Drug Resistance Mutations in Drug-Naive HIV Type 1 Subtype C-Infected Individuals from Rural Malawi

Bansode, Vijay B; Drebert, Zuzanna; Travers, Simon; Banda, Emmanuel; Molesworth, Anna; Crampin, Amelia C.; Ngwira, Bagrey; French, Neil; Glynn, Judith R.; McCormack, Grace P.

doi:10.1089/aid.2010.0203

Cited by 7 publications

(15 citation statements)

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“…All patients have been started on a fixed dose combination of stavudine, lamivudine and nevirapine on the basis of clinical staging or CD4 count. Previous work identified discrepancies or ambiguities in the presence/absence of drug resistant mutations in viral sequences from samples collected from these five individuals at sequential time-points during treatment [6]. Fifteen samples representing an average of three sampling time-points from five of these patients were selected for subsequent analysis using ultra-deep pyrosequencing in this current study (Table 1).…”

Section: Methodsmentioning

confidence: 99%

“…Recent research on HIV-1 in Karonga District, Malawi has shown that of the 40 HIV-1 subtype C infected individuals on HAART that we tested, 14% contained drug resistance mutations (DRMs) in the reverse transcriptase (RT) gene of viruses stored in the provirus [6] with clonal sequencing of latent viruses showing discrepancies in the presence and prevalence of DRMs in the proviral DNA [7]. These discrepancies further support the limitations of bulk sequencing for determining drug resistance in viruses contained within the proviral DNA.…”

Section: Introductionmentioning

confidence: 99%

“…Traditionally, methods such as single genome amplification and real-time PCR have been used to identify the presence of low abundance viral variants [8,9]. We, and others, have shown the importance of clonal sequencing in revealing the spectrum of viral variants present within an individual [6]. However cloning and other traditionally used methods are labour intensive, expensive, time consuming and/or restricted to the detection of single variants.…”

Section: Introductionmentioning

confidence: 99%

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Characterizing the emergence and persistence of drug resistant mutations in HIV-1 subtype C infections using 454 ultra deep pyrosequencing

et al. 2013

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BackgroundThe role of HIV-1 RNA in the emergence of resistance to antiretroviral therapies (ARTs) is well documented while less is known about the role of historical viruses stored in the proviral DNA. The primary focus of this work was to characterize the genetic diversity and evolution of HIV drug resistant variants in an individual’s provirus during antiretroviral therapy using next generation sequencing.MethodsBlood samples were collected prior to antiretroviral therapy exposure and during the course of treatment from five patients in whom drug resistance mutations had previously been identified using consensus sequencing. The spectrum of viral variants present in the provirus at each sampling time-point were characterized using 454 pyrosequencing from multiple combined PCR products. The prevalence of viral variants containing drug resistant mutations (DRMs) was characterized at each time-point.ResultsLow abundance drug resistant viruses were identified in 14 of 15 sampling time-points from the five patients. In all individuals DRMs against current therapy were identified at one or more of the sampling time-points. In two of the five individuals studied these DRMs were present prior to treatment exposure and were present at high prevalence within the amplified and sequenced viral population. DRMs to drugs other than those being currently used were identified in four of the five individuals.ConclusionThe presence of DRMs in the provirus, regardless of their observed prevalence did not appear to have an effect on clinical outcomes in the short term suggesting that the drug resistant viral variants present in the proviral DNA do not appear to play a role in the short term in facilitating the emergence of drug resistance.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Characterizing the emergence and persistence of drug resistant mutations in HIV-1 subtype C infections using 454 ultra deep pyrosequencing

et al. 2013

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“…The mutation has been reported to occur in ~2% of untreated persons infected with subtype C and with increased frequency in persons receiving multiple NRTIs [19] and so it may not be unexpected to find it in this cohort. It was the only DRM found in all three previous studies of drug resistance in Malawi [9,13,20] and was also reported in subtype C infected drug naïve patients from Zambia [21], Zimbabwe [22] and South Africa [19]. It has been suggested that along with drug resistance, the V118I mutation alone is a marker of advanced HIV infection and disease progression [23].…”

Section: Discussionmentioning

confidence: 78%

“…Multiple alignments were assembled of all subtype C sequences generated with the 57 reverse transcriptase sequences generated from [13] using MacClade 4.0 (Sinauer Assoc). Sequences were submitted for analysis of DRMs to the Stanford Database [14].…”

