PhD (Microbiology) / Department of Microbiology / Introduction Human Immunodeficiency Virus (HIV-1) continues to be a global public health concern, even though Antiretroviral drugs (ARV), especially Highly Active Antiretroviral Therapy (HAART) has significantly reduced morbidity and mortality due to AIDS globally in developed and developing countries. However, there is still a great need to explore every avenue for new therapeutic interventions due to the limitations and side effects of HAART. Potential major breakthroughs for future therapeutic development were the discoveries more than 10 years ago of the role of HIV-1 co-receptors and anti-viral activities of host restriction factors such as APOBEC3G protein, which is a member of the DNA cytosine deaminase family. Entry of HIV in to the host cell is through the attachment of the viral envelope glycoprotein to the CD4 receptor, and subsequent interaction, mainly with either CCR5 or CXCR4 co-receptors. Inhibitors, such as Maraviroc, which binds to CCR5 inhibiting entry of CCR5 utilizing viruses (R5 viruses), is currently reserved for salvage therapy in many countries including South Africa. In the course of HIV infection, CXCR4 utilizing viruses (X4 viruses) may emerge and outgrow R5 viruses, and potentially limit the effectiveness of Maraviroc. Several host cell APOBEC3 genes (A3D, A3F, A3G and A3H) have been shown to restrict HIV, and the HIV viral infectivity factor (Vif) protein serves to antagonize the action of APOBEC3 proteins, promoting viral replication. The CCR5 co-receptor and the HIV Env V3 loop have also been documented as playing roles in HIV-1 disease progression. The interplay between host and viral genes still needs widespread attention, given that disease outcomes of HIV depend on many factors, including host cell genetics. Since the discovery of these genes and their role in HIV replication, many studies have been conducted that show their association with viral polymorphism. The polymorphisms found in host cell genes can have significant effects on viral replication, transmission and fitness and can also contribute to the overall diversity in HIV-1 populations. It is hypothesized that there are significant polymorphisms in HIV-1 and cellular genes that may differ among different populations. Population-based studies have tried to establish a relationship between host factors such as APOBEC3 and CCR5 polymorphism and the rate of disease progression, but most studies have focused on Caucasian populations. In vi contrast, little information is available for the effects of variation in these genes in African populations such as South Africa, where the HIV epidemic has expanded at an alarming rate. Although several population studies have focused on African Americans, these do not give us a complete picture of the potential variation in Africans, though the studies can be a good guide on which to base additional studies. A more comprehensive analysis involving different African populations will likely provide a better understanding of the mechanisms underlying host-pathogen interactions, especially in view of the fact that African Americans are primarily infected with HIV subtype B, which is rarely seen in Africa. Methodology This study characterized the genetic variability of the APOBEC3 D, F, G and H genes as well as the HIV-1 vif, in an ethnically diverse HIV-1 infected South African cohort using Next Generation Sequencing (NGS). In addition, polymorphism in CCR5 was analyzed in conjunction with an analysis of the V3 loop sequences in HIV-1 from this cohort. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs) of 192 HIV-1 infected drug-experienced individuals who presented for routine care at the HIV/AIDS Prevention Group Wellness Clinic (HAPG) in Bela-Bela, Donald Fraser Hope Clinic (DFHC) in Vhufhuli and in local clinics in the Vhembe district of Limpopo Province, South Africa. Next generation sequencing custom based (Tn5 tagmentation and amplicon based) protocols to prepare libraries for host and HIV-1 genes were developed and validated with commercially available library preparation kits. The Tn5 tagmentation methods were used for longer DNA fragments and the custom amplicon based methods were used mainly for the shorter DNA fragments. To determine the variability of the APOBEC3 and CCR5 host genes, gene-specific primers were designed to amplify complete 12.16 kb A3D, 13.31 kb A3F, 10.74 kb A3G, 6.8 kb A3H and 1.3 kb CCR5 genes targeting the regions containing the exons. Libraries for the resulting amplicons were prepared using Tn5 transposase tagmentation methods and sequenced on an NGS Illumina MiSeq platforms generating millions of reads with good read coverage for variant calling. Single nucleotide polymorphisms (SNPs) and indels were determined, verified in dbSNPs and compared to SNPs in other populations reported in the 1000 Genome Phase III and HapMap. A Chi-square goodness-of-fit was used to verify if whether observed genotype frequencies were in agreement with the Hardy-Weinberg Equilibrium. Haplotypes and Linkage disequilibrium were inferred to determine SNP association. vii The HIV-1 vif