Emergence Of HIV Drug Resistance Research Articles

Immune reconstitution inflammatory syndrome drives emergence of HIV drug resistance from multiple anatomic compartments in a person living with HIV.

Reservoirs of HIV maintained in anatomic compartments during antiretroviral therapy prevent HIV eradication. However, mechanisms driving their persistence and interventions to control them remain elusive. Here we report the presence of an inducible HIV reservoir within antigen-specific CD4+T cells in the central nervous system of a 59-year-old male with progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome (PML-IRIS). HIV production during PML-IRIS was suppressed by modulating inflammation with corticosteroids; selection of HIV drug resistance caused subsequent breakthrough viremia. Therefore, inflammation can influence the composition, distribution and induction of HIV reservoirs, warranting it as a key consideration for developing effective HIV remission strategies.

Early warning indicators of HIV drug resistance in the southern highlands region of Tanzania: Lessons from a cross-sectional surveillance study.

The World Health Organization early warning indicators (EWIs) permit surveillance of factors associated with the emergence of HIV drug resistance (HIVDR). We examined cross- and within-region performance on HIVDR EWIs for selected HIV care and treatment clinics (CTCs) in five regions of southern Tanzania. We retrospectively abstracted EWI data from 50 CTCs for the January to December 2013 period. EWIs included the following: on time ART pick-up, retention on ART, ARV stockouts, and pharmacy prescribing and dispensing practices. Data for pediatric and adult people living with HIV were abstracted from source files, and frequencies and proportions were calculated for each EWI overall, as well as stratified by region, facility, and age group. Across and within all regions, on average, on-time pick-up of pills (63.0%), retention on ART (76.0%), and pharmacy stockouts (69.0%) were consistently poor for the pediatric population. Similarly, on-time pill pick up (66.0%), retention on ART (72.0%) and pharmacy stockouts (53.0%) for adults were also poor. By contrast, performance on pharmacy prescribing and dispensing practices were as desired for both pediatric and adult populations with few facility-level exceptions. In this study, regions and facilities in the southern highlands of Tanzania reported widespread presence of HIVDR risk factors, including sub-optimal timeliness of pill pickup, retention on ART, and drug stockouts. There is an urgent need to implement the WHO EWIs monitoring to minimize the emergence of preventable HIV drug resistance and to maintain the effectiveness of first and second-line ART regimens. This is particularly critical in the context of new ART drug roll-out such as dolutegravir during the COVID-19 pandemic when resultant HIV service disruptions require careful monitoring, and for virologic suppression as countries move closer to epidemic control.

Use of laboratory-developed assays in global HIV-1 treatment-monitoring and research

There has been a surge in the emergence of HIV-1 drug resistance in Low and Middle-Income Countries (LMICs) due to poor drug-adherence and limited access to viral load testing, the current standard for treatment-monitoring. It is estimated that only 75% of people living with HIV (PLWH) worldwide have access to viral load testing. In LMICs, this figure is below 50%. In a recent WHO survey in mostly LMICs, 21 out of 30 countries surveyed found HIV-1 first-line pre-treatment drug resistance in over 10% of study participants. In the worst-affected regions, up to 68% of infants born to HIV-1 positive mothers were found to harbour first-line HIV-1 treatment resistance. This is a huge public health concern. Greater access to treatment-monitoring is required in LMICs if the UNAIDS “third 95” targets are to be achieved by 2030. Here, we review the current challenges of viral load testing and present the case for greater utilization of Laboratory-based assays that quantify intracellular HIV-1 RNA and/or DNA to provide broader worldwide access to HIV-1 surveillance, drug-resistance monitoring, and cure-research.

