BACKGROUND:

Although cyclophosphamide based regimens can produce remission rates approaching 60 to 80% in endemic Burkitts lymphoma, relapses and refractory disease are fairly common in developing countries, due to advanced stage disease and cost-constraints in the implementation of optimal chemotherapeutic protocols.

OBJECTIVE:

To evaluate an affordable, tolerable and targeted approach to chemotherapy for endemic Burkitt's lymphoma as would be desirable in resource poor settings such as Africa.

METHOD:

We present data and review pertinent literature that indicates that the antiviral agent Zidovudine specifically targets this tumour through a unique and novel mechanism.

DATA SOURCE:

Our original studies, publications original and review articles searched in Pubmed indexed for Medline.

DATA EXTRACTION:

A systematic review to identify studies relating to Zidovudine, EBV+ and Burkitt's lymphoma, indicating antiviral agents zidovudine targeting BL in a unique and novel mechanisms.

DATA SYNTHESIS:

Our data and a qualitative assessment of the relevant literature was undertaken, given the heterogenicity of the study types making it inappropriate to pool results across studies.

CONCLUSION:

Our data suggests that the incorporation of Zidovudine into Burkitt's regimens may enhance tumour kill and abbreviate the duration of treatment necessary for this disease. Furthermore, the addition of the widely available and inexpensive agent hydroxyurea, markedly potentiates the tumorcidal activity of Zidovudine in Epstein Barr virus positive Burkitt's lymphomas. We recommend that further clinical studies in patients afflicted with this disease are needed to clearly define this potential use of Zidovudine.

En 1994 se publicaron los resultados del protocolo ACTG076 sobre quimioprofilaxis(QP)con Zidovudine(AZT)para la transmisión vertical del VIH,el grupo de madres que recibió QP con AZT tuvo un porcentaje de transmisión de 8,4 por ciento,comparado con el 24,2 por ciento de los que recibían placebo.El objetivo del presente trabajo fue evaluar la QP con AZT y los resultados obtenidos.Conclusiones.A partir de 1995 el número de binomios madre-hijo que recibieron QP con AZT ha ido en aumento progresivo,conn un impacto favorable al disminuir el número de niños infectados.La campaña de prevención de la transmisión vertical del VHI en Uruguay demostró resultados importantes.Una adecuada relación costo-beneficio y la disminución del número de niños infectados,debe ser la meta para el 100 por ciento de los binomios madre-hijo

Alopecia has been described in patients infected with the human immunodeficiency virus (HIV). Zidovudine reportedly influences hair growth in these patients, causing regrowth or thickening. A 33-year-old HIV-infected man developed alopecia areata after beginning zidovudine therapy. The alopecia reversed after the drug was discontinued.

En 1994 se publicaron los resultados del protocolo ACTG 076 sobre quimioprofilaxis (QP) con Zidovudine (AZT) para reducir la transmisión vertical del VIH; el grupo de madres que recibió QP con AZT tuvo un porcentaje de transmisión de 8.4 por ciento, comparado con el 24,2 por ciento de los que recibían placebo. El objetivo del presente trabajo fue evaluar la QP con AZT y los resultados obtenidos. Material y métodos. Se analizaron en forma retrospectiva los datos de 304 binomios madre-hijo captados en la Policlínica materno infantil del CHPR desde junio de 1990 al 31 de diciembre de 1998. Se definió QP incompleta, cuando faltaron una o dos fases del tratamiento. Los niños fueron clasificados como serorrevertidos (S), infectados (I) o perinatalmente expuestos (E), según criterios del C.D.C. Resultados. Hasta el 31/12/1994, se estudiaron 116 binomios madre -hijo y el porcentaje de transmisión vertical fue de 28,4 por ciento

