HIV-1 tropism and CD4 T lymphocyte recovery in a prospective cohort of patients initiating HAART in Ribeirão Preto, Brazil

Lança, André Minhoto; Collares, Jeova Keny Baima; Ferreira, João Leandro de Paula; Lima, Danielle Malta; Brígido, Luis Fernando de Macedo; Rodrigues, Rosangela; Fonseca, Benedito Antônio Lopes da

doi:10.1590/s0074-02762012000100014

Cited by 6 publications

(7 citation statements)

References 16 publications

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“…This TDR prevalence was similar to that reported in other regions of Brazil that used Stanford CPR criteria for these estimates, [4–12, 15]. The reasons for this stabilization, or even decrease of TDR prevalence in most surveys are unclear, but there may well be a plateau where the circulation of mutated isolates may come to some equilibrium, depending on multiple factors as the ARV therapy usage, therapy combinations, adherence, and social networking, among others.…”

Section: Discussionsupporting

confidence: 85%

Transmitted Drug Resistance among People Living with HIV/Aids at Major Cities of Sao Paulo State, Brazil

Ferreira

Rodrigues

Lança

et al. 2013

Advances in Virology

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Human immunodeficiency virus type 1 (HIV-1) transmitted drug resistance (TDR) is an important public health issue. In Brazil, low to intermediate resistance levels have been described. We assessed 225 HIV-1 infected, antiretroviral naïve individuals, from HIV Reference Centers at two major metropolitan areas of Sao Paulo (Sao Paulo and Campinas), the state that concentrates most of the Brazilian Aids cases. TDR was analyzed by Stanford Calibrated Population Resistance criteria (CPR), and mutations were observed in 17 individuals (7.6%, 95% CI: 4.5%–11.9%). Seventy-six percent of genomes (13/17) with TDR carried a nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutation, mostly K103N/S (9/13, 69%), potentially compromising the preferential first-line therapy suggested by the Brazilian HIV Treatment Guideline that recommends efavirenz-based combinations. Moreover, 6/17 (35%) had multiple mutations associated with resistance to one or more classes. HIV-1 B was the prevalent subtype (80%); other subtypes include HIV-1 F and C, mosaics BC, BF, and single cases of subtype A1 and CRF02_AG. The HIV Reference Center of Campinas presented more cases with TDR, with a significant association of TDR with clade B infection (P < 0.05).

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Section: Discussionsupporting

confidence: 85%

Transmitted Drug Resistance among People Living with HIV/Aids at Major Cities of Sao Paulo State, Brazil

Ferreira

Rodrigues

Lança

et al. 2013

Advances in Virology

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“…The increase in CD4+ T cell numbers in response to therapy during the three-year follow-up period was comparable between patients with or without X4-HIV variants, confirming previous reports [20-22]. However, a smaller CD4+ T cell increase during cART in patients with X4-HIV has also been reported [18,19].…”

Section: Discussionsupporting

confidence: 88%

“…The risk of virological failure was comparable for patients with or without X4-HIV at baseline. Furthermore, CXCR4 coreceptor use of the virus does not influence the increase in CD4+ T cell counts upon start of therapy, confirming previous observations [20-22]. However, patients harboring X4-HIV variants do initiate cART with lower CD4+ T cell counts, which as a consequence results in lower CD4+ T cell counts in the first years after start of cART as compared to patients with only R5-HIV.…”

Section: Discussionsupporting

confidence: 84%

“…Whether the presence of X4-HIV before start of treatment influences the response to combination antiretroviral therapy (cART) is controversial [18-22]. Some reports describe a worse treatment response regarding viral load decline or CD4+ T cell increase in patients carrying X4-HIV variants [18-20], whereas other papers show similar rates of viral suppression for patients with and without X4-HIV variants upon start of antiretroviral therapy [21,22].…”

Section: Introductionmentioning

confidence: 99%

“…Some reports describe a worse treatment response regarding viral load decline or CD4+ T cell increase in patients carrying X4-HIV variants [18-20], whereas other papers show similar rates of viral suppression for patients with and without X4-HIV variants upon start of antiretroviral therapy [21,22]. Here, we analyzed the effect of coreceptor switch before cART initiation on the response to antiretroviral therapy in a large cohort of 732 patients, of whom 31% carried X4-HIV variants at baseline, with a complete and reliable follow-up.…”