Differences in drug resistance of HIV-1 genotypes in CSF and plasma and analysis of related factors

ABSTRACT The emergence of HIV drug resistance seriously affects the quality of life of patients. However, there has been no extensive study of CSF resistance. The aim of this study is to evaluate common HIV-1 resistance in CSF and compare it with resistance in matched plasma, and analyse the influencing factors of cerebrospinal fluid drug resistance. The matched CSF and plasma samples of 62 HIV-1 patients were tested at one study site in China (Chongqing; 2019–2022). HIV genotyping and drug resistance was evaluated using the Stanford v8.7 algorithm. The diagnosis and treatment data and basic information were collected from the clinical case system, and the influencing factors of drug resistance mutations in CSF was obtained by variance analysis. CSF and matched plasma HIV-1 subtypes were confirmed in 62 patients, and the most frequent recombinant form was CRF07-BC (64.5%). Thirteen patients (21.0%) were detected with drug-resistant mutations, and the sites were consistent in both CSF and matched plasma. The drug-resistant ratios of untreated patients and treated patients were 5/51 (9.8%) and 8/11 (72.7%), respectively. The type with the highest mutation frequency was NNRTI, and no mutation was found in INSTI. Multivariate analysis indicated that ARV treatment was associated with CSF resistance (P < 0.001). The subtypes and drug resistance mutation sites are consistent in CSF and matched plasma samples of HIV-1 patients, and there is a correlation between ARV treatment and possible drug resistance, especially in CSF reservoirs. These findings highlight the concern about CSF drug resistance in HIV patients.

Epidemiology of HIV drug resistance in low- and middle-income countries and WHO global strategy to monitor its emergence.

This review summarises the latest information of the epidemiology of HIV drug resistance (HIVDR) in low- and middle-income countries and the updated WHO global strategy for HIVDR surveillance and monitoring. Finding from recent national-representative surveys show a rise in pretreatment drug resistance (PDR) to reverse transcriptase inhibitors and especially to the class of nonnucleoside reverse transcriptase inhibitors. Levels of PDR are especially high in infants <18 months and adults reporting prior exposure to antiretrovirals. Although viral suppression rates are generally high and increasing among adults on antiretroviral therapy, those with unsuppressed viremia have high levels of acquired drug resistance (ADR). Programmatic data on HIVDR to integrase-transfer-inhibitor resistance is scarce, highlighting the need to increase integrase-inhibitors resistance surveillance. As the landscape of HIV prevention, treatment and monitoring evolves, WHO has also adapted its strategy to effectively support countries in preventing and monitoring the emergence of HIVDR. This includes new survey methods for monitoring resistance emerging from patients diagnosed with HIV while on preexposure prophylaxis, and a laboratory-based ADR survey leveraging on remnant viral load specimens which are expected to strengthen dolutegravir-resistance surveillance. Monitoring HIVDR remains pivotal to ensure countries attain and sustain the global goals for ending HIV as a public health threat by 2030.

Development of HIV Drug Resistance in a Cohort of Adults on First-Line Antiretroviral Therapy in Tanzania during the Stavudine Era

As more HIV patients start combination antiretroviral therapy (cART), the emergence of HIV drug resistance (HIVDR) is inevitable. This will have consequences for the transmission of HIVDR, the success of ART, and the nature and trend of the epidemic. We recruited a cohort of 223 patients starting or continuing their first-line cART in Tanzania towards the end of the stavudine era in 2010. Patients were then followed for one year. Of those with a viral load test at baseline and follow-up time, 34% had a detectable viral load at the one-year endpoint. For 41 patients, protease and reverse transcriptase genotyping were successful. Eighteen samples were from cART-naïve patients, and 23 samples were taken under therapy either at baseline for cART-experienced patients or from follow-up samples for both cART–naïve and cART–experienced patients. The isolates were subtype A, followed by C and D in 41.5%, 22%, and 12.2% of the patients, respectively. No transmitted HIVDR was detected, as scored using the surveillance drug resistance mutations (DRMs) list. However, in 3 of the 18 samples from cART-naïve patients, the clinical Rega interpretation algorithm scored 44D or 138A as non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated polymorphisms. The most observed nucleoside reverse transcriptase inhibitor (NRTI) mutation was 184V. The mutation was found in 16 patients, causing resistance to lamivudine and emtricitabine. Nineteen patients had NNRTI resistance mutations, the most common of which was 103N, observed in eight patients. These high levels of resistance call for regular drug resistance surveillance in Tanzania to inform the control of the emergence and transmission of HIVDR.