and env V3 loop genes were also sequenced to determine their degree of variability of these genes and to infer co-receptor usage in the South African population. Gene-specific primers were designed to amplify the 579 bp Vif region and 440 bp containing the 105 bp V3 loop. Sequencing libraries from the resulting amplicons were prepared using either the Tn5 transposase or custom-based library preparation methods and sequenced on either an Illumina MiSeq or a MiniSeq platform generating millions of reads with good read coverage for variant calling. Phylogenetic analysis was done to determine the relatedness of the sequences. Major and minor variants were determined for HIV-1 and env V3 loop quasispecies was analysed for co-receptor usage; in an effort to draw inferences for the subsequent utility of Maraviroc as salvage therapy in South Africa. Results and Discussion Next generation library preparation; Tn5 tagmentation based and custom amplicon based protocols to sequence host and HIV genes were successfully developed and used to sequence and characterize variability in host cell APOBEC3D, F, G H, CCR5 and the HIV-1 vif gene and the V3 loop region of the env gene. The HIV-1 env V3 loop sequences generated (and quasispecies analyzed) were used to infer co-receptor usage in treatment-experienced individuals; in an effort to draw inferences for the subsequent utility of Maraviroc as salvage therapy in South Africa. Quality V3 loop sequences were obtained from 72 patients, with 5 years (range: 0-16) median duration on treatment. Subtypes A1, B and C viruses were identified at frequencies of 4% (3/72), 4% (3/72) and 92% (66/72) respectively. Fifty four percent (39/72) of patients were predicted to exclusively harbor R5 viral quasispecies; and 21% (15/72) to exclusively harbor X4 viral quasispecies. Twenty five percent of patients (18/72) were predicted to harbor a dual/mixture of R5X4 quasispecies. Of these 18 patients, about 28% (5/18) were predicted to harbor the R5+X4, a mixture with a majority R5 and minority X4 viruses, while about 72% (13/18) were predicted to harbor the R5X4+ a mixture with a majority X4 and minority R5 viruses. The proportion of all patients who harboured X4 viruses either exclusively or dual/mixture was 46% (33/72). Thirty-five percent (23/66) of the patients who were of HIV-1 subtype C were predicted to harbor X4 viruses (χ2=3.58; p=0.058), and 57% of these (13/23) were predicted to harbor X4 viruses exclusively. CD4+ cell count less than 350 cell/μl was associated with the presence of X4 viruses (χ2=4.99; p=0.008). The effectiveness of Maraviroc as a component in salvage therapy may be compromised for a significant number of chronically infected patients harboring CXCR4 utilizing viii viruses in the study cohort. Although from the current study a subset of patients harboring CCR5 utilizing viruses may benefit from Maraviroc, characterizing and identifying if variation in CCR5 are located at Maraviroc binding sites was of importance to investigate. The following variants; P35P, S75S, Y89Y, A335V and Y339F and their varying frequencies were detected in the CCR5 gene. The A335V variant was detected at a higher frequency of 17.4% (29/167). The G265S variant is reported for the first time in this study at 0.6% (1/167) frequency. The SNPs detected were in strong LD (D’= 1, R2 = 0.0) with minor deviation from the Hardy-Weinberg Equilibrium. These variants were not located at the binding motif of Maraviroc. The variants A335V and Y339F were detected at a higher frequency in this study than previously reported in South Africa. Variability in APOBEC3 host cell genes was also characterized in our study cohort. The following APOBEC3 variants compared to the GRCh37 consensus sequence were detected: R97C, R248K and T316T in A3D; R48P, A78V, A108S, S118S, R143R, I87L, Q87L, V231I, E245E, S229S, Y307C and S327S in A3F; S60S, H186R, R256H, Q275E and G363R in A3G and N15Δ, G105R, K140E, K121D, E178D in A3H. Minor allele frequency variants (MAF<5%); L221L, T238I, C224Y and C320Y in A3D; I87L, P97L and S229S in A3F; R256H, A109A, F119F and L371L in A3G, which are frequent in the European population, were also detected. In addition, novel R6K, L221R and T238I variants in A3D and I117I in A3F were detected. Most of the SNPs were in strong LD with minor deviation from the Hardy-Weinberg Equilibrium. Four, six, four, and three haplotypes were identified for A3D, A3F, A3G, and A3H respectively. In general, polymorphism in A3D, 3F, 3G and 3H were higher in our South African cohort than previously reported among other African, European and Asian populations. The APOBEC3 antagonist HIV-1 vif gene was also sequenced to determine the level of diversity in a South African population and also correlated with APOBEC3 variation. Functional Vif without frameshift mutation was observed in all samples except in 4 samples. The functional domain and motifs, such as Zn binding motifs, proline-rich domain, human casein kinase, and the N and C-terminal CBF interaction site were highly conserved. APOBEC binding motifs and the nuclear localization signal were less conserved in the South African