Medical Consultant
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OBSTETRICS
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The Pediatric AIDS Clinical Trials Group Study 185 Team explored the effects of obstetrical, maternal, virologic, immunologic, and infant-related variables on the risk of perinatal HIV-1 transmission in women and their infants, all of whom had been treated with zidovudine. Univariate analyses revealed that several factors are correlated with the risk of perinatal HIV-1 transmission, including lower CD4+ lymphocyte counts in mothers at base line, lower HIV-1 p24 antibody levels in mothers at base line and delivery, and higher HIV-1 titres in mothers at base line and delivery. Two other factors that were associated with the risk of perinatal transmission are increased HIV-1 RNA levels in mothers at base line and delivery and chorioamionitis at delivery. Multivariate analyses indicated that only increased HIV-1 RNA levels at base line and delivery independently raised the risk of perinatal HIV-1 transmission, and that maternal HIV-1 RNA level at delivery was the strongest predictor of the risk of transmission. The researchers suggest that HIV-infected pregnant women receive antiretroviral therapy that reduces their HIV-1 RNA levels below 500 copies per millilitre at baseline to both decrease the risk of perinatal transmission and improve the women's health.
Ref: Mofenson L M; Lambert J S, Stiehm E R, et al. New England Journal of Medicine (05/08/99) Vol. 341, No. 6, P. 385. Source: CDC HIV/STD/TB Prevention News Update
New findings from the Women and Infants Transmission Study Group suggest that the level of plasma HIV-1 RNA in HIV-1-infected pregnant women predicts the likelihood but not the time of perinatal virus transmission. The researchers measured plasma HIV-1 RNA levels in HIV-infected women who had singleton pregnancies and tested their infants for HIV-1. The infants were classified as infected early if HIV culture was positive from blood obtained in the first two days of life or late if culture was negative from blood obtained in the first seven days of life but later cultures were positive. The authors note that increasing geometric mean levels of plasma HIV-1 RNA were correlated with rising rates of perinatal HIV-1 transmission. The highest rates of vertical HIV-1 transmission occurred among women who had over 100,000 HIV-1 RNA copies per millilitre and who had not received zidovudine. The researchers note that higher levels of HIV-1 RNA in early or late pregnancy were not associated with the timing of infection in infants.
Ref: Garcia P M, Kalish L A, Pitt J, et al. New England Journal of Medicine (05/08/99) Vol. 341, No. 6, P. 394. Source: CDC HIV/STD/TB Prevention News Update
New research further indicates that the maternal plasma level of viral RNA is one of the key predictors of both intrauterine and intrapartum HIV transmission, write Drs. Martha F. Rogers and Nathan Shaffer of the Centers for Disease Control and Prevention in an editorial. When considered with data from Thailand, the new studies--which are published in the August 8th issue of the New England Journal of Medicine--suggest that one of the most useful interventions may be therapy that lowers the maternal viral level as much as possible. Rogers and Shaffer note, however, that several factors play a role in the risk of transmission. An important question that still must be answered is whether delivery by caesarean section offers any extra protective benefit for women who take potent combination antiretroviral drugs and have very low or undetectable plasma viral RNA levels. The authors point out that another area that requires further research is, for resource-poor nations, "whether short courses of peripartum antiretroviral therapy followed by passive immunisation with HIV hyperimmune globulin or active immunisation of infants with an HIV vaccine can provide protection during lactation for infants of women who breast-feed." Furthermore, they note that because little is known about the safety of antiretroviral drugs during pregnancy, it is essential to explain the risks and benefits of the therapy.
Ref: Rogers M F, Shaffer N. New England Journal of Medicine (05/08/99) Vol. 341, No. 6, P. 441. Source: CDC HIV/STD/TB Prevention News Update
HIV test will now be routinely offered, but not mandatory for all pregnant women in UK
Two-thirds of mothers in the UK are unaware they have HIV until after giving birth.
