Approximately 29.1% of South African women of childbearing age tested HIV positive during their first antenatal visit in 2006 (DoH, 2007). This rate of HIV amongst the women of childbearing age reinforces the importance of understanding the management of HIV during pregnancy. During antenatal visits the general health of the woman and her unborn baby is assessed and managed. Management includes antiretroviral therapy to the HIV infected women with a CD4 count below 200 cells/mm3, while women with a CD4 count above 200 cells/mm3 receive a single dose of nevirapine with the onset of labour provided to them by their local clinics. Currently, in Potchefstroom, women receive antenatal care at local primary health-care clinics and antiretroviral drugs at the antiretroviral clinic. There is little or no collaboration between the various clinics and the question arises if the needs of the women are being met. The aim of the research was to promote the health of HIV positive pregnant women by providing insight into the needs of these women and to formulate recommendations for antenatal care. The specific objective is to explore and describe the needs of HIV positive pregnant women regarding antenatal care. An explorative, descriptive, contextual design, following a qualitative approach was used during the research. Semi-structured interviews were used to collect data. Interview questions were compiled from the research problems. Before the commencement of data collection, permission was obtained from the district health manager and Potchefstroom Hospital. A total of sixteen (16) HIV positive women were interviewed after informed consent had been obtained. Data analysis was done after each session and themes were categorised according to the women's needs. From the interviews it was found that each woman has her own specific needs regarding antenatal care. The needs of the participants followed a similar pattern and for this reason it could be divided into various categories. These categories include a need for support, a need for education, a need for improved services and a need for a non-judgemental environment. Conclusions were drawn and recommendations were made for nursing practice, nursing education and nursing research. / Thesis (M.Cur.)--North-West University, Potchefstroom Campus, 2008.

HIV/AIDS is the most threatening and challenging infectious diseases of our time, with the highest increase of newly infected cases reported. This infectious disease was discovered in the early eighties under homosexual men and was later to be discovered in heterosexuals. HIV is a systemic immunosuppressive disorder which causes a depletion of CD4+ T cells and develops into the acquired immunodeficiency syndrome - AIDS. Africa is the continent most affected by HIV/AIDS with the southern parts of Africa having the highest prevalence rates compared to the rest of Africa. Statistics indicate that AIDS is responsible for 3% of deaths in children worldwide - one in seven people dying of an HIV-related illness is a child under the age of 15 years. It was stated by the WHO that countries should develop improved antiretrovirals regimes for the prevention of mother-to-child transmission. Difficulties in administering antiretrovirals (ARVs) to patients (especially children) are the strict dosage regimes and the severe adverse reactions. These factors complicate patient adherence. The list of problems in treating patients is endless and includes the distribution, stability as well as the low efficacy of these drugs. Most of the above mentioned problems and obstacles related to ARVs and ARV treatment could be minimized or eliminated by the use of a stable and effective drug delivery system. Enhancing ARV treatment may be accomplished by the use of the Pheroid™ drug delivery system. Pheroids™ consists mainly of fatty acids and sterile nitrous oxide gassed water. Pharmacological active substances are entrapped into submicron and micron sized structures called Pheroids™. Research showed promising results and advantages in delivering drugs through oral and transdermal routes using Pheroid™ technology. The focus of this study was to test the possible enhancement of the efficacy of antiretrovirals using Pheroid™ technology. The assays used to study this possible enhancement were a modified neutral red and a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. These assays confirmed and illustrated the toxic and protective properties of the tested ARVs (stavudine, lamivudine and nevirapine). An MT-2 cell line was used and infected with an HIV-1 strain, SW7-TCL. Applying Pheroid™ technology in these assays resulted in massive cell death, due to increased ARV toxic levels within the cells. Viability tests proved that Pheroids™ had no effect on the viability of cells at the concentration typically used. This confirmed the enhancing properties of Pheroids™ in the delivery of drugs into the cells. The MTT assay was further adapted from a seven day incubation period to a three day incubation period. By using a low concentration series and a three day incubation period the loss of cells through toxicity was partially overcome. One of the problems that arose form this study was the non-reproducibility of the results. Absorbance levels fluctuated at specific concentrations of the same ARV, which cause difficulties in comparing results. This result was repeatedly confirmed in this syncytium forming infection model. In conclusion, Pheroid™ technology enhanced the delivery of ARVs into the cells although it resulted in cell death. Both the neutral red and MTT assays were found to be inaccurate but further development, research and assay optimization could result in improved in vitro studies. The article format was used for this thesis, as described in the general academic rules in section A.13.7.3 of the North West University. Chapter 1 deals with HIV/AIDS related problems, statistics and treatment obstacles. Chapter 2 is a summary of the cell viability assays used in this study. Pheroid™ technology and its application to ARV treatment are dealt with in chapter 3. The proposed article for submission in the journal Cell Death and Differentiation has been included in chapter 4. Some of the results from the study are reported in the article and annexures, whilst other results are shown and discussed in Chapter 5. Chapter 6 gives a conclusion and final summary of this study. All other experimental methods and results are enclosed in the annexures, as is the "Guide for authors" for the article. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.

