Faster Progression to AIDS and AIDS-Related Death Among Seroincident Individuals Infected With Recombinant HIV-1 A3/CRF02_AG Compared With Sub-subtype A3

Palm, Angelica A.; Esbjörnsson, Joakim; Månsson, Fredrik; Kvist, Anders; Isberg, Per‐Erik; Biague, Antonio; Silva, Zacarias José da; Jansson, Marianne; Norrgren, Hans; Medstrand, Patrik

doi:10.1093/infdis/jit416

Cited by 35 publications

(46 citation statements)

References 38 publications

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“…Studies in East Africa, where subtypes A and D cocirculate, have established that subtype D is associated with faster disease progression than subtype A (10-13). There is also evidence that recombinant forms have a higher rate of progression to AIDS than does subtype A (10,14), although this was not observed in another study (12). There are conflicting reports regarding the rate of disease progression of subtype C relative to that of other subtypes (12,(15)(16)(17)(18).…”

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confidence: 97%

Subtype-Specific Differences in Gag-Protease-Driven Replication Capacity Are Consistent with Intersubtype Differences in HIV-1 Disease Progression

Kiguoya

Mann

Chopera

et al. 2017

J Virol

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There are marked differences in the spread and prevalence of HIV-1 subtypes worldwide, and differences in clinical progression have been reported. However, the biological reasons underlying these differences are unknown. Gag-protease is essential for HIV-1 replication, and Gag-protease-driven replication capacity has previously been correlated with disease progression. We show that Gag-protease replication capacity correlates significantly with that of whole isolates (r ϭ 0.51; P ϭ 0.04), indicating that Gag-protease is a significant contributor to viral replication capacity. Furthermore, we investigated subtype-specific differences in Gag-proteasedriven replication capacity using large well-characterized cohorts in Africa and the Americas. Patient-derived Gag-protease sequences were inserted into an HIV-1 NL4-3 backbone, and the replication capacities of the resulting recombinant viruses were measured in an HIV-1-inducible reporter T cell line by flow cytometry. Recombinant viruses expressing subtype C Gag-proteases exhibited substantially lower replication capacities than those expressing subtype B Gag-proteases (P Ͻ 0.0001); this observation remained consistent when representative Gag-protease sequences were engineered into an HIV-1 subtype C backbone. We identified Gag residues 483 and 484, located within the Alix-binding motif involved in virus budding, as major contributors to subtype-specific replicative differences. In East African cohorts, we observed a hierarchy of Gag-protease-driven replication capacities, i.e., subtypes A/C Ͻ D Ͻ intersubtype recombinants (P Ͻ 0.0029), which is consistent with reported intersubtype differences in disease progression. We thus hypothesize that the lower Gagprotease-driven replication capacity of subtypes A and C slows disease progression in individuals infected with these subtypes, which in turn leads to greater opportunity for transmission and thus increased prevalence of these subtypes.IMPORTANCE HIV-1 subtypes are unevenly distributed globally, and there are reported differences in their rates of disease progression and epidemic spread. The biological determinants underlying these differences have not been fully elucidated. Here, we show that HIV-1 Gag-protease-driven replication capacity correlates with Citation Kiguoya MW, Mann JK, Chopera D, Gounder K, Lee GQ, Hunt PW, Martin JN, Ball TB, Kimani J, Brumme ZL, Brockman MA, Ndung'u T. 2017. Subtype-specific differences in Gagprotease-driven replication capacity are consistent with intersubtype differences in HIV-1 disease progression. J Virol 91:e00253-17.

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confidence: 97%

Subtype-Specific Differences in Gag-Protease-Driven Replication Capacity Are Consistent with Intersubtype Differences in HIV-1 Disease Progression

Kiguoya

Mann

Chopera

et al. 2017

J Virol

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“…[6][7][8] Although studies have indicated that subtype differences may not have an effect on the response to cART, particularly in HIV-1 group M strains, 9,10 recombinant strains may complicate the course of HIV infection. 11 Studies have implicated globalization and the movement of people from different geographic areas in the increasing rise in recombinant HIV strains. 2,12 In South Africa, HIV-1 subtype C has been reported to be the predominant strain.…”

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confidence: 99%

“…8,[16][17][18] Monitoring the genetic diversity of circulating HIV strains has been encouraged to generate information on patient management and even vaccine strategies. 3 Recently, Palm et al 11 demonstrated increased risk of AIDS and AIDS-related death in individuals infected with recombinant strain HIV-1 A3/CRF02_AG. The recombinant virus was found to be more virulent causing AIDS and AIDSrelated death between 5.0 and 8.0 years from the time of seroconversion.…”

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confidence: 99%

“…The recombinant virus was found to be more virulent causing AIDS and AIDSrelated death between 5.0 and 8.0 years from the time of seroconversion. 11 This study describes the first unique near full length HIV-1 recombinant strain isolated from a rural South African heterosexual female who was referred to the Dr. George Mukhari Academic Hospital (DGMAH) in Pretoria.…”

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confidence: 99%

“…Palm et al 11 revealed an increased risk of AIDS and AIDS-related deaths in patients infected with an HIV recombinant A3/02 strain rather than their parental strains. This emphasizes the need for continual surveillance of HIV genetic diversity to aid in management, diagnosis, and prevention strategies.…”

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confidence: 99%

See 2 more Smart Citations

Identification and Genetic Characterization of Unique HIV-1 A1/C Recombinant Strain in South Africa

Musyoki

Rakgole

Selabe

et al. 2015

AIDS Research and Human Retroviruses

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Impact of HIV/aids epidemic on human capital development in West Africa

Dauda

2018

Health Planning & Management

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West Africa occupies the third position with respect to the burden of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) globally, after Southern and East Africa. About 5 million adults and children are infected with the disease in the subregion, while HIV prevalence in the general population hovers around 2% and 5%. This paper attempts to investigate the impact of HIV/AIDS epidemic on human capital development in 11 West African countries over the period 1990 to 2011. The study used a dynamic panel data modeling approach, using first difference, difference generalized methods of moment, and system generalized methods of moment estimating techniques. Four measures of HIV/AIDS and 2 human capital measures were used in the study. The findings revealed that HIV/AIDS pandemic had negative and significant impact on human capital in West Africa. However, the statistical significance was more pronounced on life expectancy (a measure of human capital), while the negative impact on school enrolment (another human capital measure) was not significant. It is therefore recommended that the spread of HIV/AIDS disease in West Africa should be effectively controlled, while the number of infected persons undergoing antiretroviral therapy in the subregion should be increased to a near 100% coverage.

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Faster Progression to AIDS and AIDS-Related Death Among Seroincident Individuals Infected With Recombinant HIV-1 A3/CRF02_AG Compared With Sub-subtype A3

Cited by 35 publications

References 38 publications

Subtype-Specific Differences in Gag-Protease-Driven Replication Capacity Are Consistent with Intersubtype Differences in HIV-1 Disease Progression

Subtype-Specific Differences in Gag-Protease-Driven Replication Capacity Are Consistent with Intersubtype Differences in HIV-1 Disease Progression

Identification and Genetic Characterization of Unique HIV-1 A1/C Recombinant Strain in South Africa

Impact of HIV/aids epidemic on human capital development in West Africa

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