The emergence of antiretroviral (ARV) drug-resistant human immunodeficiency virus type 1 (HIV-1) quasispecies is a major cause of treatment failure. These variants are usually replaced by drug-sensitive ones when the selective pressure of the drugs is removed, as the former have reduced fitness in a drug-free environment. This was the rationale for the design of structured ARV treatment interruption (STI) studies for the management of HIV-1 patients with treatment failure. We have studied the origin of drug-sensitive HIV-1 quasispecies emerging after STI in patients with treatment failure due to ARV drug resistance. Plasma and peripheral blood mononuclear cell samples were obtained the day of treatment interruption (day 0) and 30 and 60 days afterwards. HIV-1 pol and env were partially amplified, cloned, and sequenced. At day 60 drug-resistant variants were replaced by completely or partially sensitive quasispecies. Phylogenetic analyses of pol revealed that drug-sensitive variants emerging after STI were not related to their immediate temporal ancestors but formed a separate cluster, demonstrating that STI leads to the recrudescence and reemergence of a sequestrated viral population rather than leading to the back mutation of drug-resistant forms. No evidence for concomitant changes in viral tropism was seen, as deduced from env sequences. This study demonstrates the important role that the reemergence of quasispecies plays in HIV-1 population dynamics and points out the difficulties that may be found when recycling ARV therapies with patients with treatment failure.

Tuberculosis (TB) is a major cause of morbidity and mortality worldwide. Each year, there are eight million new Mycobacterium tuberculosis complex (MTB) infections and three million TB-related deaths. The catastrophic effects of TB are borne disproportionately among the most vulnerable. The HIV pandemic has further increased the burden so that the risk of TB reactivation from latency is 5 to 15 percent in HIV/TB coinfection. Tuberculosis reactivation fuels further primary infections, creating a vicious cycle of increasing infection, disease, and deaths. In addition, drug-resistant TB exacerbates this increasingly common problem. The clinical presentations of TB in relation to HIV and HIV-associated immune deficiency are discussed from the perspective of clinical diagnosis and treatment in patient care. Tuberculosis prophylaxis, concurrent drug treatment of TB and HIV, drug interactions, and overlapping toxicities are detailed for the practitioner. Immune reconstitution inflammatory reactions are now a common phenomenon in HIV treatment, where similar reactions have been less commonly described in TB treatment in the past. Global distributive injustices in wealth, the burden of disease, and the provision of healthcare are obvious in TB, and clearly show us that the needs of the most vulnerable populations must be met in order to address the problems.

The combination of amdoxovir plus zidovudine appeared synergistic with reduced VL variability. This combined therapy, including the use of a lower zidovudine dosage, warrants further development for the therapy of HIV infection.

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