HIV Infection in Children and Antiretroviral Therapy (ART)

"""
Pediatric HIV Quick Reference Guide - PDF Builder
Uses reportlab for professional medical reference layout
"""

from reportlab.platypus import (
    SimpleDocTemplate, Table, TableStyle, Paragraph, Spacer,
    HRFlowable, KeepTogether, PageBreak
)
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib import colors
from reportlab.lib.units import mm, inch
from reportlab.lib.pagesizes import A4
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus import Flowable

OUTPUT = "/tmp/workspace/pediatric-hiv-guide/Pediatric_HIV_Quick_Reference.pdf"

# ── Color Palette ──────────────────────────────────────────────────────────────
RED_DARK    = colors.HexColor("#C0392B")
RED_LIGHT   = colors.HexColor("#FADBD8")
TEAL_DARK   = colors.HexColor("#117A65")
TEAL_LIGHT  = colors.HexColor("#D5F5E3")
BLUE_DARK   = colors.HexColor("#1A5276")
BLUE_MED    = colors.HexColor("#2E86C1")
BLUE_LIGHT  = colors.HexColor("#D6EAF8")
ORANGE_DARK = colors.HexColor("#BA4A00")
ORANGE_LIGHT= colors.HexColor("#FAE5D3")
PURPLE_DARK = colors.HexColor("#6C3483")
PURPLE_LIGHT= colors.HexColor("#E8DAEF")
GREY_DARK   = colors.HexColor("#2C3E50")
GREY_MED    = colors.HexColor("#566573")
GREY_LIGHT  = colors.HexColor("#F2F3F4")
GREY_RULE   = colors.HexColor("#BDC3C7")
WHITE       = colors.white
YELLOW_LIGHT= colors.HexColor("#FEF9E7")
YELLOW_DARK = colors.HexColor("#D4AC0D")

# ── Document Setup ─────────────────────────────────────────────────────────────
doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    leftMargin=14*mm, rightMargin=14*mm,
    topMargin=14*mm, bottomMargin=14*mm,
    title="Pediatric HIV Quick Reference Guide",
    author="Orris Medical Reference",
    subject="Pediatric HIV Diagnosis, Treatment and Monitoring"
)

W = A4[0] - 28*mm   # usable width

# ── Styles ─────────────────────────────────────────────────────────────────────
base = getSampleStyleSheet()

def S(name, parent='Normal', **kw):
    return ParagraphStyle(name, parent=base[parent], **kw)

sTitle = S('sTitle', 'Title',
    fontSize=22, textColor=WHITE, alignment=TA_CENTER,
    spaceAfter=2, leading=26)

sSubtitle = S('sSubtitle',
    fontSize=11, textColor=colors.HexColor("#D6EAF8"),
    alignment=TA_CENTER, spaceAfter=4, leading=14)

sSectionHead = S('sSectionHead',
    fontSize=11, textColor=WHITE, fontName='Helvetica-Bold',
    alignment=TA_LEFT, leading=14, leftIndent=4)

sBody = S('sBody',
    fontSize=8.5, textColor=GREY_DARK, leading=12, spaceAfter=2)

sBullet = S('sBullet',
    fontSize=8.2, textColor=GREY_DARK, leading=11.5,
    leftIndent=10, firstLineIndent=-8, spaceAfter=1.5)

sTableHead = S('sTableHead',
    fontSize=8, textColor=WHITE, fontName='Helvetica-Bold',
    alignment=TA_CENTER, leading=10)

sTableCell = S('sTableCell',
    fontSize=7.8, textColor=GREY_DARK, leading=10.5)

sTableCellC = S('sTableCellC',
    fontSize=7.8, textColor=GREY_DARK, leading=10.5, alignment=TA_CENTER)

sWarning = S('sWarning',
    fontSize=8, textColor=colors.HexColor("#7D6608"),
    fontName='Helvetica-Bold', leading=11)

sNote = S('sNote',
    fontSize=7.5, textColor=GREY_MED, leading=10, fontName='Helvetica-Oblique')

sFooter = S('sFooter',
    fontSize=7, textColor=GREY_MED, alignment=TA_CENTER, leading=9)

sBadge = S('sBadge',
    fontSize=7.8, textColor=WHITE, fontName='Helvetica-Bold',
    alignment=TA_CENTER, leading=10)

# ── Helper Flowables ───────────────────────────────────────────────────────────
def rule(color=GREY_RULE, thickness=0.5, spB=3, spA=3):
    return HRFlowable(width="100%", thickness=thickness,
                      color=color, spaceAfter=spA, spaceBefore=spB)

def sp(h=4):
    return Spacer(1, h*mm)

def section_header(text, bg=BLUE_DARK, icon=""):
    label = f"{icon}  {text}" if icon else text
    tbl = Table([[Paragraph(label, sSectionHead)]], colWidths=[W])
    tbl.setStyle(TableStyle([
        ('BACKGROUND', (0,0), (-1,-1), bg),
        ('TOPPADDING',    (0,0), (-1,-1), 5),
        ('BOTTOMPADDING', (0,0), (-1,-1), 5),
        ('LEFTPADDING',   (0,0), (-1,-1), 8),
        ('RIGHTPADDING',  (0,0), (-1,-1), 8),
        ('ROUNDEDCORNERS', [3, 3, 3, 3]),
    ]))
    return tbl

def banner_box(text, bg=BLUE_LIGHT, border=BLUE_MED, style=sBody):
    tbl = Table([[Paragraph(text, style)]], colWidths=[W])
    tbl.setStyle(TableStyle([
        ('BACKGROUND',    (0,0), (-1,-1), bg),
        ('BOX',           (0,0), (-1,-1), 1.2, border),
        ('TOPPADDING',    (0,0), (-1,-1), 6),
        ('BOTTOMPADDING', (0,0), (-1,-1), 6),
        ('LEFTPADDING',   (0,0), (-1,-1), 10),
        ('RIGHTPADDING',  (0,0), (-1,-1), 10),
    ]))
    return tbl

