HIV: treatment and what peptide research has shown

What is HIV and how many people have it?

The human immunodeficiency virus (HIV) attacks the immune system, especially CD4 cells, and without treatment can lead to acquired immunodeficiency syndrome (AIDS). According to the World Health Organization (WHO), 41.0 million people were living with HIV at the end of 2025, 64% of them in the WHO African Region, with about 1.2 million new infections and 570,000 HIV-related deaths that year¹.

Treatment has transformed the picture: among people living with HIV, 88% knew their status in 2025, 89% of those who knew were on antiretroviral therapy (ART), and 95% of those on ART had a suppressed viral load, close to the 95-95-95 targets¹. There is no cure: ART suppresses the virus and allows people to live long, healthy lives¹.

Symptoms and how HIV is diagnosed

Early infection can cause a flu-like illness with fever, headache, rash or sore throat, although many people have no symptoms. Later signs can include swollen lymph nodes, weight loss, fever, diarrhea and cough; without treatment, serious illnesses can develop, such as tuberculosis, cryptococcal meningitis, severe bacterial infections and some cancers¹.

Rapid tests give same-day results and self-tests are available. A positive result needs confirmatory testing before treatment starts. Antibodies usually appear within 28 days of infection, so a recent exposure with a negative result warrants a retest after 28 days. Children under 18 months need virological (nucleic acid) testing, because antibody tests are not sufficient for them¹.

Standard treatment today: what the guidelines recommend

The 2024 recommendations of the International Antiviral Society-USA state that ART is recommended for all people with HIV. For most, the initial regimen combines an integrase strand transfer inhibitor, specifically bictegravir or dolutegravir, with two (and in some cases one) nucleoside or nucleotide reverse transcriptase inhibitors. Long-acting injectable therapy is available for those who prefer not to take daily oral medication or who struggle with adherence³.

The WHO, in its update of 7 January 2026, keeps dolutegravir-based regimens as the preferred option for initial and subsequent treatment, includes long-acting injectable ART in specific circumstances, and names darunavir/ritonavir as the preferred protease inhibitor when one is needed².

Two studies explain why everyone is treated, and from diagnosis. In the START trial (4,685 adults with CD4 counts above 500 cells/mm³, mean follow-up 3.0 years), the composite end point of serious AIDS-related or non-AIDS-related events, or death, occurred in 42 patients (1.8%) with immediate initiation versus 96 (4.1%) with deferred initiation (hazard ratio 0.43; 95% CI 0.30 to 0.62)⁴. In the PARTNER study (1,166 serodifferent couples, 888 of them contributing 1,238 eligible couple-years), there were zero phylogenetically linked within-couple transmissions when the partner with HIV had fewer than 200 copies/mL, with an upper 95% confidence limit of 0.30 per 100 couple-years⁵.

This section is about the disease, not peptides: the first-line regimens mentioned are not peptides. What follows describes the limited place some peptides occupy.

What peptide research has shown: enfuvirtide, tesamorelin and thymosin α1

Enfuvirtide. It is a peptide that interferes with HIV-1 entry into cells by inhibiting fusion of the viral and cellular membranes; it binds the HR1 region of gp41⁸. According to the summary of its FDA label, it is used with other antiretrovirals in treatment-experienced patients with evidence of viral replication despite ongoing therapy⁸. The pivotal trials were TORO 1 and TORO 2. In TORO 1 (501 randomized in the Americas), at 24 weeks viral load fell 1.696 log10 copies/mL with enfuvirtide plus an optimized background regimen versus 0.764 with the regimen alone, and CD4 counts rose 76 versus 32 cells/mm³⁶. In TORO 2 (512 randomized in Europe and Australia), the fall was 1.429 versus 0.648 log10 (difference 0.781; P<0.001) and the CD4 increase 65.5 versus 38.0 cells/mm³ (P=0.02)⁷. These patients had multiple prior failures and resistance, so this evidence does not apply to initial treatment.

Tesamorelin. It is a synthetic analogue of growth hormone-releasing hormone. The FDA approved it on November 10, 2010 as the first treatment for excess abdominal fat in adults with HIV and lipodystrophy, based on two placebo-controlled trials of 816 adults¹⁶. The precision matters: the indication is reduction of abdominal fat associated with lipodystrophy, not treatment of HIV infection¹⁵.