Characterization of HIV-1 drug resistance among patients with failure of second-line combined antiretroviral therapy in central Ethiopia.

As a consequence of the improved availability of combined antiretroviral therapy (cART) in resource-limited countries, an emergence of HIV drug resistance (HIVDR) has been observed. We assessed the prevalence and spectrum of HIVDR in patients with failure of second-line cART at two HIV clinics in central Ethiopia. HIV drug resistance was analysed in HIV-1-infected patients with virological failure of second-line cART using the geno2pheno application. Among 714 patients receiving second-line cART, 44 (6.2%) fulfilled the criteria for treatment failure and 37 were eligible for study inclusion. Median age was 42 years [interquartile range (IQR): 20-45] and 62.2% were male. At initiation of first-line cART, 23 (62.2%) were WHO stage III, mean CD4 cell count was 170.6 (range: 16-496) cells/µL and median (IQR) HIV-1 viral load was 30220 (7963-82598) copies/mL. Most common second-line cART regimens at the time of failure were tenofovir disoproxil fumarate (TDF)-lamivudine (3TC)-ritonavir-boosted atazanavir (ATV/r) (19/37, 51.4%) and zidovudine (ZDV)-3TC-ATV/r (9/37, 24.3%). Genotypic HIV-1 resistance testing was successful in 35 (94.6%) participants. We found at least one resistance mutation in 80% of patients and 40% carried a protease inhibitor (PI)-associated mutation. Most common mutations were M184V (57.1%), Y188C (25.7%), M46I/L (25.7%) and V82A/M (25.7%). High-level resistance against the PI ATV (10/35, 28.6%) and lopinavir (LPV) (5/35, 14.3%) was reported. As expected, no resistance mutations conferring integrase inhibitor resistance were detected. We found a high prevalence of resistance mutations, also against PIs (40%), as the national standard second-line cART components. Resistance testing before switching to second- or third-line cART is warranted.

Human Immunodeficiency Virus (HIV) Drug Resistance: A Global Narrative Review

Background: Antiretroviral Therapy (ART) has significantly improved Human Immunodeficiency Virus (HIV) patients’ survival rates. However, the emergence of HIV Drug Resistance (HIVDR) has markedly reduced the effectiveness of Antiretroviral Therapy (ART). Aim: This narrative review was conducted to review published studies on HIV drug resistance and its consequences. Materials and methods: A literature search for this narrative review was carried out and the following databases were used PubMed, Google Scholar, and The Lancet. The cited articles were published from 1999 to 2021. The keywords used in the search of literature included ‘Antiretroviral therapy’, ‘resistance’, and ‘Human Immunodeficiency Virus drug resistance’, ‘HIV’, ‘HIV drug resistance’, ‘HIV vaccines’, and the Boolean word ‘AND’. Results: There is a high prevalence of HIV drug resistance globally that has been associated with some factors such as older age, non-adherence to treatment, long treatment duration, lower cell count and high viral load. HIV drug resistance may lead to treatment failure, prolongation of the time required to achieve viral suppression and leads to increased mortality. Increasing access to viral load monitoring can help mitigate HIV drug resistance. Conclusion: HIV drug resistance is a global threat to public health and has been associated with increased morbidity and mortality. Therefore, there is a need for more research to be carried out and various strategies like the use of antiretrovirals with a high genetic barrier to resistance need to be put in place to prevent further spread resistance. HIVDR must be monitored frequently taking into consideration the geographic variability. There is an urgent need for the development of anti-HIV vaccines that will help to prevent further transmission and spread of HIV.

HIV Drug Resistance in Children and Adolescents: Always a Challenge?

Purpose of ReviewWith the expanded roll-out of antiretrovirals for treatment and prevention of HIV during the last decade, the emergence of HIV drug resistance (HIVDR) has become a growing challenge. This review provides an overview of the epidemiology and trajectory of HIVDR globally with an emphasis on pediatric and adolescent populations.Recent FindingsHIVDR is associated with suboptimal virologic suppression and treatment failure, leading to an increased risk of HIV transmission to uninfected people and increased morbidity and mortality among people living with HIV. High rates of HIVDR to non-nucleoside reverse transcriptase inhibitors globally are expected to decline with the introduction of the integrase strand transfer inhibitors and long-acting combination regimens, while challenge remains for HIVDR to other classes of antiretroviral drugs.SummaryWe highlight several solutions including increased HIV viral load monitoring, expanded HIVDR surveillance, and adopting antiretroviral regimens with a high-resistance barrier to decrease HIVDR. Implementation studies and programmatic changes are needed to determine the best approach to prevent and combat the development of HIVDR.

Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania.

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.

Population-based monitoring of HIV drug resistance early warning indicators in Uganda: A nationally representative survey following revised WHO recommendations.

IntroductionWith the scale-up of antiretroviral therapy (ART) there is a need to monitor programme performance to maximize ART efficacy and to prevent emergence of HIV drug resistance (HIVDR). In keeping with the elements of the World Health Organisation (WHO) guidance we carried out a nationally representative assessment of early warning indicators (EWI) at 304 randomly selected ART service outlets in Uganda.MethodsRetrospective patient data was extracted for the six EWIs for HIVDR including; on-time antiretroviral (ARV) drug pick-up, patient retention on ART at 12 months, ART dispensing practices, ARV drug stock-outs, viral load suppression (VLS) and viral load (VL) testing completion. Point prevalence for each clinic and national aggregate prevalence with 95% confidence intervals (CI) for all clinics were estimated and facility performances were computed and association between EWIs and programmatic factors assessed using Fisher’s Exact Test.ResultsFacilities meeting the EWI targets: on-time pill pick-up was 9.5%, more facilities in the north met this target (p = 0.040). Retention on ART at 12 months was 24.1%, facilities in Kampala region (p<0.001) and Specialized ART clinics (p = 0.01) performed better in this indicator. Pharmacy stock-outs was 33.6%, with more facilities in Kampala (p<0.001), specialized ART clinics (p<0.001) and private-for-profit (p<0.001) meeting this target. Dispensing practices was met by 100% of the facilities. VLS was met by 49.2% and 50.8% of facilities met VL completion target with facilities in central region performing better (p<0.001). National prevalence for the EWIs was: on-time pill pick-up 63.3% (CI: 58.9–67.8); retention on ART at 12 months 69.9% (CI: 63.8–76.0); dispensing practices 100.0%; VLS 85.2% (CI: 81.8–88.5) and VL completion, 60.7% (CI: 56.9–64.6).ConclusionDispensing practices in all facilities were in line with the national guidelines however, there still remains a challenge to long-term ART programmatic success in monitoring patient response to treatment, and maintaining patients on ART without interruptions arising due to poor patient adherence and as a consequence of ARV supply interruption. It is therefore of high importance that the national ART program ensures intensified follow-up for patients, ensuring uninterrupted supply of ARV drugs and increasing VL monitoring at treatment centres, in order to improve patient outcomes and avert preventable HIVDR

Impact of Suboptimal APOBEC3G Neutralization on the Emergence of HIV Drug Resistance in Humanized Mice.

HIV diversification facilitates immune escape and complicates antiretroviral therapy. In this study, we take advantage of a humanized-mouse model to probe the contribution of APOBEC3 mutagenesis to viral evolution. Humanized mice were infected with isogenic HIV molecular clones (HIV-WT, HIV-45G, and HIV-ΔSLQ) that differ in their abilities to counteract APOBEC3G (A3G). Infected mice remained naive or were treated with the reverse transcriptase (RT) inhibitor lamivudine (3TC). Viremia, emergence of drug-resistant variants, and quasispecies diversification in the plasma compartment were determined throughout infection. While both HIV-WT and HIV-45G achieved robust infection, over time, HIV-45G replication was significantly reduced compared to that of HIV-WT in the absence of 3TC treatment. In contrast, treatment responses differed significantly between HIV-45G- and HIV-WT-infected mice. Antiretroviral treatment failed in 91% of HIV-45G-infected mice, while only 36% of HIV-WT-infected mice displayed a similar negative outcome. Emergence of 3TC-resistant variants and nucleotide diversity were determined by analyzing 155,462 single HIV reverse transcriptase gene (RT) and 6,985 vif sequences from 33 mice. Prior to treatment, variants with genotypic 3TC resistance (RT-M184I/V) were detected at low levels in over a third of all the animals. Upon treatment, the composition of the plasma quasispecies rapidly changed, leading to a majority of circulating viral variants encoding RT-184I. Interestingly, increased viral diversity prior to treatment initiation correlated with higher plasma viremia in HIV-45G-infected animals, but not in HIV-WT-infected animals. Taken together, HIV variants with suboptimal anti-A3G activity were attenuated in the absence of selection but displayed a fitness advantage in the presence of antiretroviral treatment.IMPORTANCE Both viral (e.g., RT) and host (e.g., A3G) factors can contribute to HIV sequence diversity. This study shows that suboptimal anti-A3G activity shapes viral fitness and drives viral evolution in the plasma compartment in humanized mice.