More people living with HIV/AIDS reside in South Africa than any other country in the world, and the nation faces colossal challenges in broadening its response to the now-mature and widespread HIV epidemic (WHO, 2005:1). According to South Africa's Medical Research Council, HIV/AIDS has now become the single largest cause of death in South Africa (Dorrington et a/., 2001:6) and has triggered a prominent transferal in the pattern of mortality from the elderly to the young, particularly among young women (Dorrington, 2001:4). The routine treatment of HIV/AIDS with antiretroviral drugs has transformed HIV-infection from an unvaryingly rapidly terminal illness to a somewhat expensive treatable, chronic disease. Triple therapy or highly active antiretroviral therapy (three-drug combinations of ARVs or HAART) in particular have had paramount impacts on HIV-related morbidity and mortality in settings where these drugs are generally accessible. Objectives of ARV treatment are "maximum, durable suppression of viral load, restoration and/or preservation of immune function, improvement of quality of life and reduction of HIV related morbidity and mortality" (Martinson et a/., 2003:236; Martinez et a/., 2007:251; Hellinger, 2006:1; Kumarasamy, 2004:3). The Joint United Nations Programme on HIV/AIDS (UNAIDS) estimated that a total of 111 827 South Africans were accessing free antiretroviral treatment in the 200 public health sector facilities across 53 districts and a further 60 000 via the private sector by late December 2005 (UNAIDS, 2005:1). The objective of this study was to review, analyse and interpret the usage and prescribing patterns of antiretroviral drugs in a section of the South African private health care sector for the period 1 January 2005 to 31 December 2006 by utilising a medicine claims database of a pharmacy benefit management company, and to investigate the costs associated with these drugs by performing a quantitative, retrospective drug utilisation review. It was found that the prevalence as well as the total medicine cost of ARV medicine items had increased during the study period but the average number of ARV medicine items per prescription as well as both the average cost per ARV medicine item and the average cost per ARV prescription decreased during the study period. Original innovator ARV medicine items and original ARV medicine items with no generic were found to be relatively expensive in comparison with ARV medicine items in general. Conversely, generic ARV medicine items were ascertained to be relatively inexpensive with reference to ARV medicine items in general. It was perceived that the average cost of ARV medicine items and prescriptions for both genders decreased from 2005 to 2006, while there was an increase in the prevalence of medicine items and prescriptions claimed for both female and male patients. The prevalence and cost of all types of ARV medicine items were found to be higher for female patients in general. It was also established that the prevalence of patients receiving antiretroviral treatment in the private health care sector peaks at the age of >30 to 244 years, in comparison with the lower age of >25 to 239 years in the public health care sector. ARV medicine items claimed for patients in the age group >35 to 239 years represented the highest percentage of the total medicine cost incurred during both study years for all ARV medicine types. The majority of ARV medicine items were prescribed by general medical practitioners, and most ARV medicine items were dispensed by community or private institutional pharmacies. It was determined that combinations of 2NRTI + NNRTI were prescribed with the highest frequency, which is compliant with traditional HAART or 'triple therapy' regimens. Lastly, it was found that none of the top 20 prescriptions for one, two and six ARV medicine items were compliant with the National Antiretroviral Treatment (ART) Guidelines. The majority of the top 20 prescriptions for three ARV medicine items (92.67 per cent during 2005 and 89.94 per cent during 2006) were compliant with the National ART Guidelines. Finally, less than half of the top 20 prescriptions for four ARV medicine items (49.60 per cent during 2005 and 36.11 per cent during 2006) were compliant with the National ART Guidelines. Only 5.56 per cent and 3.92 per cent of the top 16 prescriptions for five ARV medicine items were compliant with the National ART Guidelines during the two study years respectively / Thesis (M. Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2009.

