Second-line ART Research Articles

Can Short-Term Use of Electronic Patient Adherence Monitoring Devices Improve Adherence in Patients Failing Second-Line Antiretroviral Therapy? Evidence from a Pilot Study in Johannesburg, South Africa.

High levels of adherence are required to achieve the full benefit of ART. We assess the effectiveness of electronic adherence monitoring devices among patients failing second-line ART, as measured by viral load suppression. Cohort study of Wisepill™ real-time adherence monitoring in addition to intensified adherence counselling over 3 months in adults with a viral load ≥400 copies/ml on second-line ART in Johannesburg, South Africa between August 2013 and January 2014. Patients were sent SMS reminders upon missing a scheduled dose. We compared outcomes to earlier historical cohorts receiving either intensified adherence counselling or adherence counselling alone. Overall, 63 % of the participants (31/49) took >80 % of their prescribed medication; this dropped from 76 to 53 and 49 % at 1, 2 and 3 months post-enrolment respectively. Compared to those with good adherence (>80 %), participants with poor adherence (≤80 %) had a higher risk for a subsequently elevated viral load ≥400 copies/ml (relative risk (RR) 1.47 95 % CI 0.97–2.23). Participants found the intervention “acceptable and useful” but by 6 months after eligibility they were only slightly more likely to be alive, in care and virally suppressed compared to those who received intensified adherence counselling (44.9 vs. 38.5 %; RR 1.19; 95 % CI 0.85–1.67) or adherence counselling alone (44.9 vs. 40.9 %; RR 1.12; 95 % CI 0.81–1.56). In patients with an elevated viral load on second-line ART electronic adherence monitoring was associated with a modest, but not significant, improvement in viral suppression.

Raltegravir in second-line ART in resource-limited settings

Raltegravir in second-line ART in resource-limited settings

Projecting the epidemiological effect, cost-effectiveness and transmission of HIV drug resistance in Vietnam associated with viral load monitoring strategies.

The objective of this study was to investigate the potential epidemiological impact of viral load (VL) monitoring and its cost-effectiveness in Vietnam, where transmitted HIV drug resistance (TDR) prevalence has increased from <5% to 5%-15% in the past decade. Using a population-based mathematical model driven by data from Vietnam, we simulated scenarios of various combinations of VL testing coverage, VL thresholds for second-line ART initiation and availability of HIV drug-resistance tests. We assessed the cost per disability-adjusted life year (DALY) averted for each scenario. Projecting expected ART scale-up levels, to approximately double the number of people on ART by 2030, will lead to an estimated 18 510 cases (95% CI: 9120-34 600 cases) of TDR and 55 180 cases (95% CI: 40 540-65 900 cases) of acquired drug resistance (ADR) in the absence of VL monitoring. This projection corresponds to a TDR prevalence of 16% (95% CI: 11%-24%) and ADR of 18% (95% CI: 15%-20%). Annual or biennial VL monitoring with 30% coverage is expected to relieve 12%-31% of TDR (2260-5860 cases), 25%-59% of ADR (9620-22 650 cases), 2%-6% of HIV-related deaths (360-880 cases) and 19 270-51 400 DALYs during 2015-30. The 30% coverage of VL monitoring is estimated to cost US$4848-5154 per DALY averted. The projected additional cost for implementing this strategy is US$105-268 million over 2015-30. Our study suggests that a programmatically achievable 30% coverage of VL monitoring can have considerable benefits for individuals and leads to population health benefits by reducing the overall national burden of HIV drug resistance. It is marginally cost-effective according to common willingness-to-pay thresholds.

High prevalence of PI resistance in patients failing second-line ART in Vietnam.