def warning_box(text):
    style = ParagraphStyle('wb', fontSize=8, textColor=colors.HexColor("#7D6608"),
                           fontName='Helvetica-Bold', leading=11)
    tbl = Table([[Paragraph("⚠  " + text, style)]], colWidths=[W])
    tbl.setStyle(TableStyle([
        ('BACKGROUND',    (0,0), (-1,-1), YELLOW_LIGHT),
        ('BOX',           (0,0), (-1,-1), 1.2, YELLOW_DARK),
        ('TOPPADDING',    (0,0), (-1,-1), 6),
        ('BOTTOMPADDING', (0,0), (-1,-1), 6),
        ('LEFTPADDING',   (0,0), (-1,-1), 10),
        ('RIGHTPADDING',  (0,0), (-1,-1), 10),
    ]))
    return tbl

def make_table(headers, rows, col_widths, header_bg=BLUE_DARK, alt=True):
    data = [[Paragraph(h, sTableHead) for h in headers]]
    for i, row in enumerate(rows):
        data.append([Paragraph(str(c), sTableCell) for c in row])
    tbl = Table(data, colWidths=col_widths)
    style_cmds = [
        ('BACKGROUND',    (0,0), (-1,0),  header_bg),
        ('TEXTCOLOR',     (0,0), (-1,0),  WHITE),
        ('FONTNAME',      (0,0), (-1,0),  'Helvetica-Bold'),
        ('ALIGN',         (0,0), (-1,-1), 'LEFT'),
        ('VALIGN',        (0,0), (-1,-1), 'TOP'),
        ('TOPPADDING',    (0,0), (-1,-1), 4),
        ('BOTTOMPADDING', (0,0), (-1,-1), 4),
        ('LEFTPADDING',   (0,0), (-1,-1), 5),
        ('RIGHTPADDING',  (0,0), (-1,-1), 5),
        ('GRID',          (0,0), (-1,-1), 0.4, GREY_RULE),
        ('ROWBACKGROUNDS',(0,1), (-1,-1), [WHITE, GREY_LIGHT] if alt else [WHITE]),
    ]
    tbl.setStyle(TableStyle(style_cmds))
    return tbl

# ═══════════════════════════════════════════════════════════════════════════════
# BUILD CONTENT
# ═══════════════════════════════════════════════════════════════════════════════
elements = []

# ── COVER HEADER ──────────────────────────────────────────────────────────────
cover_data = [[
    Paragraph("PEDIATRIC HIV", sTitle),
    Paragraph("Quick Reference Guide", sSubtitle),
    Paragraph(
        "Diagnosis  •  Treatment  •  Monitoring  •  PMTCT",
        S('cs2', fontSize=9.5, textColor=colors.HexColor("#AED6F1"),
          alignment=TA_CENTER, leading=13)
    ),
    Paragraph(
        "Sources: Red Book 2021 | Harrison's 22E | Robbins Pathology | NIH AIDSinfo Guidelines",
        S('cs3', fontSize=7.5, textColor=colors.HexColor("#85C1E9"),
          alignment=TA_CENTER, fontName='Helvetica-Oblique', leading=10)
    ),
]]
cover = Table(cover_data, colWidths=[W])
cover.setStyle(TableStyle([
    ('BACKGROUND',    (0,0), (-1,-1), BLUE_DARK),
    ('TOPPADDING',    (0,0), (-1,-1), 12),
    ('BOTTOMPADDING', (0,0), (-1,-1), 12),
    ('LEFTPADDING',   (0,0), (-1,-1), 16),
    ('RIGHTPADDING',  (0,0), (-1,-1), 16),
    ('LINEBELOW',     (0,0), (-1,-1), 3, RED_DARK),
]))
elements.append(cover)
elements.append(sp(3))

# ═══════════════════════════════════════════════════════
# SECTION 1 — EPIDEMIOLOGY & TRANSMISSION
# ═══════════════════════════════════════════════════════
elements.append(section_header("1.  EPIDEMIOLOGY & ROUTES OF TRANSMISSION", bg=BLUE_DARK))
elements.append(sp(2))

epi_left = [
    Paragraph("<b>Global Burden</b>", sBody),
    Paragraph("• ~39 million people living with HIV worldwide (2022)", sBullet),
    Paragraph("• New child (<15 yrs) infections fell from 300,000 (2010) → 120,000 (2023)", sBullet),
    Paragraph("• 67% of PLHIV live in Sub-Saharan Africa", sBullet),
    Paragraph("• ~150,000 children age 0-9 receiving ART globally (2019)", sBullet),
    sp(2),
    Paragraph("<b>HIV-1 vs HIV-2</b>", sBody),
    Paragraph("• HIV-1: dominant worldwide; 8 subtypes (clades A–K, Group M)", sBullet),
    Paragraph("• HIV-2: West Africa; milder course; longer time to AIDS", sBullet),
    Paragraph("• HIV-2 is intrinsically resistant to NNRTIs and enfuvirtide", sBullet),
]

trans_rows = [
    ["In utero", "Transplacental; ~5–10% of MTCT"],
    ["Intrapartum", "During delivery; MOST common (~65–70% of MTCT)"],
    ["Postnatal", "Breastfeeding; ~15–20% risk without prophylaxis"],
    ["Blood products", "Transfusion, contaminated needles"],
    ["Sexual abuse", "Rare; adolescent risk"],
    ["Adolescent routes", "Sexual contact, IV drug use"],
]
trans_tbl = make_table(
    ["Route", "Notes"],
    trans_rows,
    [35*mm, W - 35*mm - 4*mm],
    header_bg=TEAL_DARK
)

two_col = Table(
    [[epi_left, trans_tbl]],
    colWidths=[(W/2)-3*mm, (W/2)-1*mm]
)
two_col.setStyle(TableStyle([
    ('VALIGN', (0,0), (-1,-1), 'TOP'),
    ('LEFTPADDING', (0,0), (-1,-1), 0),
    ('RIGHTPADDING', (0,0), (-1,-1), 0),
    ('TOPPADDING', (0,0), (-1,-1), 0),
    ('BOTTOMPADDING', (0,0), (-1,-1), 0),
    ('LINEAFTER', (0,0), (0,-1), 0.5, GREY_RULE),
]))
elements.append(two_col)
elements.append(sp(2))

elements.append(warning_box(
    "CDC advises against breastfeeding by HIV-positive mothers. "
    "Zidovudine (ZDV) prophylaxis significantly reduces perinatal/vertical transmission."
))
elements.append(sp(3))

