Most people infected with HIV develop specific antibodies (i.e. seroconvert) within three to twelve weeks of the initial infection. Diagnosis of primary HIV before seroconversion is done by measuring HIV-RNA or p24 antigen. Positive results obtained by antibody or PCR testing are confirmed either by a different antibody or by PCR.

Antibody tests in children younger than 18 months are typically inaccurate due to the continued presence of maternal antibodies. Thus HIV infection can only be diagnosed by PCR testing for HIV RNA or DNA, or via testing for the p24 antigen. Much of the world lacks access to reliable PCR testing and many places simply wait until either symptoms develop or the child is old enough for accurate antibody testing. In sub-Saharan Africa as of 2007–2009 between 30 and 70% of the population were aware of their HIV status. In 2009, between 3.6 and 42% of men and women in Sub-Saharan countries were tested which represented a significant increase compared to previous years.

HIV/AIDS is diagnosed via laboratory testing and then staged based on the presence of certain signs or symptoms. HIV screening is recommended by the United States Preventive Services Task Force for all people 15 years to 65 years of age including all pregnant women. Additionally, testing is recommended for those at high risk, which includes anyone diagnosed with a sexually transmitted illness. In many areas of the world, a third of HIV carriers only discover they are infected at an advanced stage of the disease when AIDS or severe immunodeficiency has become apparent.

Prevalence measures include everyone living with HIV and AIDS, and present a delayed representation of the epidemic by aggregating the HIV infections of many years. Incidence, in contrast, measures the number of new infections, usually over the previous year. There is no practical, reliable way to assess incidence in Sub-Saharan Africa. Prevalence in 15- to 24-year-old pregnant women attending antenatal clinics is sometimes used as an approximation. The test done to measure prevalence is a serosurvey in which blood is tested for the presence of HIV.

Health units that conduct serosurveys rarely operate in remote rural communities, and the data collected also does not measure people who seek alternate healthcare. Extrapolating national data from antenatal surveys relies on assumptions which may not hold across all regions and at different stages in an epidemic.

Recent national population or household-based surveys collecting data from both sexes, pregnant and non-pregnant women, and rural and urban areas, have adjusted the recorded national prevalence levels for several countries in Africa and elsewhere. These, too, are not perfect: people may not participate in household surveys because they fear they may be HIV positive and do not want to know their test results. Household surveys also exclude migrant labourers, who are a high risk group.

Thus, there may be significant disparities between official figures and actual HIV prevalence in some countries.

A minority of scientists claim that as many as 40 percent of HIV infections in African adults may be caused by unsafe medical practices rather than by sexual activity. The World Health Organization states that about 2.5 percent of HIV infections in Sub-Saharan Africa are caused by unsafe medical injection practices and the "overwhelming majority" by unprotected sex.

A study conducted on 452 patients revealed that the genotype responsible for higher IL-10 expression makes HIV infected people more susceptible to tuberculosis infection. Another study on HIV-TB co-infected patients also concluded that higher level of IL-10 and IL-22 makes TB patient more susceptible to Immune reconstitution inflammatory syndrome (IRIS). It is also seen that HIV co-infection with tuberculosis also reduces concentration of immunopathogenic matrix metalloproteinase (MMPs) leading to reduced inflammatory immunopathology.

Many people living with HIV in low and middle income countries who need antiretroviral therapy are unable to access or remain in care. This is often because of the time and cost required to travel to health centres as well as an inadequate number of trained staff such as medical doctors and specialists to provide treatment. One approach to improve access to HIV care is to provide antiretroviral therapy close to people’s homes. A systematic review found that when antiretroviral treatment was initiated at the hospital but followed up at a health centre closer to home, fewer patients died or were lost to follow up. The research also did not detect a difference in the numbers of patients who died or were lost to follow up when they received maintenance treatment in the community rather than in a health centre or hospital.