Selective antiretroviral! (ARV) drugs are primarily metabolized by cytochrome P450 (CYP) enzymes, characteristically predisposed to variation, and are therefore primarily responsible for ARV pharmacokinetic variability and associated drug interactions. For the majority of ARV drugs, the therapeutic window is narrow and imminent toxicities due to CYP inhibition or sub-therapeutic drug levels as a result of CYP induction is inevitable. Animals provide a metabolism replica to conduct detailed investigations. We endeavored to establish a rat model to screen for variability in metabolism of selective ARV drugs responsible for treatment failure and drug interactions, over time in the liver and serum. Male Sprague-Dawley rats (n = 24) were divided into 6 groups: methylcellulose, 160mg/kg/day (n = 24) (control); efavirenz, 160mg/kg/day (n = 18); ritonavir, 20 mg/kg/day (n = 18); ritonavir, 20 mg/kg/day and verapamil 5 mg/kg/day (n = 18); Kaletra® (ritonavir/lopinavir), 20 mg/kg/day, (n = 18); Kaletra® (ritonavir/lopinavir), 20 mg/kg/day and verapamil 5 mg/kg/day (n = 18). Treatment duration varied from one day (single dose), 7 or 21 days. Blood samples were collected after decapitation on days 1, 7 and 21. A sensitive and rapid liquid chromatograph (LC) interfaced to a quadrupoie mass spectrometer (MS) and coupled with electrospray ionization (ESI) method was employed for the blood sample determinations. One single injection was required to simultaneously quantify efavirenz, lopinavir and ritonavir within the linear concentration range of 78 - 5000 ng/ml. Efavirenz blood levels increased statistically significantly (p < 0.05) from day 1 to day 21 with distinct steady state achievement prior to day 7. The levels of ritonavir increased statistically significantly (p < 0.05) from day 7 to 21 when administered alone and statistically significantly (p < 0.01) from day 1 to 21 when administered as the ritonavir/lopinavir combination. The levels of lopinavir also increased statistically significantly (p<0.01) from day 1 and 21 in the ritonavir/lopinavir combination. However, the inclusion of a P-glycoprotein inhibitor, verapamil, increased both the ritonavir (administered alone) and lopinavir blood levels significantly (p < 0.05) at day 1. The ritonavir levels were also significantly increased on day 21 (p < 0.05). When verapamil was added to the ritonavir/lopinavir combination the levels of ritonavir increased statistically significantly (p < 0.01) from day 1 to 21. A rat model can be used to detect changes in metabolism over time as measured by blood levels. The influence of drug interactions, such as verapamil, on ARV drug metabolism can be investigated by this model. These results will be substantiated by PCR liver results in the future. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2009.

More people living with HIV/AIDS reside in South Africa than any other country in the world, and the nation faces colossal challenges in broadening its response to the now-mature and widespread HIV epidemic (WHO, 2005:1). According to South Africa's Medical Research Council, HIV/AIDS has now become the single largest cause of death in South Africa (Dorrington et a/., 2001:6) and has triggered a prominent transferal in the pattern of mortality from the elderly to the young, particularly among young women (Dorrington, 2001:4). The routine treatment of HIV/AIDS with antiretroviral drugs has transformed HIV-infection from an unvaryingly rapidly terminal illness to a somewhat expensive treatable, chronic disease. Triple therapy or highly active antiretroviral therapy (three-drug combinations of ARVs or HAART) in particular have had paramount impacts on HIV-related morbidity and mortality in settings where these drugs are generally accessible. Objectives of ARV treatment are "maximum, durable suppression of viral load, restoration and/or preservation of immune function, improvement of quality of life and reduction of HIV related morbidity and mortality" (Martinson et a/., 2003:236; Martinez et a/., 2007:251; Hellinger, 2006:1; Kumarasamy, 2004:3). The Joint United Nations Programme on HIV/AIDS (UNAIDS) estimated that a total of 111 827 South Africans were accessing free antiretroviral treatment in the 200 public health sector facilities across 53 districts and a further 60 000 via the private sector by late December 2005 (UNAIDS, 2005:1). The objective of this study was to review, analyse and interpret the usage and prescribing patterns of antiretroviral drugs in a section of the South African private health care sector for the period 1 January 2005 to 31 December 2006 by utilising a medicine claims database of a pharmacy benefit management company, and to investigate the costs associated with these drugs by performing a quantitative, retrospective drug utilisation review. It was found that the prevalence as well as the total medicine cost of ARV medicine items had increased during the study period but the average number of ARV medicine items per prescription as well as both the average cost per ARV medicine item and the average cost per ARV prescription