[Report of the first 2 cases of HIV-1 group O infection in Spain]. / Descripción de los dos primeros casos de infección por VIH-1 grupo O en España.

BACKGROUND: The wide genetic variability of HIV-1 isolates has allowed to classify them into several subtypes. Very high divergent strains have been isolated recently from West Africa patients with AIDS, and they have been called HIV-1 group O ("outlier"). PATIENTS AND METHODS: In April 1995 a couple of patients was referred for medical follow-up and definitive diagnosis of HIV-1 infection. Both were white and had been born in Spain. The husband had been working for 10 years in West Africa. CD4+ T-cell counts were below 250 x 10(6)/l in both subjects, and the wife had developed seborrheic dermatitis and mild pancytopenia. Serologic and genetic studies were performed to study the presence of HIV-1 group O infection in this couple. RESULTS: Serological tests (enzyme immunoassays, Western blot, line immunoassay) yielded indeterminate results for HIV-1 testing serum from the wife, but the husband's specimen was positive. Serological test for HIV-2 were negative in both subjects. In contrast, a new test allowed recognition of specific antibodies to HIV-1 group O in these patients. Furthermore, this infection was confirmed using a discriminative PCR methodology, which demonstrated the presence of specific HIV-1 group O sequences and the absence of group M sequences. CONCLUSIONS: The first two cases of HIV-1 group O infection in Spain are described. It is pointed that diagnostic tests and therapeutic strategies need to considers the presence of this new HIV variant outside endemic areas.

[Efficacy of combining zidovudine plus didanosine in patients with and without previous exposure to zidovudine]. / Eficacia de la combinación de zidovudina y didanosina en pacientes con y sin exposición previa a zidovudina.

BACKGROUND: The virologic and immunologic efficacy of the combination of zidovudine (ZDV) and didanosine (DDI) was examined in 27 HIV-infected patients. METHODS: 27 HIV-infected patients, 15 of whom were naive for antiretroviral drugs. The remaining 12 subjects had been exposed to ZDV for at least 16 weeks. Mean plasma viral load was of 4.7 logs and 4.5 logs, respectively. All patients had less than 350 x 10(6)/l CD4+ T lymphocytes at baseline. RESULT: Significant reductions in viremia (> 0.5 logs) were seen at the first and third months, respectively, in 71.4% and 64.3% of naive patients. In contrast, it occurred only in 10% and 0%, respectively, of pre-treated patients. Moreover, the CD4 count only increased significantly (> 15%) in naive individuals. Changes in serum p24 antigenemia were not significant in both groups neither at the first nor at the third months of began therapy. CONCLUSION: The antiviral efficacy of the ZDV plus DDI combination is limited and transient in patients with advanced HIV disease, and disappears in subjects already exposed to ZDV.

[Combined antiretroviral therapy for prevention of vertical HIV-1 transmission]. / Terapia antirretroviral combinada para la prevención de la transmisión vertical de la infección por el VIH-1.

A 25-year old woman with rapid HIV disease progression had been receiving zidovudine (ZDV) for two years, when she became pregnant. She had a high viral load and carried out zidovudine-resistant viral strains. For these reasons, and with the main objective to maximally reduce viremia, the association of DDI to ZDV was introduced a few weeks before delivery. The virological follow-up for one year has confirmed the lack of HIV infection in the child. Combined antiretroviral therapy during the last weeks of pregnancy might be considered for the prevention of vertical transmission of HIV in cases of high risk of newborn infection, without adding relevant toxicity.

[Frequency and characteristics of patients treated with zidovudine and absence of progression of HIV infection]. / Frecuencia y características de los pacientes tratados con zidovudina y ausencia de progresión de la infección por VIH.

