Abstract

Pakistan is considered by the World Health Organization to currently have a “concentrated” HIV-1 epidemic due to a rapid rise in infections among people who inject drugs (PWID). Prevalence among the country’s nearly 105,000 PWID is estimated to be 37.8% but has been shown to be higher in several large urban centers. A lack of public health resources, the common use of professional injectors and unsafe injection practices are believed to have fueled the outbreak. Here we evaluate the molecular characteristics of HIV-1 sequences (n = 290) from PWID in several Pakistani cities to examine transmission dynamics and the association between rates of HIV-1 transmission with regards to regional trends in opioid trafficking. Tip-to-tip (patristic) distance based phylogenetic cluster inferences and BEAST2 Bayesian phylodynamic analyses of time-stamped data were performed on HIV-1 pol sequences generated from dried blood spots collected from 1,453 PWID as part of a cross-sectional survey conducted in Pakistan during 2014/2015. Overall, subtype A1 strains were dominant (75.2%) followed by CRF02_AG (14.1%), recombinants/unassigned (7.2%), CRF35_AD (2.1%), G (1.0%) and C (0.3%). Nearly three quarters of the PWID HIV-1 sequences belonged to one of five distinct phylogenetic clusters. Just below half (44.4%) of individuals in the largest cluster (n = 118) did seek help injecting from professional injectors which was previously identified as a strong correlate of HIV-1 infection. Spikes in estimated HIV-1 effective population sizes coincided with increases in opium poppy cultivation in Afghanistan, Pakistan’s western neighbor. Structured coalescent analysis was undertaken in order to investigate the spatial relationship of HIV-1 transmission among the various cities under study. In general terms, our analysis placed the city of Larkana at the center of the PWID HIV-1 epidemic in Pakistan which is consistent with previous epidemiological data.

Highlights

  • Pakistan is considered to have transitioned from a “low prevalence, high risk” to a “concentrated” epidemic stage owing primarily to a rapid rise in infections among people who inject drugs (PWID, www.nacp.gov.pk/whatwedo/surveillance.html) [1]

  • Even though our HIV-1 genotyping primers have been validated in-house as part of the Canadian HIV-1 Strain and Drug Resistance Surveillance program, we cannot rule out the possibility of amplification failure attributed to poor primer annealing efficiency to sequences from unique HIV-1 circulating recombinant forms (CRFs) recently reported in Pakistan [10]

  • Our results suggest that the current epidemic among PWID is no longer an onward transmission of a limited number of A1 subtype founder viruses as reported previously

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Summary

Introduction

Pakistan is considered to have transitioned from a “low prevalence, high risk” to a “concentrated” epidemic stage owing primarily to a rapid rise in infections among people who inject drugs (PWID, www.nacp.gov.pk/whatwedo/surveillance.html) [1]. While HIV-1 prevalence within the general population remains below 0.1%, prevalence among the country’s nearly 105,000 PWID is estimated to be 37.8% with even higher prevalence in selected urban centres (www.nacp.gov.pk/whatwedo/surveillance.html) [1, 2]. Perhaps more concerning is the significant rise in PWID associated HIV-1 prevalence over an extremely short interval that has been observed in certain cities, indicative of uncontrolled HIV-1 transmission resulting from a lack of public health resources. The relationship between the HIV-1 outbreak in Sargodha and HIV-1 infections occurring in PWID or associated at risk populations in other regions of Pakistan remains unclear. A better understanding of the role that PWID migration between cities, for example as commercial truck drivers or migrant agricultural workers [6], plays in driving HIV-1 expansion will be critical for the development of sound and effective public health policies

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