All pregnant women in England are to be offered an HIV test in an effort to reduce the rising number of babies born with the virus. The tests are to be recommended to women as part of their routine ante-natal screening, but there will be no element of compulsion. The measures, announced by Health Minister Tessa Jowell, are designed to cut by 80% the number of babies born HIV positive by the year 2002. They are also aimed at improving treatment for women with HIV. If women know they are infected then there is a chance they can reduce the risk of transmission from mother to baby from one in six to less than one in 20. Women known to be HIV positive can take anti-viral drugs during pregnancy to minimise the risk of transmitting the disease to their babies during birth, while not breast feeding avoids infection through the mother's milk.
Women will be "strongly advised" to have the tests, and will be told they are opting out of standard medical procedures if they refuse. The UK has one of Europe's highest maternal HIV transmission rates.
Source: http://news.bbc.co.uk/
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PAEDIATRICS
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Pubertal development is significantly delayed in HIV-infected haemophiliacs, according to members of the Hemophilia Growth and Development Study. Dr. Elizabeth M. Mahoney of the Emory University School of Medicine in Atlanta, Ga, and colleagues followed a cohort of 333 boys and adolescents with moderate or severe haemophilia. During the late 1970s and early 1980s, 62% of these patients became infected with HIV following exposure to contaminated blood products. In the 207 HIV-infected subjects, Dr. Mahoney's group assessed the patients every 6 months, measuring CD4+ cell counts, Tanner stage, and other factors. At baseline, the mean patient age was 13.9 years, and researchers estimated that the HIV-positive subjects had been infected for a mean of 6.7 years. At 4-year follow-up, they observed "...statistically significant delays in pubertal development associated with increasing levels of immune dysfunction." In addition, "...coefficients for the association between age and CD4+ cell count at each of the Tanner stage transitions showed significant negative correlation," they report in the August 1st issue of the Journal of Acquired Immune Deficiency Syndromes. Dr. Mahoney's group believes these findings "...emphasise the importance of following pubertal development in HIV-infected adolescent boys because delays in maturation may be a predictive indicator of subsequent HIV-related symptom development."
Ref: J Acquir Immune Defic Syndr 1999;21:333-337. Source: CDC HIV/STD/TB Prevention News Update
A protease inhibitor administered in combination with other antiretroviral drugs can provide "...prompt and sustained restoration of intestinal function" in children with advanced HIV disease. This is the conclusion of Dr. Alfredo Guarino, of the University Federico II in Naples, and colleagues who investigated the intestinal function of 10 HIV-infected children. Intestinal absorptive processes in these children were evaluated at baseline and again at 3 and 6 months after the initiation of combination therapy with ritonavir and 2 HIV reverse transcriptase inhibitors. At enrolment, Dr. Guarino's group found that "...9 children had carbohydrate malabsorption, 3 steatorrhea, 2 protein loss, and 7 iron deficiency." After 3 months of therapy, the results of most tests were normal. After 6 months of therapy, "...all abnormalities were abolished," the investigators report in the August 1st issue of the Journal of Acquired Immune Deficiency Syndromes. In addition to normalisation of intestinal function, Dr. Guarino's group observed a progressive decrease in viral load and an increase in CD4 cell count. They also detected a "...shift of body weight pattern toward catch-up growth...in all children." Although the researchers acknowledge the small size of the study, they believe the results provide "...compelling evidence of restoration of intestinal function following ritonavir combination therapy."
Ref: J Acquir Immune Defic Syndr 1999;21:307-312. Source: CDC HIV/STD/TB Prevention News Update
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METABOLISM & NUTRITION
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The characteristic fat redistribution associated with protease inhibitor treatment for HIV infection may be improved by exercise training, according to the findings of a pilot study.
HIV-associated lipodystrophy characterised by increased visceral fat with decreases in facial and limb fat, may increase the risk of hypertension, diabetes, and coronary artery disease, Dr. Ronenn Roubenoff, of Tufts University in Boston, Mass, and colleagues explain. However, no effective treatments for this condition are available. This led Dr. Roubenoff's group to conduct a 16-week, open-label pilot study of "...progressive resistance training with an aerobic component." Ten HIV-infected men with signs of lipodystrophy trained 3 times per week. The investigators monitored total body lean and fat mass, and trunk fat mass using dual-energy x-ray absorptiometry.