decreased during the study period. Original innovator ARV medicine items and original ARV medicine items with no generic were found to be relatively expensive in comparison with ARV medicine items in general. Conversely, generic ARV medicine items were ascertained to be relatively inexpensive with reference to ARV medicine items in general. It was perceived that the average cost of ARV medicine items and prescriptions for both genders decreased from 2005 to 2006, while there was an increase in the prevalence of medicine items and prescriptions claimed for both female and male patients. The prevalence and cost of all types of ARV medicine items were found to be higher for female patients in general. It was also established that the prevalence of patients receiving antiretroviral treatment in the private health care sector peaks at the age of >30 to 244 years, in comparison with the lower age of >25 to 239 years in the public health care sector. ARV medicine items claimed for patients in the age group >35 to 239 years represented the highest percentage of the total medicine cost incurred during both study years for all ARV medicine types. The majority of ARV medicine items were prescribed by general medical practitioners, and most ARV medicine items were dispensed by community or private institutional pharmacies. It was determined that combinations of 2NRTI + NNRTI were prescribed with the highest frequency, which is compliant with traditional HAART or 'triple therapy' regimens. Lastly, it was found that none of the top 20 prescriptions for one, two and six ARV medicine items were compliant with the National Antiretroviral Treatment (ART) Guidelines. The majority of the top 20 prescriptions for three ARV medicine items (92.67 per cent during 2005 and 89.94 per cent during 2006) were compliant with the National ART Guidelines. Finally, less than half of the top 20 prescriptions for four ARV medicine items (49.60 per cent during 2005 and 36.11 per cent during 2006) were compliant with the National ART Guidelines. Only 5.56 per cent and 3.92 per cent of the top 16 prescriptions for five ARV medicine items were compliant with the National ART Guidelines during the two study years respectively / Thesis (M. Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2009.

Selective antiretroviral! (ARV) drugs are primarily metabolized by cytochrome P450 (CYP) enzymes, characteristically predisposed to variation, and are therefore primarily responsible for ARV pharmacokinetic variability and associated drug interactions. For the majority of ARV drugs, the therapeutic window is narrow and imminent toxicities due to CYP inhibition or sub-therapeutic drug levels as a result of CYP induction is inevitable. Animals provide a metabolism replica to conduct detailed investigations. We endeavored to establish a rat model to screen for variability in metabolism of selective ARV drugs responsible for treatment failure and drug interactions, over time in the liver and serum. Male Sprague-Dawley rats (n = 24) were divided into 6 groups: methylcellulose, 160mg/kg/day (n = 24) (control); efavirenz, 160mg/kg/day (n = 18); ritonavir, 20 mg/kg/day (n = 18); ritonavir, 20 mg/kg/day and verapamil 5 mg/kg/day (n = 18); Kaletra® (ritonavir/lopinavir), 20 mg/kg/day, (n = 18); Kaletra® (ritonavir/lopinavir), 20 mg/kg/day and verapamil 5 mg/kg/day (n = 18). Treatment duration varied from one day (single dose), 7 or 21 days. Blood samples were collected after decapitation on days 1, 7 and 21. A sensitive and rapid liquid chromatograph (LC) interfaced to a quadrupoie mass spectrometer (MS) and coupled with electrospray ionization (ESI) method was employed for the blood sample determinations. One single injection was required to simultaneously quantify efavirenz, lopinavir and ritonavir within the linear concentration range of 78 - 5000 ng/ml. Efavirenz blood levels increased statistically significantly (p < 0.05) from day 1 to day 21 with distinct steady state achievement prior to day 7. The levels of ritonavir increased statistically significantly (p < 0.05) from day 7 to 21 when administered alone and statistically significantly (p < 0.01) from day 1 to 21 when administered as the ritonavir/lopinavir combination. The levels of lopinavir also increased statistically significantly (p<0.01) from day 1 and 21 in the ritonavir/lopinavir combination. However, the inclusion of a P-glycoprotein inhibitor, verapamil, increased both the ritonavir (administered alone) and lopinavir blood levels significantly (p < 0.05) at day 1. The ritonavir levels were also significantly increased on day 21 (p < 0.05). When verapamil was added to the ritonavir/lopinavir combination the levels of ritonavir increased statistically significantly (p < 0.01) from day 1 to 21. A rat model can be used to detect changes in metabolism over time as measured by blood levels. The influence of drug interactions, such as verapamil, on ARV drug metabolism can be investigated by this model. These results will be substantiated by PCR liver results in the future. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2009.