HIV-1 Vif. APOBEC3 H variation strongly correlates with Vif variation. All the Vif sequences were subtype C, except one sample, which was identified as an A1/C recombinant. The vif gene in a South African population was under purifying selection, with the dS= 0.2581 and dN= 0.0684 and the dN/dS value = 0.265. There is a high genetic diversity in the South African vif gene, which may ix influence the neutralization and restriction of APOBEC genes. Conclusions In conclusion, the protocols developed in this study can be applied to amplify and sequence any host and HIV-1 genes of interest allowing much deeper and more sensitive profiling of host gene and HIV-1 genetic diversity. Our findings show that a highly significant number of chronically HIV-1 subtype C infected patients in Maraviroc-free treatment harbor CXCR4 utilizing viruses. The data is useful in the consideration of whether to include entry antagonists such as Maraviroc in alternative forms of treatment for patients failing second line treatment regimen in the study setting. The determination of co-receptor usage prior to initiation of therapy consisting of Maraviroc is suggested. Variation in the CCR5 coding region were observed at higher frequencies compare to other studies conducted in South African populations at different locations. This data may suggest that different populations in South Africa have different SNP frequencies. All the polymorphisms identified in the study were not located at the Maraviroc binding motif, therefore the subset of patient infected by R5 viruses may benefit from this drug. We have shown that significant APOBEC3 variation exists among an ethnically diverse population of South Africa by providing extensive data for 4 different A3 genes that are known to restrict HIV infection, but have only been sparsely studied in African populations. This study provides a baseline for future studies that would functionally characterize SNPs identified in this population, in order to understand the role of novel and/or low frequency variants observed. Ex vivo and in vivo studies will increase our understanding of how these variants might have cumulatively impacted the epidemic in Northern South Africa. This study also shows that there is a high level of HIV-1 Vif diversity in the study area. This diversity may impact the expression and packaging of Vif proteins, and the infectivity of HIV. In addition, a significant correlation was observed between HIV-1 Vif variation and APOBEC3 H haplotypes. / NRF

La modélisation mathématique de la dynamique des maladies auto-immunes contribue à la compréhension de leurs mécanismes, offrant ainsi une meilleure orientation pour les traite- ments. Dans ce contexte, ce mémoire fait l’analyse d’un système d’équations différentielles à délai distribué modélisant l’évolution du VIH dans un corps infecté, mettant en relation les cellules CD4-T non infectées, les cellules infectées, les particules de virus et la réponse immunitaire. Aavani [1] a étudié un tel modèle à délai discret, que nous généralisons et qui demande une méthode alternative d’analyse de stabilité des points fixes. Le comportement asymptotique des solutions est alors caractérisé entièrement par le délai, noté \(\tau \) , représentant le temps que prend une cellule infectée avant de produire des particules de virus. Nous démontrons que pour une valeur de \(\tau \) assez grande, soit au-dessus d’un certain seuil \(\tau_1 \), l’infection tend à s’éteindre puisque le point fixe sans maladie est asymptotiquement stable. Pour un délai en dessous de ce seuil, l’infection perdure : le point fixe sans maladie est instable. Dans ce cas, le point fixe aigu et le point fixe chronique s’échangent la stabilité asymptotique selon un autre seuil \(\tau_2 \). Des simulations numériques appuient finalement les conclusions obtenues analytiquement / The mathematical modeling of the dynamics of autoimmune diseases contributes to the understanding of their mechanisms, thus providing better guidance for treatments. In this context, this thesis analyzes a distributed delay differential equations system modeling the evolution of HIV in an infected body, describing the interactions between uninfected CD4-T cells, infected cells, virus particles and the immune response. Aavani [1] studied a similar but simpler model, incorporating a discrete delay, which we generalize using alternative methods for the investigation of stability of stationary solutions. The asymptotic behavior of the solutions is entirely characterized by the delay, denoted \(\tau \) , representing the time before an infected cell produces virus particles. It is shown that for a sufficiently large value of \(\tau \) , i.e. above a certain threshold \(\tau_1 \), the infection tends to die out since the disease-free steady-state is asymptotically stable. Then, for a delay below this threshold, the infection persists : the disease-free steady-state being unstable. In this case, the acute steady-state and the chronic stage exchange asymptotic stability according to another threshold \(\tau_2 \). Numerical simulations finally support the conclusions obtained analytically.

