EFFECT OF MICRONUTRIENT SUPPLEMENTATION ON SOME INDICES OF HIV INFECTION PROGRESSION AMONG ANTIRETROVIRAL NAÏVE PATIENTS ATTENDING HIV CLINICS IN ZARIA AND KADUNA, NIGERIA
Nigeria has the second highest HIV/AIDS burden in the world with an estimated 3,391,546 people living with HIV and AIDS; an estimated 239,155 people acquired new infections in 2013; and about 174,253 people died from AIDS related illness (s) in 2014. HIV infection causes a chronic disease that progresses from stage one (seroconversion or asymptomatic) to stage four (advanced disease/AIDS) over a median period of 5 years. The course of the HIV infection is characterized by a persistent pro-oxidant state that leads to programmed CD4+ cell apoptosis, elaboration of proinflammatory cytokines and acute phase proteins, HIV RNA replications, hyper-catabolism, increased utilization of antioxidants and micronutrients, and subsequent micronutrient deficiencies. The aim of this study was to evaluate the effect of micronutrient supplementation on some indices of HIV infection progression among ART-naïve patients. To achieve the aim of the study, 90 ART naïve HIV infected adult patients with CD4+ cell count ≥520/µL were enrolled. After obtaining informed written consent, their sociodemographic data, CD4+ cell counts (cc), body mass index (BMI), vital signs, symptoms and signs of HIV infection, were obtained, and blood samples for plasma HIV RNA load (pVL), haemoglobin, and serum C-reactive protein (CRP), interleukin-6 (IL-6), albumin, lipids and micronutrients (vitamin B12, zinc, and copper) were collected. After these, each patient was given a daily dose of one capsule of Synovit supplements and two tablets of co-trimoxazole. Eligible patients were re-evaluated every 12 weeks, and data on vital signs, BMI, symptoms and signs of HIV infection, CD4+ cc, and haemoglobin were obtained; while blood samples for pVL, CRP, IL-6, albumin, lipids and micronutrients were collected at 24 weeks and 48 weeks of Synovit supplementation respectively.Patients who defaulted from one scheduled clinic visit, became pregnant, or became eligible for ART before the 48 weeks of Synovit supplementation were dropped. The socio-demographic characteristics, vital signs, BMI, haemoglobin, and serum albumin, zinc, copper and vitamin B12 of the patients were compared with those of 90 age and sex-matched HIV negative apparently healthy volunteers from the same environments.Patients comprised 21 males and 69 females, aged 42.9±9.8 years and 34.6±8.6 years respectively (p≤0.05). They were mainly low income earners and were enrolled within a median of 4 months of HIV infection diagnosis. Ninety (90) patients were initially evaluated, 78 and 68 were re-evaluated at 12 and 24 weeks respectively, while 57 patients were re-evaluated at 36 and 48 weeks respectively. The sociodemographic factors that determined retention of patients on micronutrient supplementation were found to be the age, occupation and source of income of the patients. The patients‘ baseline median CD4+ cc (704.5/µL) was within reference range(365-1571/µL) for healthy Nigerians. Their vital signs (temperature=38.2±0.7oC; pulse rate=78.0±10.1 beats/minute; respiratory rate=12.0±3.0 breaths/minutes; systolic blood pressure=128.0±13.7 mmHg) were higher than those of healthy controls (temperature=36.8±0.2oC; pulse rate=72.0±21.1 beats/minute; respiratory rate=16.0±1.0 breaths/minutes; systolic blood pressure=138.0±37.4 mmHg) (p≤0.05). Although they were overweight (median BMI of 25.8kg/m2), their baseline median haemoglobin (11.0 g/dL), serum albumin (36.0g/L), zinc (0.01ppm), copper (-0.4ppm), vitamin B12 (15.0ng/L) and total cholesterol (4.6mmol/L) were significantly lower than those of healthy volunteers (p≤0.05). Their serum CRP (27.8 ng/ml), and IL-6 (1.9 pg/ml) were also significantly higher than reference values (p≤0.05).Micronutrient supplementation significantly decreased incidence of opportunistic illnesses (OIs), pVL, CRP and IL-6; and increased haemoglobin, serum zinc, copper, vitamin B12, total cholesterol and high density lipoproteins (p≤0.05); but did not increase CD4+ cc. The pVL maintained significant negative correlations with CD4+ cc, zinc and copper (p≤0.05), and positive correlations with IL-6 and CRP (p≤0.05). Significant predictors of HIV RNA load at baseline were zinc(p=0.00) and IL-6 (p =0.05); while serum IL-6 (p=0.00) and haemoglobin (p=0.02) were the predictors at 24 weeks and 48 weeks of micronutrient supplementation respectively. In conclusion, micronutrient supplementation enhanced retention of patients on the pre-ART care and support service programme and reduced the indices of progression of HIV infection with the exception of CD4+ cell counts.