# ═══════════════════════════════════════════════════════
# SECTION 2 — MATERNAL RISK STRATIFICATION
# ═══════════════════════════════════════════════════════
elements.append(section_header("2.  MATERNAL RISK STRATIFICATION (Red Book 2021)", bg=TEAL_DARK))
elements.append(sp(2))

risk_rows = [
    [
        Paragraph("<b>LOW RISK</b>", S('lr', fontSize=8.5, textColor=colors.HexColor("#117A65"), fontName='Helvetica-Bold', alignment=TA_CENTER)),
        Paragraph(
            "Mother received standard ART during pregnancy WITH sustained viral suppression "
            "(HIV RNA below lower limit of detection of ultrasensitive assay) AND no adherence concerns.",
            sTableCell
        )
    ],
    [
        Paragraph("<b>HIGHER RISK</b>", S('hr', fontSize=8.5, textColor=RED_DARK, fontName='Helvetica-Bold', alignment=TA_CENTER)),
        Paragraph(
            "• No prenatal care   • No antepartum or intrapartum ARVs<br/>"
            "• Intrapartum ARVs only   • ART initiated late (late 2nd / 3rd trimester)<br/>"
            "• Acute HIV infection during pregnancy<br/>"
            "• Detectable viral load close to delivery (even if on combination ARVs)<br/>"
            "• No sustained viral suppression",
            sTableCell
        )
    ],
]
risk_tbl = Table(risk_rows, colWidths=[28*mm, W - 28*mm])
risk_tbl.setStyle(TableStyle([
    ('BACKGROUND',    (0,0), (0,0), TEAL_LIGHT),
    ('BACKGROUND',    (0,1), (0,1), RED_LIGHT),
    ('BOX',           (0,0), (-1,-1), 0.8, GREY_RULE),
    ('INNERGRID',     (0,0), (-1,-1), 0.4, GREY_RULE),
    ('VALIGN',        (0,0), (-1,-1), 'MIDDLE'),
    ('TOPPADDING',    (0,0), (-1,-1), 6),
    ('BOTTOMPADDING', (0,0), (-1,-1), 6),
    ('LEFTPADDING',   (0,0), (-1,-1), 6),
    ('RIGHTPADDING',  (0,0), (-1,-1), 6),
]))
elements.append(risk_tbl)
elements.append(sp(1))
elements.append(Paragraph(
    "* For higher-risk infants: additional virologic testing at birth AND 2–4 weeks after cessation of ARV prophylaxis (8–10 weeks of life)",
    sNote
))
elements.append(sp(3))

# ═══════════════════════════════════════════════════════
# SECTION 3 — DIAGNOSIS
# ═══════════════════════════════════════════════════════
elements.append(section_header("3.  DIAGNOSIS", bg=PURPLE_DARK))
elements.append(sp(2))

elements.append(banner_box(
    "<b>KEY RULE:</b> In infants <18 months, maternal IgG antibodies cross the placenta — "
    "standard HIV antibody tests are UNRELIABLE. Use virologic (PCR/NAAT) testing only.",
    bg=PURPLE_LIGHT, border=PURPLE_DARK,
    style=S('bx', fontSize=8.5, textColor=GREY_DARK, leading=12)
))
elements.append(sp(2))

# Testing by age
diag_rows = [
    ["<b>< 18 months</b>", "HIV-1 DNA PCR or HIV RNA PCR (NAAT)",
     "2 positive virologic tests confirm infection.\nAntibody testing unreliable (maternal IgG)."],
    ["<b>≥ 18 months</b>", "4th-gen HIV Ag/Ab combo assay",
     "Standard serology valid. Confirm positive screen with supplemental test."],
    ["<b>Acute retroviral syndrome</b>", "HIV Ag/Ab immunoassay + HIV RNA NAAT",
     "Do NOT assume negative antibody = uninfected. RNA NAAT needed for acute infection."],
]
diag_tbl = Table(
    [[Paragraph(h, sTableHead) for h in ["Age / Situation", "Test of Choice", "Notes"]]] +
    [[Paragraph(r[0], sTableCell), Paragraph(r[1], sTableCell), Paragraph(r[2], sTableCell)] for r in diag_rows],
    colWidths=[30*mm, 60*mm, W-93*mm]
)
diag_tbl.setStyle(TableStyle([
    ('BACKGROUND',    (0,0), (-1,0), PURPLE_DARK),
    ('TEXTCOLOR',     (0,0), (-1,0), WHITE),
    ('FONTNAME',      (0,0), (-1,0), 'Helvetica-Bold'),
    ('GRID',          (0,0), (-1,-1), 0.4, GREY_RULE),
    ('ROWBACKGROUNDS',(0,1), (-1,-1), [WHITE, PURPLE_LIGHT]),
    ('VALIGN',        (0,0), (-1,-1), 'TOP'),
    ('TOPPADDING',    (0,0), (-1,-1), 5),
    ('BOTTOMPADDING', (0,0), (-1,-1), 5),
    ('LEFTPADDING',   (0,0), (-1,-1), 5),
    ('RIGHTPADDING',  (0,0), (-1,-1), 5),
]))
elements.append(diag_tbl)
elements.append(sp(2))

# Testing Schedule
elements.append(Paragraph("<b>Recommended Virologic Testing Schedule for HIV-Exposed Infants</b>", sBody))
elements.append(sp(1))
sched_rows = [
    ["Birth", "Higher-risk infants only", "If positive — repeat ASAP; initiate ART"],
    ["14–21 days", "All exposed infants", "First routine test"],
    ["1–2 months", "All exposed infants", "—"],
    ["4–6 months", "All exposed infants", "If negative × 2 after 1 month AND not breastfeeding → presumptive uninfected"],
    ["8–10 weeks*", "Higher-risk infants", "2–4 weeks after cessation of ARV prophylaxis"],
    ["≥18 months", "All exposed children", "Confirmatory antibody test if prior virologic tests negative"],
]
sched_tbl = make_table(
    ["Timepoint", "Population", "Action if Positive"],
    sched_rows,
    [28*mm, 50*mm, W-81*mm],
    header_bg=PURPLE_DARK
)
elements.append(sched_tbl)
elements.append(sp(3))

