Human Immunodeficiency Virus Type 1 Subtypes Differ in Disease Progression

Kanki, Phyllis J.; Hamel, Donald J.; Sankalé, Jean-Louis; Hsieh, Chung‐Cheng; Thior, Ibou; Barin, Françis; Woodcock, Stephen A.; Guèye-Ndiaye, Aı̈ssatou; Er, Zhang; Montano, Monty; Siby, Tidiane; Marlink, Richard; Ndoye, Ibrahima; Essex, M.; Mboup, Souleymane

doi:10.1086/314557

Cited by 335 publications

(215 citation statements)

References 24 publications

(28 reference statements)

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“…HIV-1 clade C-infected sex workers in Nairobi and Senegal showed higher viral loads 37 and more advanced disease 38 than those with subtype A or D infection. The viral loads in our study were also higher than those reported for Uganda, although we used an older version of the Roche Monitor HIV-1 PCR (1.0 vs. version 1.5 used in the Uganda study).…”

Section: Discussionmentioning

confidence: 89%

Virologic and Immunologic Determinants of Heterosexual Transmission of Human Immunodeficiency Virus Type 1 in Africa

Fideli

Allen

Musonda

et al. 2001

AIDS Research and Human Retroviruses

331

281

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More than 80% of the world's HIV-infected adults live in sub-Saharan Africa, where heterosexual transmission is the predominant mode of spread. The virologic and immunologic correlates of femaleto-male (FTM) and male-to-female (MTF) transmission are not well understood. A total of 1022 heterosexual couples with discordant HIV-1 serology results (one partner HIV infected, the other HIV uninfected) were enrolled in a prospective study in Lusaka, Zambia and monitored at 3-month intervals. A nested case-control design was used to compare 109 transmitters and 208 nontransmitting controls with respect to plasma HIV-1 RNA (viral load, VL), virus isolation, and CD4 + cell levels. Median plasma VL was significantly higher in transmitters than nontransmitters (123,507 vs. 51,310 copies/ml, p < 0.001). In stratified multivariate Cox regression analyses, the risk ratio (RR) for FTM transmission was 7.6 (95% CI: 2.3, 25.5) for VL ≥ 100,000 copies/ ml and 4.1 (95% CI: 1.2, 14.1) for VL between 10,000 and 100,000 copies/ml compared with the reference group of <10,000 copies/ ml. Corresponding RRs for MTF transmission were 2.1 and 1.2, respectively, with 95% CI both bounding 1. Only 3 of 41 (7%) female transmitters had VL < 10,000 copies/ml compared with 32 of 93 (34%) of female nontransmitters (p < 0.001). The transmission rate within couples was 7.7/100 person-years and did not differ from FTM (61/862 person-years) and MTF (81/978 person-years) transmission. We conclude that the association between increasing plasma viral load was strong for female to male transmission, but was only weakly predictive of male to female transmission in Zambian heterosexual couples. FTM and MTF transmission rates were similar. These data suggest gender-specific differences in the biology of heterosexual transmission.Address reprint requests to: Grace M. Aldrovandi,

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Section: Discussionmentioning

confidence: 89%

Virologic and Immunologic Determinants of Heterosexual Transmission of Human Immunodeficiency Virus Type 1 in Africa

Fideli

Allen

Musonda

et al. 2001

AIDS Research and Human Retroviruses

331

281

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“…In addition, clinical follow-up studies revealed that subtype C-infected individuals might develop AIDS easier than those infected with other subtypes (27). This appears to be derived from biologically different viruses derived from individual subtype such as rapid and high replication rates as well as more efficient transmission rate.…”

Section: Discussionmentioning

confidence: 99%

“…3, similar results were obtained by pLTR-Luc derived from subtype E and C LTR sequences (data not shown). When we constructed the mutant Tat with serine in place of Cys 27 , Cys 30 , Cys 31 , and Cys 34 , it was found that the resultant Tats including C-Tat similarly lost their activities in Jurkat cells (data not shown). Together, these results suggest that the cysteine-rich motif in C-Tat is important for interaction to human cyclin T1.…”

