Acquired HIV drug resistance among children and adults receiving antiretroviral therapy in Tanzania: a national representative survey protocol.
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ABSTRACT: Introduction
Tanzania is making an enormous effort in scaling-up of antiretroviral therapy (ART). However, people living with HIV (PLHIV) continue to succumb to the challenge of drug resistance. Evidence on drug resistance for a national survey is unavailable in Tanzania. Therefore, we sought to assess viral suppression (vs) rates and magnitude of acquired drug resistance (ADR) among PLHIV.Methods and analysis
A national survey will be conducted from 26 July to 29 October 2021 in 22 regions, recruiting 2160 participants. These will include adults on ART for 9-15 months and ≥48 months and children on ART for 9-15 months and ≥36 months. A standardised questionnaire will capture participants' demographic and clinical data. Plasma and dried blood spot will be prepared for viral load testing and drug resistance genotyping. Statistical analyses to determine the burden of ADR, characteristics and factors associated therewith will be done using STATA V.15.Ethics and dissemination
Ethical approval has been obtained from the National Health Research Ethics Committee of Tanzania (NIMR/HQ/R.8a/Vol.IX/3432). Appropriate participant informed consent or parental consent and assent will be obtained. Dissemination will include a survey report, conference presentations, policy briefs and peer-reviewed publications.
SUBMITTER: Rugemalila J
PROVIDER: S-EPMC8689191 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundIn order to assess the level of transmitted and/or pre-treatment antiretroviral drug resistance to HIV-1, the World Health Organization (WHO) recommends that regular surveys are conducted. This study's objective was to assess the frequency of HIV-1 antiretroviral drug resistance in patients initiating antiretroviral treatment (ART) in the public sector throughout South Africa.MethodsA prospective cross-sectional survey was conducted using probability proportional to size sampling. This method ensured that samples from each province were proportionally collected, based on the number of patients receiving ART in each region. Samples were collected between March 2013 and October 2014. Pol sequences were obtained using RT-PCR and Sanger sequencing and submitted to the Stanford Calibrated Population Resistance tool v6.0.ResultsA total of 277 sequences were available for analysis. Most participants were female (58.8%) and the median age was 34 years (IQR: 29-42). The median baseline CD4-count was 149 cells/mm3 (IQR: 62-249) and, based on self-reporting, participants had been diagnosed as HIV-positive approximately 44 days prior to sample collection (IQR: 23-179). Subtyping revealed that 98.2% were infected with HIV-1 subtype C. Overall, 25 out of 277 patients presented with ≥1 surveillance drug resistance mutation (SDRM, 9.0%, 95% CI: 6.1-13.0%). Non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations were the most numerous mutations detected (n = 23). Only two patients presented with a protease inhibitor (PI) mutation. In four patients ≥4 SDRMs were detected, which might indicate that these patients were not truly ART-naïve or were infected with a multi-resistant virus.ConclusionsThese results show that the level of antiretroviral drug resistance in ART-naïve South Africans has reached moderate levels, as per the WHO classification. Therefore, regular surveys of pre-treatment drug resistance levels in all regions of South Africa is highly recommended to monitor the changing levels of pre-treatment antiretroviral drug resistance.
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Project description:The World Health Organization (WHO) has recommended guidelines for a HIV drug resistance (HIVDR) survey for resource-limited countries. Eligibility criteria for patients include age below 25 years in order to focus on the prevalence of transmitted HIVDR (tHIVDR) in newly-infected individuals. Most of the participating sites across Africa have so far reported tHIVDR prevalences of below 5%. In this study we investigated whether the rate of HIVDR in patients <25 years is representative for HIVDR in the rest of the therapy-naïve population.HIVDR was determined in 88 sequentially enrolled ART-naïve patients from Mwanza, Tanzania (mean age 35.4 years). Twenty patients were aged <25 years and 68 patients were aged 25-63 years. The frequency of HIVDR in the study population was 14.8% (95%; CI 0.072-0.223) and independent of NVP-resistance induced by prevention of mother-to-child transmission programs. Patients >25 years had a significantly higher HIVDR frequency than younger patients (19.1%; 95% CI 0.095-0.28) versus 0%, P?=?0.0344). In 2 out of the 16 patients with HIVDR we found traces of antiretrovirals (ARVs) in plasma.ART-naïve patients aged over 25 years exhibited significantly higher HIVDR than younger patients. Detection of traces of ARVs in individuals with HIVDR suggests that besides transmission, undisclosed misuse of ARVs may constitute a significant factor in the generation of the observed high HIVDR rate. The current WHO tHIVDR survey that is solely focused on the transmission of HIVDR and that excludes patients over 25 years of age may therefore result in substantial underestimation of the prevalence of HIVDR in the therapy-naïve population. Similar studies should be performed also in other areas to test whether the so far reported optimistic picture of low HIVDR prevalence in young individuals is really representative for the rest of the ART-naïve HIV-infected population.