# ═══════════════════════════════════════════════════════
# SECTION 4 — CLINICAL MANIFESTATIONS
# ═══════════════════════════════════════════════════════
elements.append(section_header("4.  CLINICAL MANIFESTATIONS OF PEDIATRIC HIV", bg=RED_DARK))
elements.append(sp(2))

def symptom_col(title, items, bg, border):
    content = [Paragraph(f"<b>{title}</b>",
                         S('st2', fontSize=8.5, textColor=border, fontName='Helvetica-Bold', leading=12))]
    for item in items:
        content.append(Paragraph(f"• {item}", sBullet))
    tbl = Table([content], colWidths=[(W/3)-2*mm])
    tbl.setStyle(TableStyle([
        ('BACKGROUND',    (0,0), (-1,-1), bg),
        ('BOX',           (0,0), (-1,-1), 1, border),
        ('TOPPADDING',    (0,0), (-1,-1), 6),
        ('BOTTOMPADDING', (0,0), (-1,-1), 6),
        ('LEFTPADDING',   (0,0), (-1,-1), 7),
        ('RIGHTPADDING',  (0,0), (-1,-1), 7),
    ]))
    return tbl

col1 = symptom_col("Constitutional", [
    "Recurrent unexplained fevers",
    "Failure to thrive / poor weight gain",
    "Generalized lymphadenopathy",
    "Hepatomegaly & splenomegaly",
    "Parotitis",
    "Chronic diarrhea",
], RED_LIGHT, RED_DARK)

col2 = symptom_col("Neurological / Pulmonary", [
    "Encephalopathy (most serious)",
    "Developmental delay / regression",
    "Hyperreflexia, hypertonia, floppiness",
    "Psychiatric disorders (adolescence)",
    "Lymphoid interstitial pneumonia (LIP)",
    "PCP (Pneumocystis jirovecii)",
], BLUE_LIGHT, BLUE_DARK)

col3 = symptom_col("Infections / Malignancies", [
    "Persistent oral & diaper candidiasis",
    "Recurrent invasive bacterial infections",
    "CMV, HSV, VZV reactivation",
    "M. avium complex (MAC)",
    "Cryptococcal meningitis",
    "Burkitt lymphoma, Leiomyosarcoma",
], PURPLE_LIGHT, PURPLE_DARK)

three_col = Table([[col1, col2, col3]], colWidths=[(W/3)-1*mm, (W/3)-1*mm, (W/3)])
three_col.setStyle(TableStyle([
    ('VALIGN',        (0,0), (-1,-1), 'TOP'),
    ('LEFTPADDING',   (0,0), (-1,-1), 1),
    ('RIGHTPADDING',  (0,0), (-1,-1), 1),
    ('TOPPADDING',    (0,0), (-1,-1), 0),
    ('BOTTOMPADDING', (0,0), (-1,-1), 0),
]))
elements.append(three_col)
elements.append(sp(2))

elements.append(banner_box(
    "<b>IRIS (Immune Reconstitution Inflammatory Syndrome):</b> Paradoxical clinical deterioration "
    "shortly after ART initiation as cell-mediated immunity is restored. Common triggers: "
    "Mycobacteria (TB, BCG), herpesviruses, Cryptococcus. Monitor closely in the first weeks of ART.",
    bg=ORANGE_LIGHT, border=ORANGE_DARK,
    style=S('iris', fontSize=8, textColor=GREY_DARK, leading=12)
))
elements.append(sp(3))

# ═══════════════════════════════════════════════════════
# SECTION 5 — ART DRUG CLASSES
# ═══════════════════════════════════════════════════════
elements.append(section_header("5.  ANTIRETROVIRAL DRUG CLASSES & MECHANISMS", bg=TEAL_DARK))
elements.append(sp(2))

art_rows = [
    ["NRTIs\n(Nucleoside/Nucleotide RTIs)",
     "Competitive inhibition of reverse transcriptase; chain termination — block RNA→DNA conversion",
     "Tenofovir (TDF/TAF), Zidovudine (ZDV/AZT), Lamivudine (3TC), Emtricitabine (FTC), Abacavir (ABC)"],
    ["NNRTIs\n(Non-Nucleoside RTIs)",
     "Non-competitive allosteric inhibition of reverse transcriptase",
     "Efavirenz (EFV), Rilpivirine, Nevirapine, Doravirine\n⚠ HIV-2 is intrinsically resistant"],
    ["PIs\n(Protease Inhibitors)",
     "Block viral protease; prevent Gag/Pol polyprotein cleavage → immature non-infectious virions",
     "Ritonavir (pharmacokinetic booster), Lopinavir/r, Atazanavir, Darunavir"],
    ["INSTIs\n(Integrase Strand Transfer Inhibitors)",
     "Block integration of proviral DNA into host genome; preferred class in modern regimens",
     "Dolutegravir (DTG) ★ preferred, Raltegravir, Bictegravir, Cabotegravir"],
    ["Fusion Inhibitors",
     "Block gp41-mediated membrane fusion between HIV and target cell",
     "Enfuvirtide (T-20)\n⚠ HIV-2 intrinsically resistant"],
    ["CCR5 Antagonists\n(Entry Inhibitors)",
     "Block CCR5 coreceptor; prevent R5-tropic HIV entry. Tropism testing required before use.",
     "Maraviroc"],
]

