human immunodeficiency virus, PLWHIV
Human immunodeficiency virus (HIV) infection is a viral infection that progressively destroys certain white blood cells and can cause acquired immunodeficiency syndrome (AIDS). The HIV (Pic. 1) is virus spread through certain body fluids that attacks the body's immune system, specifically the CD4+ cells, often called T cells (Pic. 2). People who are diagnosed with HIV are said to be HIV positive, even if their infection has not progressed to AIDS. If HIV is left untreated, it may progress to AIDS.
After initial symptoms disappear, HIV may not cause any symptoms for many years. During this time, the virus can be passed on without people knowing. Whilst patient may look and feel healthy, the untreated virus could be doing harm to a body.
HIV may be transmitted when blood, semen or vaginal fluid from an infected person enters the body of an uninfected person. This can happen through:
HIV positive mothers who are not on effective treatment can transmit the virus to their babies:
HIV can also be transmitted through donated blood and blood products if they are contaminated with HIV.
It is important to know that HIV cannot be transmitted through saliva, sweat, tears, mucous, vomit, urine or faeces. You cannot transmit HIV by kissing, hugging, sharing eating utensils, shaking hands or any other everyday social contact.
A specific HIV blood test is needed to detect HIV infection. It can take 6 to 12 weeks after someone has acquired HIV before HIV is able to be detected in the blood through a blood test. This is called the ‘window period’. Testing at a health service where support and treatment advice is readily available is the best and recommended testing option.
Screening tests like the HIV point of care tests (also known as ‘rapid tests’) can be used outside the laboratory by trained professionals and peers with results available in 20 to 30 minutes. A ‘reactive’ result on this test is not a diagnosis of HIV and the test result needs to be confirmed by a laboratory blood test.
HIV can affect a person's immune system if left untreated (usually many years), leaving the body less able to protect itself from disease. When a person has undiagnosed or untreated HIV the immune system can be damaged and the person can get sick from related infections or cancers.
Biological changes caused by HIV, including systemic illnesses, stress, and weight loss, may affect the function of reproductive organs and result in infertility. Newly diagnosed HIV infection may cause psychological trauma and decrease in sexual drive and sexual activity.
Associated diseases
Several HIV/acquired immune deficiency syndrome (AIDS)-related comorbidities have been reported to be associated with infertility. These include orchitis (inflammation of testes), acute epididymitis (inflammation of epididymis), pelvic inflammatory disease (PID) caused by opportunistic pathogens and coinfections with sexually transmitted infections (STIs) acquired through a similar route of transmission as HIV.
Epididymitis and orchitis
Inflammation of epididymis (epididymitis) and testes (orchitis) is usually due to infection, most commonly from a urine infection or a sexually transmitted infection. As the epididymis and testis lie next to each other, it is often difficult to tell if the epididymis, the testis, or both are inflamed; therefore, the term epididymo-orchitis is often used.
It could cause azoospermia (no sperm in semen), most likely due to testicular tissue necrosis. Necrosis appears to be the dominant cell death pathway in infected testis.
Pelvic inflammatory disease
Pelvic inflammatory disease (PID) is an infection of the female upper reproductive tract, including the endometrium, fallopian tubes, ovaries, and pelvic peritoneum. The diagnosis of PID is made difficult by variation in clinical manifestations: subclinical patients with PID are asymptomatic, while patients with more severe disease present with abdominal pain requiring surgical intervention.
The rates of PID are concerning given the serious potential sequelae of PID, including tubal infertility, ectopic pregnancy, and chronic pelvic pain (CPP). Damage to the female reproductive tract from PID is usually irreversible; therefore, prompt antibiotic treatment is necessary to prevent any scarring of the reproductive tract.
Sexually transmitted infections
The impact of STIs on fertility among PLWHIV depends on the local prevalence of the STIs. Given the common route of transmission of causative agents and immunosuppressive status caused by HIV, STIs tend to be more prevalent, to be more severe, to take longer to resolve, and to be more prone to treatment failure in HIV-infected persons compared to the general population.
Common causative pathogens for STIs among PLWHIV include bacteria, such as Neisseria gonorrhoeae, Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium, Treponema pallidum, Haemophilus ducreyi, and Klebsiella granulomatis; viruses, such as hepatitis B and C viruses, herpes simplex virus (HSV), and human papillomavirus (HPV); and protozoa, such as Trichomonas vaginalis.
The underlying pathogenesis for STI-related infertility is direct damage and subsequent anatomical and functional abnormalities of the genital organs, including the testes and epididymis in men and cervix, uterus, fallopian tubes, and ovaries in women.
