The Spread of HIV in Pakistan: Bridging of the Epidemic between Populations

In the last two decades, ‘concentrated epidemics’ of human immunodeficiency virus (HIV) have established in several high risk groups in Pakistan, including Injecting Drug Users (IDUs) and among men who have sex with men (MSM). To explore the transmission patterns of HIV infection in these major high-risk groups of Pakistan, 76 HIV samples were analyzed from MSM, their female spouses and children, along with 26 samples from a previously studied cohort of IDUs. Phylogenetic analysis of HIV gag gene sequences obtained from these samples indicated a substantial degree of intermixing between the IDU and MSM populations, suggesting a bridging of HIV infection from IDUs, via MSM, to the MSM spouses and children. HIV epidemic in Pakistan is now spreading to the female spouses and offspring of bisexual MSM. HIV control and awareness programs must be refocused to include IDUs, MSM, as well as bisexual MSM, and their spouses and children

Population-specific evolution of HIV Gag epitopes in genetically diverged patients.

BACKGROUND: Under the host selection pressure HIV evolves rapidly to override crucial steps in the antigen presentation pathway. This allows the virus to escape binding and recognition by cytotoxic T lymphocytes. Selection pressures on HIV can be unique depending on the immunogenetics of host populations. It is therefore logical to hypothesize that the virus evolving in a given population will carry signature mutations that will allow it to survive in that particular host milieu. OBJECTIVES: The aim of this study was to perform a comparative analysis of HIV-1 Gag subtype A sequences from two genetically diverged populations, namely, Kenyan and Pakistani. We analyzed unique mutations that could intercept the antigen processing pathway and potentially change the repertoire of Gag epitopes in each study group. METHODS: Twenty-nine Kenyan and 56 Pakistani samples from HIV-1 subtype A-infected patients were used in this study. The HIV-1 gag region p24 and p2p7p1p6 was sequenced and mutations affecting proteasomal degradation, TAP binding, HLA binding and CTL epitope generation, were analyzed using the in silico softwares NetChop and MAPPP, TAPPred, nHLAPred and CTLPred, respectively. RESULTS: Certain mutations unique to either Pakistani or Kenyan patients were observed to affect sites for proteasomal degradation, TAP binding, and HLA binding. As a consequence of these mutations, epitope pattern in these populations was altered. CONCLUSION: Unique selection pressures can steer the direction of viral epitope evolution in the host populations. Population-specific HIV epitopes have to be taken into account while designing treatment as well as vaccine for HIV

Burden of communicable disease among the native and repatriating Afghans

Owing to the capricious political and economic conditions of Afghanistan during the past few decades, the burden of communicable disease, especially bloodborne and sexually transmitted infections, has been steadily mounting in this population. Afghan refugees who sought asylum and settled in foreign countries encountered many a barrier to standard health care, which led to the establishment of several epidemics in the refugee population as well. In recent years, repatriation of these refugees back to their homeland has raised new concerns about control and prevention of potential epidemics in the returning and indigenous Afghan populations. Mixing of existing infections, as well as of risk behaviors and practices, in the two populations, if left unattended, can lead to unforeseen, uncontrollable outcomes

Fast dissemination of new HIV-1 CRF02/A1 recombinants in Pakistan

A number of HIV-1 subtypes are identified in Pakistan by characterization of partial viral gene sequences. Little is known whether new recombinants are generated and how they disseminate since whole genome sequences for these viruses have not been characterized. Near full-length genome (NFLG) sequences were obtained by amplifying two overlapping half genomes or next generation sequencing from 34 HIV-1-infected individuals in Pakistan. Phylogenetic tree analysis showed that the newly characterized sequences were 16 subtype As, one subtype C, and 17 A/G recombinants. Further analysis showed that all 16 subtype A1 sequences (47%), together with the vast majority of sequences from Pakistan from other studies, formed a tight subcluster (A1a) within the subtype A1 clade, suggesting that they were derived from a single introduction. More in-depth analysis of 17 A/G NFLG sequences showed that five shared similar recombination breakpoints as in CRF02 (15%) but were phylogenetically distinct from the prototype CRF02 by forming a tight subcluster (CRF02a) while 12 (38%) were new recombinants between CRF02a and A1a or a divergent A1b viruses. Unique recombination patterns among the majority of the newly characterized recombinants indicated ongoing recombination. Interestingly, recombination breakpoints in these CRF02/A1 recombinants were similar to those in prototype CRF02 viruses, indicating that recombination at these sites more likely generate variable recombinant viruses. The dominance and fast dissemination of new CRF02a/A1 recombinants over prototype CRF02 suggest that these recombinant have more adapted and may become major epidemic strains in Pakista