At follow-up, there was "...a significant decline in total body fat by 1.5 kg," they report in the July 30th issue of AIDS. They observed that "...most of the decline in body fat occurred in trunk fat, which decreased by 1.1 kg." The men increased their strength in 3 out of 4 exercises tested. "No adverse effects were seen from the training." The exercise regimen appeared to have no impact on weight, lean mass, or bone mineral density.
These preliminary findings "...indicate that exercise has the potential to improve body composition in HIV-associated lipodystrophy." Dr. Roubenoff's group therefore suggests that "...further investigation of the role of exercise training in treating and preventing HIV-associated fat redistribution is warranted."
Ref: AIDS 1999;13:1373-1375. Source: CDC HIV/STD/TB Prevention News Update
HIV infection is thought to lead to increased oxidative stress which may in turn lead to faster progression of HIV disease. Therefore, antioxidants may have a role in the treatment of HIV disease. We review the data on the relations of selected antioxidants to HIV disease progression. Results from observational epidemiologic studies suggest that vitamin A deficiency may accelerate HIV disease progression. In observational studies conducted among vitamin A replete populations, associations between intake or status of vitamin A (both preformed vitamin A and beta-carotene) and HIV disease progression have been less consistent. Available data from intervention studies are not entirely consistent with a beneficial effect of supplementation with preformed vitamin A or beta- carotene. The relations of vitamins C and E to HIV disease progression have been examined in a small number of epidemiologic studies; results from such studies are compatible with a protective effect of high intakes or levels of these vitamins. In two prospective studies, low selenium levels were found to be associated with an increased risk of progression of HIV disease. Available epidemiologic data are consistent with a protective effect of multivitamin (or multivitamin-mineral) supplements, preparations which typically include several of the above antioxidants. Finally, limited epidemiologic data support a protective role of N- acetylcysteine (NAC) in HIV disease. Many studies conducted to date have been observational prospective studies; the interpretation of such studies is problematic, however, given the possibility of confounding by infection duration and other factors. Thus, well designed randomised trials are essential to properly investigate the role of antioxidants, particularly vitamin E, vitamin C, selenium, and NAC, in HIV disease. Such trials are urgently needed since dietary administration of antioxidants to HIV infected persons would be an inexpensive intervention appropriate for the developing world.
Ref: Garland,M., Fawzi,W.W.: Nutr.Res.,19 (8):1259-1276 (1999 Aug)
The development of diabetes in HIV-infected patients treated with a protease inhibitor resembles non-insulin-dependent diabetes mellitus (type 2) with impaired insulin action in the periphery, as opposed to insulin-dependent diabetes mellitus (type 1), according to a multicentre team.
The underlying mechanism of hyperglycaemia and diabetes associated with protease inhibitor treatment is not completely understood, Dr. Kevin E. Yarasheski, of the Washington University Medical School in St. Louis, Mo, and colleagues explain. The researchers therefore investigated the mechanisms by which these drugs may cause diabetes. To this end, they evaluated a group of 47 men, which included HIV-infected patients with or without diabetes, on protease inhibitor therapy or protease inhibitor-naive and uninfected healthy controls. They also looked at a group of normoglycaemic HIV-infected subjects on protease inhibitor therapy who were matched by body mass index (BMI) to the diabetic group. In all cases, indinavir was the protease inhibitor used.
The researchers measured a variety of parameters that define diabetes type 1 or type 2. They also conducted in vitro studies using rat pancreatic beta-cells to determine if indinavir directly inhibits proinsulin-to-insulin conversion or inhibits insulin and C-peptide secretion.
