Effect of Human Immunodeficiency Virus Type 1 (HIV‐1) Subtype on Disease Progression in Persons from Rakai, Uganda, with Incident HIV‐1 Infection

Kiwanuka, Noah; Laeyendecker, Oliver; Robb, Merlin L.; Kigozi, Godfrey; Arroyo, Mônica; McCutchan, Francine E.; Eller, Leigh Anne; Eller, Michael A.; Makumbi, Fred; Birx, Deborah L.; Wâbwire-Mângen, Fred; Serwadda, David; Sewankambo, Nelson; Quinn, Thomas C.; Wawer, Maria J.; Gray, Ronald H.

doi:10.1086/527416

Cited by 242 publications

(236 citation statements)

References 28 publications

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“…A significantly higher baseline CD4 count (median 68 versus 19; Mann-Whitney test, two-tailed, p = 0.04) was observed in AMU participants who achieved suppression within 180 days posttherapy (Supplementary Tables S2 and S3). Subtype bias may be introduced because subtype D has been shown with limited evidence to have a more rapid disease progression in treatment-naive individuals in Africa [24][25][26][27] ; no statistically significant difference was found between D and non-D subtypes (Supplementary Tables S1-3).…”

Section: Virologic Consequencesmentioning

confidence: 99%

Prevalence and Virologic Consequences of Transmitted HIV-1 Drug Resistance in Uganda

Lee

Bangsberg

Muzoora

et al. 2014

AIDS Research and Human Retroviruses

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Few reports have examined the impact of HIV-1 transmitted drug resistance (TDR) in resource-limited settings where there are fewer regimen choices and limited pretherapy/posttherapy resistance testing. In this study, we examined TDR prevalence in Kampala and Mbarara, Uganda and assessed its virologic consequences after antiretroviral therapy initiation. We sequenced the HIV-1 protease/reverse transcriptase from n = 81 and n = 491 treatment-naive participants of the Uganda AIDS Rural Treatment Outcomes (UARTO) pilot study in Kampala (AMU 2002(AMU -2004 and main cohort in Mbarara (MBA 2005(MBA -2010. TDR-associated mutations were defined by the WHO 2009 surveillance mutation list. Posttreatment viral load data were available for both populations. Overall TDR prevalence was 7% (Kampala) and 3% (Mbarara) with no significant time trend. There was a slight but statistically nonsignificant trend indicating that the presence of TDR was associated with a worse treatment outcome. Virologic suppression (£ 400 copies/ml within 6 months posttherapy initiation) was achieved in 87% and 96% of participants with wildtype viruses versus 67% and 83% of participants with TDR (AMU, MBA p = 0.2 and 0.1); time to suppression (log-rank p = 0.3 and p = 0.05). Overall, 85% and 96% of study participants achieved suppression regardless of TDR status. Surprisingly, among the TDR cases, approximately half still achieved suppression; the presence of pretherapy K103N while on nevirapine and fewer active drugs in the first regimen were most often observed with failures. The majority of patients benefited from the local HIV care system even without resistance monitoring. Overall, TDR prevalence was relatively low and its presence did not always imply treatment failure.

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Section: Virologic Consequencesmentioning

confidence: 99%

Prevalence and Virologic Consequences of Transmitted HIV-1 Drug Resistance in Uganda

Lee

Bangsberg

Muzoora

et al. 2014

AIDS Research and Human Retroviruses

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“…4,5 Different HIV-1 subtypes exhibit differences in frequency and route of virus transmission, in the pathogenesis of the disease as well as in the kinetics and mechanisms of drug resistance development, thus potentially affecting HIV-1 disease management. 3,6,7 In view of the above, we aimed to investigate key resistance mutations in the reverse transcriptase (RT) and protease genes following ART rollout in a rural setting in Ifakara, Tanzania.…”

mentioning

confidence: 99%

Prevalence of Drug Resistance Mutations and HIV Type 1 Subtypes in an HIV Type 1-Infected Cohort in Rural Tanzania

Masimba

Kituma

Klimkait

et al. 2013

AIDS Research and Human Retroviruses

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The development of resistance mutations in drug-targeted HIV-1 genes compromises the success of antiretroviral therapy (ART) programs. Genotyping of these mutations enables adjusted therapeutic decisions both at the individual and population level. We investigated over time the prevalence of HIV-1 primary drug resistance mutations in treatment-naive patients and described the HIV-1 subtype distribution in a cohort in rural Tanzania at the beginning of the ART rollout in 2005-2007 and later in 2009. Viral RNA was analyzed in 387 baseline plasma samples from treatment-naive patients over a period of 5 years. The reverse transcriptase (RT) and protease genes were reversely transcribed, polymerase chain reaction (PCR) amplified, and directly sequenced to identify HIV-1 subtypes and single nucleotide polymorphisms associated with drug resistance (DR-SNPs). The prevalence of major DR-SNPs in 2005-2007 in the RT gene was determined: K103N (5.0%), Y181C (2.5%), M184V (2.5%), and G190A (1.7%), and M41L, K65KR, K70KR, and L74LV (0.8%). In samples from 2009 only K103N (3.3%), M184V, and T215FY (0.8%) were detected. Initial frequencies of subtypes C, A, D, and recombinants were 43%, 32%, 18%, and 7%, respectively. Later similar frequencies were found except for the recombinants, which were found twice as often (15%), highlighting the subtype diversity and a relatively stable subtype frequency in the area. DR-SNPs were found at initiation of the cohort despite very low previous ART use in the area. Statistically, frequencies of major mutations did not change significantly over the studied 5-year interval. These mutations could reflect primary resistances and may indicate a possible risk for treatment failure.

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“…The probability of having a CXCR4-using virus is higher in subtype D than in subtype A infections in non-AIDS clinical status in Uganda [35,36]. A high prevalence of X4 tropism among CRF14_BG-infected IDUs was also recently reported in Spain [37] as well as the association of CRF01_AE with the predicted X4 phenotype in Thailand [38].…”

Section: Discussionmentioning

confidence: 74%

Co-Receptor Tropism Determined by Genotypic Assay in HIV-1 Circulating in Cuba

Kourí¹,

Alemán²

2016

J AIDS Clin Res

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Effect of Human Immunodeficiency Virus Type 1 (HIV‐1) Subtype on Disease Progression in Persons from Rakai, Uganda, with Incident HIV‐1 Infection

Abstract: HIV disease progression is affected by HIV-1 subtype. This finding may impact decisions on when to initiate antiretroviral therapy and may have implications for future trials of HIV-1 vaccines aimed at slowing disease progression.

Cited by 242 publications

References 28 publications

Prevalence and Virologic Consequences of Transmitted HIV-1 Drug Resistance in Uganda

Prevalence and Virologic Consequences of Transmitted HIV-1 Drug Resistance in Uganda

Prevalence of Drug Resistance Mutations and HIV Type 1 Subtypes in an HIV Type 1-Infected Cohort in Rural Tanzania

Co-Receptor Tropism Determined by Genotypic Assay in HIV-1 Circulating in Cuba

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