what to start

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Issues as to when to start are still being explored (tho I think all agree definitely over 200, and possibly 200-350, based on other issues like co-morbidities (e.g., HCV), viral load and rate of CD4 decline). But what to start with? Perhaps some guidance below.(Of course, therapy should start IMMEDIATELY upon HIV seropositivity diagnosis in my view. That therapy being a multivitamin/mineral.) M. **Clinical Infectious Diseases 2008;47:712–722© 2008 by the Infectious Diseases Society of America. All rights reserved.1058-4838/2008/4705-0019$15.00DOI: 10.1086/590943HIV/AIDSMAJOR ARTICLEEmergence of Drug Resistance in HIV Type 1–Infected Patients after Receipt of First-Line Highly Active Antiretroviral Therapy: A Systematic Review of Clinical TrialsRavindra Gupta,1   Hill,2   W. Sawyer,4  Deenan Pillay1,31Division of Infection and Immunity, University College London, London, 2Pharmacology Research Laboratories, University of Liverpool, Liverpool, and 3Centre for Infectious, Health Protection Agency, United Kingdom; and4SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, ThailandBackground.  Resistance to antiretroviral combination therapy is associated with increased mortality. Understanding the relative risks of emerging resistance to first-line therapy is of importance for both resource-rich and resource-poor settings.Methods.  We undertook an overview of clinical trials of adults receiving first-line highly active antiretroviral therapy (HAART), which consisted of dual nucleoside reverse-transcriptase inhibitors (NRTIs) combined with a third agent (either a nonnucleoside reverse-transcriptase inhibitor [NNRTI] or a ritonavir-boosted protease inhibitor [bPI]). The primary outcome measures were incidences of mutations conferring resistance to key drugs (NRTIs, NNRTIs, or bPIs) per trial at week 48. For meta-analysis, inverse-variance weighting was used to create estimates of overall incidences per group, with exact 95% confidence intervals (95% CIs).Results.  The study included 20 clinical trials that comprised 30 treatment arms and 7970 patients. Virologic failure at 48 weeks occurred in 4.9% (95% CI, 3.9%–6.1%) of NNRTI recipients, compared with 5.3% (95% CI, 4.4%–6.4%;  ) of bPI recipients. Of failures that were successfully genotyped, the M184V mutation in the HIV reverse transcriptase (lamivudine resistance) occurred in 35.3% (95% CI, 29.3%–41.6%) of patients who started NNRTI-based HAART, compared with 21.0% (95% CI, 14.4%–28.8%;  ) for those who received a bPI. For the K65R mutation in the HIV reverse transcriptase (multinucleoside resistance), incidences were 5.3% (95% CI, 2.4%–9.9%) and 0.0% (95% CI, 0.0%–3.6%;  ), respectively, in patients treated with non–zidovudine-containing regimens. Resistance to the third agent (an NNRTI or PI) occurred in 53% (95% CI, 46%–60%) and 0.9% (95% CI, 0.0%–6.2%;  ) of such patients, respectively.Conclusions.  Initial therapy with bPI-based regimens resulted in less resistance within and across drug classes. This finding is of particular significance for the developing world, where rates of resistance to NRTIs and NNRTIs at 48 weeks are much higher than has been seen in both cohorts and clinical trials in well-resourced countries.Received 4 March 2008; accepted 1 April 2008; electronically published 28 July 2008.Reprints or correspondence: Dr. Ravindra Gupta, University College London, Windeyer Bldg., 46 Cleveland St., London W1T 4JF, United Kingdom (Rgupta2@...).Cited by B. . (2008) Editorial Commentary: Choice of an Initial Antiretroviral Regimen in the Resource-Limited Setting: The Cost of Virologic Failure. Clinical Infectious Diseases 47:5, 723-725Online publication date: 1-Sep-2008.Citation-Full Text-PDF Version (163 kB) (See the editorial commentary by  on pages 723–5)