Объектом исследования является система оказания психологической и социальной помощи ВИЧ-инфицированным пациентам. Предмет исследования: роль и участие специалистов учреждений социального обслуживания населения в системе профилактики и оказания медицинской помощи больным ВИЧ-инфекцией. Целью магистерской диссертации является выявление роли специалистов «немедицинского сервиса» по профилактике и преодолению ВИЧ-инфекции, как социально-значимого заболевания в рамках межведомственного взаимодействия (на примере Свердловской области). Выпускная квалификационная работа посвящена изучению роли специалистов «немедицинского сервиса» в профилактике и преодолении социально-значимого заболевания в рамках межведомственного взаимодействия (на примере Свердловской области). В работе рассмотрены теоретические основы межведомственного взаимодействия как социальной технологии, в процессе профилактики ВИЧ-инфекции; с использованием авторской анкеты выявлены основные возможности и затруднения специалистов учреждений социального обслуживания населения в оказании помощи здравоохранению по преодолению распространения ВИЧ-инфекции, а так же выявлены основные потребности ЛЖВ (людей, живущих с ВИЧ); проведён контент-анализ существующей и разработано авторское дополнение к основной образовательной программе ГАУЗ СО ОЦ СПИД по подготовке специалистов «немедицинского сервиса» к мотивационному консультированию, которая при апробации показала положительные результаты в части удовлетворения потребностей и пациентов ВИЧ+, и учреждений здравоохранения. Работа будет интересна студентам и специалистам в области социальной работы с ЛЖВ. / The final qualifying work is devoted to the study of the role of specialists of the "non-medical service" in the prevention and overcoming of socially significant diseases within the framework of interdepartmental interaction (on the example of the Sverdlovsk region). The paper considers the theoretical foundations of interdepartmental interaction as a social technology in the process of HIV infection prevention; using the author's questionnaire, the main opportunities and difficulties of specialists from social service institutions in providing health care to overcome the spread of HIV infection are identified, as well as the basic needs of PLHIV (people living with HIV) are identified; an author's supplement is developed to the main educational program of the State Medical Institution of the Russian Academy of Sciences on the preparation of specialists of the "non-medical service" for motivational training, which, when tested, showed positive results in meeting the needs of both HIV+ patients and healthcare institutions. The work will be of interest to students and specialists in the field of social work with PLHIV.

Quantitative, descriptive research, using self-completion questionnaires, was conducted to determine the level of HIV/AIDS knowledge of the learners in Sefhare. The sample, comprising 92 learners, was selected from forms 1-3. Of the learners, 53.4% knew what HIV/AIDS stand for, but only 13.6% said AIDS is caused by HIV and only 4.5% said AIDS is an incurable disease. The ABC of protecting oneself against HIV (abstain from sex, be faithful to one sex partner, use condoms) was mentioned by merely 57.6% of the learners. The learners’ lack of knowledge should be addressed by school HIV/AIDS programmes offered at schools in Botswana. As 81.5% of the learners were willing to be tested for HIV, this service should be made available with simultaneous confidential personal HIV/AIDS education, irrespective of the HIV test results. Teachers’ and parents’ HIV/AIDS knowledge should also be updated regularly. / Health Studies / M.A. (Public Health)

Thesis in English, Annexure E: Consent form (leaf 81) as well as KABP Survey Questionnaire (leaves 87-91) in English and SiSwati. / The purpose of the study was to assess knowledge, explore attitudes and determine practices of breastfeeding mothers living with HIV regarding post-natal PMTCT interventions and services. The study was quantitative and descriptive in nature, utilising a retrospective cohort design. The study sample included breastfeeding mothers living with HIV, who attended the King Sobhuza II public health unit in the Manzini region of Swaziland. A written questionnaire was administered to a non-random sample of 90 consecutively selected mothers living with HIV attending the above-cited public health unit for post-natal health purposes. The overall study results revealed that the majority of breastfeeding mothers living with HIV in the afore-mentioned region (77.8%) presented high levels of knowledge on PMTCT, and 90% demonstrated a positive attitude; while a further 90% also demonstrated positive behaviour towards PMTCT. However, stigma and discrimination among family members, non-disclosure of HIV status to sexual partners; as well as poverty and fear of future drug-resistance are the cause of non-adherence to ARV prophylaxis. Furthermore, inconsistent condom use, mixed-feeding methods and wet-nursing also emerged as other contributing factors to the increase of post-natal mother-to-child transmission of HIV among breastfeeding mothers living with HIV. / Health Studies / M.A. (Nursing Science)