1.1 Human Immunodeficiency Virus(HIV)
1.1.1 Family and types
HIV belongs to the virus family Retroviridae and subfamily Lentiviridae. Lentiviruses typically cause a slowly progressive disease with prolonged subclinical infection (Yuet al., 2005). HIV comprises HIV-1 and HIV-2. HIV-1 is closely related to a naturally occurring virus of sub-species of chimpanzees called SIVcpz, while HIV-2 is closely related to SIVsm, a virus that naturally infects sooty mangabey monkeys (Diopet al., 2002). In contrast to HIV-1, there has been little international spread of HIV-2 despite the fact that the two viruses share similar modes of transmission. Most HIV-2 infections were reported in West Africa, and only few cases were identified in other countries (Kankiet al., 1997). Co-infection of HIV-1 and 2 can occur but recombinants of the 2 types were reported to be rare (Kankiet al., 1997).
Electronmicroscopic studies showed that HIV has a cylindrical structure consisting of viral genome, core proteins and lipid bilayer membrane & envelopes (Yu et al., 2005). The viral genome is diploid, with a 60-70s complex of two identical RNA copies. The genome is flanked on both sides by long terminal repeat sequences that contain gag, pol and env structural genes that code for capsid proteins, viral enzymes and envelopes respectively. The genome has five other regulatory & accessory genes: tat, rev, nef, vif&vpu(HIV-1) or vpx (HIV-2). The viral enzymes are the reverse transcriptase (RT), protease (PR) & integrase (IN) which are encoded by pol geneThe core protein is made up of capsid protein (p24) and nucleocapsid protein (p18) encoded by the gag genes. The envelopes surround the core proteins that enclose the viral RNA genome and enzymes. The envelopes consist of external surface (gp 120) and transmembrane (gp 41) that connects to the core proteins. The gp 120 contains binding sites for CD4+ receptor and co-receptors. The gp41 tranverses through the lipid bilayer and both are partially acquired from the surface of host cells as mature virions are released. Figure 1 below shows a schematic structure of HIV.
Figure 1.1: Human Immunodeficiency Virus
1.1.3 Genetic Diversity
HIV strains can be classified into three groups – major (M), non-major (N) and outlier (O) (McCutchan, 2000). Group M, the most common globally, is further divided into nine subtypes (A, B, C, D, F, G, H, J and K) and several circulating recombinant forms (CRFS). Subtype C has been documented to account for more than 50% of prevalent global HIV-1 infections and a higher proportion of new infections, particularly in China and the African continent; subtypes A, C and D were found more frequently in India and Central, Southern and the Horn of Africa; subtype B strains were only isolated from the USA and Western Europe through 1994, and subtype A/E recombinant were observed in South-East Asia (McCutchan, 2000). In Nigeria and West Africa, the dominant subtype was the CRF 02/A/G; while HIV-1 N and O groups were rare and limited to Cameroon and neighbouring countries (Kanki, et al., 1997; McCutchan, 2000).