BackgroundThere are limited data from resource-limited settings on antiretroviral resistance mutations that develop in patients failing second-line PI ART.MethodsWe performed a cross-sectional virological assessment of adults on second-line ART for ≥6 months between November 2006 and December 2011, followed by a prospective follow-up over 2 years of patients with virological failure (VF) at the Hospital for Tropical Diseases, Vietnam. VF was defined as HIV RNA concentrations ≥1000 copies/mL. Resistance mutations were identified by population sequencing of the pol gene and interpreted using the 2014 IAS-USA mutation list and the Stanford algorithm. Logistic regression modelling was performed to identify predictors of VF.ResultsTwo hundred and thirty-one patients were enrolled in the study. The median age was 32 years; 81.0% were male, 95.7% were on a lopinavir/ritonavir-containing regimen and 22 (9.5%) patients had VF. Of the patients with VF, 14 (64%) carried at least one major protease mutation [median: 2 (IQR: 1–3)]; 13 (59%) had multiple protease mutations conferring intermediate- to high-level resistance to lopinavir/ritonavir. Mutations conferring cross-resistance to etravirine, rilpivirine, tipranavir and darunavir were identified in 55%, 55%, 45% and 27% of patients, respectively. Higher viral load, adherence <95% and previous indinavir use were independent predictors of VF. The 2 year outcomes of the patients maintained on lopinavir/ritonavir included: death, 7 (35%); worsening virological/immunological control, 6 (30%); and virological re-suppression, 5 (25%). Two patients were switched to raltegravir and darunavir/ritonavir with good HIV control.ConclusionsHigh-prevalence PI resistance was associated with previous indinavir exposure. Darunavir plus an integrase inhibitor and lamivudine might be a promising third-line regimen in Vietnam.

Efficacy and HIV drug resistance profile of second-line ART among patients having received long-term first-line regimens in rural China.

Antiretroviral therapy has significantly expanded and an increased proportion of patients have switched to second-line regimens in China. We describe the outcomes of second-line therapy among patients having received long-term first-line ART. A prospective follow-up study was conducted in rural areas in China. We compared the virological, immunological outcomes and genotypic drug resistance (DR) profiles before and after regimen switches. A total of 303 patients were enrolled, 283 (93.4%) were retained at 12 months. Of 90 participants with HIV-RNA ≥ 1000 copies/ml before switch, the proportion of viral load (VL) ≥ 1000 copies/ml at 6 and 12 months was 49.4% and 43.9%, respectively. Of 213 patients with HIV-RNA < 1000 copies/ml before switch, the proportion of VL ≥ 1000 copies/ml at 6 and 12 months was 4.8% and 6.5%, respectively. The rates of drug resistance to NNRTIs, NRTIs, PIs decreased from 65.5%, 53.3%, and 1.1% before regimen switch to 26.8%, 18.3%, and 0% at 12 months, respectively. DDI-based initial ART regimens and missing doses in past month were associated with HIV RNA ≥ 1000 copies/ml at 12 months. The results showed that patients having received long-term first-line ART and experiencing virological failure had good virological outcomes after switching to second-line treatment in China.

Immunological and Virological Outcomes of Patients Switched from LPV/r to ATV/r-Containing Second- Line Regimens

Atazanavir/ritonavir (ATV/r) recently became the preferred protease inhibitor (PI) for use in Nigeria since it is dosed once daily, which may improve treatment adherence and has fewer side effects than lopinavir/ritonavir (LPV/r)--the most widely available PI in resource-limited settings. We, therefore, aimed to evaluate the immunologic and virologic effects of switching patients to an ATV/r-containing regimen. In a large antiretroviral treatment programme at the Lagos University Teaching Hospital in Nigeria, 400 patients were switched to ATV/r-based second-line ART. We conducted a retrospective evaluation of immunologic and virologic outcomes following 24 months on the ATV/r regimens. Of the 400 patients switched to an ATV/r containing regimen, 255 were virologically suppressed on LPV/r prior to switch, 107 were switched due to failure on a first-line regimen, 28 were on saquinavir/ritonavir (SQV/r)-based regimen, while 10 were unintentionally switched while non-suppressed on a LPV/r-based regimen. Demonstrable and sustained immunological responses were documented as the median (IQR) CD4+ cell count increased steadily from 466 (323) cells/mm3 at the time of switch to 490 (346) cells/mm3 at 6 months, and 504 (360) cells/mm3 at 24 months. Of 99 patients evaluated 12 months after ATV/r switch, 2 (2%) had detectable viral load (VL). None of the 26 (0%) in this group evaluated at 24 months had detectable viral load. In a comparison group of 576 patients who were maintained on LPV/r-based second line regimens, 359 (62.3%) had undetectable viral loads. Of 318 patients with VL data 24 months later, 25 (7.9%) had detectable VL. There was no significant difference between the proportion of patients maintained on LPV/r (7.9%) and those switched to ATV/r (0%) in the development of virologic failure after 24 months of follow-up. Among patients that were switched to ATV/r-containing regimens, we found improvements in immunological responses and no increase in risk of virologic failure.

