Circular viral DNA and anomalous junction sequence in PBMC of HIV-infected individuals with no detectable plasma HIV RNA.

Closed circular (cc) forms of extrachromosomal HIV DNA are detected in patients with high viral loads; however, it is unclear whether these forms remain if virus replication is suppressed to undetectable levels by combination antiretroviral therapy. A nested primer polymerase chain reaction amplification assay was used to detect the presence of ccDNA containing two long terminal repeat sequences (2-LTR) in PBMC of patients with low or undetectable plasma HIV RNA. Fifty percent of patients with plasma RNA levels <50 copies/ml of blood had detectable 2-LTR DNA. Sequencing of the products identified normal LTR--LTR junctions in the minority of cases with the majority containing anomalies including deletions and insertions. The persistence of HIV ccDNA in patients with no detectable plasma RNA could be consistent with ongoing de novo infection of dividing cells or with stability of this form of DNA in nondividing cells.

Effect of antiviral drugs and hematopoietic growth factors on in vitro erythropoiesis.

BACKGROUND: The purpose of these studies was to improve our understanding of nucleoside analog, antiviral, drug-induced anemia in HIV infection. METHODS: Peripheral blood erythroid progenitor cells (BFU-E) from HIV-positive (HIV+) patients and normal donors were compared in methylcellulose cultures with erythropoietin, with and without antiviral drugs, and with and without the hematopoietic growth factors, stem cell factor (SCF), hemin, and interleukin-3 (IL-3). RESULTS: Normal numbers of BFU-E-derived colonies were observed in cultures from HIV+ patients (mean +/- 1 SD BFU-E/10(5) cells plated: normal = 14.1 +/- 7.9, HIV+ = 17.2 +/- 14.2, p = 0.39). The antiviral drugs zidovudine (AZT), dideoxyinosine (ddI), and didehydrodideoxythymidine (d4T) all inhibited erythroid colonies in HIV+ and normal cultures. AZT was the most erythropoietically inhibitory drug (AZT ID50, mean +/- 1 SD for normal cultures = 2.64 +/- 4.15 microM, for HIV+ cultures = 6.28 +/- 10.79 microM, p = 0.24). Hematologic toxicity was less with ddI and d4T. However, doses of ddI and d4T < or = 10 microM inhibited colony growth in 9/14 and 8/12 cultures, respectively, from HIV+ patients. CONCLUSIONS: Stem cell factor (SCF), hemin, and interleukin-3 (IL-3) increased colony growth in HIV+ and normal cultures. In control cultures, hematopoietic growth factors added singly increased growth 1.3- to 8-fold. Hematopoietic growth factors increased growth even in cultures containing antiviral drugs. In some instances growth factors restored growth to control levels. SCF, hemin, and IL-3 were most effective when combined.

Comparison of hydroxychloroquine with zidovudine in asymptomatic patients infected with human immunodeficiency virus type 1.

Hydroxychloroquine (HCQ), an antimalarial agent used to treat patients with autoimmune diseases, has been shown to suppress human immunodeficiency virus type 1 (HIV-1) replication in T cells and monocytes in vitro by inhibiting posttranscriptional modification of the virus. An initial randomized, placebo-controlled clinical trial conducted in 38 asymptomatic HIV-1-infected patients who had CD4+ counts between 200 and 500 cells/mm3 demonstrated that the amount of recoverable virus declined significantly in the HCQ group compared with the placebo group over the 8-week study period. These preliminary observations were expanded into a second 16-week clinical trial comparing the efficacy of HCQ with that of zidovudine (ZDV) in 72 asymptomatic HIV-1-infected patients with CD4+ counts between 200 and 500 cells/mm3. Patients were randomly assigned to receive either HCQ 800 mg/d (n = 35) or ZDV 500 mg/d (n = 37) for 16 weeks. No adverse reactions to the study medications were observed in either the HCQ or ZDV group. Patients in both groups had reduced levels of recoverable HIV-1 RNA in the plasma, reduced levels of cultured virus, and reduced levels of serum p24 antigen after the 16-week study period. However, no difference was noted in absolute CD4+ counts between the two groups. Interleukin-6 and serum immunoglobulin G levels were significantly reduced in the HCQ group but not in the ZDV group. These findings support the results of the previous clinical trial. Thus HCQ may be potentially useful in the treatment of patients with HIV-1 infection.

Intramuscular pentamidine for the prevention of Pneumocystis carinii pneumonia in patients infected with human immunodeficiency virus.

We retrospectively reviewed the charts of 96 patients infected with human immunodeficiency virus (HIV) who received intramuscular pentamidine for the prevention of Pneumocystis carinii pneumonia (PCP). These patients, all of whom had either a history of PCP or a CD4 lymphocyte count of < or = 0.2 x 10(9)/L, were intolerant of sulfa drugs, neutropenic, or intolerant of aerosolized treatment. Intramuscular pentamidine was given monthly by the Z-track technique at a dosage of 300 mg (4 mg/kg if the patient weighed < 50 kg). During a total of 350 months of primary prophylaxis in 47 patients and 426 months of secondary prophylaxis in 49 patients, only three cases of PCP occurred. More than 73% of the patients were receiving zidovudine concomitantly. Adverse reactions to intramuscular pentamidine included two episodes of hypotension, three of sterile abscess, two of glucose intolerance, and one of asymptomatic hypoglycemia. The administration of intramuscular pentamidine by the Z-track technique for PCP prophylaxis appears to be highly effective and minimally toxic.

Positive Kveim test in patients with coexisting sarcoidosis and human immunodeficiency virus infection.

We present two cases of sarcoidosis complicated by HIV infection. Each case had a different level of sarcoidosis activity and coexisted with either an AIDS-related infection or a HIV-positive state. Manifestations of sarcoidosis were not apparent in the patient with the AIDS-defining opportunistic infection, but were active in the patient with asymptomatic HIV infection. Both patients had granulomatous reactions to Kveim antigen, and one had such a reaction following an AIDS-defining infection. These findings suggest that non-T-cell mechanisms may be involved in granuloma formation in sarcoidosis.