Explain microbiology of HIV and TB with effects on genital tract and pregnancy.

HIV and Tuberculosis

Start with one sentence for each organism, because everything else in this chapter is a consequence of it.

HIV is a virus that hides inside the immune cells meant to fight it, and copies itself there for life. That single fact explains why infection is lifelong, why treatment suppresses but never cures, why a blood marker (viral load) predicts who passes the virus on, and why the cervix, placenta and breast milk are all routes of transmission.

Tuberculosis is a slow, waxy-coated bacterium that survives inside the very cells sent to destroy it, and the body's attempt to wall it off is what causes the disease. That fact explains why TB hides for years, why immune suppression lets it reactivate, why diagnosis is slow, and why pregnancy and HIV both tip the balance towards active disease.

HIV and tuberculosis are core South African O&G infections because they sit at the intersection of microbiology, pregnancy physiology, cervical disease, contraception, breastfeeding, sepsis and maternal mortality. The Primary task is not to memorise treatment protocols. It is to understand why HIV persists, why viral load drives transmission, why TB can be missed in pregnancy, and why HIV/TB coinfection multiplies risk. Each section below presupposes only the one before it: we build the organism first, then its biology, then what that biology forces us to do clinically.

The exam answer should move from organism to clinical consequence:

HIV replication -> immune injury -> high viral load and genital tract shedding -> vertical and sexual transmission risk -> ART suppresses replication -> transmission and maternal disease risk fall.

Mycobacterium tuberculosis inhalation -> macrophage survival -> granuloma and latency -> reactivation or progressive disease when immunity shifts -> pulmonary or extrapulmonary disease -> maternal illness, fetal growth and neonatal exposure risk.

HIV: the Organism

Build up from the particle itself. HIV is an enveloped, positive-sense single-stranded RNA retrovirus. Inside its envelope sit two copies of an RNA genome of only about ten thousand bases, plus the enzymes the virus needs to hijack a cell. That genome encodes, among others, three proteins worth knowing by name because each is both a step in the life cycle and a drug target: reverse transcriptase (copies RNA into DNA), integrase (splices that DNA into our chromosomes) and protease (cuts the long viral polyproteins into working parts).

The "retro" in retrovirus is the whole story. Normal biology runs DNA -> RNA -> protein. HIV runs it backwards at the first step: its enzyme reverse transcriptase copies viral RNA into DNA, and integrase then stitches that DNA permanently into the host genome as a provirus. Once integrated, the provirus is treated by the cell as part of its own blueprint. This is why infection is lifelong and why even perfect therapy cannot delete the virus: you cannot un-write a gene the cell now copies as its own. Treatment stops new replication; it does not erase the integrated reservoir.

Reverse transcriptase has no proofreading, so it makes frequent copying errors. Each error is a mutation. When replication continues under drug pressure, this error-prone copying is exactly what generates drug-resistant variants — a basic-science fact with direct clinical consequence: adherence keeps replication low, and low replication means fewer chances to mutate to resistance.

How does the virus get into a cell at all? The envelope carries a glycoprotein spike. Its outer part (gp120) grips the CD4 receptor, which is displayed mainly on helper T cells, macrophages and dendritic cells. CD4 binding alone is not enough; gp120 must then engage a second receptor, a co-receptor (usually CCR5 early in infection, sometimes CXCR4 later). Only when both CD4 and a co-receptor are engaged does the inner part of the spike (gp41) fuse the viral envelope with the cell membrane and let the genome in. This two-key entry mechanism explains the cellular target (CD4-bearing cells), the basis of one class of prevention drugs, and why depleting CD4 cells is the central injury of HIV.

HIV-1 causes most infection in South Africa. HIV-2 is less transmissible and more geographically concentrated in West Africa, but the retroviral principles are the same.

HIV Pathogenesis

Now follow the infection through time, because the same virus behaves very differently in week one versus year ten. HIV causes disease by infecting and depleting CD4 T cells, damaging lymphoid tissue, activating chronic inflammation and impairing mucosal immunity. The falling CD4 count explains susceptibility to opportunistic infections. The plasma viral load explains infectiousness and treatment response. Hold those two numbers apart: CD4 measures the damage, viral load measures the activity.

Untreated infection runs in three phases. In acute (primary) infection, the first few weeks after acquisition, the virus replicates explosively before antibodies appear; viral load is at its lifetime peak and the person is intensely infectious, often with a flu-like or glandular-fever-like illness or none at all. Then the immune system partially catches up and the infection settles into a long chronic (clinical latency) phase, where viral load plateaus and CD4 cells fall slowly over years. Finally, when CD4 cells are depleted enough that the immune system can no longer hold opportunistic organisms in check, the person has advanced HIV disease (AIDS). Effective ART interrupts this trajectory at any point.

Two timing facts flow directly from this and matter enormously in pregnancy. First, antibody tests only turn positive after the immune system mounts a response — the window period. The earliest stage, before any test is positive, is the eclipse phase; then the viral protein p24 antigen and viral RNA become detectable days before antibody. This is why a fourth-generation antigen/antibody assay (which detects p24 as well as antibody) closes the window earlier than antibody alone, and why a single negative test cannot exclude very recent infection. Second, seroconversion — the appearance of antibody — is exactly the acute, high-viral-load window. A woman who acquires HIV during pregnancy or breastfeeding may therefore be at her most infectious to the fetus or infant precisely when a routine test still reads negative.