It is currently recommended that HIV-infected individuals with TB receive combined treatment for both diseases, irrespective of CD4+ cell count. ART (Anti Retroviral Therapy) along with ATT (Anti Tuberculosis Treatment) is the only available treatment in present time. Though the timing of starting ART is the debatable question due to the risk of immune reconstitution inflammatory syndrome (IRIS). The advantages of early ART include reduction in early mortality, reduction in relapses, preventing drug resistance to ATT and reduction in occurrence of HIV-associated infections other than TB. The disadvantages include cumulative toxicity of ART and ATT, drug interactions leading to inflammatory reactions are the limiting factors for choosing the combination of ATT and ART.

A systematic review investigated the optimal timing of starting antiretroviral therapy in adults with newly diagnosed pulmonary tuberculosis. The review authors included eight trials, that were generally well-conducted, with over 4500 patients in total. The early provision of antiretroviral therapy in HIV-infected adults with newly diagnosed tuberculosis improved survival in patients who had a low CD4 count (less than 0.050 x 109 cells/L). However, such therapy doubled the risk for IRIS. Regarding patients with higher CD4 counts (more than 0.050 x 109 cells/L), the evidence is not sufficient to make a conclusion about benefits or risks of early antiretroviral therapy.

AIDS-related complex, or ARC, was introduced after discovery of the HIV (Human Immunodeficiency Virus) when the medical community became aware of the inherent difficulties associated with treating patients suffering from an advanced case of HIV which gave rise to the term Acquired Immune Deficiency Syndrome (AIDS). The necessity for doctors to quickly and accurately understand the special needs of unknown patients suffering from AIDS in an emergency room situation was addressed with the creation of the term ARC.

ARC is "A prodromal phase of infection with the human immunodeficiency virus (HIV). Laboratory criteria separating AIDS-related complex ( ARC) from AIDS include elevated or hyperactive B-cell humoral immune responses, compared to depressed or normal antibody reactivity in AIDS; follicular or mixed hyperplasia in ARC lymph nodes, leading to lymphocyte degeneration and depletion more typical of AIDS; evolving succession of histopathological lesions such as localization of Kaposi's sarcoma, signaling the transition to the full-blown AIDS."

Clinical use of this term was widely discontinued by the year 2000 in the United States after having been replaced by modern laboratory criteria.

The virus that causes AIDS is the best known of the transfusion-transmitted infections because of high-profile cases such as Ryan White, a haemophiliac who was infected through factor VIII, a blood-derived medicine used to treat the disease. Another person who died of medically acquired HIV/AIDS was Damon Courtenay, who died in 1991 due to a bad batch of factor VIII.

The standard test for HIV is an enzyme immunoassay test that reacts with antibodies to the virus. This test has a window period where a person will be infected but not yet have an immune response. Other tests are used to look for donors during this period, specifically the p24 antigen test and nucleic acid testing.

In addition to the general risk criteria for viruses, blood donors are sometimes excluded if they have lived in certain parts of Africa where subtypes of HIV that are not reliably detected on some tests are found, specifically HIV group O. People who have been in prison for extended periods are also excluded for HIV risk.

Long-term nonprogressors (LTNPs), sometimes also called "elite controllers", are individuals infected with HIV, who maintain a CD4 count greater than 500 without antiretroviral therapy with a detectable viral load. Many of these patients have been HIV positive for 30 years without progressing to the point of needing to take medication in order not to develop AIDS. They have been the subject of a great deal of research, since an understanding of their ability to control HIV infection may lead to the development of immune therapies or a therapeutic vaccine. The classification "Long-term non-progressor" is not permanent, because some patients in this category have gone on to develop AIDS.

Long-term nonprogressors typically have viral loads under 10,000 copies RNA/ml blood, do not take antiretrovirals, and have CD4+ counts within the normal range. Most people with HIV not on medication have viral loads which are much higher.

It is estimated that around 1 in 300 people with HIV are long-term nonprogressors. Without the symptoms of AIDS, many LTNP patients may not know they are infected.