Objective: Criminal liability for the sexual-transmission of HIV raises complex questions for both clinicians and service-users regarding their responsibilities and legal obligations to disclose information to others. This is the first research study to address the impact of these issues upon everyday clinical and professional management in the UK. The prevalence and incidence of clinical and HIV-legal issues reported by the 107 psychologists sampled are reported. Design: A cross-sectional approach comprising two components was utilised: Firstly, questionnaire survey (Response rate 22%) scoping the experiences of practice issues among psychologists from sexual-health and generic settings. Attitudes towards HIV-prosecutions and various measures of professional self-efficacy were also collected. Secondly, three focus groups (N=15) exploring the impact of practice issues upon clinicians’ likely confidentiality breaking behaviours. Methods: Clinical and legal issues are presented. Further statistical analyses explored the interaction of various demographic, clinical and attitudinal variables upon clinician’s perceived self-efficacy. Focus Group transcripts analysed using Thematic Analysis (Data-driven approach) with eight emergent themes. Results: Although no direct involvements in police investigations reported, two instances of psychology notes being subpoenaed plus multiple ‘near miss’ clinical experiences described. High proportions of sexual-health psychologists experienced HIV-clients disclosing problematic behaviours, including intentional transmission (9%; N=5) and/or ‘reckless’ behaviour (72%). Focus groups expressed high levels of anxiety regarding these scenarios associated to multiple influences (interpersonal, clinician, professional and service factors). Quantitative and qualitative results were triangulated to provide a detailed analysis of how psychologists manage the clinical impact of the issues. Conclusions: Psychologists broadly supported HIV-prosecutions for intentional transmission (81%) but only limited support around ‘reckless’ cases (44%), particularly among those sexual-health experienced. Those ‘critical’ attempted to mitigate the impact of legal issues by proactively raising awareness among HIV-clients and resisting overly-defensive service changes; whereas those ‘less-critical’ were more accepting. Clinical, training and therapeutic implications are briefly considered.

Quantitative, descriptive research, using self-completion questionnaires, was conducted to determine the level of HIV/AIDS knowledge of the learners in Sefhare. The sample, comprising 92 learners, was selected from forms 1-3. Of the learners, 53.4% knew what HIV/AIDS stand for, but only 13.6% said AIDS is caused by HIV and only 4.5% said AIDS is an incurable disease. The ABC of protecting oneself against HIV (abstain from sex, be faithful to one sex partner, use condoms) was mentioned by merely 57.6% of the learners. The learners’ lack of knowledge should be addressed by school HIV/AIDS programmes offered at schools in Botswana. As 81.5% of the learners were willing to be tested for HIV, this service should be made available with simultaneous confidential personal HIV/AIDS education, irrespective of the HIV test results. Teachers’ and parents’ HIV/AIDS knowledge should also be updated regularly. / Health Studies / M.A. (Public Health)

Thesis in English, Annexure E: Consent form (leaf 81) as well as KABP Survey Questionnaire (leaves 87-91) in English and SiSwati. / The purpose of the study was to assess knowledge, explore attitudes and determine practices of breastfeeding mothers living with HIV regarding post-natal PMTCT interventions and services. The study was quantitative and descriptive in nature, utilising a retrospective cohort design. The study sample included breastfeeding mothers living with HIV, who attended the King Sobhuza II public health unit in the Manzini region of Swaziland. A written questionnaire was administered to a non-random sample of 90 consecutively selected mothers living with HIV attending the above-cited public health unit for post-natal health purposes. The overall study results revealed that the majority of breastfeeding mothers living with HIV in the afore-mentioned region (77.8%) presented high levels of knowledge on PMTCT, and 90% demonstrated a positive attitude; while a further 90% also demonstrated positive behaviour towards PMTCT. However, stigma and discrimination among family members, non-disclosure of HIV status to sexual partners; as well as poverty and fear of future drug-resistance are the cause of non-adherence to ARV prophylaxis. Furthermore, inconsistent condom use, mixed-feeding methods and wet-nursing also emerged as other contributing factors to the increase of post-natal mother-to-child transmission of HIV among breastfeeding mothers living with HIV. / Health Studies / M.A. (Nursing Science)