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Project description:Objective:Female sex workers (FSW) have increased risk of HIV infection. Antiretroviral treatment (ART) can improve HIV outcomes and prevent HIV transmission. We analyzed antiretroviral (ARV) drug use and HIV drug resistance among HIV-positive FSW in the Dominican Republic and Tanzania.Methods:Plasma samples collected at study entry with viral loads >1,000 copies/mL were tested for ARV drugs and HIV drug resistance. ARV drug testing was performed using a qualitative assay that detects 22 ARV drugs in five classes. HIV genotyping was performed using the ViroSeq HIV-1 Genotyping System. Phylogenetic analyses were performed to determine HIV subtype and assess transmission clusters.Results:Among 410 FSW, 144 (35.1%) had viral loads >1,000 copies/mL (DR: n = 50; Tanzania: n = 94). ARV drugs were detected in 36 (25.0%) of 144 samples. HIV genotyping results were obtained for 138 (95.8%) cases. No transmission clusters were observed in either country. HIV drug resistance was detected in 54 (39.1%) of 138 samples (31/35 [88.6%] with drugs detected; 23/103 [22.3%] without drugs detected); 29/138 (21.0%) had multi-class resistance (MCR). None with MCR had integrase strand transfer inhibitor resistance. In eight cases, one or more ARV drug was detected without corresponding resistance mutations; those women were at risk of acquiring additional drug resistance. Using multivariate logistic regression, resistance was associated with ARV drug detection (p<0.001), self-reported ART (full adherence [p = 0.034]; partial adherence [p<0.001]), and duration of HIV infection (p = 0.013).Conclusions:In this cohort, many women were on ART, but were not virally suppressed. High levels of HIV drug resistance, including MCR, were observed. Resistance was associated with detection of ARV drugs, self-report of ART with full or partial adherence, and duration of HIV infection. These findings highlight the need for better HIV care among FSW to improve their health, reduce HIV drug resistance, and decrease risk of transmission to others.
| S-EPMC7595323 | biostudies-literature
Project description:IntroductionWe evaluated HIV drug resistance in adults who received early vs. delayed antiretroviral therapy (ART) in a multinational trial [HIV Prevention Trials Network (HPTN) 052, enrollment 2005-2010]. In HPTN 052, 1763 index participants were randomized to start ART at a CD4 cell count of 350-550 cells/mm (early ART arm) or <250 cells/mm (delayed ART arm). In May 2011, interim study results showed benefit of early ART, and all participants were offered ART regardless of CD4 cell count; the study ended in 2015.MethodsVirologic failure was defined as 2 consecutive viral loads >1000 copies/mL >24 weeks after ART initiation. Drug resistance testing was performed for pretreatment (baseline) and failure samples from participants with virologic failure.ResultsHIV genotyping results were obtained for 211/249 participants (128 early ART arm and 83 delayed ART arm) with virologic failure. Drug resistance was detected in 4.7% of participants at baseline; 35.5% had new resistance at failure. In univariate analysis, the frequency of new resistance at failure was lower among participants in the early ART arm (compared with delayed ART arm, P = 0.06; compared with delayed ART arm with ART initiation before May 2011, P = 0.032). In multivariate analysis, higher baseline viral load (P = 0.0008) and ART regimen (efavirenz/lamivudine/zidovudine compared with other regimens, P = 0.024) were independently associated with higher risk of new resistance at failure.ConclusionsIn HPTN 052, the frequency of new drug resistance at virologic failure was lower in adults with early ART initiation. The main factor associated with reduced drug resistance with early ART was lower baseline viral load.