Genetic traits that confer greater resistance or more robust immune response to HIV are thought to explain why LTNP patients are able to live much longer with HIV than patients who are not LTNP. Some LTNP are infected with a weakened or inactive form of HIV, but it is now known that many LTNP patients carry a fully virulent form of the virus. Genetic traits that may affect progression include:

- Gene mutation. A mutation in the FUT2 gene affects the progression of HIV-1 infection. 20% of Europeans who have that mutation are called "non secretor" because of their absence of a certain type of antigen that also provides strong resistance against norovirus.

- Mitochondrial DNA. Different mitochondrial DNA haplotypes in humans may increase or decrease rates of AIDS progression. Haplotypes associated with more loosely coupled mitochondrial respiration, with reduced ATP and ROS generation, have been associated with faster progression and vice versa.

- Receptor mutations. A low percentage of long-term nonprogressors have been shown to have inherited mutations of the CCR5 receptor of T cell lymphocytes. HIV uses CCR5 to enter these cells. It is believed that the Δ32 (delta 32) variant of CCR5 impairs HIV ability to infect cells and cause disease. An understanding of this mechanism led to the development of a class of HIV medicines, the entry inhibitors. The presence of this mutation, however, is not a unifying theme among LTNPs and is observed in an exceedingly small number of these patients.

- HLA type has also been correlated with long-term non-progressor cohorts. In particular, strong correlations have been found between possessing the class 1 HLA-B*5701, HLA-B*5703, and/or HLA-B*2705 alleles and ability to exert control over HIV.

- Antibody production. All individuals with HIV make antibodies against the virus. In most patients, broadly neutralizing antibodies do not emerge until approximately 2–4 years after the initial infection. At this point, the latent reservoir has already been established and the presence of broadly neutralizing antibodies is not enough to prevent disease progression. In some rare patients, these antibodies emerge earlier and can result in a delayed disease course. These patients, however, are not typically classified as LTNPs, but rather as slow progressors, who will eventually develop AIDS. Induction of broadly neutralizing antibodies in healthy individuals is a potential strategy for a preventive HIV vaccine, as is the elicitation of these antibodies through rationally designed immunogens. Direct production of these antibodies in somatic tissue through plasmid transfection also pose a viable method for making these antibodies available in a large number of humans.

- APOBEC3G protein production. In a small number of people infected with HIV, the virus is naturally suppressed without medical treatment. These people may carry high quantities of a protein called APOBEC3G that disrupts viral replication in cells. APOBEC3G, or "A3" for short, is a protein that sabotages reverse transcription, the process HIV relies on for its replication. This process involves the virus transcribing its singe-stranded RNA genome into double-stranded DNA that is incorporated into the cell's genome. A3 usually stops dormant viruses in the human genome, called endogenous retroviruses, from reawakening and causing infections.

Many of these viruses are controlled through laboratory screening tests. These fall into three basic varieties: antibody tests, nucleic acid tests (NAT), and surrogate tests. Antibody tests look for the immune system's response to the infection. Nucleic acid tests look for the genetic material of the virus itself. The third variety are tests that are not specific to the disease but look for other related conditions.

High risk activities for transfusion transmitted infections vary, and the amount of caution used for screening donors varies based on how dangerous the disease is. Most of the viral diseases are spread by either sexual contact or by contact with blood, usually either drug use, accidental needle injuries among health care workers, unsterilized tattoo and body piercing equipment, or through a blood transfusion or transplant. Other vectors exist.

Whether a donor is considered to be at "too high" of a risk for a disease to be allowed to donate is sometimes controversial, especially for sexual contact. High risk sexual activity is defined in many different ways, but usually includes:

- Sex in exchange for money or drugs.

- Men who have sex with men, the most controversial criterion.

- A recent history of sexually transmitted disease.

- Sex with a person who has had a positive test or was at high risk for a disease that can be spread in blood transfusions.

