Positively charged amino acid substitutions at positions 11 and 25 within the loop of the third variable region (V3) of HIV-1 subtype B envelope have been shown to be associated with the syncytium-inducing (SI) phenotype of the virus. The present study was designed to examine SI and NSI-associated V3 mutations in HIV-1 subtypes other than B. HIV-1 RNA was isolated from 53 virus stocks and 26 homologous plasma samples from 53 recently infected individuals from Brazil, Rwanda, Thailand, and Uganda. The C2-V3 region of the viral envelope was converted to cDNA, amplified, and sequenced. Of 53 primary virus stock samples 49 were biologically phenotyped through measurement of the syncytium-inducing capacity in MT-2 cells (to differentiate between SI and NSI phenotypes). In addition, after passage of primary isolates through PHA stimulated donor PBMC, the replication capacity was determined in U937-2, CEM, MT-2, and Jurkat-tat cell lines (to differentiate rapid/high and slow/low phenotypes). According to the sequence analysis 9 (17.0%) of the viruses belonged to subtype A, 15 (28.3%) to subtype B, 1 (1.9%) to subtype C, 13 (24.5%) to subtype D, and 15 (28.3%) to subtype E. Sequence analysis of virus RNA, obtained from 26 homologous plasma samples, confirmed the homogeneity of sequence populations in plasma compared to primary virus isolates. Of the 49 viruses tested 12 had the SI phenotype, 5 were confirmed to be rapid/high, and 4 appeared to be slow/low pattern 3 replicating. Of 49, 29 had the NSI phenotype, 24 were confirmed to be slow/low pattern 1 or 2, and 3 appeared to be slow/low pattern 3 replicating. Analysis of mutations at V3 loop amino acid positions 11 and 25 revealed that 10/12 (83.3%) of the SI viruses had SI-associated V3 mutations and that 28/29 (96.6%) of the NSI viruses lacked these mutations. V3 loop heterogeneity, length polymorphism, and a high number of positively charged amino acid substitutions were most frequently found among subtype D variants. These results indicate that both the phenotypic distinction between SI and NSI viruses and the association of biological phenotype with V3 mutations is present among HIV-1 subtypes other than B.
BackgroundGlobal HIV-1 genetic diversity and evolution form a major challenge to treatment and prevention efforts. An increasing number of distinct HIV-1 recombinants have been identifiedworldwide, but their contribution to the global epidemic is unknown. We aimed to estimate the global and regional distribution of HIV-1 recombinant forms during 1990-2015.
MethodsWe assembled a global HIV-1 molecular epidemiology database through a systematic literature review and a global survey. We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published from Jan 1, 1990, to Dec 31, 2015. Unpublished original HIV-1 subtyping data was collected through a survey among experts in the field who were members of the WHO-UNAIDS Network for HIV Isolation and Characterisation. We included prevalence studies with HIV-1 subtyping data collected during 1990-2015. Countries were grouped into 14 regions and analyses conducted for four time periods (1990-99, 2000-04, 2005-09 and 2010-15). The distribution of circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV in each country to generate regional and global estimates of numbers and proportions of HIV-1 recombinants in each time period. The systematic review is registered with PROSPERO, number CRD42017067164.
The AIDS Information Center (AIC) was established in Kampala, Uganda in 1990 in response to increasing interest by members of the general public who wished to know their HIV serostatus. By 1996, >300,000 clients had been seen. HIV serologic testing was performed at a central laboratory and results reported back to AIC after 2 weeks. Approximately 25% of clients failed to learn their HIV serostatus as a result of failure to return or late arrival of results. To address these issues, AIC carried out an evaluation of 3 rapid HIV assays, Sero-Strip, SeroCard, and Capillus, against a standard criterion to identify a testing algorithm that could be used as an on-site confirmatory testing strategy. The study was carried out over a period of 5 working days and 325 clients were seen. An algorithm was identified, which gave no indeterminate results with unambiguously positive or negative specimens, which was 100% sensitive and specific, and which could be integrated with minimal disruption into existing counseling procedures. All clients left AIC knowing their HIV serostatus and having spent <2 hours at the Center. The results of this evaluation demonstrate that "same-day" results can be provided in counseling and testing settings without compromising the quality of counseling or the accuracy of HIV testing.
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