In the first trial (412 people, 26 weeks), visceral fat measured by CT fell 15.2% with tesamorelin and rose 5.0% with placebo; triglycerides fell 50 mg/dL versus a 9 mg/dL rise; IGF-I rose 81.0%; and glycemic measures did not differ significantly, although more patients in the active group withdrew because of adverse events⁹. In the pooled analysis of the two phase 3 trials (806 people), visceral fat fell 24 cm² versus a 2 cm² rise (treatment effect -15.4%), and the reduction was maintained to 52 weeks in those who continued¹⁰. A later analysis showed that people who achieved at least an 8% reduction in visceral fat had better triglycerides and less worsening of glucose than non-responders¹¹. A 2026 meta-analysis of four trials and 909 patients estimated a mean difference of -21.47 cm² in visceral fat (95% CI -34.73 to -8.22), -1.61 cm in waist and +1.42 kg of lean mass, with higher treatment discontinuation (RR 2.25; 95% CI 0.98 to 5.17; P=0.06)¹⁴.

Outside the approved indication, a randomized trial of 61 people with HIV and metabolic-associated fatty liver disease found an absolute reduction in liver fat of 4.1 percentage points (95% CI -7.6 to -0.7) with tesamorelin versus placebo, and 35% versus 4% ended with liver fat below 5%; the authors conclude it might be beneficial and that more studies are needed¹². A secondary analysis in people on integrase inhibitors (15 on tesamorelin and 16 on placebo completed 12 months) showed a median change of -25 versus +14 cm² in visceral fat, with no worsening of glycemic control¹³.

Thymosin alpha-1. It is a 28-amino-acid thymic peptide that modulates the immune response; its general history and its use in sepsis are covered in Thymosin alpha-1 after TESTS. In HIV, a 2017 review notes that despite the benefit of ART, complete immune reconstitution is often not achieved, and it summarizes in vitro and in vivo studies of the peptide¹⁹. The clinical evidence is small. In a phase II randomized, open-label trial of 20 people with CD4 counts below 200 cells/µL and suppressed viral load (13 on thymosin and 7 controls, 12 weeks), there were no differences in CD4, CD8 or subset counts at week 12, although sjTREC levels, a marker of thymic output, rose more in the treated group¹⁷. In a single-arm study of 20 immunological non-responders, CD4 count and sjTREC increased with no significant difference from baseline at 24 weeks, while the proportion of CD4 T cells and of naive T cells rose and PD-1 expression fell (P<0.001); there were no severe adverse events¹⁸. The sources consulted show no FDA or EMA approval of thymosin alpha-1 for HIV, and the treatment guidelines reviewed do not include it³.

Safety: adverse effects and precautions

Enfuvirtide. Injection-site reactions occurred in 98% of subjects in the pooled trials (pain 96%, induration 90%, erythema 91%, nodules or cysts 80%), and 7% stopped because of those reactions or injection difficulties; the most common non-injection-site events were diarrhea (31.7%), nausea (22.8%) and fatigue (20.2%)⁸. The label warns about systemic hypersensitivity reactions (under 1%), after which treatment should not be restarted, and about a higher rate of bacterial pneumonia (3.2 versus 0.6 per 100 patient-years in the control arm): an observational study gave a hazard ratio of 1.34 (95% CI 0.90 to 2.00) and the label concludes that an increased risk cannot be excluded⁸. It is contraindicated only in known hypersensitivity⁸.

Tesamorelin. Per the label (revised 3/2025), it is contraindicated in disruption of the hypothalamic-pituitary axis, active malignancy, known hypersensitivity and pregnancy. Warnings include a possible increased risk of neoplasms, elevated IGF-1, fluid retention, glucose intolerance or diabetes (HbA1c of 6.5% or more in 5% versus 1% with placebo), hypersensitivity (about 4%) and injection-site reactions (25% versus 14%). Among the limitations of use, long-term cardiovascular safety has not been established, it is not indicated for weight management, and there are no data showing improved adherence to ART¹⁵.

Thymosin alpha-1. The two studies described recorded no serious adverse events, but each had 20 participants, so they do not allow a robust safety estimate¹⁷¹⁸.

Summary by agent

Frequently asked questions

How many people live with HIV? The WHO estimated 41.0 million at the end of 2025, with about 1.2 million new infections that year¹.

Is there an approved peptide to treat HIV? Yes: enfuvirtide is indicated, per its FDA label, with other antiretrovirals in treatment-experienced patients with ongoing replication; it is not a first-line option³⁸.

Does tesamorelin treat HIV? No. It is FDA-approved to reduce excess abdominal fat in adults with HIV and lipodystrophy, and its label states it is not indicated for weight management¹⁵¹⁶.

Does thymosin alpha-1 cure HIV? There is no evidence that it does. The clinical studies enrolled 20 people each, and the randomized trial found no CD4 difference at 12 weeks¹⁷¹⁸; the WHO states there is no cure and that ART suppresses the virus¹.

Can a person with a suppressed viral load transmit HIV? In PARTNER there were no linked within-couple transmissions over 1,238 couple-years with a viral load below 200 copies/mL, with an upper limit of 0.30 per 100 couple-years⁵.