"In hyperglycaemic HIV-positive subjects, circulating concentrations of insulin, C-peptide, proinsulin, glucagon, and the proinsulin/insulin ratio were increased when compared with those of the other 4 groups," they report in the July 1st issue of the Journal of Acquired Immune Deficiency Syndromes. No differences in morning fasting serum cortisol concentrations were seen in any of the subjects. They also found that glutamic acid decarboxylase antibody titres were uncommon in all subjects, and that BMI was not necessarily associated with diabetes. In addition, the results of the in vitro studies indicated that "...indinavir did not inhibit proinsulin to insulin conversion or impair glucose-induced secretion of insulin and C-peptide from rat beta-cells."
Based on the findings, Dr. Yarasheski's group concludes that "...protease inhibitor-associated diabetes involves peripheral insulin resistance with insulin deficiency relative to hyperglucagonemia and a high BMI." Since there was no evidence that indinavir impairs pancreatic beta-cell function, "HIV [protease inhibitor]-associated diabetes mirrors that of non-insulin-dependent diabetes mellitus and impaired insulin action in the periphery."
Ref: J Acquir Immune Defic Syndr 1999;21:209-216. Source: Reuters Health
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ANTIRETROVIRALS
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Boehringer Ingelheim (BI) has announced plans to conduct a large multicentre open-label study to directly assess the efficacy of nevirapine (Viramune(r)), the first European approved non-nucleoside reverse transcriptase inhibitor (NNRTI), and the recently approved NNRTI efavirenz. The study will compare triple therapy regimens of either NVP or EFZ + d4T + 3TC and a double NNRTI regimen of NVP and EFZ + d4T + 3TC. The trial is designed to support current US and draft UK guidelines which recommend the choice of NNRTIs first line and will provide UK physicians with additional data to assist in the selection of the most appropriate NNRTI for use as a first line regimen.
It is estimated that 450 patients will be enrolled into the 48 week study and randomised to receive one of the three drug regimens.
Source: Boehringer Ingelheim Press Release.
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OPPORTUNISTIC EVENTS
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Researchers from Toronto Hospital, Glaxo Wellcome, and elsewhere studied the efficacy of atovaquone suspensions versus aerosolised pentamidine for the prevention of Pneumocystis carinii pneumonia (PCP) in HIV-infected individuals who are intolerant to trimethoprim, sulfonamides, or both drugs. There were no significant differences for intent-to-treat analyses regarding incidence of PCP and mortality, but treatment-limiting adverse events occurred more frequently with atovaquone. The subjects who received 1500 mg of atovaquone had lower incidences of PCP and mortality than those were received a 750 mg dose. The researchers concluded that atovaquone suspension given in a 1500 mg dose once a day is as effective as aerosolised pentamidine in preventing PCP in HIV patients. In addition, they said that atovaquone suspension is safe for patients who cannot tolerate trimethoprim or sulfonamides.
Ref: Chan, Charles; Montaner, Julio; Lefebvre, Eric-Albert; et al. Journal of Infectious Diseases Online (08/99) Vol. 180, No. 2, P. 369. Source: CDC HIV/STD/TB Prevention News Update
HIV-infected homosexual men appear to have a high prevalence of anal intraepithelial neoplasia (AIN) and infection with multiple oncogenic human papillomaviruses (HPV), according to UK investigators.
Dr. H. B. Lacey of the Manchester Hospital and associates prospectively followed a cohort of 41 HIV-infected homosexual men for an average of 17 months. During this time, the subjects had 181 follow-up visits and 38 patients underwent anoscopy and anal biopsy. At baseline, the subjects' average CD4 cell count was 273/µL. "Oncogenic HPV types were detected in 84% and high grade dyskaryosis in 10.5%" of the subjects at enrolment, Dr. Lacey's group reports in the July issue of Sexually Transmitted Infections. They also observed a "...70% incidence of high grade dyskaryosis during follow-up in patients with negative/warty or low grade dyskaryosis at enrolment." Results of cytology and/or anoscopy predicted all of the 23 cases of high-grade AIN. Although the progression from low-grade to high-grade AIN was rapid in this cohort, the UK group detected no cases of anal carcinoma. Overall, there was a "...surprising high incidence of oncogenic HPV and anal cytological abnormalities" in this relatively small sample. Because of the degree of immunosuppression in most of the subjects, the authors suggest that this cohort "...may not be representative of HIV-positive men as a whole."