Sub-Saharan Africa bears 70% of the global HIV burden with KwaZulu-Natal (KZN) identified as the epicenter of this pandemic. HIV related nephropathy (HIVRN) exceeds any other causes of kidney diseases responsible for end stage renal disease, and has been increasingly recognized as a significant cause of morbidity and mortality. There is nonetheless a general lack of surveillance and reporting for HIVRN exists in this geographical region. Consequentially, the aim of this study was to outline the histopathogical spectrum of HIVRN within KZN. Moreover, from a pathology standpoint, it is important to address whether HIVRN was a direct consequence of viral infection of the renal parenchyma or is it a secondary consequence of systemic infection. Additionally, an evaluation of the efficacy of Highly Active Anti-Retroviral Therapy (HAART) in combination with angiotensin converting enzyme inhibitors (ACE-I) was performed via a genetic appraisal of localized replication of HIV-1 in the kidney, ultrastructural review and immunocytochemical expression of a podocyte maturity and proliferation marker pre and post-HAART. Blood and renal biopsies were obtained from 30 children with HIV related nephropathy pre- HAART, followed-up clinically for a period of 1 year. This cohort formed the post-HAART group. Clinical and demographic data were collated and histopathology, RT-PCR, sequencing, immunocytochemistry and transmission electron microscopy was performed. The commonest histopathological form of HIVRN in children (n = 30) in KZN was classical focal segmental glomerular sclerosis (FSGS) presented in 13(43.33%); mesangial hypercellularity 10(30%); mesangial, HIV associated nephropathy 3(11%) and minimal change disease 2(6.67%). Post-HAART (n = 9) the predominant pathology was mesangial hypercellularity 5(55.56%); FSGS 3(33.33%) and sclerosing glomerulopathy 1(11.11%). This study also provides data on the efficacy of HAART combined with ACE-I. The immunostaining pattern of synaptopodin, Ki67 and p24 within the glomerulus expressed as a mean field area percentage was significantly downregulated in the pre-HAART compared to the post-HAART group respectively (1.14 vs. 4.47%, p = 0.0068; 1.01 vs.4.68, p < 0.001; 4.5% vs 1.4%, p = 0.0035). The ultrastructural assessment of all biopsies conformed to their pathological appraisal however, features consistent with viral insult were observed. Latent HIV reservoirs were observed within the podocyte cytoplasm but was absent in mesangial or endothelial cells. Real-Time polymerase chain reaction assays provided evidence of HIV-1 within the kidney. Sequence analysis of the C2-C5 region of HIV-1 env revealed viral diversity between renal tissue to blood. In contrast to a collapsing type of FSGS that occurs in adults, the spectrum of paediatric nephropathy in treatment-naive children within KwaZulu-Natal was FSGS with mesangial hypercellularity. Additionally, our study demonstrates podocyte phenotype dysregulation pre- HAART and reconstitution post therapy. Evidence of ultrastructural viral reservoirs within epithelial cells is supported by a genetic appraisal confirming the ubiquitous presence of HIV DNA in renal tissue. Moreover, sequence analysis showed viral evolution and compartmentalization between renal viral reservoirs to blood. Finally, the interplay of viral genes and host response, influenced by genetic background, may contribute to the variable manifestations of HIV-1 infection in the kidney in our paediatric population. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2012.

