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

Brazilian network for HIV Drug Resistance Surveillance (HIV-BresNet): a survey of treatment-naive individuals

Introduction: In Brazil, more than 487,450 individuals are currently undergoing antiretroviral treatment. In order to monitor the transmission of drug-resistant strains and HIV subtype distribution in the country, this work aimed to estimate its prevalence and to characterize the nationwide pretreatment drug resistance in individuals recently diagnosed with HIV between 2013 and 2015. Methods: The HIV threshold survey methodology (HIV-THS, WHO) targeting antiretroviral-naive individuals with recent HIV diagnosis was utilized, and subjects were selected from 51 highly populated cities in all five Brazilian macroregions. The HIV pol genotypic test was performed by genomic sequencing. Results: We analysed samples from 1568 antiretroviral-naive individuals recently diagnosed with HIV, and the overall transmitted drug resistance (TDR) prevalence was 9.5% (150 sequences). The regional prevalence of resistance according to Brazilian geographical regions was 9.4% in the northeast, 11.2% in the southeast, 6.8% in the central region, 10.2% in the north and 8.8% in the south. The inhibitor-specific TDR prevalence was 3.6% for nucleoside reverse transcriptase inhibitors (NRTIs), 5.8% for non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 1.6% for protease inhibitors (PIs)1.0% of individuals presented resistance to more than one class of inhibitors. Overall, subtype B was more prevalent in every region except for the southern, where subtype C prevails. Conclusions: To the best of our knowledge, this is the first TDR study conducted in Brazil with nationwide representative sampling. The TDR prevalence revealed a moderate rate in the five Brazilian geographical regions, although some cities presented higher TDR prevalence rates, reaching 14% in Sao Paulo, for example. These results further illustrate the importance of surveillance studies for designing future strategies in primary antiretroviral therapy, aiming to mitigate TDR, as well as for predicting future trends in other regions of the globe where mass antiretroviral (ARV) treatment was implemented.Brazilian Ministry of HealthUniv Fed Rio de Janeiro, Lab Virol Mol, Dept Genet IB, Rio De Janeiro, RJ, BrazilFdn Med Trop Amazonas, Manaus, Amazonas, BrazilLAPI Univ Fed Bahia, Hosp Univ Prof Edgar Santos, Lab Pesquisa, Salvador, BA, BrazilLab Cent Saude Publ Ceara Lacen CE, Fortaleza, Ceara, BrazilLab Cent Saude Publ Dist Fed, Setor Grandes Areas Norte SGAN 601, Brasilia, DF, BrazilUniv Fed Minas Gerais UFMG, Fac Med, Lab Imunol & Biol Mol DIP, Belo Horizonte, MG, BrazilLab Cent Saude Publ Mato Grosso Sul, Campo Grande, MS, BrazilLab Cent Saude Publ Pernambuco, Recife, PE, BrazilLab Municipal Curitiba, Curitiba, PR, BrazilFiocruz MS, Lab AIDS & Imunol Mol, Dept Imunol, Rio De Janeiro, RJ, BrazilUniv Fed Rio de Janeiro, Hosp Univ Clementino Fraga Filho, Lab Carga Viral, Rio de Janeiro, RJ, BrazilInst Biol Exercito, Rio De Janeiro, RJ, BrazilLab Cent Saude Publ Rio Grande Sul, Porto Alegre, RS, BrazilLab Hosp Nossa Senhora Conceicao, Porto Alegre, RS, BrazilLab Cent Saude Publ Santa Catarina, Florianopolis, SC, BrazilUNESP, Lab Biol Mol Hemocentro Botucatu, Fac Med, Botucatu, SP, BrazilUniv Estadual Campinas, Lab Pesquisa AIDS, Hosp Clin, Campinas, SP, BrazilInst Adolfo Lutz Sao Jose do Rio Preto, Lab Biol Mol, Sao Jose Do Rio Preto, SP, BrazilUniv Fed Sao Paulo UNIFESP, Escola Paulista Med, Lab Retrovirol, Sao Paulo, SP, BrazilInst Adolfo Lutz Cent, Lab Retrovirus, Ctr Virol, Nucleo Doencas Sanguineas & Sexuais, Sao Paulo, SP, BrazilMinist Saude, Dept Vigilancia Prevencao & Controle DST AIDS & H, Setor Adm Fed Sul SAFS 02, Secretaria Vigilancia Saude, Brasilia, DF, BrazilUniv Brasilia, Programa Pos Grad Saude Colet, Fac Med, Fac Ciencias Saude, Brasilia, DF, BrazilUniv Sao Paulo, Fac Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Escola Paulista Med, Lab Retrovirol, Sao Paulo, SP, BrazilBMH: TC 298/12Web of Scienc

Demographic details of HIV gag PCR positive participants.