Liver disease is now a leading cause of non-AIDS related morbidity and mortality in people living with HIV (PLWH). The present study investigated the interplay between adverse lifestyle factors that are prevalent in PLWH, biological mediators of liver pathogenesis, and a non-invasive measure of liver fibrosis (FIB-4 index) in HIV mono- and HIV/HCV co-infected individuals. The results of this investigation in the Miami Adult Studies of HIV (MASH) cohort show that the odds of liver fibrosis progression significantly increased over two years for HIV mono-infected participants who drank alcohol hazardously (OR 3.038, P=0.048), and had BMI ≥ 28kg/m2 (OR 2.934, P=0.027). Cocaine use reduced the odds of advancing one stage of liver fibrosis (OR 0.228, P=0.038), but an interaction between high BMI and cocaine use slightly raised the odds by 4.8% of liver fibrosis progression (P=0.072). HIV/HCV co-infected participants showed interactions between cocaine use and high BMI with increased FIB-4 stage (OR 4.985, P= 0.034), however no lifestyle factors could independently predict FIB-4 stage in this group. Biological mediators previously associated with liver pathogenesis were associated with higher FIB-4 index over 2 years in a subset of (n=65) HIV mono-infected participants. Plasma measures of oxidative stress (% oxidized glutathione: OR 4.342, P= 0.046), hepatocyte-specific apoptosis (Cytokeratin-18 (CK-18): OR 1.008, P=0.021), and microbial endotoxin (lipopolysaccharide (LPS): OR 1.098, P= 0.097) were associated with having higher odds of progressing at least one stage of FIB-4 over 2 years. The same biological mediators were also associated with liver fibrosis within HIV infected people who also had a harmful lifestyle characteristic. FIB-4 index was significantly associated with % oxidized glutathione in obese subjects (β=0.563, P=0.018), TGF-β1 in cocaine users (β=0.858, P=0.027), and CK-18 in HIV infected individuals without any adverse lifestyle factors (β=0.435, P=0.015). Taken together, the findings of these studies describe interrelationships between HIV disease status, lifestyle, and biological mediators of liver fibrosis. The results show interactions between lifestyle conditions and the mediators of liver fibrosis may account for higher rates of liver disease in HIV infection. Research is warranted to develop personalized therapeutics for PLWH to curb the burden of liver disease.

PhD (Health) / Department of Public Health / The Government of South Africa in response to a prevalent human immunodeficiency virus (HIV) has adopted an approach of integrating HIV/AIDS service into primary health care, as a key to achieving universal access to antiretroviral treatment (ART). Despite the government’s efforts of integrating HIV service into Primary Health Care (PHC), insufficient numbers of PHC staff and inadequate infrastructure is challenging when integrating HIV/AIDS service into PHC. This study explored the extent of HIV service integration into PHC and whether the clinic/health centre’s environment is enabling to integrate HIV service into PHC. Barriers to HIV/AIDS services integration as well as attitudes of PHC nurses were assessed. The overall purpose of this study was to develop guidelines to facilitate the integration of HIV/AIDS services into PHC in Vhembe district of Limpopo province, South Africa. An exploratory sequential mixed methods design was used. The qualitative data was collected and analysed before and results for qualitative approach used to build a subsequent quantitative phase. The current study revealed that HIV/AIDS services are integrated into every existing programme at the PHC clinic and health centres; these include: Immunisation programme, Family planning, PMTCT and ANC programmes, STIs, minor ailments and chronic illness and TB. The study further revealed that the environments at PHC clinics and health centres are not enabling the integration of HIV/AIDS services into PHC due to insufficient staff and inadequate infrastructure. Guidelines to facilitate the integration of HIV/AIDS services based on the findings was developed. The study recommendations comprise; increasing knowledge of HIV serostatus, accelerating HIV prevention, accelerating the scale-up of HIV treatment and care, creating of enabling environment for the integration of HIV/AIDS services into PHC, nursing education and training and nursing education and training.