art_tbl = Table(
    [[Paragraph(h, sTableHead) for h in ["Drug Class", "Mechanism of Action", "Key Agents"]]] +
    [[Paragraph(r[0], S('tc2', fontSize=7.8, fontName='Helvetica-Bold', textColor=TEAL_DARK, leading=11)),
      Paragraph(r[1], sTableCell),
      Paragraph(r[2], sTableCell)] for r in art_rows],
    colWidths=[38*mm, 72*mm, W-113*mm]
)
art_tbl.setStyle(TableStyle([
    ('BACKGROUND',    (0,0), (-1,0), TEAL_DARK),
    ('TEXTCOLOR',     (0,0), (-1,0), WHITE),
    ('FONTNAME',      (0,0), (-1,0), 'Helvetica-Bold'),
    ('GRID',          (0,0), (-1,-1), 0.4, GREY_RULE),
    ('ROWBACKGROUNDS',(0,1), (-1,-1), [WHITE, TEAL_LIGHT]),
    ('VALIGN',        (0,0), (-1,-1), 'TOP'),
    ('TOPPADDING',    (0,0), (-1,-1), 5),
    ('BOTTOMPADDING', (0,0), (-1,-1), 5),
    ('LEFTPADDING',   (0,0), (-1,-1), 5),
    ('RIGHTPADDING',  (0,0), (-1,-1), 5),
]))
elements.append(art_tbl)
elements.append(sp(3))

# ═══════════════════════════════════════════════════════
# PAGE 2
# ═══════════════════════════════════════════════════════
elements.append(PageBreak())

# ── PAGE 2 MINI HEADER ────────────────────────────────
pg2_hdr = Table(
    [[Paragraph("PEDIATRIC HIV QUICK REFERENCE  —  Page 2", 
                S('ph', fontSize=9, textColor=WHITE, fontName='Helvetica-Bold',
                  alignment=TA_LEFT))]],
    colWidths=[W]
)
pg2_hdr.setStyle(TableStyle([
    ('BACKGROUND',    (0,0), (-1,-1), BLUE_DARK),
    ('TOPPADDING',    (0,0), (-1,-1), 5),
    ('BOTTOMPADDING', (0,0), (-1,-1), 5),
    ('LEFTPADDING',   (0,0), (-1,-1), 10),
    ('RIGHTPADDING',  (0,0), (-1,-1), 10),
    ('LINEBELOW',     (0,0), (-1,-1), 2, RED_DARK),
]))
elements.append(pg2_hdr)
elements.append(sp(3))

# ═══════════════════════════════════════════════════════
# SECTION 6 — ART REGIMENS
# ═══════════════════════════════════════════════════════
elements.append(section_header("6.  ART REGIMENS — WHEN TO START & FIRST-LINE CHOICES", bg=BLUE_DARK))
elements.append(sp(2))

# When to start
start_box_data = [
    Paragraph("<b>WHEN TO START ART</b>", S('ws', fontSize=9, textColor=BLUE_DARK, fontName='Helvetica-Bold', leading=12)),
    Paragraph("ART is indicated for ALL HIV-infected individuals — infants, children, adolescents, and adults — "
              "regardless of CD4 count. Initiate as soon as possible after diagnosis is confirmed.", sBody),
    sp(1),
    Paragraph("• <b>Infants:</b> Start ART immediately after confirmed positive virologic test", sBullet),
    Paragraph("• <b>Children:</b> ART regardless of CD4 count or clinical stage", sBullet),
    Paragraph("• <b>Adolescents/Adults:</b> ART for all, regardless of CD4 count, once medication readiness is confirmed", sBullet),
    Paragraph("• <b>Goal:</b> HIV RNA undetectable (<50 copies/mL) and maintained indefinitely", sBullet),
    Paragraph("• <b>Minimum:</b> At least 3 active drugs from ≥2 drug classes", sBullet),
    Paragraph("• <b>Before starting:</b> ARV resistance testing (viral genotyping) is recommended", sBullet),
]
start_box = Table([start_box_data], colWidths=[W])
start_box.setStyle(TableStyle([
    ('BACKGROUND',    (0,0), (-1,-1), BLUE_LIGHT),
    ('BOX',           (0,0), (-1,-1), 1.2, BLUE_MED),
    ('TOPPADDING',    (0,0), (-1,-1), 7),
    ('BOTTOMPADDING', (0,0), (-1,-1), 7),
    ('LEFTPADDING',   (0,0), (-1,-1), 10),
    ('RIGHTPADDING',  (0,0), (-1,-1), 10),
]))
elements.append(start_box)
elements.append(sp(2))

regimen_rows = [
    ["Adults & Adolescents\n(Preferred, WHO/US)",
     "TDF (or TAF) + FTC (or 3TC) + DTG",
     "Dolutegravir-based; <$45/patient/year in LMICs.\nFixed-dose combination tablet available."],
    ["Adults — Alternative",
     "ABC/3TC + DTG  or  TAF/FTC + BIC  or  TAF/FTC + RPV",
     "ABC/3TC: check HLA-B*5701 first (abacavir hypersensitivity risk)"],
    ["Children (age/weight-based)",
     "Consult pediatric HIV specialist + current NIH guidelines",
     "clinicalinfo.hiv.gov/en/guidelines/pediatric-arv"],
    ["Infants <4 weeks",
     "ZDV + 3TC + NVP (or LPV/r)",
     "Lopinavir/r preferred if possible; NVP if LPV/r unavailable"],
    ["Infants 4 weeks – 3 years",
     "ABC or ZDV + 3TC + LPV/r\nor RAL-based if <4 weeks",
     "LPV/r is preferred PI backbone in young children"],
    ["Pregnancy / PMTCT",
     "Continue/start effective ART immediately\nZDV + 3TC + LPV/r or TDF/FTC + DTG",
     "ZDV for infant prophylaxis × 4–6 weeks. Breastfeeding DISCOURAGED (CDC)."],
]
regimen_tbl = Table(
    [[Paragraph(h, sTableHead) for h in ["Population", "Preferred Regimen", "Notes"]]] +
    [[Paragraph(r[0], S('rp', fontSize=8, fontName='Helvetica-Bold', textColor=BLUE_DARK, leading=11)),
      Paragraph(r[1], S('rr', fontSize=8.5, fontName='Helvetica-Bold', textColor=TEAL_DARK, leading=11)),
      Paragraph(r[2], sTableCell)] for r in regimen_rows],
    colWidths=[42*mm, 65*mm, W-110*mm]
)
regimen_tbl.setStyle(TableStyle([
    ('BACKGROUND',    (0,0), (-1,0), BLUE_DARK),
    ('TEXTCOLOR',     (0,0), (-1,0), WHITE),
    ('FONTNAME',      (0,0), (-1,0), 'Helvetica-Bold'),
    ('GRID',          (0,0), (-1,-1), 0.4, GREY_RULE),
    ('ROWBACKGROUNDS',(0,1), (-1,-1), [WHITE, BLUE_LIGHT]),
    ('VALIGN',        (0,0), (-1,-1), 'TOP'),
    ('TOPPADDING',    (0,0), (-1,-1), 5),
    ('BOTTOMPADDING', (0,0), (-1,-1), 5),
    ('LEFTPADDING',   (0,0), (-1,-1), 5),
    ('RIGHTPADDING',  (0,0), (-1,-1), 5),
]))
elements.append(regimen_tbl)
elements.append(sp(3))