Blood tests to detect antibodies against KSHV have been developed and can be used to determine whether a person is at risk for transmitting infection to their sexual partner, or whether an organ is infected prior to transplantation. However, these tests are not available except as research tools, and, thus, there is little screening for persons at risk for becoming infected with KSHV, such as people following a transplant.

Specific age groups, persons who participate in risky sexual behavior, or those have certain health conditions may require screening. The CDC recommends that sexually active women under the age of 25 and those over 25 at risk should be screened for chlamydia and gonorrhea yearly. Appropriate times for screening are during regular pelvic examinations and preconception evaluations. Nucleic acid amplification tests are the recommended method of diagnosis for gonorrhea and chlamydia. This can be done on either urine in both men and women, vaginal or cervical swabs in women, or urethral swabs in men. Screening can be performed:

- to assess the presence of infection and prevent tubal infertility in women

- during the initial evaluation before infertility treatment

- to identify HIV infection

- for men who have sex with men

- for those who may have been exposed to hepatitis C

- for HCV

AIDS dysmorphic syndrome, also called HIV embryopathy, is a cluster of facial malformations seen in children with perinatal HIV infection. Its status as a syndrome is disputed by the research community. Common symptoms of perinatal HIV infection include candidiasis, lymphocytic interstitial pneumonitis, hepatosplenomegaly, and lymphadenopathy.

An elevated concentration of autoantibodies that block interferon-gamma was detected in most patients.

Adult-onset immunodeficiency syndrome is a provisional name for a newly diagnosed immunodeficiency illness. The name is proposed in the first public study to identify the syndrome. It appears to be chronic and non-contagious, affecting mainly people of Asian descent aged around 50. Cases first started appearing in 2004, primarily in Thailand and Taiwan.

The definitive diagnosis is arrived at from tissue, i.e. a biopsy, by a pathologist.

MRI or contrast enhanced CT classically shows multiple ring-enhancing lesions in the deep white matter. The major differential diagnosis (based on imaging) is cerebral toxoplasmosis, which is also prevalent in AIDS patients and also presents with a ring-enhanced lesion, although toxoplasmosis generally presents with more lesions and the contrast enhancement is typically more pronounced. Imaging techniques cannot distinguish the two conditions with certainty, and cannot exclude other diagnoses. Thus, patients undergo a brain biopsy.

"Penicillium marneffei" demonstrates in vitro susceptibility to multiple antifungal agents including ketoconazole, itraconazole, miconazole, flucytosine, and amphotericin B. Without treatment patients have a poor prognosis; death occur by liver failure as the fungus releases toxins in the bloodstream. The elevation of liver enzyme in the blood helps to establish a diagnosis.

With the decrease in the death rate among people with HIV/AIDS receiving new treatments in the 1990s, the rates and severity of epidemic KS also decreased. However, the number of people living with HIV/AIDS is increasing in the United States, and it is possible that the number of people with AIDS-associated Kaposi sarcoma will again rise as these people live longer with HIV infection.

Cryptococcosis is a very subacute infection with a prolonged subclinical phase lasting weeks to months in persons with HIV/AIDS before the onset of symptomatic meningitis. In Sub-Saharan Africa, the prevalence rates of detectable cryptococcal antigen in peripheral blood is often 4–12% in persons with CD4 counts lower than 100 cells/mcL.

Cryptococcal antigen screen and preemptive treatment with fluconazole is cost saving to the healthcare system by avoiding cryptococcal meningitis. The World Health Organization recommends cryptococcal antigen screening in HIV-infected persons entering care with CD4<100 cells/μL. This undetected subclinical cryptococcal (if not preemptively treated with anti-fungal therapy) will often go on to develop cryptococcal meningitis, despite receiving HIV therapy. Cryptococcosis accounts for 20-25% of the mortality after initiating HIV therapy in Africa. What is effective preemptive treatment is unknown, with the current recommendations on dose and duration based on expert opinion. Screening in the United States is controversial, with official guidelines not recommending screening, despite cost-effectiveness and a 3% U.S. cryptococcal antigen prevalence in CD4<100 cells/μL.

