HIV Type 1 Genetic Diversity and Genotypic Drug Susceptibility in the Republic of Moldova

Abstract

HIV-1 genetic diversity and, for the first time, genotypic drug susceptibility was investigated for strains circulating in the Republic of Moldova (of the former Soviet Union). Eighty-three samples from adults recently infected by intravenous drug use (IDU) (n = 60), heterosexual contact (n = 8), and from blood donors (n = 15) that tested positive from 1997 to 1998, and originating from different regions of Moldova were serotyped. By group-specific and subtype-specific peptide ELISA, patients were infected by serotype A (n = 65), serotype B (n = 1), or were nontypable (n = 17). Heteroduplex mobility assay (HMA) confirmed 11 subtype A and the one subtype B infection. Analyses of pol and env sequences for six of the IDUs confirmed that they were infected with subtype A strain. These strains clustered tightly with subtype A strains isolated from the former Soviet Union in phylogenetic analysis. No mutations associated with drug resistance were detected. The Republic of Moldova is culturally more closely related to Romania (where subtype F dominates the epidemic), but depends economically on Russia (where subtype A is established among IDUs). Thus, our results suggest that the spread of HIV in this region is driven by drug networks rather than being due to cultural similarities.

Diversity of Human Immunodeficiency Virus Type 1 Subtype A and CRF03_AB Protease in Eastern Europe: Selection of the V77I Variant and Its Rapid Spread in Injecting Drug User Populations

“…Figure 1 shows a neighbor-joining tree of the protease encoding sequences. As expected, all 27 sequences belonged to the HIV-1 genetic subtype A (A1) and clustered with the nucleotide sequences from the HIV-1 GenBank previously derived from IDUs in Russia, the Ukraine, Belarus, and Moldova (25,26,28,34). The clustering with subtype A was also observed for the nucleotide sequences 97RU1306, 97RU1308, 97RU1313, and 01RU879 derived from individuals infected with the circulating recombinant form CRF03AB, as well as for the CRF03AB variants CRF03AB KAL153, RU98001, and 98BY10443 published previously (25,26).…”

“…Phylogenetic relationships were determined as described in Materials and Methods. The Eastern European nucleotide sequences from the Ukraine (98UA0116), Belarus (97BL006 and BY10443), Russia (RU98001 and KAL153), Moldova (97MD10 to -19), and Spain (LP27) published previously (GenBank accession numbers AF413987, AF193275, AF414006, AF193277, AF193276, AF400675 to AF400680, and AF455622, respectively) (18,25,26,28,34), as well as the representative sequences of genetic subtypes A1, A2, B, and C from the Los Alamos database, were also included in the analysis.…”

“…At present, within the territory of the Russian Federation and a number of other former Soviet Union republics (the Ukraine, Moldova, Belarus, Kazakhstan, Estonia, Latvia, Lithuania, Uzbekistan, Georgia, and Azerbaijan) HIV-1 subtype A variants predominate, circulating among injecting drug users (IDUs) and their sexual partners (3,6,7,23,25,27,31,32,34 (4,5,25). To obtain such information, we analyzed HIV-1 genetic variants, along with conventional sequencing, by using oligonucleotide microarrays that have already been proven to be used as a diagnostic tool for identifying nucleic acid polymorphisms (24,29,41).…”

Distinct HIV Type 1 Strains in Different Risk Groups and the Absence of New Infections by Drug-Resistant Strains in Lithuania

“…1 Molecular epidemiological studies demonstrated that of these two viruses, the IDU-A strains have spread throughout the whole FSU territory and account for around 90% of over a million of HIV-1-infected individuals in the region. 2 These strains are dominating in Azerbaijan, 3 Belarus, 4,5 Georgia, 6 Kazakhstan, 7,8 Latvia, 9,10 Moldova, 11 Russia, 2,12 Tajikistan, 13 Ukraine, 1,14,15 and Uzbekistan 16,17 and are the second (after CRF06_cpx strains) major cause of infections in Estonia. 18,19 In this explosive HIV-1 epidemic in the FSU, Lithuania remains among the least affected countries with 1,900 registered HIV-1 infections (as of January 1, 2012, 0.06% of the population, our own data), with the UNAIDS estimation of the prevalence of HIV-1 in the adult population being 0.1% (all UNAIDS estimations are from www.unaids.org/en/ dataanalysis/tools/aidsinfo/).…”

Unequal Evolutionary Rates in the Human Immunodeficiency Virus Type 1 (HIV-1) Pandemic: the Evolutionary Rate of HIV-1 Slows Down When the Epidemic Rate Increases

“…Until 1995, countries of the FSU experienced only a few hundred cases of HIV-1 infection, most of which were associated with sexual transmissions. The first outbreaks of HIV-1 among IDUs in the FSU were reported in 1995 in southern Ukraine (48), followed by rapid spread of the virus in this risk group in the Russian Federation (3,5) and its neighboring countries Belarus and the Republic of Moldova in 1996 (41,50). In 1997, the virus had spread to the Baltic region, inducing a fast-growing epidemic among IDUs in Latvia and later Estonia (2,15,64).…”