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The manifestation of HIV-1 infection is different in children and adults. Most of the children who acquire HIV perinatally progress to disease within the first two years of life, while adults can remain asymptomatic for up to ten years. However, a small minority group of children can control the virus for years in the absence of antiretroviral therapy. We characterized CD8+ T cell responses critical for the containment of HIV infection in a cohort of infants HIV infected from birth using IFN- γ ELISPOT, multicolour flow cytometry and viral sequencing of the Gag protein. We investigated whether the age at the time of infection, specificity and functionality of the generated responses, genetic make up and the maternal immune responses to HIV, influenced disease progression in the child. We found that the majority of in-utero infected infants mounted CD8+ T cell responses from the first days of life. In contrast to chronically infected children or adults, the specificity of the initial response in acutely infected infants was directed towards Env and Rev proteins and CD4+ T cell responses were minimal during the first 6 months of life. Slow progression to disease was associated with possession of one of the protective HLA-B alleles by either the mother or the child (P=0.007) and targeting of Gag epitopes presented by the protective HLA-B alleles. Mothers who expressed protective alleles but whose children did not possess these alleles, transmitted less fit viruses that benefited their children. Furthermore, slow progressor children had more polyfunctional CD8+ T cell responses in early infection when compared to rapid progressors (P=0.05). The ability of infants to induce CD8+ T cell responses early in life is encouraging for vaccine interventions. The differences in the specificity of the initial responses between adults and children, insufficient priming of these responses as a result of minimal CD4+ T cell help during infancy and possession of non-protective HLA alleles shared between mother and child, may explain the rapid disease progression generally noted in most infants. However, slow progression to disease in the minority group of children may be attributed to functional capacity of the CD8+ T cells generated by the child, mediation by protective HLA alleles, acquisition of low fitness viruses from the mother or de novo attenuation of the virus by the child’s own immune responses. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2011.

Reverse transcription of human immunodeficiency virus type-1 (HIV-1) is primed by cellular tRNALys3, which is selectively packaged into viral particles where it is bound at its 3' terminus to a complementary sequence of viral RNA termed the primer binding site (PBS). In addition to the PBS, other regions within the viral genome also interact with tRNALys3. Initiation of HIV-1 reverse transcription requires specific recognition of the viral genome, tRNA primer, and reverse transcriptase (RT). In this work, we study the important role played by the initiation complex in the initiation of HIV-1 reverse transcription. An "A-rich loop" located upstream of the PBS has been shown to interact with the anticodon loop of tRNALys3 and deletion of this A-rich loop caused diminished viral replication fitness. We have now studied the mechanisms involved in the altered replication capacities of the deletion-containing viruses in the context of both wild type HIV-1 and viruses also containing the M184V substitution in RT. We found that the M184V mutation in RT compromises the ability of deletion-containing viruses to restore wild-type replication. Further biochemical study indicates that both the M184V mutation in RT and deletion of sequences upstream of PBS caused diminished viral replication fitness by compromising the efficiency of reverse transcription initiation. / Since the initiation of DNA synthesis was shown to be a highly specific process, it represents a potential target for the development of novel antiviral agents. We developed strategies for inhibition of the HIV-1 replication via interference with the tRNALys3/viral RNA complex. To target primer tRNALys3, we employed oligodeoxyribonucleotides (ODNs) that are complementary to different parts of the tRNA primer. To target viral RNA, we devised a tRNALys3-like molecule, termed tRNA Lys*, that contained sequence alterations that direct initiation from a region distant from the natural PBS, designated PBS*. PBS* is involved in the formation of the natural tRNA/PBS complex and binding of tRNALys* was shown to interfere specifically with the initiation of reverse transcription. Inhibition of the synthesis of (-) strand strong-stop DNA was achieved successfully with both strategies by interfering with the formation of the initiation complex.