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Project description: Not available
| S-EPMC10655941 | biostudies-literature
Project description:BackgroundWe aimed to describe the frequency, risk factors, and costs attributable to drug-drug interactions (DDIs) among an aging French HIV population.MethodsWe conducted a retrospective cohort study using French nationwide health care e-records: the SNIIRAM database. People living with HIV (PLWH) aged >65 years and receiving combined antiretroviral treatment (cART) during 2016 were included. A DDI was defined as "These drugs should not be co-administered," represented by a red symbol on the University of Liverpool website. Attributable DDIs' cost was defined as the difference between individuals with and without DDIs regarding all reimbursed health care acts.ResultsOverall, 9076 PLWH met the study criteria. Their baseline characteristics were: mean age, 71.3 ± 4.9 years; 25% female; median HIV duration (interquartile range [IQR]), 16.2 (9.5-20.3) years; median comorbidities (IQR), 2 (1-3). During 2016, they received a median (IQR) of 14 (9-21) comedications (non-cART), and 1529 individuals had at least 1 DDI (16.8%; 95% confidence interval [CI], 16.1-17.6). In multivariate analysis, raltegravir or dolutegravir plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs) significantly and independently reduced the risk of DDIs (adjusted odds ratio [aOR], 0.02; 95% CI, 0.005-0.050; P < .0001) compared with non-nucleoside reverse-transcriptase inhibitor plus 2 NRTIs, whereas cART with boosted agents (protease inhibitors or elvitegravir) significantly increased the risk (aOR, 4.12; 95% CI, 3.34-5.10; P < .0001). Compared with propensity score-matched PLWH without DDIs, the presence of DDIs was associated with a $2693 additional cost per year (P < .0001).ConclusionsThe presence of DDIs is frequent and significantly increases health care costs in the aging population of PLWH.
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Project description:ObjectiveWe estimated and compared the risk of clinically identified acquired drug resistance under immediate initiation [the currently recommended antiretroviral therapy (ART) initiation strategy], initiation with CD4 cell count less than 500 cells/μl and initiation with CD4 cell count less than 350 cells/μl.DesignCohort study based on routinely collected data from the HIV-CAUSAL collaboration.MethodsFor each individual, baseline was the earliest time when all eligibility criteria (ART-naive, AIDS free, and others) were met after 1999. Acquired drug resistance was defined using the Stanford classification as resistance to any antiretroviral drug that was clinically identified at least 6 months after ART initiation. We used the parametric g-formula to adjust for time-varying (CD4 cell count, HIV RNA, AIDS, ART regimen, and drug resistance testing) and baseline (calendar period, mode of acquisition, sex, age, geographical origin, ethnicity and cohort) characteristics.ResultsIn 50 981 eligible individuals, 10% had CD4 cell count more than 500 cells/μl at baseline, and 63% initiated ART during follow-up. Of 2672 tests for acquired drug resistance, 794 found resistance. The estimated 7-year risk (95% confidence interval) of acquired drug resistance was 3.2% (2.8,3.5) for immediate initiation, 3.1% (2.7,3.3) for initiation with CD4 cell count less than 500 cells/μl, and 2.8% (2.5,3.0) for initiation with CD4 cell count less than 350 cells/μl. In analyses restricted to individuals with baseline in 2005-2015, the corresponding estimates were 1.9% (1.8, 2.5), 1.9% (1.7, 2.4), and 1.8% (1.7, 2.2).ConclusionOur findings suggest that the risk of acquired drug resistance is very low, especially in recent calendar periods, and that immediate ART initiation only slightly increases the risk. It is unlikely that drug resistance will jeopardize the proven benefits of immediate ART initiation.
