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Evidence for possible biological advantages of the newly emerging HIV-1 circulating recombinant form from Malaysia - CRF33_01B in comparison to its progenitors - CRF01_AE and subtype B

Lau KA, Wang B, Miranda-Saksena M, Boadle R, Kamarulzaman A, Ng KP, et al.

Curr. HIV Res., 2010 Apr;8(3):259-71.
PMID: 20214658

In Malaysia, co-circulation of CRF01_AE and subtype B has resulted in the emergence of the second generation derivative; CRF33_01B in approximately 20% of its HIV-1 infected individuals. Our objective was to identify possible biological advantages that CRF33_01B possesses over its progenitors. Biological and molecular comparisons of CRF33_01B against its parental subtypes clearly show that CRF33_01B replicated better in activated whole peripheral blood mononuclear cells (PBMCs) and CD4+ T-lymphocytes, but not monocyte-derived macrophages (MDMs). Also, its acquired fitness was greater than CRF01_AE but not subtype B. Moreover, CRF33_01B has higher rate of apoptotic cell death and syncytia induction compared to subtype B. These adaptive and survival abilities could have been acquired by CRF33_01B due to the incorporation of subtype B fragments into the gag-RT region of its full-length genome. Our studies confirm the previously held belief that HIV-1 strains may harbor enhanced biological fitness upon recombination. We therefore estimate a possible gradual replacement of the current predominance of CRF01_AE, as well as wider dissemination of CRF33_01B, together with the identification of other new CRF01_AE/B inter-subtype recombinants in Malaysia.
Continuous crossover(s) events of HIV-1 CRF01_AE and B subtype strains in Malaysia: evidence of rapid and extensive HIV-1 evolution in the region

Lau KA, Wang B, Kamarulzaman A, Ngb KP, Saksena NK

Curr. HIV Res., 2008 Mar;6(2):108-16.
PMID: 18336258

The Asian HIV epidemic appears to be complex, characterized by the prevalence of multiple subtypes and circulating recombinant forms with gradual replacement of pure HIV-1 subtypes in several geographical regions. The main objectives of the present study are to identify and analyse the full-length viral genomes of three unique recombinant forms (URFs); the HIV-1 isolates 07MYKLD47, 07MYKLD48 and 07MYKLD49 from Malaysia. Long-range polymerase chain reaction (PCR) amplification of seven overlapping reading frames was used to derive near full-length HIV-1 genomes. Detailed phylogenetic and bootscanning analyses were performed to determine phylogenetic associations and subtypic assignments. We further confirmed the mosaic composition of these CRF01_AE/B inter-subtype recombinant forms, which are composed of B-subtype fragment(s) in the backbone of CRF01_AE. Both 07MYKLD47 and 07MYKLD48 have an insertion of B subtype (880 bp and 532 bp) in the gag-pol and gp41-env gene regions, respectively. Whereas the isolate 07MYKLD49 has three B-subtype fragments inserted in different gene region along the genome; one each in the gag-pol (1862 bp) and pol-vif (1935 bp) regions, and a short B-subtype insertion (541 bp) in the 5' LTR-gag region. This highlights the public health relevance of newly emerging second generation HIV-1 recombinant forms and their dispersal, along with their rapid and continuous evolution in the region.
AIDS-defining illnesses: a comparison between before and after commencement of highly active antiretroviral therapy (HAART)

Lian YL, Heng BS, Nissapatorn V, Lee C

Curr. HIV Res., 2007 Sep;5(5):484-9.
PMID: 17896968

Attempts to address the significant impact of HAART on medical variables on the Malaysian HIV/AIDS population have yet to be evaluated. This study aims to analyze the proportions of AIDS-defining illnesses (ADIs) before and after HAART. A retrospective study was carried out on 128 new cases of HIV infected patients who first commenced HAART in 2004 at the national HIV reference center. Before commencement of HAART, 76 clinical episodes of ADIs were recorded in 52 patients. Most common being pulmonary Mycobacterium tuberculosis (28.9%), PCP (27.6%) and disseminated and extrapulmonary Mycobacterium tuberculosis (11.8%). During HAART, 8 clinical episodes of ADIs were documented in 7 patients with a median time of onset of 10 weeks after initiation of HAART (range, 4-36 weeks). The median CD4 count at the time of the commencement of HAART for these patients was 11 cells/mm(3). ADIs reported include PCP (2 episodes), disseminated and extrapulmonary Mycobacterium tuberculosis (2 episodes), extrapulmonary cryptococcosis (1 episode), esophageal candidiasis (1 episode), recurrent pneumonia (1 episode) and disseminated or extrapulmonary histoplasmosis (1 episode). Three (37.5%) of these occurred despite a reduction of viral load by at least 2 log(10) and an increased in the CD4 cell count. In conclusion, ADIs can still present after the initiation of successful HAART especially in those with CD4 counts below 100 cells/mm(3). In Malaysia, ADIs are the major causes of HIV/AIDS associated morbidity and mortality, thus increased awareness on the management of these illnesses is warranted especially in the months following HAART.
HIV-specific T-cell Responses and Generalized Activation in HIV-1 Infected Long-term Non-progressors and Progressors from South India

Swathirajan CR, Vignesh R, Waldrop G, Shanmugasundaram U, Nandagopal P, Solomon SS, et al.

Curr. HIV Res., 2018;16(4):302-314.
PMID: 30543175 DOI: 10.2174/1570162X17666181212122607

BACKGROUND: Anti-viral cytokine expressions by cytotoxic T-cells and lower activation rates have been reported to correlate with suppressed HIV replication in long-term non-progressors (LTNP). Immune mechanisms underlying disease non-progression in LTNP might vary with HIV-1 subtype and geographical locations.
OBJECTIVE: This study evaluates cytokine expression and T-cells activation in relation to disease non-progression in LTNP.
METHODS: HIV-1 Subtype C infected LTNP (n=20) and progressors (n=15) were enrolled and flowcytometry assays were performed to study HIV-specific CD8 T-cells expressing IL-2, IFN-γ, TNF-α and MIP-1β against gag and env peptides. CD4+ T-cell activation was evaluated by surface expression of HLADR and CD38.
RESULTS: Proportions of cytokines studied did not differ significantly between LTNP and progressors, while contrasting correlations with disease progression markers were observed in LTNP. CD4+ T-cell activation rates were significantly lower in LTNP compared to progressors which indicate the potential role of T-cell activation rates in disease non-progression in LTNP.
CONCLUSION: LTNP and progressors showed similar CD8+ T-cell responses, but final conclusions can be drawn only by comparing multiple immune factors in larger LTNP cohort with HIV-1 infected individuals at various levels of disease progression. A possible role of HIV-1 subtype variation and ethnic differences in addition to host-genetic and viral factors cannot be ruled out.