The HIV and Aids pandemic not only has an impact on women but also on men. Young people in their early and late adolescent years, between the ages 12 and 24 years of age, find themselves in a period of exploration and experimentation that can enhance high-risk sexual behaviour. In research done in South Africa it was estimated that half of all young men and woman are sexually active by the age of 16. Unfortunately, we in South Africa live in an era where HIV and AIDS do not allow such behaviours and this situation makes male youths one of the most vulnerable groups in our society to be infected by the HI-virus. This study focused on male youths on ARV therapy (ART). The antiretroviral therapy requires maximum adherence from the people living with HIV and AIDS. Adherence to antiretroviral therapy poses a great challenge to the youth, especially if they are unemployed and have families who depend on them for financial as well as emotional support. The aim of this study was to evaluate the impact of a social group work empowerment programme on male youths undergoing ARV therapy. To achieve the aim of this study the following objectives were set: • To investigate the needs of male youths on ARV therapy in a rural area. This objective was achieved by obtaining a theoretical perspective from the literature as well as undertaking empirical research by means of the interviewing process. According to these findings male youths on ARV therapy have many needs, such as the need for more information on ARV therapy, the role of the Departments of Health and Social Development, the role of social workers, and how to disclose their HIV status to people other than their family members. •To determine the role of social group work in empowering male youths who are on antiretroviral therapy to cope with the illness and ARV therapy by means of a literature study. It was important for the researcher to do a literature study on social group work to enhance her knowledge and skills, because this is a method of social work that she not often implemented in practice. • To develop and implement a social group work programme for male youths on ARV therapy. The social group work empowerment programme for male youth on ARV therapy was implemented over nine group work sessions and tested on 10 respondents who were part of the needs assessment and were willing to be part of the group work programme in the rural area of the Motheo District. The programme consisted of nine group sessions with different topics discussed in each session for the empowerment of the target group. According to the group members, they acquired adequate skills to enable them to act properly in solving their problems. The programme impacted a lot on how they felt about themselves and the circumstances around them. • To evaluate the effectiveness of the social group work empowerment programme on male youths on ARV therapy. This objective was achieved in the sense that the general satisfaction of the young men had increased according to the Generalized Contentment Scale (GCS) of Perspective Training College. The measuring scale was utilized before the first session started, at the end of the fifth session (in the middle measurement phase), and at the end of the last session. The findings from the research indicated that significant personal growth had taken place among the male youth on ARV therapy in a rural area. Scientifically proven research emerged from this study and proved that a well-designed social group work empowerment programme can enhance the social functioning and general contentment of the male youths on ARV therapy. / Thesis (PhD (Social Work))--North-West University, Potchefstroom Campus, 2013

The HIV and Aids pandemic not only has an impact on women but also on men. Young people in their early and late adolescent years, between the ages 12 and 24 years of age, find themselves in a period of exploration and experimentation that can enhance high-risk sexual behaviour. In research done in South Africa it was estimated that half of all young men and woman are sexually active by the age of 16. Unfortunately, we in South Africa live in an era where HIV and AIDS do not allow such behaviours and this situation makes male youths one of the most vulnerable groups in our society to be infected by the HI-virus. This study focused on male youths on ARV therapy (ART). The antiretroviral therapy requires maximum adherence from the people living with HIV and AIDS. Adherence to antiretroviral therapy poses a great challenge to the youth, especially if they are unemployed and have families who depend on them for financial as well as emotional support. The aim of this study was to evaluate the impact of a social group work empowerment programme on male youths undergoing ARV therapy. To achieve the aim of this study the following objectives were set: • To investigate the needs of male youths on ARV therapy in a rural area. This objective was achieved by obtaining a theoretical perspective from the literature as well as undertaking empirical research by means of the interviewing process. According to these findings male youths on ARV therapy have many needs, such as the need for more information on ARV therapy, the role of the Departments of Health and Social Development, the role of social workers, and how to disclose their HIV status to people other than their family members. •To determine the role of social group work in empowering male youths who are on antiretroviral therapy to cope with the illness and ARV therapy by means of a literature study. It was important for the researcher to do a literature study on social group work to enhance her knowledge and skills, because this is a method of social work that she not often implemented in practice. • To develop and implement a social group work programme for male youths on ARV therapy. The social group work empowerment programme for male youth on ARV therapy was implemented over nine group work sessions and tested on 10 respondents who were part of the needs assessment and were willing to be part of the group work programme in the rural area of the Motheo District. The programme consisted of nine group sessions with different topics discussed in each session for the empowerment of the target group. According to the group members, they acquired adequate skills to enable them to act properly in solving their problems. The programme impacted a lot on how they felt about themselves and the circumstances around them. • To evaluate the effectiveness of the social group work empowerment programme on male youths on ARV therapy. This objective was achieved in the sense that the general satisfaction of the young men had increased according to the Generalized Contentment Scale (GCS) of Perspective Training College. The measuring scale was utilized before the first session started, at the end of the fifth session (in the middle measurement phase), and at the end of the last session. The findings from the research indicated that significant personal growth had taken place among the male youth on ARV therapy in a rural area. Scientifically proven research emerged from this study and proved that a well-designed social group work empowerment programme can enhance the social functioning and general contentment of the male youths on ARV therapy. / Thesis (PhD (Social Work))--North-West University, Potchefstroom Campus, 2013