Hypogonadism and HIV/AIDS
Hypogonadism was recognized as a relatively common condition early in the HIV epidemic and characterized by a low level of testosterone among HIV-infected men. Hypogonadism can be categorized into primary hypogonadism, which is a disorder of the testes, and secondary hypogonadism, which is a disorder of the pituitary or hypothalamus.
Hypogonadism can be associated with various signs and symptoms, including muscle wasting, weight loss, low bone mineral density, and decreased libido. During the early course of HIV disease, men tend to have normal serum testosterone levels. As the disease progresses to AIDS, low serum testosterone levels become more frequent, particularly in those with more advanced immunosuppression.
The prevalence of hypogonadism in HIV-infected men has decreased with combination antiretroviral therapy (cART) initiation occurring at earlier stages of HIV infection. Effective HIV therapy can normalize testosterone levels over time. Most cases of decreased testosterone levels in HIV-infected men are related to secondary hypogonadism.
HIV-infected men with symptomatic hypogonadism may present with loss of facial and body hair, decreased muscle mass and strength, diminished libido, impotence, testicular atrophy, gynecomastia, depression, low energy, and poor concentration. To distinguish between primary and secondary hypogonadism, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels need to be measured. The elevated FSH and LH levels suggest primary hypogonadism, whereas normal or low levels of FSH and LH are consistent with secondary hypogonadism.
Complications
Opportunistic Infections
HIV-infected persons are at increased risk for opportunistic infections (OIs) depending on their degree of immunosuppression (dampening of the immune response). Tuberculosis is a common OI in HIV-tuberculosis endemic locales and its prevalence is higher among people living with HIV (PLWHIV) compared to non-HIV-infected persons. Genital tract infection caused by Mycobacterium tuberculosis contributes to infertility and poorer reproductive health outcomes in both sexes.
Salmonellosis, toxoplasmosis, and cryptococcosis can manifest as disseminated infections (spreads from one site of the body to other) involving the genital organs. Although cytomegalovirus (CMV) can cause orchitis and epididymitis in HIV infected men, there are no data on its effect on sperm characteristics. Candidiasis is frequently reported among HIV-infected persons with CD4+ cell counts less than 200 cells/ mm3. It is the cause of balanitis (inflammation of glans penis) in men and vaginitis and cervicitis (cervical inflammation) in women, which may affect fertility.
Malignancy
Patients with HIV/AIDS have a heightened risk for the development of cancer. The duration of HIV infection, age greater than 40 years, and a history of opportunistic infection are the primary risk factors identified for the development of non–AIDS-defining cancers. A complex interplay between variables such as immunosuppression, co-infection with human oncogenic biologic agents, an advanced age and traditional risk factors are thought lead to the evolution of malignancy in HIV/AIDS patients.
Kaposi's sarcoma is the most common cancer occurring in 10 to 20% of people with HIV. The second most common cancer is lymphoma, which is the cause of death of nearly 16% of people with AIDS and is the initial sign of AIDS in 3 to 4%. Both these cancers are associated with human herpesvirus 8. Cervical cancer occurs more frequently in those with AIDS because of its association with human papillomavirus (HPV). Conjunctival cancer (of the layer that lines the inner part of eyelids and the white part of the eye) is also more common in those with HIV.
Obsteric complications
Caesarian section is the method of choice for the delivery of babies in mothers known to be HIV positive, as it is known to be protective against mother-to-child transmission. It has however been shown, as in other surgical specialties, to be associated with a higher morbidity than in HIV-negative women, with a higher rate of the need for blood transfusion, a higher incidence of post-operative fever and wound infection, even with the use of peri-operative antibiotics.
Risk factors
Hypogonadism especially in men with AIDS is one of the important endocrine disorders that cause infertility. Although assisted reproductive technology (ART) provides significant benefits in reducing morbidity and mortality among HIV-infected persons, some antiretroviral drugs, including nucleoside reverse transcriptase inhibitors, are toxic to sperm and oocytes.
Despite the infertility in women living with HIV, pregnancy rates among this population have increased steadily over the past 10 years to between 4 and 6 pregnancies per 100 person-years, varying by region due to the advances in HIV treatment and mother-to-child transmission prevention. This may reflect an increase in reproductive desire and/or unexpected preg‐ nancies and indicate the need for reproductive health care, fertility management, and family planning along with HIV comprehensive care among PLWHIV.