# ═══════════════════════════════════════════════════════
# SECTION 7 — WHEN TO CHANGE ART
# ═══════════════════════════════════════════════════════
elements.append(section_header("7.  WHEN TO CHANGE ART & TREATMENT FAILURE", bg=ORANGE_DARK))
elements.append(sp(2))

change_rows = [
    ["Virologic Failure", "Detectable HIV RNA on therapy (confirm × 2); most common failure type",
     "Check adherence first → genotype resistance testing → switch ≥2 active drugs"],
    ["Immunologic Failure", "Declining CD4 count despite ART; CD4 <200 in child previously higher",
     "Distinguish from IRIS; intensify regimen if confirmed failure"],
    ["Clinical Failure", "New or recurrent WHO Stage 3/4 event after ≥6 months ART",
     "Evaluate for OIs; confirm virologic failure before switching"],
    ["Toxicity / Intolerance", "Adverse drug effects limiting adherence or causing harm",
     "Substitute single offending drug if possible; maintain backbone"],
    ["Drug Resistance", "Resistance mutations on genotyping",
     "Select ≥2 fully active agents; consult expert"],
    ["Better Regimen Available", "New formulations, fixed-dose combos, or superior tolerability profile",
     "Simplification or optimization; maintain viral suppression during switch"],
]
change_tbl = make_table(
    ["Reason to Change", "Definition / Trigger", "Action"],
    change_rows,
    [38*mm, 70*mm, W-111*mm],
    header_bg=ORANGE_DARK
)
elements.append(change_tbl)
elements.append(sp(3))

# ═══════════════════════════════════════════════════════
# SECTION 8 — MONITORING
# ═══════════════════════════════════════════════════════
elements.append(section_header("8.  MONITORING ON ART", bg=TEAL_DARK))
elements.append(sp(2))

mon_rows = [
    ["HIV RNA (Viral Load)",
     "Primary measure of ART efficacy",
     "At baseline, 2–4 weeks after starting, then every 3–6 months once suppressed.\nGoal: <50 copies/mL"],
    ["CD4+ T-cell Count",
     "Immune status; primary indicator of disease progression.\nAge-adjust in children.",
     "At baseline; every 3–6 months initially; every 6–12 months once stable on ART with suppressed VL"],
    ["ARV Resistance Genotyping",
     "Guide regimen selection; detect transmitted resistance",
     "Before starting ART AND at virologic failure"],
    ["CBC + Differential",
     "Monitor for ZDV-associated anemia/neutropenia; baseline cytopenias",
     "Baseline; monitor per regimen"],
    ["Renal Function (Cr, eGFR, urine)",
     "TDF nephrotoxicity (Fanconi syndrome); TAF preferred if renal disease",
     "Baseline; every 6–12 months on TDF-containing regimen"],
    ["Liver Function Tests",
     "Hepatotoxicity (NVP, EFV); hepatitis B co-infection (TDF has anti-HBV activity)",
     "Baseline; periodic monitoring; check HBV/HCV status"],
    ["Fasting Lipids & Glucose",
     "PI/INSTI metabolic effects; cardiovascular risk",
     "Baseline; annually; more often if abnormal"],
    ["HLA-B*5701",
     "Required BEFORE prescribing Abacavir (ABC); positive → do NOT use ABC",
     "Once before initiating ABC-containing regimen"],
    ["OI Prophylaxis Thresholds",
     "Cotrimoxazole (PCP/Toxo prophylaxis); Azithromycin (MAC prophylaxis)",
     "Cotrimoxazole: all HIV-infected children <5 yrs regardless of CD4;\n≥5 yrs if CD4 <200. MAC: CD4 <50 cells/μL"],
    ["Growth & Development",
     "Height, weight, head circumference (infants); neurodevelopment milestones",
     "Every visit; plot on growth charts; address FTT actively"],
]
mon_tbl = Table(
    [[Paragraph(h, sTableHead) for h in ["Parameter", "Purpose", "Schedule / Target"]]] +
    [[Paragraph(r[0], S('mp', fontSize=7.8, fontName='Helvetica-Bold', textColor=TEAL_DARK, leading=11)),
      Paragraph(r[1], sTableCell),
      Paragraph(r[2], sTableCell)] for r in mon_rows],
    colWidths=[40*mm, 65*mm, W-108*mm]
)
mon_tbl.setStyle(TableStyle([
    ('BACKGROUND',    (0,0), (-1,0), TEAL_DARK),
    ('TEXTCOLOR',     (0,0), (-1,0), WHITE),
    ('FONTNAME',      (0,0), (-1,0), 'Helvetica-Bold'),
    ('GRID',          (0,0), (-1,-1), 0.4, GREY_RULE),
    ('ROWBACKGROUNDS',(0,1), (-1,-1), [WHITE, TEAL_LIGHT]),
    ('VALIGN',        (0,0), (-1,-1), 'TOP'),
    ('TOPPADDING',    (0,0), (-1,-1), 4),
    ('BOTTOMPADDING', (0,0), (-1,-1), 4),
    ('LEFTPADDING',   (0,0), (-1,-1), 5),
    ('RIGHTPADDING',  (0,0), (-1,-1), 5),
]))
elements.append(mon_tbl)
elements.append(sp(3))