Profile of HIV Patients on Second Line Antiretroviral Therapy: The Indian Experience

Background: The proportion of patients on second line in resource limited settings are estimated between 1-5%. The present study describes the profile and outcomes of Indian patients receiving second line ART. Methods: Information on HIV patients on second line ART was gathered. Socio demographic data, probable transmission route, baseline clinical parameters and comorbidities during therapy are studied along with first-line ART regimen initially introduced, its adherence and the reason for switch and components of the second-line ART regimen. Results: Out of the total 2174 HIV patients 53% were on first line ART and of these 51 patients on second line ART were studied. The average time of initiation of first line ART was 17.67 months with median of 2 months whereas switch to second line ART was in 53.75 months with median of 60 months. Almost 71% of the patients on second line ART had been diagnosed with HIV infection with low CD4 count of <200. However 54%, 67% and 58% patients show more than 50% rise in their CD4 count post switch to second line after 3, 6 and 12 months of treatment which is a substantial improvement. Twenty-five per cent of patients showed non adherence. Tenofovir based regimens had a slight advantage with lesser number of side effects being reported. Conclusion: Early diagnoses of infection, early initiation of ART and drug adherence are the cornerstones for success in managing HIV patients. Understanding the profile and drug resistance pattern is necessary for ensuring effective and long term survival.

A clinical prediction tool for targeted pre-antiretroviral therapy creatinine testing applied to the TREAT Asia HIV observational database cohort.

A clinical prediction tool for targeted pre-antiretroviral therapy creatinine testing applied to the TREAT Asia HIV observational database cohort.

Second-Line ART Regimens for Resource-Limited Settings

A boosted protease inhibitor (PI) plus two nucleoside reverse-transcriptase inhibitors (NRTIs) is currently recommended by the WHO as second-line therapy, despite limited data on efficacy and safety. Raltegravir, an integrase inhibitor, offers the option of removing or replacing NRTIs for higher efficacy and lower toxicity. In the Europe–Africa Research Network for Evaluation of Second-Line Therapy (EARNEST) trial, which involved 1277 HIV-infected individuals from five sub-Saharan African countries, researchers assessed whether a PI plus raltegravir was superior to a ritonavir-boosted PI plus two or three NRTIs. The …

Correction: Persistent Difficulties in Switching to Second-Line ART in Sub-Saharan Africa — A Systematic Review and Meta-Analysis

Correction: Persistent Difficulties in Switching to Second-Line ART in Sub-Saharan Africa — A Systematic Review and Meta-Analysis

Correction: Coadministration of Lopinavir/Ritonavir and Rifampicin in HIV and Tuberculosis Co-Infected Adults in South Africa.

[This corrects the article DOI: 10.1371/journal.pone.0044793.].

The Impact of HIV Drug Resistance on the Selection of First- and Second-Line ART in Resource-Limited Settings

The Impact of HIV Drug Resistance on the Selection of First- and Second-Line ART in Resource-Limited Settings

Modeling Clinical Endpoints as a Function of Time of Switch to Second-line ART With Incomplete Data on Switching Times

Modeling Clinical Endpoints as a Function of Time of Switch to Second-line ART With Incomplete Data on Switching Times

Coadministration of Lopinavir/Ritonavir and Rifampicin in HIV and Tuberculosis Co-Infected Adults in South Africa

BackgroundIn HIV-infected patients receiving rifampicin-based treatment for tuberculosis (TB), the dosage of lopinavir/ritonavir (LPV/r) is adjusted to prevent sub-therapeutic lopinavir concentrations. In this setting, South African clinicians were advised to administer super-boosted LPV/r (400 mg/400 mg) twice daily, instead of standard dosed LPV/r (400 mg/100 mg) twice daily. We sought to determine – in routine practice – the tolerability and HIV treatment outcomes associated with super-boosted LPV/r compared to unadjusted LPV/r in combination with rifampicin-based TB treatment.Methodology/Principle FindingsWe conducted a retrospective review of HIV-infected patients who receiving second-line ART with a LPV/r-containing regimen who required concomitant TB treatment. We identified 29 patients; the median age was 36 years (IQR 29–40), 22 (76%) were female, the median CD4 cell count and viral load at first-line ART failure was 86 cells/mm3 (IQR 21–159) and 39,457 copies/mL (IQR 6,025–157,500), respectively. According to physician preference, 15 (52%) of 29 patients received super-boosted LPV/r (400 mg/400 mg) every 12 hours during TB treatment and 14 (48%) of 29 patients received standard dose LPV/r (400 mg/100 mg) twice daily during TB treatment. Among patients who received super-boosted LPV/r there was a trend towards a higher rate of symptomatic transaminitis (27% vs. 7%; p = 0.3), gastrointestinal toxicity (20% vs. 0%; p = 0.2) and a significantly increased need for treatment discontinuation (47% vs. 7%; p = 0.035. The durability of coadministered treatment was significantly shorter in patients who received super-boosted lopinavir/ritonavir with TB treatment compared to patients who received standard lopinavir/ritonavir dosing (log rank, P = 0.036). The rate of virologic failure was not higher in patients with unadjusted LPV/r dosing.Conclusions/SignificanceWe observed a high rate of toxicity and need for treatment discontinuation among patients on standard rifampicin-based TB treatment who received super-boosted LPV/r.