Development of A Fission Yeast Cell-Based Platform for High Throughput Screening of HIV-1 Protease Inhibitors.

HIV-1 protease inhibitor (PI) is one of the most potent classes of drugs in combinational antiretroviral therapies (cART). When a PI is used in combination with other anti- HIV drugs, cART can often suppress HIV-1 below detection thus prolonging the patient's lives. However, the challenge often faced by patients is the emergence of HIV-1 drug resistance. Thus, PIs with high genetic-barrier to drug-resistance are needed. The objective of this study was to develop a novel and simple fission yeast (Schizosaccharomyces pombe) cell-based system that is suitable for high throughput screening (HTS) of small molecules against HIV-1 protease (PR). A fission yeast RE294-GFP strain that stably expresses HIV-1 PR and green fluorescence protein (GFP) under the control of an inducible nmt1 promoter was used. Production of HIV-1 PR induces cellular growth arrest, which was used as the primary endpoint for the search of PIs and was quantified by an absorbance-based method. Levels of GFP production were used as a counter-screen control to eliminate potential transcriptional nmt1 inhibitors. Both the absorbance-based HIV-1 PR assay and the GFP-based fluorescence assay were miniaturized and optimized for HTS. A pilot study was performed using a small drug library mixed with known PI drugs and nmt1 inhibitors. With empirically adjusted and clearly defined double-selection criteria, we were able to correctly identify the PIs and to exclude all hidden nmt1 inhibitors. We have successfully developed and validated a fission yeast cell-based HTS platform for the future screening and testing of HIV-1 PR inhibitors.

A novel HIV-1 protease inhibitor, GRL-044, has potent activity against various HIV-1s with an extremely high genetic barrier to the emergence of HIV-1 drug resistance.

We designed, synthesized, and identified two novel nonpeptidic HIV-1 protease inhibitors (PIs), GRL- 037 and GRL-044, containing P2-tetrahydropyrano-tetrahydrofuran (Tp-THF), P1-benzene and P1-methoxybenzene, respectively, and P2'-isopropyl-aminobenzothiazole (Ip-Abt), based on the structure of the prototypic PI, darunavir (DRV). The 50% inhibitory concentrations (IC50s) of GRL-037 and GRL-044 against wild-type HIV-1NL4-3 were 0.042 and 0.0028-0.0033 nM with minimal cytotoxicity profiles compared to the IC50 values of four most potent FDA-approved PIs, ranging from 2.6 to 70 nM. GRL-044 was also potent against HIV-2EHO (IC50=0.0004 nM) and various PI-resistant HIV-1 variants (IC50 ranging from 0.065 to 19 nM). In the selection assays we conducted, the emergence of HIV-1 variants resistant to GRL-044 was significantly delayed compared to that against DRV. Thermal stability test using differential scanning fluorimetry employing purified HIV-1 protease (PR) and SYPRO® Orange showed that both GRL-037 and GRL-044 tightly bound to PR. A28S substitution emerged in the homologous recombination-based selection assays with GRL-044. Structural analyses showed that the larger size of GRL-044 over DRV, enabling GRL-044 to fit better to the hydrophobic cavity of protease, contributed to the greater potency of GRL- 044 against HIV-1. Structural analyses also suggested that the van der Waals surface contact of GRL-044 with A28' appears to be better compared to that of DRV because of the larger surface of Ip-Abt of GRL-044, which may be partially responsible for the emergence of A28S. The present antiviral data and structural features of GRL-044 should provide molecular insights for further design and development of potent and "resistance-repellant" novel PIs.

