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Human Immunodeficiency Virus infection in South Africa
Human immunodeficiency virus (HIV) is a lentivirus, which in early infection, primarily results in a rapid and irreversible depletion of mucosal CD4+ memory T cells, particularly those expressing the HIV co-receptor CC chemokine receptor 5 (CCR5) [32]. The consequence of this process is depletion in the number of CD4+ T cells due to increased apoptosis of infected cells and a decreased generation of CD4+ T cells [33]. The HI-virus has consequent secondary effects whose end-product is immune depletion of cells other than T cells involved in innate and adaptive immune responses. Therefore, the immune deficiency affects T-cells, B-cells, macrophages, complement, phagocytes and neutrophil activity and function [34]. There are two types of HIV, namely, HIV-1 and HIV-2. HIV type-1 is the more ubiquitous type, resulting in more serious infections [35,36]. There are nine subtypes or clades of HIV-type-1, namely A, B, C, D, F, G, H, J and K [37,38]. These subtypes can be further divided into subtype A1, A2, A3, A4, F1 and F2. F1 and F2 and subtypes are found mostly in Central and West Africa [38]. Recombination can occur between the different HIV clades to form circulating recombinant forms (CRF) and unique recombinant forms (URF). These may be identified with full-genome sequencing [39]. These recombinations between subtypes can occur within a dually infected person, from whom the recombinant forms can then be passed to other individuals. In sub-Saharan Africa clade C is the most common subtype, as opposed to subtype B that is found more commonly in Europe and the United States [39-41]. Previous studies have indicated preferential in-utero transmission of HIV-1 subtype C when compared to subtypes A and D and hence higher rates of mother-to-child transmission from this clade [42,43]. The worldwide incidence of HIV infection has increased since the first identified cases of HIV in the United States in 1981 [44]. The number of people living with HIV in 2009 was estimated at 22.5 million in sub-Saharan Africa [1]. South Africa has been at the epicentre of the HIV epidemic, since the first reported case in 1988 [45]. Thereafter, the antenatal infection rates have increased exponentially. In 1990 the prevalence of HIV was 0.4% and this rose to 29% in 2009 [46-48]. Children acquire HIV via three possible routes, namely, perinatal (in utero), intrapartum (during delivery) and postpartum (via breastfeeding). Perinatal transmission accounts for more than 90% of all childhood infections [49]. The natural history of untreated HIV infection is either rapid progression with death by one year of age, accounting for 25–30% of cases, a milder course with death by age five years, accounting for 50–60% of cases, or long-term survival beyond the age of 8 years, accounting for 5-25% of cases [49,50]. These long-term survivors of un- treated HIV-infection have been referred to as the “slow-progressor” phenotype. In the search for a strategy to prevent perinatal mother-to-child transmission (PMTCT) of HIV infection in developed countries, initial trials of monotherapy with azidothymidine administered to pregnant women and their newborn infants (in the 1994 Paediatric AIDS Clinical Trial Group protocol 076), revealed a significant reduction in mother-to-child transmission of HIV, from 25% to 8% [51]. Prior to the availability of HAART in 1997, 25% of patients survived 5 years after diagnosis of acquired immunodeficiency syndrome (AIDS) [52]. This has now improved, with the use of HAART, to more than 75% of children living 9 years after a diagnosis of AIDS in the United States [52]. The use of HAART together with other interventions such as elective caesarean section, avoidance of breastfeeding and treatment of concurrent sexually transmitted diseases can result in a reduction in transmission of HIV to as low as to 1-2% [53- 56]. The use of antiretroviral therapy for PMTCT alone can also decrease the perinatal infection rates significantly. In order for this strategy to be implemented, expectant mothers need to attend antenatal clinics. Studies in the United States have shown that HIV-infected mothers have lower ANC attendance rates, with 15% of HIV-infected mothers having no prenatal care [57]. This is in contra-distinction to only 2% non-attendance rates in the general population. In South Africa 56% of expectant mothers attend antenatal clinics, this despite the service being