BACKGROUND: the efficacy of zidovudine (ZDV) is lost in many treated individuals after a few weeks or months of monotherapy. The development of drug resistance seems to explain this adverse event. However, some individuals seem to persistently benefit clinically and immunologically from ongoing ZDV monotherapy. The degree and causes of this phenomenon remain unclear. PATIENTS AND METHODS: we studied 280 HIV-infected patients who have been receiving ZDV monotherapy for more than 18 months (mean 28 +/- 7 months), and whom has a CD4+ count between 200 and 500 x 10(6)/l at baseline. We classified them into two groups: Non-progressors with ZDV (NP-ZDV), subjects with an increase or a reduction < 15% in the CD4+ count; and Progressors with ZDV (P-ZDV), subjects showing a decline in the CD4 count > 15%. Epidemiological, immunological and virological features of each group were compared. RESULTS: the prevalence of NP-ZDV in this population was 15.7% (44/280). Age, gender, and risk behaviour were not significantly different in NP-ZDV and P-ZDV. Although the CD4/CD8 ratio, as well as the CD45R0/CD45RA ratio into the CD4+ subpopulation, were higher in NP-ZDV than in P-ZDV, the values did not achieve statistical significance. Virological studies were performed on 36 (81.8%) NP-ZDV and 55 (23.3%) P-ZDV. Mean HIV-RNA titer was higher in P-ZDV than in NP-ZDV (8.4 x 10(4) vs. 1.5 x 10(3) copies/ml; p < 0.01). Virus isolation from circulating mononuclear cells was made more frequently in P-ZDV than in NP-ZDV (90.9% vs. 81.5%), although it did not achieve statistical significance. The syncitium-inducing (SI) phenotype was detected in more than a quarter (27.3%) of P-ZDV but was absent in NP-ZDV (p < 0.01). The prevalence of RT mutations at codon 215 was much lower in NP-ZDV than in P-ZDV, and it showed a strong statistical significance (13.9% vs. 74.5%; p < 0.01). CONCLUSIONS: prolonged (> 2 years) lack of immunological and clinical progression can be observed in 15% of HIV-infected persons with mild immunosuppression, undertaking ZDV monotherapy. This effect seems to be associated with a characteristic virological profile, in which a low viral load, the absence of SI phenotype, and a lack of development of ZDV-resistance are the most relevant features.

Lower HIV-2 plasma viral loads may explain differences between the natural histories of HIV-1 and HIV-2 infections.

To explain the low transmissibility and pathogenicity of HIV-2 infection's plasma viral loads in both HIV-1- and HIV-2-infected persons were compared by using the polymerase chain reaction (PCR)-based Amp-RT assay to measure levels of reverse transcriptase (RT) activity. The study comprised a total of 155 HIV-infected-people including 58 who were infected with HIV-2 with CD4+ cell counts <500 x 106/L (n = 15), CD4+ cell counts >500 x 106/L (n = 26), or with tuberculosis (TB; n = 17), and 97 HIV-1-infected people with CD4+ cell counts <500 x 106/L (n = 32), CD4+ cell counts >500 x 106/L (n = 25), or TB (n = 40). Among persons with CD4+ cell counts <500 x 106/L, 11 (73.3%) of 15 HIV-2-infected persons had detectable plasma RT activity compared with 25 (78.1%) of 32 HIV-1-infected persons (p =.725). However, the median HIV-2 plasma RT activity in this group was significantly lower (2561 x 10-10 U/ml; p =.036; detectable range, 1712-644,868 x 10-10 U/ml) than the RT activity of HIV-1-infected persons with similar CD4+ cell counts (13,241 x 10-10 U/ml; detectable range, 8482-1,478,880 x 10-10 U/ml). Among TB patients, 10 (58.8%) of 17 HIV-2-infected persons had detectable plasma RT activity compared with 30 (75%) of 40 HIV-1-infected persons (p =.342). In contrast, among patients with CD4+ cell counts >500 x 106/L, none of 26 HIV-2-infected persons had detectable RT activity compared with 13 (52%) of 25 HIV-1-infected persons (p <.001). Our data suggest that unlike HIV-1 infection, HIV-2 infections with CD4+ cell counts >500 x 106/L are associated with a low level of viral replication, which may explain the longer clinical latency and lower transmissibility seen in HIV-2 infection.