# ═══════════════════════════════════════════════════════
# SECTION 9 — OI PROPHYLAXIS
# ═══════════════════════════════════════════════════════
elements.append(section_header("9.  OPPORTUNISTIC INFECTION PROPHYLAXIS IN CHILDREN", bg=RED_DARK))
elements.append(sp(2))

oi_rows = [
    ["Pneumocystis jirovecii (PCP)",
     "Cotrimoxazole (TMP-SMX)",
     "ALL HIV-infected children <5 yrs, regardless of CD4.\n≥5 yrs: if CD4 <200 cells/μL or CD4% <15%",
     "Discontinue when CD4 ≥200 sustained ≥3 months on ART"],
    ["Toxoplasma gondii",
     "Cotrimoxazole (TMP-SMX)",
     "CD4 <100 cells/μL (adults/older children); cotrimoxazole covers both PCP + Toxo",
     "Discontinue when CD4 >200 for >3 months"],
    ["MAC (M. avium complex)",
     "Azithromycin 20 mg/kg/wk (max 1200 mg) or Clarithromycin",
     "CD4 <50 cells/μL (age-adjusted for young children)",
     "Discontinue when CD4 >100 for >3 months on ART"],
    ["Cryptococcal meningitis",
     "Fluconazole",
     "Screen serum CrAg if CD4 <100; treat if positive even if asymptomatic",
     "Lifelong secondary prophylaxis after first episode"],
    ["Tuberculosis (TB)",
     "Isoniazid (INH) preventive therapy (IPT)",
     "All HIV-infected children in endemic settings, regardless of tuberculin test result",
     "6–36 months depending on guidelines; manage INH-ARV interactions"],
    ["CMV Retinitis",
     "Valganciclovir / Ganciclovir",
     "Treatment, not primary prophylaxis. Screen by fundoscopy if CD4 <50",
     "Maintenance therapy until CD4 >100 sustained ≥3–6 months"],
]
oi_tbl = Table(
    [[Paragraph(h, sTableHead) for h in ["Pathogen", "Drug", "Indication", "Stopping Rule"]]] +
    [[Paragraph(r[0], S('op', fontSize=7.5, fontName='Helvetica-Bold', textColor=RED_DARK, leading=10)),
      Paragraph(r[1], sTableCell),
      Paragraph(r[2], sTableCell),
      Paragraph(r[3], sTableCell)] for r in oi_rows],
    colWidths=[32*mm, 35*mm, 60*mm, W-130*mm]
)
oi_tbl.setStyle(TableStyle([
    ('BACKGROUND',    (0,0), (-1,0), RED_DARK),
    ('TEXTCOLOR',     (0,0), (-1,0), WHITE),
    ('FONTNAME',      (0,0), (-1,0), 'Helvetica-Bold'),
    ('GRID',          (0,0), (-1,-1), 0.4, GREY_RULE),
    ('ROWBACKGROUNDS',(0,1), (-1,-1), [WHITE, RED_LIGHT]),
    ('VALIGN',        (0,0), (-1,-1), 'TOP'),
    ('TOPPADDING',    (0,0), (-1,-1), 4),
    ('BOTTOMPADDING', (0,0), (-1,-1), 4),
    ('LEFTPADDING',   (0,0), (-1,-1), 5),
    ('RIGHTPADDING',  (0,0), (-1,-1), 5),
]))
elements.append(oi_tbl)
elements.append(sp(3))

# ═══════════════════════════════════════════════════════
# SECTION 10 — CDC CLASSIFICATION
# ═══════════════════════════════════════════════════════
elements.append(section_header("10.  CDC CLASSIFICATION & IMMUNOLOGIC CATEGORIES", bg=GREY_DARK))
elements.append(sp(2))

cdc_left_data = [
    [Paragraph("CD4 Category", sTableHead), Paragraph("Count", sTableHead), Paragraph("Significance", sTableHead)],
    [Paragraph("1 – No suppression", sTableCell),
     Paragraph("≥500 cells/μL\n(or ≥25% in <5 yrs)", sTableCell),
     Paragraph("Intact immunity", sTableCell)],
    [Paragraph("2 – Moderate suppression", sTableCell),
     Paragraph("200–499 cells/μL\n(15–24% in <5 yrs)", sTableCell),
     Paragraph("Moderate risk OIs", sTableCell)],
    [Paragraph("3 – Severe suppression (AIDS)", S('red', fontSize=7.8, textColor=RED_DARK, fontName='Helvetica-Bold', leading=10.5)),
     Paragraph("<200 cells/μL\n(<15% in <5 yrs)", S('red2', fontSize=7.8, textColor=RED_DARK, leading=10.5)),
     Paragraph("High risk OIs; AIDS diagnosis", S('red3', fontSize=7.8, textColor=RED_DARK, leading=10.5))],
]
cdc_tbl = Table(cdc_left_data, colWidths=[45*mm, 38*mm, (W/2)-88*mm])
cdc_tbl.setStyle(TableStyle([
    ('BACKGROUND',    (0,0), (-1,0), GREY_DARK),
    ('TEXTCOLOR',     (0,0), (-1,0), WHITE),
    ('FONTNAME',      (0,0), (-1,0), 'Helvetica-Bold'),
    ('BACKGROUND',    (0,3), (-1,3), RED_LIGHT),
    ('GRID',          (0,0), (-1,-1), 0.4, GREY_RULE),
    ('VALIGN',        (0,0), (-1,-1), 'TOP'),
    ('TOPPADDING',    (0,0), (-1,-1), 5),
    ('BOTTOMPADDING', (0,0), (-1,-1), 5),
    ('LEFTPADDING',   (0,0), (-1,-1), 5),
    ('RIGHTPADDING',  (0,0), (-1,-1), 5),
]))