Female fertility
Demographic characteristics that have been reported to be associated with low rates of pregnancy among HIV-infected women include advanced age, white ethnicity (compared to black ethnicity), having CD4+ cell count of less than 100 cells/mm3 , and poor adherence to cART. Systemic illnesses from HIV and its related comorbidities, stress, and weight loss generally impact the reproductive potential of both sexes. HIV-infected women are more likely than non-HIV-infected women to have protracted absence of ovulation (anovulation) and absence of period (amenorrhea). The number of ovulatory cycles was found to correlate with the severity of immunosuppression and having an AIDS diagnosis. Although there have been no reports of ovarian aging or failure, HIV-infected women may have reduced ovarian reserve.
Male fertility
In HIV-infected men, impairment of sperm parameters affecting fertility has been described. The impairment includes lower ejaculation volume, sperm count, and progressive motility (defined as the percent of sperm with forward motility) despite normal morphology compared to non-HIVinfected men. Sperm concentration levels, total count, and motility were found to positively correlate with the height of the CD4+ cell count, indicating the adverse effect of worsening immunodeficiency on these sperm parameters. Other studies demonstrated that the semen of HIV-infected men was more viscous and contained fewer motile sperm but more round cells. Although recent data indicate that cART significantly decreased total sperm count and progressive motility and increased the proportion of abnormal sperm forms, these adverse effects are balanced by the overwhelming benefits of cART for immune reconstitution, morbidity and mortality reduction, and overall improvement of sperm characteristics associ‐ ated with higher CD4+ cell counts.
Currently, there is no vaccine to prevent HIV infection. The best way to prevent acquiring HIV and other STIs through sexual contact is to practice safer sex and always using condoms when anyone has vaginal or anal sex. Using water-based lubricant with condoms is recommended to reduce the risk of condom breakage. Oral sex has a very low to negligible risk for the transmission of HIV, but there is still a risk for the transmission of other STIs.
Male circumcision has been shown to protect men against HIV infection during vaginal sex with women, providing evidence that circumcision has the potential to significantly reduce transmission.
HIV can also be transmitted through the sharing or reuse of blood contaminated equipment used for injecting drugs. It is important that needles, syringes and other injecting or piercing equipment are never shared between people.
Medication to prevent HIV include:
Post-Exposure Prophylaxis (PEP)
Post exposure prophylaxis (PEP) is a treatment that may prevent HIV infection when taken immediately after exposure to HIV, preferably within 2 hours, but it may still be effective if taken within 72 hours (3 days) of exposure. PEP is a combination of anti-HIV drugs that must be taken exactly as prescribed at very specific times for a 4 week period.
It is extremely important that a person who may have been exposed to HIV through contact with blood or body fluids from an HIV positive person seeks medical advice as soon as possible.
Pre-Exposure Prophylaxis (PrEP)
Pre-Exposure Prophylaxis (PrEP) for HIV is the use of HIV medication by someone who is HIV negative taken once daily to prevent the virus becoming established in the body. Clinical trials have shown that taking PrEP is very effective in preventing the transmission of HIV.
There are three main stages of HIV infection:
Acute infection
The initial period following the contraction of HIV is called acute HIV (Pic. 3), primary HIV or acute retroviral syndrome. Many individuals develop an influenza-like illness or a mononucleosis-like illness 2–4 weeks post exposure while others have no significant symptoms. Symptoms occur in 40–90% of cases and most commonly include fever, large tender lymph nodes, throat inflammation, a rash (20–50% of cases), headache, and/or sores of the mouth and genitals. Some people also develop opportunistic infections at this stage. Gastrointestinal symptoms, such as vomiting or diarrhea may occur. Neurological symptoms also occur. The duration of the symptoms varies, but is usually one or two weeks.
Due to their nonspecific character, these symptoms are not often recognized as signs of HIV infection. Even cases that do get seen by a family doctor or a hospital are often misdiagnosed as one of the many common infectious diseases with overlapping symptoms. Thus, it is recommended that HIV be considered in people presenting an unexplained fever who may have risk factors for the infection.
Clinical latency
Without treatment, this second stage of the natural history of HIV infection can last from about three years to over 20 years (on average, about eight years). While typically there are few or no symptoms at first, near the end of this stage many people experience fever, weight loss, gastrointestinal problems and muscle pains.
Acquired immunodeficiency syndrome
In the absence of specific treatment, around half of people infected with HIV develop acquired immunodeficiency syndrome (AIDS) within ten years. Opportunistic infections may be caused by bacteria, viruses, fungi, and parasites that are normally controlled by the immune system. Which infections occur depends partly on what organisms are common in the person's environment. These infections may affect nearly every organ system.