<p>The frequencies of all values are given in parentheses.</p

Phylogenetic analysis of HIV transmission between IDUs, MSM, and MSM families.

<p>The studied population sequences were compared to the IDU sequences obtained from a previous study, which are highlighted in black. The 47 strains from MSM and M-IDU (highlighted) are shown in blue, 15 MSM spouses (MS-) are shown in green and 14 MSM children (MC-) are shown in red. Members of each family are assigned by similar digit label following the letter prefix. The numbers along the monophyletic branches correspond to bootstrap values. Branch lengths in nucleotide substitutions per site were scaled according to the bar at the bottom of the tree.</p

ML Phylogenetic tree of HIV-1 A Pakistani strains.

<p>ML trees where obtained with the ML method using the best fitting nucleotide substitution model. Branch lengths are scaled in nucleotide substitutions per site according to the bar at the bottom of each tree. Each tree includes the newly sequenced strains from Pakistan as well as reference strains from the HIV databases. Branches in each tree are colored according to the color legend in the figure. Pakistani sequences were labeled according to risk behavior as follows: M = male having sex with male (MSM), MS = spouses with infected partner, MC = MSM children with infected parent(s) and M-IDU = MSM who were injecting drug users. Reference strains were labeled using the HIV databases ID, which include a two letter code indicating the country of origin (<a href="http://www.hiv.lanl.gov/" target="_blank">http://www.hiv.lanl.gov/</a>).</p

HIV-1 <i>gag</i> p24 genealogies for all six HLA-B*5701 subjects displaying different branch sets.

<p>Internal and external branches are shown for each subject (P1-P6), colored in purple and black, respectively. Orange branches indicate one of the possible backbone paths in the genealogy (see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003830#s4" target="_blank">Methods</a>). Specific estimates were based on 200 randomly sampled trees from the posterior distribution obtained with a Bayesian coalescent framework enforcing a relaxed molecular clock. Branch lengths are drawn proportional to the time scale (in days) at the bottom of each tree.</p

Replication capacity in six HLA-B*5701 subjects.

1<p>Replication capacity (RC) was determined by using PhenoSense Gag-Pro assay, and expressed as a percentage of viral infectivity (luciferase activity) relative to NL4-3 reference control.</p><p>Replication capacity in six HLA-B*5701 subjects.</p

HIV-1 mean nonsynonymous and synonymous substitution rates for internal branches in HLA-B*5701 subjects.

<p>Subject- specific estimates were based on 200 randomly sampled trees from the posterior distribution obtained with a Bayesian coalescent framework enforcing a relaxed molecular clock. HRPs (P1-P3) and LRPs (P4-P6) are shown in orange and purple, respectively. The <i>p</i>-value is marked in bold when there is a significant difference between the two groups of patients. Along the y-axis, internal refers to all internal branches; backbone refers to rates averaged along all the possible backbone paths.</p

HIV-1 mean nucleotide substitution rate for different branches for all six HLA-B*5701 subjects.

<p>Estimates along internal branches (purple), backbone paths (orange) and external branches (black) are shown for the HRPs (P1-P3) and the LRPs (P4-P6).</p

HIV-1 mean synonymous substitution rates along backbone paths <i>vs</i>. CD4⁺ T cell count at baseline for each subject.

<p>HIV-1 synonymous rates (dS) in <i>gag</i> p24 within each HLA-B*5701 subject (y-axis) were plotted against baseline CD4⁺ T cell counts (10–11 wpi). The squared correlation coefficient (r²) is given in the graph and resulted highly significant (<i>p</i> = 0.002).</p