Section: No Involvement Of a Cysteine-rich Motif And 2nd Exon Of Tat mentioning

confidence: 99%

Human Immunodeficiency Virus Type 1 Subtype C Exhibits Higher Transactivation Activity of Tat than Subtypes B and E

Kurosu

Mukai

Komoto

et al. 2002

Microbiology and Immunology

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Although human immunodeficiency virus type 1 (HIV‐1) subtypes C and E are expanding faster and seem to be of greater global significance than HIV‐1 subtype B, there is only little information about Tat activity of such non‐B subtypes. Here, we showed evidence that subtype C Tat exhibits higher transcriptional activity from the HIV‐1 long‐terminal repeat (LTR) in a human T‐cell line, compared with subtypes B and E. This higher activity of subtype C Tat was not due to the LTR, but to the Tat sequence variability. We examined three candidate regions with sequence for the higher activity of subtype C Tat, such as the cysteine‐rich motif, the basic domain, and the 2nd exon. The results showed that the variation in subtype C Tat at two amino acid residues, Ser57 and Glu63 in stead of Arg57 and Gln63 in subtypes B and E, within and close to the basic domain were involved in the higher activity of subtype C Tat. This variation did not affect its nuclear localization activity. Thus, there may be a significant advantage for the high Tat activity on subtype C replication.

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“…Available data from African and Caribbean populations strongly suggest that time to development of clinical outcome, after HIV infection, is significantly compressed compared to US and European populations, and that differences in the health care delivery systems account for only a part of this accelerated disease process. These therapeutic programs and approaches must also be carefully considered and anchored in what is known about the pathogenesis of HIV/AIDS in such populations and not simply the blanket application of known US and Europe therapeutic strategies [43][44][45][46].…”

Section: Opportunities For Successmentioning

confidence: 99%

Approaches to antiretroviral therapy in China

Gilliam

Redfield

2005

Cell Res

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China has recognized the threat of HIV to its population and responded with a national antiretroviral treatment (ART) program. However, high ART failure rates and the spread of resistance within populations are important realities to consider when developing and managing ART programs in China and worldwide. Concepts which will define treatment success and local and national programmatic goals are 1) access to ART, 2) durability of ART at the patient level, 3) scalability of treatment modalities, and the 4) sustainability of the program at the community or national level. In the face of limited resources, China must also consider when to start ARV therapy, which agents to use, when to switch them, and how to treat highly experienced patients with drug resistance. The optimal ARV regimen to start with is changing frequently with the introduction of new agents and the presentation of new data. Currently, a regimen including tenofovir, emtricitabine or lamivudine and a nonnucleoside reverse transcriptase inhibitor appears to have optimal characteristics to treat HIV/AIDS in China. However, critical to all of these choices is the evaluation of programs implemented to insure wide scale success. China has wisely begun this process of evaluating the performance of local programs through systematic monitoring and evaluation of treatment outcomes. This will allow regimens and programs that work to be expanded, and programs with high failure rates to be eliminated. In the end, evidence based data supporting treatment strategies will allow China to successfully confront its AIDS epidemic early and prevent its tragic consequences

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Human Immunodeficiency Virus Type 1 Subtypes Differ in Disease Progression

Cited by 335 publications

References 24 publications

Virologic and Immunologic Determinants of Heterosexual Transmission of Human Immunodeficiency Virus Type 1 in Africa

Virologic and Immunologic Determinants of Heterosexual Transmission of Human Immunodeficiency Virus Type 1 in Africa

Human Immunodeficiency Virus Type 1 Subtype C Exhibits Higher Transactivation Activity of Tat than Subtypes B and E

Approaches to antiretroviral therapy in China

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