INTRODUCCIÓN: El tratamiento antirretroviral de gran actividad (TARGA) ha permitido reducir la morbilidad y la mortalidad de la infección por el VIH, pero no puede erradicar la infección. Por eso se buscan alternativas como las terapias inmunomediadas, que potencian la respuesta inmune del paciente, para poder retirar, al menos temporalmente, el TARGA. Estas respuestas inmunes, tanto CD4+ como CD8+, existen al inicio de la infección, pero desaparecen con el TARGA, probablemente debido a la pérdida de estimulación del sistema inmune. En este sentido, los pacientes que presentan episodios de viremia intermitente (EVI), es decir, elevaciones transitorias de la carga viral (CV), se ha demostrado que aumentan estas respuestas. Dichos EVI se han asociado a diferentes circunstancias, entre ellas las vacunaciones. Como los pacientes VIH son inmunodeprimidos, se aconseja que sean vacunados. Por tanto, si dichas vacunaciones inducen EVI, esto se podría asociar a dos efectos antagónicos: por un lado, un aumento en las respuestas anti-VIH con un potencial mejor control de la infección; pero por otro lado, un potencial riesgo de aparición de resistencias al TARGA y fracaso terapéutico. PACIENTES Y MÉTODOS: Para evaluar esta circunstancia se llevó a cabo un ensayo clínico unicéntrico, prospectivo, randomizado, doble ciego y controlado con placebo en el que 26 pacientes con infección por el VIH se randomizaron a recibir durante 12 meses su TARGA junto a, o bien un calendario vacunal de 10 vacunas comerciales diferentes (hepatitis B, hepatitis A, gripe, neumococo, varicela, triple vírica (sarampión-rubéola-parotiditis) y tétanos-difteria), o bien placebo, suspendiendo el TARGA a los 12 meses. Se estudió el efecto del calendario vacunal, tanto durante el TARGA como tras su interrupción, sobre la CV (incluyendo la aparición de resistencias), las subpoblaciones linfocitarias, las respuestas específicas anti-VIH, la función tímica y las respuestas vacunales humorales y celulares. Además, mediante tres subestudios se evaluó el efecto de los EVI (superiores a 20 y 200 copias) sobre los mismos aspectos, y el efecto de la interrupción del TARGA sobre la función tímica, el sistema de la IL-7 y su receptor y las respuestas adquiridas a los antígenos vacunales. RESULTADOS: Ni el calendario vacunal en general ni ninguna vacuna en particular se asoció a un aumento en la frecuencia de CV detectables, aunque sí provocaron un descenso en los linfocitos T CD4+, un aumento en la activación y maduración linfocitaria hacia células memoria, así como en las respuestas linfoproliferativas, sin cambios en las respuestas específicas CD8+ anti-VIH. Tras la interrupción, el grupo vacunado presentó un rebote igual al que recibió el placebo, sin más resistencias virales, aunque presentó mayores respuestas específicas CD8+ anti-VIH en el periodo sin tratamiento. Cuando se analizó la influencia de los EVI sobre el sistema inmune se observó que los pacientes detectables presentaban durante el tratamiento menor número de linfocitos CD4+ y mayor de CD8+, así como un aumento en las respuestas específicas anti-VIH CD8+. Tras la interrupción, los pacientes detectables presentaron también un mayor rebote viral y un aumento de las respuestas linfoproliferativas anti-VIH. Las diferencias entre pacientes detectables e indetectables disminuyeron cuando se definieron por un ensayo con límite de 20 c/mL. Cuando se analizó la función tímica tras la interrupción se observó un descenso inicial con una recuperación parcial posterior. Y las respuestas vacunales humorales descendieron tras la interrupción, aumentando las celulares. CONCLUSIONES: El calendario vacunal fue seguro y no se asoció a efectos secundarios valorables ni elevaciones de la CV, pero tampoco fue útil como inmunoterapia. Además, la estimulación continuada produjo un aumento de la activación linfocitaria y una disminución en el recuento de linfocitos T CD4+. PALABRAS CLAVE: Infección por VIH, vacunaciones, inmunoterapia, timo, interrupciones de tratamiento antirretroviral. / "Study of the influence of immunological repeated stimuli with commercial vaccines over the Viral Load (VL), resistance development and specific immunological response against HIV in early stage HIV patients with undetectable VL after HAART"INTRODUCTION: As HIV-infected patients are considered immunocompromised, it is generally recommended that they have to receipt appropriate vaccines. However data are conflicting concerning potential harmful effects following the administration of commercial vaccines in HIV-infected patients. Transient