"While questions remain...about the significance of high grade AIN in this group of patients," Dr. Lacey's group believes that "...it seems wise to urge caution when considering screening programs until more data about the natural history and efficacy of treatment options are known."
Ref: Sex Transm Infect 1999;75:172-177. Source: Reuters Health
Abstract
Although invasive cervical cancer (ICC) has been included among the AIDS-defining conditions since 1993, it remains controversial whether HIV infection increases the risk of developing such neoplasm. In this study, ICC risk was longitudinally investigated among 1,340 HIV-positive intravenous drug user (IDU), 811 HIV-negative IDU, and 801 HIV-positive heterosexual women. These women, aged 15-49 years, were followed up at the Italian HIV Seroconverter Study, at the San Patrignano Community (Rimini, North Italy), and in South-eastern France (the DMI-2 study). The number of observed cases of ICC was compared with the expected one, based on ICC incidence rates among women of the same age in the general population of Italy or France, and standardised incidence ratios (SIR) were computed; 9,070 person-years of observation were accumulated among HIV-positive women and 2,310 among HIV-negative ones. Ten cases of ICC were diagnosed among HIV-positive women (SIR = 12.8): ICC risk was apparently higher among HIV-positive IDU (SIR = 16.7) than among heterosexual women (SIR = 6.7). No cases of ICC were diagnosed among HIV-negative IDU women admitted to the San Patrignano Community (0.15 cases were expected). Our findings confirm previous suggestions showing an increased risk of ICC among HIV-infected women and have important implications at the individual and public health levels.
Ref: Serraino,D., Carrieri,P., Pradier,C., Bidoli,E., Dorrucci,M., Ghetti,E., Schiesari,A., Zucconi,R., Pezzotti,P., Dellamonica,P., Franceschi,S., Rezza,G.: Int.J.Cancer,82 (3):334-337 (1999 Jul 30)
European regulatory authorities have approved fomivirsen (Vitravene(r)) for the local treatment of cytomegalovirus (CMV) retinitis in patients with AIDS, according to a statement from Isis Pharmaceuticals in Carlsbad, Calif. A Community Marketing Authorisation was issued following an application by CIBAVison, a division of Novartis AG, which will market the drug in the European Union. Isis will receive $2.5 million from CIBAVision under the terms of a world-wide distribution agreement between the 2 companies. Fomivirsen has been approved for the local treatment of newly diagnosed HIV-related CMV retinitis or for use in patients with advanced CMV retinitis who have failed or who cannot tolerate other therapies. Fomivirsen, an antisense inhibitor of CMV replication, was approved by the Food and Drug Administration in August 1998 for use in the United States.
Source: CDC HIV/STD/TB Prevention News Update
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HIV RESISTANCE
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Abstract
To investigate the occurrence of multinucleoside analogue resistance during therapy failure, we surveyed the drug susceptibilities and genotypes of nearly 900 human immunodeficiency virus type 1 (HIV-1) samples. For 302 of these, the 50% inhibitory concentrations of at least four of the approved nucleoside analogues had fourfold-or-greater increases. Genotypic analysis of the reverse transcriptase (RT)-coding regions from these samples revealed complex mutational patterns, including the previously recognised codon 151 multidrug resistance cluster. Surprisingly, high-level multinucleoside resistance was associated with a diverse family of amino acid insertions in addition to "conventional" point mutations. These insertions were found between RT codons 67 and 70 and were commonly 69Ser-(Ser-Ser) or 69Ser-(Ser-Gly). Treatment history information showed that a common factor for the development of these variants was AZT (3'-azido-3'-deoxythymidine, zidovudine) therapy in combination with ddI (2',3'-dideoxyinosine) or ddC (2',3'-dideoxycytidine), although treatment patterns varied considerably. Site-directed mutagenesis studies confirmed that 69Ser-(Ser-Ser) in an AZT resistance mutational background conferred simultaneous resistance to multiple nucleoside analogues. The insertions are located in the "fingers" domain of RT. Modelling the 69Ser-(Ser-Ser) insertion into the RT structure demonstrated the profound direct effect that this change is likely to have in the nucleoside triphosphate binding site of the enzyme. Our data highlight the increasing problem of HIV-1 multidrug resistance and underline the importance of continued resistance surveillance with appropriate, sufficiently versatile genotyping technology and phenotypic drug susceptibility analysis.
