Human immunodeficiency virus type 1 (HIV-1) subtype C viruses with different coreceptor usage profiles were isolated from 29 South African patients with advanced AIDS. All 24 R5 isolates were inhibited by the CCR5-specific agents, PRO 140 and RANTES, while the two X4 viruses and the three R5X4 viruses were sensitive to the CXCR4-specific inhibitor, AMD3100. The five X4 or R5X4 viruses were all able to replicate in peripheral blood mononuclear cells that did not express CCR5. When tested using coreceptor-transfected cell lines, one R5 virus was also able to use CXCR6, and another R5X4 virus could use CCR3, BOB/GPR15, and CXCR6. The R5X4 and X4 viruses contained more-diverse V3 loop sequences, with a higher overall positive charge, than the R5 viruses. Hence, some HIV-1 subtype C viruses are able to use CCR5, CXCR4, or both CXCR4 and CCR5 for entry, and they are sensitive to specific inhibitors of entry via these coreceptors. These observations are relevant to understanding the rapid spread of HIV-1 subtype C in the developing world and to the design of intervention and treatment strategies.

A proportion of patients with drug-resistant and drug-susceptible tuberculosis (TB) have sputum that is smear and culture positive for Mycobacterium tuberculosis for a prolonged period of time, despite conventional therapy. Among such patients with refractory TB, an unblinded, observational study was undertaken that used conventional TB therapy and adjunctive aerosol aminoglycosides. Patients with persistent smear- and culture-positive sputum for M. tuberculosis (despite > or =2 months of optimal systemic therapy) were selected for adjunctive treatment via inhalation with aminoglycosides, and microbiological responses were monitored. Thirteen of 19 patients converted to smear negativity during the study: 6 of 7 with drug-susceptible TB and 7 of 12 with drug-resistant TB. Among patients with drug-susceptible TB, the median time to sputum conversion was 23 days, a shorter time than for a population of historical control patients. Recurrent infection was not observed. Adjunctive aerosol aminoglycosides may expedite sterilization of sputum among certain patients with refractory TB and diminish the risk of transmission.

Nosocomial multidrug-resistant tuberculosis (MDR-TB) in human immunodeficiency virus (HIV)-infected people is recognized in Europe and America. We report the first such outbreak in South Africa. Six hospitalized women, identified by DNA fingerprinting, were infected with an outbreak strain of MDR-TB while receiving treatment for drug-susceptible tuberculosis. The putative source case was identified as an HIV-positive woman who underwent prolonged hospitalization for chronic cavitary tuberculosis. Compared with other HIV-positive patients in the hospital, outbreak patients were more immunocompromised, had fewer cavitary lung changes, and were less likely to have been treated before. They had high fevers, infiltrative patterns on chest radiographs, and a mean survival of 43 days. When individual isolation is not possible, separating highly immunocompromised patients with first-time tuberculosis from previously treated patients with cavitary lesions and from those with established drug resistance may reduce nosocomial transmission.

We developed a diagnostic and therapeutic algorithm for intracranial mass lesions in patients with HIV/AIDS that obviates the need for neurosurgical intervention. The approach is based upon CD4(+) lymphocyte count, serum toxoplasma immunoglobulin G (IgG) serology, chest X-ray, routine lumbar puncture studies, cerebrospinal fluid (CSF) cytology, CSF adenosine deaminase or Mycobacterium tuberculosis polymerase chain reaction testing, single positron emission-computed tomography (SPECT) scanning for intracranial enhancing lesions, and limited therapeutic trials. Over a 12-month period involving 26 patients, we found that the algorithm correctly identified the aetiology of focal intracranial lesions in all 23 evaluable patients. Costs for SPECT scanning for the entire study cohort were more than offset by the savings achieved by reduced hospital stays for the four patients with lymphoma alone. An algorithmic approach can accurately identify the cause(s) of central nervous system (CNS) mass lesions in HIV-infected patients, and SPECT scanning can replace stereotactic brain biopsy in most cases where opportunistic malignancy is suspected.

During a 22-month period, we identified 39 patients with human immunodeficiency virus (HIV) infection (mean CD4(+) count, 90 cells/mm(3)) who were hospitalized with pneumonia and who had sputum and/or other specimens that tested concurrently positive for both Mycobacterium tuberculosis and Pneumocystis carinii. The most common chest x-ray abnormality was a reticulonodular pattern or bilateral infiltrates (n=26). Serum lactate dehydrogenase levels were elevated in 17 (85%) of 20 of patients tested (mean value, 2208 U/L). Mean O(2) saturation and PO(2) were 89% and 64 mm Hg, respectively. A majority (24 patients [62%]) received both antituberculous and anti-PCP therapy (17 with steroids), and 22 improved. All ten patients who received no treatment for PCP improved and were discharged from the hospital, whereas 4 (80%) of the 5 persons who received no antituberculous treatment had a poor outcome (P<.001; OR=43). Patients with HIV or acquired immune deficiency syndrome may present with both TB and PCP; of the 2, TB seems to account for the most severe features of disease.