increases ("blips") in the viral load have been described associated with a single dose of vaccine, with the potential risk of developing resistance to HAART. On the other hand, there has been described that patients with blips can have an increase in HIV-specific immune responses, which may help to improve the viral control. PATIENTS AND METHODS: We have performed a clinical trial to evaluate the effect of a vaccination program in successfully treated HIV-infected adults on HAART compared to placebo. Its influence over viral load (including resistances), lymphocyte subsets, specific anti-HIV responses, thymic function and responses to vaccinations were analysed. There were also studied the influence of blips over immunity and the influence of interrupting HAART over thymic function and vaccination responses. RESULTS: Vaccinations were not associated to more detectable viral loads, but induced an increase in lymphocyte activation and a loss of CD4+ T-cells. They were not useful as immunotherapy because viral load rebounded after HAART interruption in the same way in placebo and vaccinated group, although specific CD8+ responses against HIV were higher in the latest. Patients with blips had less CD4+ T-cells, more specific CD8+ responses against HIV, and a higher rebound of viral load after discontinuing HAART. After HAART interruption, thymic function decreased firstly, but later presented a partial recovery. Humoral responses to vaccines decreased after stopping HAART.CONCLUSIONS: Vaccinations in HIV patients were safe and did not associate with more detectable viral loads. However, they induce a loss in CD4 T cells. They were not useful as immunotherapy.

Els tractaments antiretrovirals actuals són altament efectius en aturar la progressió de la infecció VIH a la sida. No estan lliures, però, d'efectes secundaris tant a curt com a llarg termini, tant importants com la lipodistròfia o la malaltia cardiovascular, les altracions del perfil dels lípids o d'altres efectes que segur que queden encara per descriure a causa dels pocs anys d'evolució del tractament antiretroviral. En general, les persones infectades pel VIH tenen una supervivència menor, més risc d'infeccions oportunistes i tumors, tenen limitacions per ser receptors d'òrgans i tenen alterada la seva funció reproductiva.Les persones infectades tenen dificultats per trobar parelles amb qui desenvolupar el seu projecte familiar, limitacions a l'hora de la seva sexualitat que obliguen a l'ús de preservatiu i limiten, per tant, la capacitat de tenir fills. En el cas de tenir-los, el risc d'infecció del nadó ha esdevingut un autèntic repte per als professionals de la sanitat dedicats a l'atenció dels pacients afectes de la infecció VIH.En els darrers anys, el control relatiu de la malaltia, la no-evolució a la mort i la possibilitat d'un ple desenvolupament personal ha fet sorgir nous problemes associats a la infecció, a l'estil de vida i al propi tractament.Partim de la hipòtesi que la dona infectada pel virus de la immunodeficiència humana adquirida té unes característiques particulars, condicionades tant pel fet d'estar infectada pel VIH com pel tractament de la malaltia, que repercuteixen en el maneig del seu procés reproductiu. Per conèixer en cada esgraó del procés reproductiu quins són els trets diferencials de la dona infectada pel VIH hem creat les següents hipòtesis:A) Abans de la concepció:La resposta immunològica que es produeix en els individus exposats no infectats al virus de la immunodeficiència adquirida, respon al nivell exposat de virus. Existeixen paràmetres capaços de predir la reducció de fertilitat de la dona infectada pel VIH.B) En el moment de la concepció:La pacient infectada pel VIH té una fertilitat reduïda inherent a la pròpia malaltia o al tractament.La dotació de DNAmt dels oòcits de la dona infèrtil infectada pel VIH, que rep tractament altament efectiu, és menor que la de la dona no infectada.C) En el maneig de l'embaràs:La dona infectada pel VIH pot accedir a tècniques de diagnòstic d'aneuploïdies en un marc concret d'actuació sense que això impliqui un risc important de iatrogènia.La dona infectada tractada amb tractaments antirretrovirals de gran activitat té un risc superior a la població de dones no infectades de presentar complicacions obstètriques severes tals com la mort fetal intrauterina o la preeclàmpsia.D) En el moment del part:La dona infectada pel VIH pot optar per un part vaginal quan rep TARGA i té una resposta virològica excel·lent de forma sostinguda.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 6 uppsatser.