Assess Therapeutic Efficacy and Emergence of HIV Drug Resistance Following Initiation of TLD

Assess Therapeutic Efficacy and Emergence of HIV Drug Resistance Following Initiation of TLD

HIV-1 drug resistance surveillance among parturient women on anti-retroviral therapy in the Eastern Cape, South Africa: Implications for elimination of mother-to-child transmission

BackgroundThe emergence of HIV drug resistance poses a significant threat to achieving the goal of elimination of mother-to-child transmission. ObjectivesWe assessed the extent and patterns of HIV-1 drug resistance mutations (DRMs) within the context of the public sector prevention of mother-to-child transmission (PMTCT) programme in the Eastern Cape, South Africa. Study designWe conducted analysis of the Pol sub-genomic sequence of RNA extracted from plasma samples of women with probable virological failure at delivery between January and May 2018 from two large maternity centres in the Eastern Cape using standard protocols. Partial pol gene covering 1030bp were amplified and sequenced according to previously reported protocol. DRMs were determined by submitting the generated partial pol sequences to the Stanford drug resistance database for query on mutations associated with drug resistance in HIV viruses. We examined the correlates of DRMs using bivariate analysis. ResultsThe age of parturient women ranged from 16 to 43 years. The majority of the parturient women were currently on Efavirenz-based regimen (first line ART) (82.5%) and had been on ART for more than 12 months (65.0%). The prevalence of DRMs was 72.5% (n = 58). The CD4 count demonstrated a negative linear association with the DRMs (p = 0.002). The predominant DRMs were K103 N (n = 43; 74.1%), M184 V (n = 28; 48.3%) and K65R (n = 11; 19%). Among the parturient women on EFV-based regimen treatment; 79.1% already had K103 N while nine patients on protease inhibitor-based regimen still harboured K103 N. The majority of the M184 V mutations were observed in parturient women on first line regimen (n = 23; 82.1%). ConclusionsWe found a high prevalence of DRMs in women delivering their index babies at high viral loads in the study settings. Drug resistance surveillance using point-of-care reverse transcriptase-PCR strategies for the screening of pregnant women on ART could be a game-changer in the resource-constrained settings.

Genotypic Characterization of Human Immunodeficiency Virus Type 1 Isolated from Antiretroviral Treatment-Experienced Individuals in Buleleng Regency, Bali, Indonesia.

Bali, the first province to report a case of HIV in 1987, was placed sixth among Indonesian provinces with the highest cumulative number of HIV cases in 2017. As a popular tourist destination, the spread of genetic variants of HIV through international travel may become a cause for concern in Bali. Tourism is mostly concentrated in south Bali; thus, HIV in less popular regions in north Bali, such as Buleleng Regency, may have viral characteristics different from that in south Bali. Forty-three protease (PR), 40 reverse transcriptase (RT), 27 gag, and 23 env genes were sequenced from 48 samples derived from antiretroviral treatment-experienced individuals. Subtyping revealed CRF01_AE as the dominant circulating recombinant form of HIV-1 in north Bali. Although no major mutation was detected in PR genes, several major mutations were identified in 4 out of the 40 RT genes (10%), indicating the emergence of HIV-1 drug resistance in this region.

Primary HIV Drug Resistance among Recently Infected Cases of HIV in North-West India.