En 1994 se publicaron los resultados del protocolo ACTG 076 sobre quimioprofilaxis (QP) con zidovudine (AZT) para reducir la transmisión vertical del VIH. El grupo de madres que recibió QP con AZT tuvo un porcentaje de transmisión de 8,4 por ciento, comparado con el 24,2 por ciento de los que recibían placebo. Material y métodos: Se analizaron en forma retrospectiva los datos de 304 binomios madre - hijo captados en la Policlínica materno-infantil del CHPR desde junio de 1990 al 31 de diciembre de 1998. Se definió QP completa cuando la mujer VIH(+) embarazada recibió AZT vía oral las primeras 6 semanas. Se definió QP incompleta, cuando faltaron una o dos fases del tratamiento. Los niños fueron clasificados como serorevertidos (S), infectados (I), o perinatalmente expuestos (E), según criterios del CDC. Resultados. Hasta el 31 de diciembre de 1994 se estudiaron 116 binomios madre - hijo, y el porcentaje de trasmisión vertical fue de 28,4 por ciento. En 1995, en 31 binomios, el porcentaje de transmisión fue 29,03 por ciento, ningún binomio recibió QP completa y 5 (15,6 por ciento) la recibieron en forma incompleta. En 1996, en 60 binomios, el porcentaje de transmisión fue 31,6 por ciento, 7 (11,66 por ciento) recibieron QP completa y 22 (36 por ciento) incompleta. En 1997, en 50 binomios, el porcentaje de transmisión fue de 12 por ciento, 26 (52,9 por ciento) recibieron QP completa 16 (31,3 por ciento) e incompleta. En 1998, en 47 binomios, el porcentaje de transmisión fue de 8,5 por ciento, recibieron QP completa 31 (65 por ciento) e incompleta 14 (29,78 por ciento). Analizados desde el 1 de enero de 1995, recibieron QP completa 64 binomios, el porcentaje de transmisión fue 31,6 por ciento, 7 (11,66 por ciento) recibieron QP completa y 22 (36 por ciento) incompleta. En 1997, en 50 binomios, el porcentaje de transmisión fue de 12 por ciento, 26 (52,9 por ciento) recibieron QP completa y 16 (31,3 por ciento) incompleta. En 1998, en 47 binomios el porcentaje de transmisión fue de 8,5 por ciento, recibieron QP completa 31 (65 por ciento) e incompleta 14 (29,78 por ciento). Analizados desde el 1 de enero de 1995, recibieron QP completa 64 binomios, el porcentaje de transmisión fue 6,25 por ciento. Recibieron QP incompleta 57 binomios, el porcentaje de transmisión fue 8,7 por ciento. El porcentaje de transmisión en los binomios que no recibieron QP fue de 43,2 por ciento...

The objective was to investigate the relationships among health beliefs, attitudes, and zidovudine compliance in individuals with HIV infection. A survey was administered to 52 individuals with HIV infection. The survey items, which reflected concerns expressed about zidovudine, were generated based on barriers to and benefits of zidovudine and the perceived susceptibility to and perceived severity of HIV as described by the health belief model (HBM). These items were expressed as attitudes and beliefs. Items were subjected to factor analysis, and survey results were correlated with laboratory data to predict adherence to their prescribed medication-taking regimen. Data indicated that 42.3% of the subjects were compliant with zidovudine. Factor analysis identified four dimensions: problems taking and scepticism about zidovudine; degree of concern about HIV; perceived severity of HIV; and physical barriers to taking zidovudine. Logistic regression analysis (forward conditional entry) identified those who were having problems taking zidovudine and who were sceptical about its effectiveness, and ethnicity as significant independent predictors of compliance, correctly classifying 75% of cases (p < 0.01). The fact that subjects who have problems taking zidovudine or are sceptical about the value of zidovudine are less compliant, and that this dimension is a significant predictor of compliance, suggests that non-compliance is related to attitudes and beliefs about zidovudine. This is consistent with the HBM, which holds that the balance between barriers and benefits of a health-related behaviour are significant determinants of outcome.

OBJECTIVES:

To extend the range of CD4 counts in which a plasma viral load nadir (pVL) <20 copies/ml was known to be predictive of the duration of virologic response. To determine whether baseline pVL is predictive of virologic response during the study periods.

METHODS:

A meta-analysis was conducted of the original individual patient data from two randomized controlled trials comparing zidovudine (ZDV)/didanosine (ddI) with ZDV/ddI/nevirapine (NVP).

RESULTS:

In total, 87 patients received ZDV/ddI and 83 received ZDV/ddI/NVP. Study subjects on triple therapy with baseline pVL <100,000 copies/ml were more likely to achieve a pVL <400 copies/ml (odds ratio [OR] = 2.49; p = .02) and <20 copies/ml (OR = 4.76; p = .001) during the trial than those with baseline pVL > 100,000 copies/ml. Among triple therapy patients, the relative risk of virologic failure was higher for patients with higher baseline pVL (rate ratio [RR] = 2.51/log10 copies/ ml; p = .01), after controlling for compliance and pVL nadir. The relative risks of virologic failure associated with pVL nadir <20 copies/ml and between 21 and 400 copies/ml were .04 (p = .0001) and .56 (p = .26), respectively, compared with patients with a pVL nadir >400 copies/ml.

CONCLUSIONS:

We have extended our earlier results that achieving a pVL nadir <20 copies/ml is important for maintaining virologic suppression. In particular, we have demonstrated that a pVL nadir <20 copies/ml is at least fivefold more protective against virologic failure than achieving a pVL nadir between 20 and 400 copies/ml. Baseline pVL is significantly associated with the probability of achieving and sustaining virologic suppression.