Immunological response after initiation of second line anti-retroviral therapy in HIV patients

Introduction Treatment with second line ART is initiated when the first line therapy fails. There is less experience with the immunologic response for second-line ART for adults. Hence this study was done to find out the immunological response after initiation of second line ART by analysis of CD4 counts. Methods This retrospective study was conducted in a tertiary level hospital attached to a medical college that caters to a large number of HIV positive patients. The study population for this analysis included all HIV positive individuals who were undergoing second line ART treatment.The data was collected using semi-structured pre-tested proforma from the hospital records of HIV positive individuals. The immunological response after the initiation of second line ART was analyzed using the CD4 cell counts taken at intervals of 3 months and 6 months after the initiation. Results Out of the 32 patients studied, 27(84.4%) were males and only 5(15.6%) were females. Mean age of the patients was 40.56±6.78 years. The mean CD4 value at initiation was 152.35±142.89cells/μL, which significantly increased to 324.43 ±163.65cells /μLby 3 months after initiation (p value= .000) and to 348.21± 253.57cells /μLby 6 months after initiation.Around 91.3% of patients had a baseline CD4 T cell count <350 cells L-6. After 3 months of therapy, 65.2% of patients and after 6 months 46.2% had a baseline CD4 T cell count <350 cells /μL.The mean weight at initiation was 50.548± 11.37 kg, which very significantly increased to 53.30± 11.1 kg by 3 months of therapy (p = .001, table 1) and to 54.63 ± 10.29kg at the end of 6 months. Conclusion The CD4 counts increase very significantly within the first 3 months of initiation of second line therapy.The rise in CD4 count between 3 months and 6 months is not as statistically significant as the earlier one. Also, there is significant gain in weight within 6 months of initiation of second line therapy.

Benefit of viral load testing for confirmation of immunological failure in HIV patients treated in rural Malawi

Viral load testing is used in the HIV programme of Chiradzulu, Malawi, to confirm the diagnosis of immunological failure to prevent unnecessary switching to second-line therapy. Our objective was to quantify the benefit of this strategy for management of treatment failure in a large decentralized HIV programme in Africa. Retrospective analysis of monitoring data from adults treated with first-line antiretroviral regimens for >1 year and meeting the WHO immunological failure criteria in an HIV programme in rural Malawi. The positive predictive value of using immunological failure criteria to diagnose virological failure (viral load >5000 copies/ml) was estimated. Of the 227 patients with immunological failure (185 confirmed with a repeat CD4 measurement), 155 (68.2%) had confirmatory viral load testing. Forty-four (28.4%) had viral load >5000 copies/ml and 57 (36.8%) >1000 copies/ml. Positive predictive value was 28.4% (95% CI 21.4-36.2%). Repeat CD4 count testing showed that 41% of patients initially diagnosed with immunological failure did no longer meet failure criteria. Our results support the need for confirming all cases of immunological failure with viral load testing before switching to second-line ART to optimize the use of resources in developing countries.

A biregional survey and review of first‐line treatment failure and second‐line pediatric antiretroviral access and use in Asia and southern Africa

The article published in [1], contains incorrect data in Table 1 regarding the nationally recommended paediatric second-line ART regimen after NNRTI failure in India. This has been corrected. The editors and authors regret the inconvenience caused to readers by the error in the original paper.