Ref: Larder BA, Bloor S, Kemp SD, Hertogs K, Desmet RL, Miller V, Sturmer M, Staszewski S, Ren J, Stammers DK, Stuart DI, Pauwels R. Antimicrob Agents Chemother 1999 Aug;43(8):1961-7.
Italian researchers report "unexpected beneficial effects" following the emergence of the lamivudine-associated mutation M184V in HIV-1 reverse transcriptase during triple therapy with lamivudine, zidovudine, and a protease inhibitor. In addition to resensitisation of zidovudine-resistant virus to zidovudine, viral suppression may be greater in patients who develop this mutation compared with those who do not.
Dr. Maurizio Zazzi and colleagues at the University of Sienna conducted a retrospective study of 56 HIV-1-infected patients who began treatment with zidovudine, lamivudine, and a protease inhibitor. Forty subjects had received previous reverse transcriptase (RT) inhibitor treatment and 16 subjects were drug-naive. At baseline and after 24 and 48 weeks of triple therapy, the investigators evaluated the patients' plasma viral load and pol genotype. None of the subjects had the M184V mutant virus at baseline. "Emergence of the M184V RT mutation at week 48 was detected in 3 of 16 (18.7%) initially drug-naive subjects as opposed to 21 of 40 (52.5%) [zidovudine]-pre-treated subjects," the researchers report in the July 1st issue of the Journal of Acquired Immune Deficiency Syndromes. Overall, the best predictor of selection of the M184V mutant was HIV-1 RNA load at 24 weeks. At 24 weeks, the research team found that 17 of the zidovudine-resistant subjects "...with mutant RT M184V codon had a more favourable HIV-1 RNA slope than those with wild-type RT 184M codon." A more favourable HIV-1 RNA slope was also observed in pre-treated subjects who were still zidovudine-sensitive, although the trend was not as strong.
Dr. Zazzi's group concludes that "...if an intrinsically beneficial role of the M184V mutation were definitely proven in larger studies, [lamivudine] treatment should not only be continued in the presence of genotypic resistance but even deliberately used to select for and maintain an altered genotype with reduced pathogenic potential."
Ref: J Acquir Immune Defic Syndr 1999;21:203-208. Source: Reuters Health
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IMMUNOLOGY
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HIV-infected patients with advanced disease show a partial reconstitution of T-cell competence following treatment with highly active antiretroviral therapy (HAART), according to a Dutch group. However, they found no evidence of regeneration of T-cell repertoire in these patients.
Dr. Oscar Pontesilli of Erasmus University in Rotterdam and associates evaluated the degree of protective immunity and evidence of immune control over HIV-1 in 12 patients with long-standing HIV-1 infection who were treated with HAART. Specifically, they assessed the subjects' lymphoproliferative responses (LPRs) to recall antigens (Ags) and HIV-1 Gag, along with the frequency of HIV-1-specific cytotoxic T cell lymphocyte precursors (CTLp). "LPRs to at least 1 recall Ag became detectable or increased in all patients during HAART," they report in the July issue of the Journal of Infectious Diseases. "No significant LPRs to Gag-p24 were observed, whereas 4 of 8 patients tested presented with Gag-p17-specific LPRs."
Dr. Pontesilli's group also found that 6 of 10 patients tested had measurable or increased HIV-1-specific CTLp frequencies during early treatment. However, HIV-1-specific CTLp frequencies continued to increase only in 1 patient who experienced partial HAART failure.