Section: Methodsmentioning

confidence: 99%

Reverse transcriptase drug resistance mutations in HIV-1 subtype C infected patients on ART in Karonga District, Malawi

et al. 2011

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BackgroundDrug resistance testing before initiation of, or during, antiretroviral therapy (ART) is not routinely performed in resource-limited settings. High levels of viral resistance circulating within the population will have impact on treatment programs by increasing the chances of transmission of resistant strains and treatment failure. Here, we investigate Drug Resistance Mutations (DRMs) from blood samples obtained at regular intervals from patients on ART (Baseline-22 months) in Karonga District, Malawi. One hundred and forty nine reverse transcriptase (RT) consensus sequences were obtained via nested PCR and automated sequencing from blood samples collected at three-month intervals from 75 HIV-1 subtype C infected individuals in the ART programme.ResultsFifteen individuals showed DRMs, and in ten individuals DRMs were seen from baseline samples (reported to be ART naïve). Three individuals in whom no DRMs were observed at baseline showed the emergence of DRMs during ART exposure. Four individuals who did show DRMs at baseline showed additional DRMs at subsequent time points, while two individuals showed evidence of DRMs at baseline and either no DRMs, or different DRMs, at later timepoints. Three individuals had immune failure but none appeared to be failing clinically.ConclusionDespite the presence of DRMs to drugs included in the current regimen in some individuals, and immune failure in three, no signs of clinical failure were seen during this study. This cohort will continue to be monitored as part of the Karonga Prevention Study so that the long-term impact of these mutations can be assessed. Documenting proviral population is also important in monitoring the emergence of drug resistance as selective pressure provided by ART compromises the current plasma population, archived viruses can re-emerge

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Prevention, treatment and future challenges of HIV/AIDS: A decade of INDEPTH research

Sankoh

Arthur

Nyide³

et al. 2015

HIV & AIDS Review

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a b s t r a c tAim: To present a systematic review that evaluates the contributions of the INDEPTH Network of health and demographic surveillance systems (HDSSs) to research efforts on prevention and treatment of HIV/AIDS in low-and middle-income countries. Methods: Publication titles were sent to INDEPTH by member centres. These were uploaded onto the Zotero research tool from different databases (most from PubMed). We searched for publications using the keyword "HIV" and the publication date. The 540 relevant papers were all published in peer-reviewed English language journals between 1999 and 2012. For a paper to be included in this study it must have extensively tackled the issue of HIV (1), prevention (2) and challenges associated with the treatment. After a thorough review, 89 papers were finally selected. Results: Consistent condom use has been found to be highly protective against HIV infection. Although women feel at risk of contracting HIV from their partners and many women knew about condoms, they were unable to use them due to the partner's refusal. Infection with STDs is associated with HIV infection, populations with high rates of STDs and high-risk sexual behaviour, interventions to treat STDs can help prevent HIV transmission. The study also found that mother-to-child transmission was 2.7 times higher in infants breastfed for more than six months than in those breastfed for less than six months. The study found that the most promising prevention intervention discovered so far is male circumcision. Conclusion: INDEPTH member centres have tracked the course of the HIV/AIDS epidemic in sub-Saharan Africa. They have analysed how the virus is transmitted and how it impacts families, communities and economies. Prevention and treatment policies and technologies have also come under scrutiny, including prevention of mother-to-child transmission of HIV, male circumcision, behaviour change polices, antiretroviral treatment and other key interventions. The robust and extensive data HDSSs have generated provide critical insights to policy-makers as the epidemic moves into its fourth decade.

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Drug Resistance Mutations in Drug-Naive HIV Type 1 Subtype C-Infected Individuals from Rural Malawi

Cited by 7 publications

References 14 publications

Characterizing the emergence and persistence of drug resistant mutations in HIV-1 subtype C infections using 454 ultra deep pyrosequencing

Characterizing the emergence and persistence of drug resistant mutations in HIV-1 subtype C infections using 454 ultra deep pyrosequencing

Reverse transcriptase drug resistance mutations in HIV-1 subtype C infected patients on ART in Karonga District, Malawi

Prevention, treatment and future challenges of HIV/AIDS: A decade of INDEPTH research

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