Project description:Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 07_BC has caused serious HIV-1 epidemics among injecting drug users (IDUs) in East Asia. Little is known about the characteristics of the virus and its impact on disease progression among the infected individuals. In this study, we compared immunological progression between 423 IDUs infected with CRF07_BC and 194 men who have sex with men (MSM) with primary subtype B infection, and a representative full-length CRF07_BC molecular clone, pCRF07_BC, was constructed to characterize the virus. We found that IDUs infected with CRF07_BC had significantly slower immunological progression in the Cox proportional hazards model (hazard ratio: 0.30; 95% confidence interval: 0.13-0.69; P=0.004). The constructed recombinant CRF07_BC viruses had a reduced processing of the Gag/Gag-Pol polyproteins, a decreased incorporation of Vpr in the virus particle, tethering of virus particles on the plasma membrane and decreased virus growth kinetics. These phenotypes are related to the unique 7-amino acid deletion in the p6 of CRF07_BC, since complementation of the 7-amino acid in pCRF07_BC could improve the defective phenotypes. In summary, compared with MSM infected with HIV-1 subtype B, IDUs infected with CRF07_BC had slower immunological progression, which is likely correlated with interference of virus particle maturation by the 7-amino acid deletion in p6.
| S-EPMC3880871 | biostudies-literature
Project description:ObjectiveTo define a clinical syndrome associated with active drug abuse in HIV-infected individuals.MethodsWe performed a retrospective review to identify individuals treated at the Johns Hopkins Hospital from 1993 to 2008 who were HIV-infected and were actively abusing drugs and had bilateral basal ganglia lesions on MRI. They were identified using a key word search in the radiology database, autopsy database, and the Moore HIV clinic database. Clinical, laboratory, and radiographic findings were correlated to define the syndrome.ResultsTen individuals were identified who presented with a change in mental status or seizures, used cocaine or cocaine with heroin, had uncontrolled HIV infection (>190,000 copies/mL of plasma), elevated CSF protein (63-313 mg/dL), and diffuse hyperintense bilateral basal ganglia lesions on imaging. The majority of patients (8/10) had renal failure and despite supportive therapy most (7/9) ultimately died (median survival 21 days). Postmortem examination in one individual showed the presence of overwhelming microglial activation in the basal ganglia. The 2 surviving individuals were started on combined antiretroviral therapy (CART) during hospitalization.ConclusionWe describe a unique clinical syndrome of a fulminant encephalopathy associated with primarily basal ganglia involvement in HIV-infected drug abusers. This syndrome is a rare but serious condition that is associated with a high mortality rate. Early CART institution may be useful and neuroprotective in this disorder, although this requires further investigation.
| S-EPMC3053334 | biostudies-literature
Project description:Recent studies indicate that sexual transmission of human immunodeficiency virus type 1 (HIV-1) generally results from productive infection by only one virus, a finding attributable to the mucosal barrier. Surprisingly, a recent study of injection drug users (IDUs) from St. Petersburg, Russia, also found most subjects to be acutely infected by a single virus. Here, we show by single-genome amplification and sequencing in a different IDU cohort that 60% of IDU subjects were infected by more than one virus, including one subject who was acutely infected by at least 16 viruses. Multivariant transmission was more common in IDUs than in heterosexuals (60% versus 19%; odds ratio, 6.14; 95% confidence interval [CI], 1.37 to 31.27; P = 0.008). These findings highlight the diversity in HIV-1 infection risks among different IDU cohorts and the challenges faced by vaccines in protecting against this mode of infection.
| S-EPMC2876625 | biostudies-literature