Virological findings from the SARA trial: boosted PI monotherapy as maintenance second-line ART in Africa

Background: The SARA trial recently demonstrated a non-inferior CD4 response, over median follow-up of 60 weeks, with a boosted protease inhibitor monotherapy (bPImono) maintenance second-line regimen compared with continuous combination therapy (CT), suggesting this approach could maintain effectiveness whilst improving tolerability and decreasing costs [International AIDS Conference 2010, LBPE16]. Analysis of virological response and genotypic drug resistance is reported here. Methods: Eligible participants in the DART trial who received 24 weeks of lopinavir/ritonavir-containing second-line CT were randomised to maintain current CT or to reduce to bPImono within a nested pilot trial (SARA). No real-time virology was performed, but stored plasma samples from time at switch to second-line, randomisation after 24 weeks of second-line, and 24 weeks after randomisation were assayed for HIV-1 RNA viral load (VL) by Roche Amplicor v1.5. Genotypic resistance was assessed on samples with VL >1000 c/ml at this latest time point, along with paired samples at switch to second-line. All analyses are intention-to-treat. Results: 192 participants were randomised to CT (n=95) or bPImono (n=97). 77% (135/173) had VL 1000 c/ml at week 24, 12 (2 CT, 10 bPImono) have been assessed genotypically. IAS major PI mutations at week 24, not present at switch to second-line, were detected in 2 bPImono participants only. One participant (VL=3600 c/ml) had I54V only, the other (VL=1490 c/ml) M46IM+V82AV. Both isolates were considered fully susceptible to darunavir. Conclusions: In this study based on retrospective virological testing, bPImono following 24 week second-line induction was associated with an increase in low level viraemia, although generally in the absence of PI resistance. Longer-term trials are required before definitive conclusions can be drawn about the effectiveness of PI monotherapy in populations without access to virological monitoring. Supplement: Abstracts of the Tenth International Congress on Drug Therapy in HIV Infection http://www.biomedcentral.com/content/pdf/1758-2652-13-S4-info.pdf Conference: Tenth International Congress on Drug Therapy in HIV Infection 7-11 November 2010 Glasgow, UK (Published: 8 November 2010) doi:10.1186/1758-2652-13-S4-O20 Cite this article as: Pillay et al.: O214. Virological findings from the SARA trial: boosted PI monotherapy as maintenance second-line ART in Africa. Journal of the International AIDS Society 2010 13(Suppl 4):O20. Full text: PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112833/

Antiretroviral regimens for patients with HIV who fail first-line antiretroviral therapy

Highly active antiretroviral therapy has reduced the morbidity and mortality of patients with HIV/AIDS. A common first-line ART regimen in low-resource settings includes a non-nucleoside reverse transcriptase inhibitor (NNRTI) and two nucleoside reverse transcriptase inhibitors (NRTIs). If treatment failure occurs, a change to second-line therapy is necessary. This systematic review aimed to assess the optimum antiretroviral regimen for patients with HIV who fail first-line therapy (ART-naive) with a recommended World Health Organization (WHO) first-line regimen. Electronic databases and conference proceedings were searched with relevant search terms without limits to language. Randomised controlled trials of HIV-infected adolescent and adult patients administered second-line ART after virologic failure of a first-line regimen were included. Observational studies were included given the insufficient number of trials identified. The primary outcome measure included mortality. Secondary outcome measures included rate of adverse events, change in mean CD4 cell count, clinical resolution of symptoms, proportion of patients achieving undetectable viral load (VL) and acquisition of genotypic mutations. Two authors assessed each reference for inclusion and exclusion criteria established a priori. Data were abstracted independently using a standardised abstraction form. Risk of bias was assessed for individual studies and the GRADE approach for assessing the quality of evidence across a body of evidence was also applied. One randomised trial in 136 patients studied maintaining lamivudine in second-line regimens or not. There was no difference in virological outcomes in the group who maintained lamivudine and those who did not in their subsequent regimens. Two other small observational studies reported in abstract form also did not report a difference in the proportion of those with viral suppression after six months and time to HIV-1 RNA suppression among those on a lamivudine (3TC) or emtricitabine (FTC) regimen compared to those on a 3TC/FTC-sparing second-line regimen. There were no trials identified comparing boosted protease inhibitors (PIs) or nucleoside backbone combinations after first-line failure on non-thymidine analog combinations. Observational studies of populations starting ART in resource-limited settings suggest that short-term response on boosted PI-based regimens is encouraging. There is limited evidence to evaluate second-line therapies in patients with HIV who fail first-line treatment with a WHO-recommended regimen. One randomised trial in 136 patients and two observational studies (both of low quality) suggest no difference in virological suppression whether or not lamivudine is maintained in a second-line regimen. While outcomes of second-line regimens with boosted PIs are favourable in general, there are no studies comparing boosted PIs directly in populations starting second-line regimens. Current recommendations are based on available resources and patient- and public-health-level considerations.