note_right = [
    Paragraph("<b>Important Notes on CD4 in Children</b>",
              S('cn', fontSize=8.5, textColor=GREY_DARK, fontName='Helvetica-Bold', leading=12)),
    sp(1),
    Paragraph("• Children normally have HIGHER CD4 counts than adults — age-adjustment is required", sBullet),
    Paragraph("• CD4 percentage is more reliable than absolute count in young children", sBullet),
    Paragraph("• Viral load is the primary measure of ART efficacy; CD4 count measures immune status", sBullet),
    Paragraph("• Viral set point (established after acute infection) predicts rate of CD4 decline", sBullet),
    Paragraph("• Long-term nonprogressors: ~1% remain asymptomatic >10 years with stable CD4", sBullet),
]
note_box = Table([note_right], colWidths=[(W/2)+4*mm])
note_box.setStyle(TableStyle([
    ('BACKGROUND',    (0,0), (-1,-1), GREY_LIGHT),
    ('BOX',           (0,0), (-1,-1), 0.8, GREY_RULE),
    ('TOPPADDING',    (0,0), (-1,-1), 7),
    ('BOTTOMPADDING', (0,0), (-1,-1), 7),
    ('LEFTPADDING',   (0,0), (-1,-1), 8),
    ('RIGHTPADDING',  (0,0), (-1,-1), 8),
]))

two_col2 = Table([[cdc_tbl, note_box]], colWidths=[(W/2)-3*mm, (W/2)+3*mm])
two_col2.setStyle(TableStyle([
    ('VALIGN',        (0,0), (-1,-1), 'TOP'),
    ('LEFTPADDING',   (0,0), (-1,-1), 0),
    ('RIGHTPADDING',  (0,0), (-1,-1), 0),
    ('TOPPADDING',    (0,0), (-1,-1), 0),
    ('BOTTOMPADDING', (0,0), (-1,-1), 0),
]))
elements.append(two_col2)
elements.append(sp(3))

# ═══════════════════════════════════════════════════════
# SECTION 11 — QUICK REFERENCE CHECKLIST
# ═══════════════════════════════════════════════════════
elements.append(section_header("11.  CLINICAL CHECKLIST — HIV-EXPOSED / INFECTED CHILD", bg=BLUE_DARK))
elements.append(sp(2))

check_items_col1 = [
    ("DIAGNOSIS", [
        "Virologic test (HIV DNA/RNA PCR) at 14–21 days if <18 months",
        "Repeat at 1–2 months and 4–6 months",
        "Confirmatory antibody test at ≥18 months",
        "Assess maternal risk category (low vs. higher risk)",
        "Order ARV resistance genotyping before starting ART",
    ]),
    ("ART INITIATION", [
        "Start ART immediately after confirmed diagnosis — all ages, all CD4 counts",
        "Select age/weight-appropriate regimen",
        "Educate caregiver on adherence — critical for viral suppression",
        "Check HLA-B*5701 before prescribing Abacavir",
        "Enroll in clinical trial if available",
    ]),
]

check_items_col2 = [
    ("MONITORING", [
        "HIV RNA at baseline, 2–4 wks after ART start, then q3–6 months",
        "CD4 count at baseline; q3–6 months initially; q6–12 months when stable",
        "CBC, LFTs, renal function at baseline and per regimen",
        "Fasting lipids and glucose annually",
        "Growth parameters and neurodevelopmental assessment every visit",
    ]),
    ("PROPHYLAXIS & PREVENTION", [
        "Cotrimoxazole: all children <5 yrs with HIV (regardless of CD4)",
        "MAC prophylaxis if CD4 <50 cells/μL",
        "Screen for TB; offer INH preventive therapy in endemic areas",
        "Advise against breastfeeding (CDC)",
        "Ensure immunizations are up to date (live vaccines may need timing consideration)",
    ]),
]

def checklist_box(items_list, bg, border):
    content = []
    for section_title, bullets in items_list:
        content.append(Paragraph(f"<b>{section_title}</b>",
                                  S('ct', fontSize=8, fontName='Helvetica-Bold',
                                    textColor=border, leading=12)))
        for b in bullets:
            content.append(Paragraph(f"☐  {b}", sBullet))
        content.append(sp(1))
    tbl = Table([content], colWidths=[(W/2)-3*mm])
    tbl.setStyle(TableStyle([
        ('BACKGROUND',    (0,0), (-1,-1), bg),
        ('BOX',           (0,0), (-1,-1), 1, border),
        ('TOPPADDING',    (0,0), (-1,-1), 7),
        ('BOTTOMPADDING', (0,0), (-1,-1), 7),
        ('LEFTPADDING',   (0,0), (-1,-1), 8),
        ('RIGHTPADDING',  (0,0), (-1,-1), 8),
    ]))
    return tbl

check_left  = checklist_box(check_items_col1, BLUE_LIGHT, BLUE_DARK)
check_right = checklist_box(check_items_col2, TEAL_LIGHT, TEAL_DARK)

two_check = Table([[check_left, check_right]], colWidths=[(W/2)-2*mm, (W/2)+2*mm])
two_check.setStyle(TableStyle([
    ('VALIGN',        (0,0), (-1,-1), 'TOP'),
    ('LEFTPADDING',   (0,0), (-1,-1), 0),
    ('RIGHTPADDING',  (0,0), (-1,-1), 0),
    ('TOPPADDING',    (0,0), (-1,-1), 0),
    ('BOTTOMPADDING', (0,0), (-1,-1), 0),
]))
elements.append(two_check)
elements.append(sp(3))

# ═══════════════════════════════════════════════════════
# FOOTER
# ═══════════════════════════════════════════════════════
elements.append(rule(GREY_RULE, 1))
elements.append(sp(1))
elements.append(Paragraph(
    "Sources: Red Book 2021 (AAP Committee on Infectious Diseases) | Harrison's Principles of Internal Medicine 22E (2025) | "
    "Robbins, Cotran & Kumar Pathologic Basis of Disease | Cellular & Molecular Immunology (Abbas et al.) | "
    "NIH AIDSinfo Guidelines (clinicalinfo.hiv.gov) | WHO HIV Guidelines.  "
    "This guide is a clinical quick-reference tool and does not replace specialist consultation. "
    "Always refer to current NIH pediatric ARV guidelines for up-to-date dosing recommendations.",
    sFooter
))

# ═══════════════════════════════════════════════════════
# BUILD
# ═══════════════════════════════════════════════════════
doc.build(elements)
print(f"PDF created: {OUTPUT}")

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