Background Antiretroviral treatment may lead to the emergence of HIV drug resistance, which can be transmitted. HIV primary drug resistance (PDR) is of great public health concern because it has the potential to compromise the efficacy of antiretroviral therapy (ART) at the population level. Objective To estimate the level of primary drug resistance among recently infected cases of HIV in 6 ART centres of North-Western India from September 2014 to June 2016. Methods The level of primary drug resistance was studied among 37 recently infected HIV cases identified by Limiting antigen (Lag) avidity assay based on modified Recent Infection Testing Algorithm (RITA). The reverse transcriptase region of HIV-1 pol gene (1-268 codons) was genotyped. The sequences were analyzed using the Calibrated Population Resistance (CPR) tool of Stanford University HIV drug resistance (DR) database to identify drug resistance. Results Among 37 isolates studied, 6 (16.2%) samples showed primary drug resistance (PDR) against reverse transcriptase (RT) inhibitor. The proportion of primary drug resistance was 22.2% (2/9) among female sex workers, 14.3% (1/7) among men having sex with men, and 14.3% (3/21) among injecting drug users. Observed mutations were K219R, L74V, K219N, and Y181C. Injecting drug user (IDU) has showed resistance to either nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) or nonnucleotide reverse transcriptase inhibitors (NNRTI). Conclusion Resistance to either NRTI or NNRTI among the recently is a new challenge that needs to be addressed. The fact that both Y181C isolates are IDUs is important and represents 2/21 (~10%) NNRTI drug resistance. Surveillance for primary drug resistance (PDR) needs to be integrated into next generation of HIV surveillance as access to ART is increasing due to introduction of test and treat policy.

Pretreatment HIV drug resistance among adults initiating ART in Namibia.

Continued use of standardized, first-line ART containing NNRTIs and NRTIs may contribute to ongoing emergence of HIV drug resistance (HIVDR) in Namibia. A nationally representative cross-sectional survey was conducted during 2015-16 to estimate the prevalence of significant pretreatment HIV drug resistance (PDR) and viral load (VL) suppression rates 6-12 months after initiating standardized first-line ART. Consenting adult patients (≥18 years) initiating ART were interviewed about prior antiretroviral drug (ARV) exposure and underwent resistance testing using dried blood spot samples. PDR was defined as mutations causing low-, intermediate- and high-level resistance to ARVs according to the 2014 WHO Surveillance of HIV Drug Resistance in Adults Initiating ART. The prevalence of PDR was described by patient characteristics, ARV exposure and VL results. Results were weighted to be nationally representative. Successful genotyping was performed for 381 specimens; 144 (36.6%) specimens demonstrated HIVDR, of which 54 (12.7%) demonstrated PDR. Resistance to NNRTIs was most prevalent (11.9%). PDR was higher in patients with previous ARV exposure compared with no exposure (30.5% versus 9.6%) (prevalence ratio = 3.17; P < 0.01). This survey demonstrated overall PDR at >10% among adults initiating ART in Namibia. Patients with prior ARV exposure had higher rates of PDR. Introducing a non-NNRTI-based regimen for first-line ART should be considered to maximize benefit of ART and minimize the emergence of HIVDR.

Viral load suppression and acquired HIV drug resistance in adults receiving antiretroviral therapy in Viet Nam: results from a nationally representative survey.

ObjectiveThe purpose of this survey was to estimate the prevalence of viral load (VL) suppression and emergence of HIV drug resistance (HIVDR) among individuals receiving antiretroviral therapy (ART) for 36 months or longer in Viet Nam using a nationally representative sampling method.MethodsThe survey was conducted between May and August 2014 using a two-stage cluster design. Sixteen ART clinics were selected using probability proportional to proxy size sampling, and patients receiving ART for at least 36 months were consecutively enrolled. Epidemiological information and blood specimens were collected for HIV-1 VL and HIVDR testing; HIVDR was defined by the Stanford University HIVDR algorithm.ResultsOverall, 365 eligible individuals were recruited with a mean age of 38.2 years; 68.4% were men. The mean time on ART was 75.5 months (95% confidence interval [CI]: 69.0–81.9 months), and 93.7% of the patients were receiving non-nucleoside reverse transcriptase inhibitor-based regimens. Of the 365 individuals, 345 (95.1%, 95% CI: 92.3–96.9%) had VL below 1000 copies/mL and 19 (4.6%, 95% CI: 2.8-–7.5) had HIVDR mutations.DiscussionOur nationally representative survey found a high level of VL suppression and a low prevalence of HIVDR among individuals who received ART for at least 36 months in Viet Nam. Continued surveillance for HIVDR is important for evaluating and improving HIV programs.