The following are the causes of HIV transmission: ^(1,2)

• Blood and blood-related products
• Contaminated injecting equipment(incl. Needle stick injuries and tattooing)
• Vaginal secretions
• Breastfeeding
• Semen
• Pregnancy and child delivery
• Tissue transplantation

After early 2-3 weeks of HIV infection, flu-like symptoms may manifest associated with ⁽³⁾

• Generalized body aches, weakness and fatigue
• Lymphadenopathy
• Fever with chills and rash
• Oral ulcers

Late or end-stage is manifested by AIDS. HIV treatment prolongs the delay of AIDS onset and improves prognosis. Contrary to that, untreated cases land into serious complications as follows: ⁽⁴⁾

• Unexplained weight loss and extreme fatigue
• Night sweats
• Opportunistic infections, i.e. pneumonia or TB
• Obvious lymphadenopathy
• Mood disorders and memory loss

Pathological mechanisms behind HIV and weight loss will help us understand clearly. Although there is no direct effect that causes weight, however, certain indirect factors will cause sudden unexplained weight loss in AIDS, i.e. 

CD4 molecules are present on the surface of T-lymphocytes; HIV attacks these molecules and replicates inside them, destroying these cells. ⁽⁵⁾

Gut-associated lymphoid tissues(GALT) are the major producers of CD4. HIV damages membrane permeability of intestinal mucosa and  causes CD4 reservoir depletion in these lymphoid tissues. ⁽⁶⁾

The normal CD4 cell count is 500-1500 cells/mm³. In contrast, in AIDS, it falls below 200 cells/mm³. ⁽⁷⁾

It is also associated with severe diarrhea and GIT disturbance, i.e.⁽⁸⁾

• Nausea
• Loss of appetite

Resultantly, the patient suffers from protein-energy malnutrition followed by cachexia or muscle wasting. It is one of the mechanisms that explains the HIV and weight loss relation.

HIV and weight loss are also interlinked due to superimposed or opportunistic infections, the major culprits, i.e.,⁽⁹⁾

• Tuberculosis
• Herpes simples
• Toxoplasmosis
• Pneumonia
• Cryptococcal meningitis
• Histoplasmosis

Evidently, infections and septicemia further increase metabolism, and each disease has a particular impact on organ functions.

Some of the above cause GIT disturbance, others cause mental disorders, and so on, indirectly impacting weight(most of the time, cause weight loss).

Cytokines are hormone-like polypeptides that have pleiotropic action on various cells. They play an essential role in the host defense mechanisms.

Not only do they act in an autocrine fashion, but they can also be endocrine(acting as hormones on distant organs/tissues).

In AIDS, cytokines increase proteolysis(protein breakdown) and alter energy expenditure, leading to wasting.

Some researchers also reveal that cytokines, TNF-α, and IL-1 promote HIV-1 gene expression and production. ^(10,11)

Weight loss in HIV of 5% doubles the mortality chances. So, weight management is of prime importance.

HAART has dramatically changed the treatment outcomes of HIV. In some patients, anti-retroviral therapy can further aggravate weight loss, but generally, HAART prolongs the delay of AIDS onset and can improve quality of life.

INSTIs (e.g., bictegravir and dolutegravir), when administered with tenofovir alafenamide fumarate(TAF), can strongly antagonize weight loss and even increase weight in some patients. ⁽¹²⁾

In the advanced stage of AIDS(CD4 cells<50/mm³), weight loss can be lethal. HIV causes anorexia, nausea, and malabsorption. In addition to ART, following diet/medications may help to prevent weight loss;⁽¹³⁾

• Marijuana and its derivatives
• Megestrol acetate (Megace ES)
• Dronabinol
• Sumatriptan
• Thalidomide
• Whey protein

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9. Justiz Vaillant AA, Naik R. HIV-1–Associated Opportunistic Infections. [Updated 2023 Jan 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539787/
10. Okamoto T., Matsuyama T., Mori S. Augmentation of human immunodeficiency virus type 1 gene expression by tumor necrosis factor-α. AIDS Res Hum Retroviruses. 1989;5:131. doi: 10.1089/aid.1989.5.131.
11. Poli G, Kinter AL, Fauci AS. Interleukin 1 induces expression of the human immunodeficiency virus alone and in synergy with interleukin 6 in chronically infected U1 cells: inhibition of inductive effects by the interleukin 1 receptor antagonist. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):108-12. doi: 10.1073/pnas.91.1.108. PMID: 7506410; PMCID: PMC42895.
12. Markakis, K.; Tsachouridou, O.; Georgianou, E.; Pilalas, D.; Nanoudis, S.; Metallidis, S. Weight Gain in HIV Adults Receiving Antiretroviral Treatment: Current Knowledge and Future Perspectives. Life2024, 14, 1367. https://doi.org/10.3390/life14111367
13. https://www.webmd.com/hiv-aids/aids-wasting-syndrome