Thesis (Ph.D.)--Kent State University, 2007. / Title from PDF t.p. (viewed Mar. 11, 2009). Advisor: Miguel Quiñones-Mateu. Keywords: HIV/AIDS, drug discovery, small molecule library screening, characterization of new antiretroviral drugs, highly active antiretroviral therapy. Includes bibliographical references (p. 180-200).

Thesis (M.A.)--Kent State University, 2009. / Title from PDF t.p. (viewed April 16, 2010). Advisor: John Gunstad. Keywords: HIV; executive function; adherence. Includes bibliographical references (p. 41-54).

“Cartas al editor” / Revisión por pares

Adherence to antiretroviral therapy (ART) is one of the most important issues in pediatric patients living with Human Immunodeficiency Virus (HIV). Combined with the fact that young patients face a large array of adherence barriers, interventions that can increase adherence are of great interest. Financial incentives (FIs) are a novel approach in pediatric HIV settings, and have not been studied previously in this disease for this age group. Thus, we sought to evaluate the effects FIs had in helping pediatric HIV patients achieve and maintain virologic suppression (VS). Furthermore, a post-incentive survey was administered to evaluate the self-perceived effects of FIs. In our study, FIs were not associated with achieving VS among pediatric and adolescent patients. The post-incentive survey has demonstrated many aspects of patients' and guardians' perceptions of FIs that should be considered in future FI studies. First, it was likely that patients who effectively grasped the concept of financial reward were most positively influenced by FIs. Second, the study data suggested that FIs may be contra-effective to those patients who report strong emotional responses to negative outcomes. Further and more comprehensive studies are required to fully characterize these effects.

Southern Africa has the highest prevalence of HIV worldwide, and South Africa has the highest number of HIV infected people. South Africa and other resource-limited countries provide antiretroviral therapy (ART) for people with HIV, with limited, standardized regimens for first line and second line. Patients who fail first line treatment are put on second line regimens, yet options for third line are very limited. The first study looks at predictors of first line treatment failure in South Africa and develops a predictive model that can estimate absolute risk of treatment failure over 5 years on ART, given a baseline profile of clinical and demographic factors. The model was developed with accelerated failure time models, using predictors that maximized discrimination between patients. The model can be used to identify patients who need adherence interventions, and to estimate how changes in baseline parameters in the population influence long-term need for second line ART. The second study explores whether delays from detection of first line treatment failure until second line treatment initiation, which are widespread in South Africa, decrease the effectiveness of second line ART. Marginal structural models were used to include patients who never switched to second line after failure in analysis. This study shows that, despite potency of second line drugs, short delays in second line among very sick patients can lead to worse outcomes. These findings may be due to drug resistance, immune system damage, and/or lack of adherence to medication. The third study examines whether switch in type of NRTI (nucleoside reverse transcriptase inhibitor, which is a drug class used in both first and second line regimens) from first line to second line improves outcomes on second line ART. While a switch in NRTI is recommended by treatment guidelines, it cannot always occur due to contraindications to some NRTIs. Using clinical data from South Africa and Zambia and adjusting for propensity scores, we see that switching from zidovudine in first line to a different NRTI in second line leads to less treatment failure on second line, suggesting that NRTI resistance may play a role in second line outcomes.