| S-EPMC5758415 | biostudies-literature
Project description:BACKGROUND:The World Health Organization (WHO) recommends a method to estimate nationally representative pretreatment HIV drug resistance (PDR) in order to evaluate the effectiveness of first -line treatments. The objective of the present study was to determine the prevalence of PDR in Cuban adults infected with HIV-1. MATERIALS AND METHODS:A cross-sectional study in Cuban adults infected with HIV-1 over 18 years was conducted. The probability proportional to size method for the selection of municipalities and patients without a prior history of antiretroviral treatment during the period from January 2017 to June 2017 was used. The plasma from 141 patients from 15 municipalities for the determination of viral subtype and HIV drug resistance was collected. Some clinical and epidemiological variables were evaluated. RESULTS:80. 9% of the patients corresponded to the male sex and 76.3% were men who have sex with other men (MSM). The median CD4 count was 371 cells / mm3 and the median viral load was 68000 copies / mL. The predominant genetic variants were subtype B (26.9%), CRF19_cpx (24.1%), CRF 20, 23, 24_BG (23.4%) and CRF18_cpx (12%). Overall, the prevalence of PDR was 29.8% (95%, CI 22.3-38.1). The prevalence was 12.8% (95%, CI 6.07-16.9) for any nucleoside reverse transcriptase inhibitor (NRTI), 23.4% (95%, CI 16.7-31.3) for any non-reverse transcriptase inhibitor (NNRTI) and 1.4% (95%, CI 0.17-5.03) for any protease inhibitor (PI). The most frequent mutations detected were K103N (12.9%), G190A (6.4%) and Y181C (4.8%). CONCLUSIONS:The NNRTI prevalence above 10% in our study indicates that the first-line antiretroviral therapy in Cuba may be less effective and supports the need to look for new treatment options that contribute to therapeutic success and help the country achieve the global goals 90-90-90 set forth by UNAIDS.
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Project description:Emergence of HIV drug resistance poses a serious risk of inactivity to all currently approved antiretroviral drugs. Profiles of HIV drug resistance mutations (HIVDRM) and virological failure (VF) are not extensively studied in Tanzania. This study aimed to determine HIVDRM and predictors of VF in HIV-infected individuals failing first-line HIV drugs in Moshi, Northern Tanzania. A case-control study was conducted at Kilimanjaro Christian Medical Centre, Mawenzi, Pasua and Majengo health facilities with HIV-care and treatment clinics from October, 2017 to August, 2018. Cases and controls were HIV-infected individuals with VF and viral suppression (VS) respectively. HIV-1 reverse transcriptase and protease genes were amplified and sequenced. Stanford University's HIV drug resistance database and REGA subtyping tool 3.0 determined HIVDRM and HIV-1 subtypes respectively. Odds ratios (OR) with 95% confidence interval (95% CI) investigated predictors of VF. P-value < 5% was considered statistically significant. A total of 124 participants were recruited, of whom 63 (50.8%) had VF, 61 (49.2%) had VS and 82 (66.1%) were females. Median [IQR] age and duration on ART were 45 [35-52] years and 72 [48-104] months respectively. Twenty-five out of 26 selected samples from cases were successfully sequenced. Twenty-four samples (96%) had at least one major mutation conferring resistance to HIV drugs, with non-nucleoside analogue reverse transcriptase inhibitor (NNRTI)-resistance associated mutations as the majority (92%). Frequent NNRTI-resistance associated mutations were K103N (n = 11), V106M (n = 5) and G190A (n = 5). Prevalent nucleoside analogue reverse transcriptase inhibitors-resistance associated mutations were M184V (n = 17), K70R (n = 7) and D67N (n = 6). Dual-class resistance was observed in 16 (64%) samples. Thirteen samples (52%) had at least one thymidine analogue-resistance associated mutation (TAM). Three samples (12%) had T69D mutation with at least 1 TAM. Two samples (8%) had at least one mutation associated with protease inhibitor resistance. Age [aOR = 0.94, 95% CI (0.90-0.97), p < 0.001] and occupation [aOR = 0.35, 95% CI (0.12-1.04), p = 0.059] associated with VF. In conclusion, HIV drug resistance is common among people failing antiretroviral therapy. Resistance testing will help to guide switching of HIV drugs.
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