They conclude that "...HAART during advanced HIV-1 infection induces a partial regaining of T cell competence with no evidence of repertoire regeneration." However, they do not rule out the possibility that this may occur at a later stage. The findings also suggest that "...active immunisations to optimise protection against infections" may be feasible.
Source: Reuters Health
Abstract
Lymphoproliferative responses (LPRs) to recall antigens (Ags) and human immunodeficiency virus type 1 (HIV-1) Gag and frequencies of circulating HIV-1specific cytotoxic T lymphocyte precursors (CTLps) were measured in 12 patients undergoing highly active antiretroviral therapy (HAART) after long-standing HIV-1 infection. LPRs to at least 1 recall Ag became detectable or increased in all patients during HAART. No significant LPRs to Gag-p24 were observed, whereas 4 of 8 patients tested presented with Gag-p17specific LPRs. HIV-1specific CTLp frequencies became measurable or increased early during therapy in 6 of 10 patients tested and were maintained or decreased thereafter. Increasing HIV-1specific CTLp frequencies were seen only in association with partial HAART failure in 1 patient. In conclusion, restoration of CD4+ T lymphocyte responsiveness to recall Ags is achieved during HAART. The data provide evidence for limited HIV-1specific CD4+ memory T cells during advanced HIV-1 infection and suggest that both CD4+ and CD8+ HIV-1specific T cells are poorly stimulated when viral load is suppressed.
Ref: Oscar Pontesilli, Susana Kerkhof-Garde, Daan W. Notermans, et al. T Cell Reconstitution and Human Immunodeficiency Virus1Specific Cell-Mediated Immunity during Highly Active Antiretroviral Therapy, J Infect Dis 1999;180:76-86.
Partial immune recovery feasible for patients with advanced HIV disease
Highly active antiretroviral therapy (HAART) can substantially benefit even severely immunocompromised patients. However, Italian investigators found that the immune recovery in these patients is slower and incomplete compared with patients treated in earlier stages of infection.
Dr. Fernando Aiuti of the University of Rome 'La Sapienza' and associates evaluated T cell subset and function in 21 AIDS patients during 24 months of HAART. The subjects had a mean baseline CD4 cell count of 20/µL, and all of the subjects were antiretroviral drug experienced. The patients were analysed at 4, 12, and 24 months for clinical symptoms, plasma HIV load, and several parameters of immune restoration, including lymphocyte subpopulations and response to recall or immunisation antigens. They found that the patients experienced clinical improvements that were indirectly associated with immune recovery. Specifically, Dr. Aiuti's group observed improvements in Karnofsky's index scores, increases in body weight and decreases in opportunistic infections. Although patients with significant decreases in viral load had a greater magnitude of immune recovery, 7 of 21 subjects without a sustained suppression of viral load had an increase in T cell subsets. The clinicians also observed an increase in CD4 T lymphocytes shortly after HAART was initiated. An increase in naive CD4 T cells was observed as well, but "...this increase was observed later than in less immunocompromised patients studied by others as it consistently occurred only after 12 months of therapy." These findings "...demonstrate the possibility of a partial restoration in T-cell subsets and immune functions also in patients starting HAART at an advanced stage of HIV-1 disease." Because some patients maintain clinical benefits despite virologic failure, it appears that "...even a partial reduction in viral load may be beneficial, at least in this group of patients."
Ref: AIDS 1999;13:1187-1193. Source: CDC HIV/STD/TB Prevention News Update
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ATP Syposium II Report: New HIV Treatments & Implications for Clinical Practice
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Many of the drugs featured have been developed to offer the most hope for people whose treatment is currently failing and the report looks at how to minimise the risk of wasting new treatments by using them as part of a treatment strategy.
Sessions from the symposium also covered include HIV lifecycle, drug development from a clinical and pharmacological point of view, access to and safety within clinical trials and NHS initiatives such as developing databases.
The report is available free.
For single or bulk copies please call:
Charles Bowman at ATP on 0171 407 0777
page 9
AIDS Treatment Project (Registered Charity No. 1070431) DocFax Issue 73 (13/08/99)