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CONTEXT:

</b>Abacavir, a nucleoside analogue, has demonstrated suppression of human immunodeficiency virus (HIV) replication alone and in combination therapy. However, the role of abacavir in a triple nucleoside combination regimen has not been evaluated against a standard protease inhibitor-containing regimen for initial antiretroviral treatment.<b>

OBJECTIVE:

</b>To evaluate antiretroviral equivalence and safety of an abacavir-lamivudine-zidovudine regimen compared with an indinavir-lamivudine-zidovudine regimen.<b>Design and

SETTING:

</b>A multicenter, phase 3, randomized, double-blind trial with an enrollment period from August 1997 to June 1998, with follow-up through 48 weeks at 73 clinical research units in the United States, Canada, Australia, and Europe.<b>

PATIENTS:

</b>Five hundred sixty-two antiretroviral-naive, HIV-infected adults with a plasma HIV RNA level of at least 10 000 copies/mL and a CD4 cell count of at least 100 x 10(6)/L.<b>

INTERVENTIONS:

</b>Patients were stratified by baseline HIV RNA level and randomly assigned to receive a combination tablet containing 150 mg of lamivudine and 300 mg of zidovudine twice daily plus either 300 mg of abacavir twice daily and indinavir placebo or 800 mg of indinavir every 8 hours daily plus abacavir placebo. After 16 weeks, patients with confirmed HIV RNA levels greater than 400 copies/mL were eligible to continue receiving randomized treatment or receive open-label therapy.<b>Main Outcome Measure: </b>Virologic suppression, defined as HIV RNA concentration of 400 copies/mL or less at week 48.<b>

RESULTS:

</b>The proportion of patients who met the end point of having an HIV RNA level of 400 copies/mL or less at week 48 was equivalent in the abacavir group (51% [133/262]) and in the indinavir group (51% [136/265]) with a treatment difference of -0.6% (95% confidence interval [CI], -9% to 8%). In patients with baseline HIV RNA levels greater than 100 000 copies/mL, the proportion of patients achieving less than 50 copies/mL was greater in the indinavir group than in the abacavir group with 45% (45/100) vs 31% (30/96) and a treatment diference of -14% (95% CI, -27% to 0%). The 2 treatments were comparable with respect to their effects on CD4 cell count. There was no difference between groups in the frequency of treatment-limiting adverse events or laboratory abnormalities. One death in the abacavir group was attributed to hypersensitivity reaction, which occurred following rechallenge with abacavir, approximately 3 weeks after initiating study treatment.<b>

CONCLUSIONS:

</b>In this study of antiretroviral-naive HIV-infected adults, the triple nucleoside regimen of abacavir-lamivudine-zidovudine was equivalent to the regimen of indinavir-lamivudine-zidovudine in achieving a plasma HIV RNA level of less than 400 copies/mL at 48 weeks.

OBJECTIVE:

There is inconsistent evidence that zidovudine use during pregnancy increases overall, cardiac, and male genital malformations.

DESIGN:

We conducted a systematic review and meta-analysis of zidovudine use and malformations and, using Bayesian methods, combined it with data from a cohort study of mother-infant pairs in the nationwide Medicaid Analytic eXtract (MAX).

METHODS:

Using MAX data (2000-2010), we identified pregnant women with HIV treated with antiretroviral therapy (ART). Women with ≥1 zidovudine dispensing during the first trimester were compared to women receiving ART without zidovudine in the first trimester. Malformation outcomes were defined using diagnosis/procedure codes. To adjust for confounding, we performed 1:1 propensity score matching. Bayesian methods require specification of a prior, which we developed in the meta-analysis. Logistic regression models combined MAX data with the prior, estimating odds ratios (ORs) and 95% credible intervals.

RESULTS:

Fourteen articles contributed information on overall malformations, 7 on cardiac malformations, and 5 on male genital malformations. In MAX, matching led to a sample of 735 women each in the zidovudine and comparator groups. When comparing first trimester zidovudine use to other ART, the Bayesian procedure yielded OR estimates slightly above the null for overall (OR = 1.11, 95% credible interval [0.80-1.55]) and cardiac (OR = 1.30 [0.63-2.71]) malformations. There were no zidovudine-exposed cases of male genital malformations in MAX, but the meta-analysis yielded elevated OR estimates (OR = 2.57 [1.26-5.24]).

CONCLUSIONS:

For most malformations, first trimester zidovudine was not associated with increased risk. The potential increase in male genital malformations was small in absolute terms, and should be evaluated further.

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