Dependent on the infectious syndrome, symptoms include fever, fatigue, dry cough, headache, blurred vision, and confusion. Symptom onset is often subacute, progressively worsened over several weeks. The two most common presentations are meningitis (an infection in and around the brain) and pulmonary (lung) infection.

Detection of cryptococcal antigen (capsular material) by culture of CSF, sputum and urine provides definitive diagnosis. Blood cultures may be positive in heavy infections. India ink of the CSF is a traditional microscopic method of diagnosis, although the sensitivity is poor in early infection, and may miss 15-20% of patients with culture-positive cryptococcal meningitis. Unusual morphological forms are rarely seen. Cryptococcal antigen from cerebrospinal fluid is the best test for diagnosis of cryptococcal meningitis in terms of sensitivity. Apart from conventional methods of detection like direct microscopy and culture, rapid diagnostic methods to detect cryptococcal antigen by latex agglutination test, lateral flow immunochromatographic assay (LFA), or enzyme immunoassay (EIA). A new cryptococcal antigen LFA was FDA approved in July 2011. Polymerase chain reaction (PCR) has been used on tissue specimens.

Cryptococcosis can rarely occur in the non-immunosuppressed people, particularly with "Cryptococcus gattii".

Testing may be for a single infection, or consist of a number of tests for a range of STIs, including tests for syphilis, trichomonas, gonorrhea, chlamydia, herpes, hepatitis and HIV. No procedure tests for all infectious agents.

STI tests may be used for a number of reasons:

- as a diagnostic test to determine the cause of symptoms or illness

- as a screening test to detect asymptomatic or presymptomatic infections

- as a check that prospective sexual partners are free of disease before they engage in sex without safer sex precautions (for example, when starting a long term mutually monogamous sexual relationship, in fluid bonding, or for procreation).

- as a check prior to or during pregnancy, to prevent harm to the baby

- as a check after birth, to check that the baby has not caught an STI from the mother

- to prevent the use of infected donated blood or organs

- as part of the process of contact tracing from a known infected individual

- as part of mass epidemiological surveillance

Early identification and treatment results in less chance to spread disease, and for some conditions may improve the outcomes of treatment. There is often a window period after initial infection during which an STI test will be negative. During this period, the infection may be transmissible. The duration of this period varies depending on the infection and the test. Diagnosis may also be delayed by reluctance of the infected person to seek a medical professional. One report indicated that people turn to the Internet rather than to a medical professional for information on STIs to a higher degree than for other sexual problems.

Diagnosis is usually made by identification of the fungi from clinical specimens. Biopsies of skin lesions, lymph nodes, and bone marrow demonstrate the presence of organisms on histopathology.

The most common symptoms are fever, skin lesions, anemia, generalized lymphadenopathy, and hepatomegaly.

When physical examination of the newborn shows signs of a vertically transmitted infection, the examiner may test blood, urine, and spinal fluid for evidence of the infections listed above. Diagnosis can be confirmed by culture of one of the specific pathogens or by increased levels of IgM against the pathogen.

CRMO/CNO is a diagnosis of exclusion. This means that other diseases must be ruled out before the diagnosis can be made. Generally, many tests are required, such as blood tests, x-rays, bone scans, MRI and often a bone biopsy.

Primary cerebral lymphoma (or "primary central nervous system lymphoma") is a form of NHL. It is very rare in immunocompetent people, with an incidence of 5–30 cases per million person-years. However the incidence in immunocompromised individuals is greatly increased, up to 100 per million person-years.

Primary cerebral lymphoma is strongly associated with Epstein–Barr virus (EBV). The presence of EBV DNA in cerebrospinal fluid is highly suggestive of primary cerebral lymphoma.

Treatment of AIDS patients with antiretroviral drugs reduces the incidence of primary cerebral lymphoma.