Patients Infected with HIV Type 1 Subtype CRF01_AE and Failing First-Line Nevirapine- and Efavirenz-Based Regimens Demonstrate Considerable Cross-Resistance to Etravirine

AIDS Research and Human RetrovirusesVol. 26, No. 6 Letter to the EditorPatients Infected with HIV Type 1 Subtype CRF01_AE and Failing First-Line Nevirapine- and Efavirenz-Based Regimens Demonstrate Considerable Cross-Resistance to EtravirineWeerawat Manosuthi, David M. Butler, Wasun Chantratita, Chonlaphat Sukasem, Douglas D. Richman, and Davey M. SmithWeerawat ManosuthiBamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand.Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.Search for more papers by this author, David M. ButlerUniversity of California San Diego, La Jolla, California.Search for more papers by this author, Wasun ChantratitaFaculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.Search for more papers by this author, Chonlaphat SukasemFaculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.Search for more papers by this author, Douglas D. RichmanUniversity of California San Diego, La Jolla, California.Veterans Affairs San Diego Healthcare System, San Diego, California.Search for more papers by this author, and Davey M. SmithUniversity of California San Diego, La Jolla, California.Veterans Affairs San Diego Healthcare System, San Diego, California.Search for more papers by this authorPublished Online:20 Jun 2010https://doi.org/10.1089/aid.2009.0107AboutSectionsView articleView Full TextPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetailsCited ByGlobal Comparison of Drug Resistance Mutations After First-Line Antiretroviral Therapy Across Human Immunodeficiency Virus-1 Subtypes3 November 2015 | Open Forum Infectious Diseases, Vol. 3, No. 2High prevalence of PI resistance in patients failing second-line ART in Vietnam11 December 2015 | Journal of Antimicrobial Chemotherapy, Vol. 71, No. 3A simian-human immunodeficiency virus carrying the rt gene from Chinese CRF01_AE strain of HIV is sensitive to nucleoside reverse transcriptase inhibitors and has a highly genetic stability in vivoMicrobes and Infection, Vol. 16, No. 6Extensive Drug Resistance in HIV-Infected Cambodian Children Who Are Undetected as Failing First-Line Antiretroviral Therapy by WHO 2010 Guidelines Mia Coetzer, Benjamin Westley, Allison DeLong, Chhraing Tray, Dim Sophearin, Eric Nerrienet, Leeann Schreier, and Rami Kantor13 June 2013 | AIDS Research and Human Retroviruses, Vol. 29, No. 7The Potential Cost and Benefits of Raltegravir in Simplified Second-Line Therapy among HIV Infected Patients in Nigeria and South Africa15 February 2013 | PLoS ONE, Vol. 8, No. 2High Plasma Efavirenz Concentration and CYP2B6 Polymorphisms in Thai HIV-1 InfectionsDrug Metabolism and Pharmacokinetics, Vol. 28, No. 5Unusual Insertion and Deletion at Codon 67 and 69 of HIV Type 1 Subtype C Reverse Transcriptase Among First-Line Highly Active Antiretroviral Treatment-Failing South Indian Patients: Association with Other Resistance Mutations Shanmugam Saravanan, Vidya Madhavan, Rami Kantor, Sathasivam Sivamalar, Selvamurthi Gomathi, Sunil S. 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Butler, Wasun Chantratita, Chonlaphat Sukasem, Douglas D. Richman, and Davey M. Smith.Patients Infected with HIV Type 1 Subtype CRF01_AE and Failing First-Line Nevirapine- and Efavirenz-Based Regimens Demonstrate Considerable Cross-Resistance to Etravirine.AIDS Research and Human Retroviruses.Jun 2010.609-611.http://doi.org/10.1089/aid.2009.0107Published in Volume: 26 Issue 6: June 20, 2010Online Ahead of Print:May 27, 2010PDF download