Section: Introductionmentioning

confidence: 99%

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The Presence of CXCR4-Using HIV-1 Prior to Start of Antiretroviral Therapy Is an Independent Predictor of Delayed Viral Suppression

et al. 2013

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The emergence of CXCR4-using HIV variants (X4-HIV) is associated with accelerated disease progression in the absence of antiretroviral therapy. However, the effect of X4-HIV variants on the treatment response remains unclear. Here we determined whether the presence of X4-HIV variants influenced the time to undetectable viral load and CD4+ T cell reconstitution after initiation of cART in 732 patients. The presence of X4-HIV variants was determined by MT-2 assay prior to cART initiation and viral load and CD4+ T cell counts were analyzed every 3 to 6 months during a three year follow-up period. Kaplan-Meier and Cox proportional hazard analyses were performed to compare time to viral suppression and the absolute CD4+ T cell counts and increases in CD4+ T cell counts during follow-up were compared for patients with and without X4-HIV at start of cART. Patients harboring X4-HIV variants at baseline showed a delay in time to achieve viral suppression below the viral load detection limit. This delay in viral suppression was independently associated with high viral load and the presence of X4-HIV variants. Furthermore, the absolute CD4+ T cell counts were significantly lower in patients harboring X4-HIV variants at all time points during follow-up. However, no differences were observed in the increase in absolute CD4+ T cell numbers after treatment initiation, indicating that the reconstitution of CD4+ T cells is independent of the presence of X4-HIV variants. The emergence of X4-HIV has been associated with an accelerated CD4+ T cell decline during the natural course of infection and therefore, patients who develop X4-HIV variants may benefit from earlier treatment initiation in order to obtain faster reconstitution of the CD4+ T cell population to normal levels.

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Association of X4 tropism with disease progression in antiretroviral-treated children and adolescents living with HIV/AIDS in São Paulo, Brazil

Almeida

Zaparoli

Moreira

et al. 2014

The Brazilian Journal of Infectious Diseases

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Management of children with HIV/AIDS is specially challenging. Age-related issues do not allow for direct transposition of adult observations to this population. CXCR4 tropism has been associated with disease progression in adults. The geno2pheno web-base is a friendly tool to predict viral tropism on envelope V3 sequences, generating a false positive rate for a CXCR4 prediction. We evaluated the association of HIV-1 tropism prediction with clinical and laboratory outcome of 73 children with HIV/AIDS in São Paulo, Brazil. The CXCR4 tropism was strongly associated with a lower (nadir) CD4 documented during follow-up (p<0.0001) and with disease severity (clinical event and/or CD4 below 200cells/mm(3)) at the last observation, using commonly applied clinical cutoffs, such as (10%)FPRclonal (p=0.001). When variables obtained during follow-up are included, both treatment adherence and viral tropism show a significant association with disease severity. As for viremia suppression, 30% (22/73) were undetectable at the last observation, with only adherence strongly associated with suppression after adjustment. The study brings further support to the notion that antiretroviral treatment adherence is pivotal to management of HIV disease, but suggests that tropism prediction may provide an additional prognostic marker to monitor HIV disease in children.

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HIV-1 tropism and CD4 T lymphocyte recovery in a prospective cohort of patients initiating HAART in Ribeirão Preto, Brazil

Cited by 6 publications

References 16 publications

Transmitted Drug Resistance among People Living with HIV/Aids at Major Cities of Sao Paulo State, Brazil

Transmitted Drug Resistance among People Living with HIV/Aids at Major Cities of Sao Paulo State, Brazil

The Presence of CXCR4-Using HIV-1 Prior to Start of Antiretroviral Therapy Is an Independent Predictor of Delayed Viral Suppression

Association of X4 tropism with disease progression in antiretroviral-treated children and adolescents living with HIV/AIDS in São Paulo, Brazil

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