freely available since 1995 in the public health sector [58]. Myer et al, described the barriers to antenatal clinic attendance in a rural setting and concluded that these include the perception that pregnancy poses no threat to health [59]. Expectant mothers in South Africa have on average one or two visits per pregnancy, whilst the World Health Organization (WHO) recommends at least four goal-directed visits in resource limited settings [59,60]. Caesarean section is not offered to all mothers, as an HIV prevention strategy, in South Africa due to cost-constraints; this despite caesarean section having a proven track record, with one meta-analysis revealing a reduction in vertical transmission rates from 7.3% down to 2% in patients offered this intervention [61]. Postnatal acquisition of HIV is another important mode of transmission, with reported transmission rates of 16% in breastfed infants [62]. This mode of transmission may be as high as 29% during acute maternal infection [62,63]. Between 200 000 of the 500 000 new HIV infections that occur each year in children, a majority are accounted for by infection through breast milk [64]. In the developing world, breastfeeding rates are high. A Malawian study revealed that roughly two thirds of HIV-infected women breastfeed beyond 6 months of an infant’s life [65]. In a resource-limited country, such as South Africa, breastfeeding is known to be one of the most effective interventions to improve childhood survival [66,67]. This poses a challenge in balancing the risk of increased mortality from diarrhoeal disease, respiratory tract infections and malnutrition, with the risk of HIV transmission to an already vulnerable population of infants [66]. Kunh et al, demonstrated (in a Zambian trial) that abrupt cessation of breastfeeding at 4 months was associated with an increased risk of death in HIV-infected infants [65]. The use of replacement feeding has also been shown to significantly increase mortality in HIV-exposed and -infected infants, where clean water sources are not guaranteed [68]. The benefits of peri- partum prophylaxis and a short course of anti-retroviral therapy in this context, is negated by the continued breastfeeding, as prophylactic therapy does not usually extend beyond 4 to 6 weeks. Due to these challenges, and despite availability of HAART for PMTCT, the number of infections in children has remained high in Sub- Saharan Africa.
CONTENTS Page :
- List of Tables
- List of Figures
- List of Boxes
- CHAPTER I
- Introduction
- CHAPTER II Background and literature review
- 2.1 HIV infection in South Africa
- 2.2 Lung diseases and HIV infection
- 2.3 Bronchiectasis
- 2.4 Immunological markers and bronchiectasis
- 2.5 Treatment of bronchiectasis
- 2.6 Immunomodulators and bronchiectasis
- A. Macrolides and bronchiectasis
- B. Macrolide resistance and safety
- 2.7 Metabolic imaging and bronchiectasis
- CHAPTER III
- Scope of research and hypothesis
- CHAPTER IV
- Subjects and methods
- CHAPTER V Demographic characteristics and epidemiologic determinants of children with HIV-related bronchiectasis
- 5.1 Objectives
- 5.2 Subjects and methods
- 5.2.1 Subjects
- 5.2.2 Methods
- 5.3 Results
- 5.4 Discussion
- 5.5 Conclusion
- CHAPTER VI Pulmonary and systemic cytokine and chemokine profiles in children with HIV- related bronchiectasis
- 6.1 Objective
- 6.2 Subjects and methods
- 6.2.1 Subjects
- 6.2.2 Methods
- 6.3 Results
- 6.4 Discussion
- 6.5 Conclusion
-
CHAPTER VII Soluble triggering receptor expressed on myeloid cells in sputum of children with HIV-related bronchiectasis
- 7.1 Objective
- 7.2 Subjects and methods
- 7.2.1 Subjects
- 7.2.2 Methods
- 7.3 Results
- 7.4 Discussion
- 7.5 Conclusion
- CHAPTER VIII Positron emission tomography in the prediction of inflammation in children with HIV-related bronchiectasis
- 8.1 Objectives
- 8.2 Subjects and methods
- 8.2.1 Subjects
- 8.2.2 Methods
- 8.3 Results
- 8.4 Discussion
- 8.5 Conclusion
- CHAPTER IX The efficacy of low dose erythromycin in improving the outcome of HIV-infected children with bronchiectasis
- 9.1 Objectives
- 9.2 Subjects and methods
- 9.2.1 Subjects
- 9.2.2 Methods
- 9.3 Results
- 9.4 Discussion
- 9.5 Conclusion
- CHAPTER X Summary and conclusions
- CHAPTER XI Study limitations and recommendations
- APPENDICES
- Appendix A Subject data collection sheet
- Appendix B Ethics Committee approval
- Appendix C Patient information leaflet, consent and assent form
- Appendix D Bhalla score
- REFERENCES
- TERMINOLOGY AND ABBREVIATIONS