Additionally, people with AIDS frequently have systemic symptoms (Pic. 4) such as prolonged fevers, sweats (particularly at night), swollen lymph nodes, chills, weakness, and unintended weight loss. Diarrhea is another common symptom, present in about 90% of people with AIDS. They can also be affected by diverse psychiatric and neurological symptoms independent of opportunistic infections and cancer.
Diet
The World Health Organization (WHO) has issued recommendations regarding nutrient requirements in HIV/AIDS. A generally healthy diet is promoted. Dietary intake of micronutrients at RDA (Recommended Dietary Allowances) levels by HIV-infected adults is recommended by the WHO; higher intake of vitamin A, zinc, and iron can produce adverse effects in HIV positive adults, and is not recommended unless there is documented deficiency. Dietary supplementation for people who are infected with HIV and who have inadequate nutrition or dietary deficiencies may strengthen their immune systems or help them recover from infections, however evidence indicating an overall benefit in morbidity or reduction in mortality is not consistent.
Evidence for supplementation with selenium is mixed with some tentative evidence of benefit. For pregnant and lactating women with HIV, multivitamin supplement improves outcomes for both mothers and children. If the pregnant or lactating mother has been advised to take anti-retroviral medication to prevent mother-to-child HIV transmission, multivitamin supplements should not replace these treatments. There is some evidence that vitamin A supplementation in children with an HIV infection reduces mortality and improves growth.
Alternative medicine
In the US, approximately 60% of people with HIV use various forms of complementary or alternative medicine, even though the effectiveness of most of these therapies has not been established. There is not enough evidence to support the use of herbal medicines. There is insufficient evidence to recommend or support the use of medical cannabis to try to increase appetite or weight gain.
Medical research has made great progress in reducing the impact of HIV infection on the immune system and managing other illnesses associated with HIV. Currently, while there remains no cure for HIV and AIDS, close adherence to cART enables people living with HIV to lead long and healthy lives.
Starting treatment for HIV as early as possible after diagnosis will improve long term health prospects. Starting treatment late increases the time the virus has to damage the immune system.
When treatment starts, it continues with regular blood tests to monitor the level of HIV virus in system. The aim of treatment is to make HIV undetectable, which will benefit both sexual partners. Having a sustained undetectable viral load means that the risk of passing on the HIV virus is negligible. Along with other prevention methods like condoms and PrEP, being undetectable can offer effective protection against HIV.
Pharmacotherapy
Antiretroviral agents
New forms of antiviral treatments keep the virus from multiplying and provide the immune system with relief from HIV infection and allow it to strengthen. There can be some side effects to cART, but they differ from person to person and some newer treatments can cause no side effects at all. It is uncommon to experience serious side effects.
Nucleoside reverse transcriptase inhibitors (NRTIs) remain key components of recommended cART regimens, which improve disease control. However, these medications can also result in cell injury. Theoretically, an HIV-infected person’s fertility may be affected by NRTI use via the damage of gametes. Unfortunately, there have been no studies examining fertility effect of NRTIs in humans.
Surgical therapy
Not used.
Given that worldwide many HIV-infected individuals are in the reproductive age, fertility and reproductive desire have emerged as clinically important issues among this population. Fertility management for people living with HIV (PLWHIV) should be comprehensive and involve cART, specific management (Pic. 5) for factors associated with infertility (Pic. 6), and assisted reproduction while minimizing the risk of horizontal (between members of the same species that are not in a parent-child relationship) and vertical (mother-to-child) transmission of HIV.
An HIV-infected partner should be treated with cART until HIV RNA suppression has been achieved prior to assisted reproduction. Partners who have STIs need to be treated to reduce transmission risks of HIV and STI-associated pathogens. Trauma during sexual intercourse should be avoided or minimized, and safer sex practices should be encouraged outside the conception attempts.
Assisted reproduction when only the female partner is infected
If a woman is HIV infected and her male partner is uninfected, HIV transmission can be avoided by using homologous insemination (prepared in laboratory) with the male partner’s sperm. However, if this option is not feasible, such as the desire to become pregnant naturally, couples should limit unprotected sexual intercourse to the time of ovulation (timed intercourse) using ovulation kits or basal body temperature monitoring to predict ovulation. These measures allow couples to limit the number of unprotected sexual encounters. In addition, the HIV-infected women should be on cART with a suppressed viral load. The male partner may choose to take PEP and/or PrEP to reduce the risk of HIV transmission; however, these options are not as safe as homologous insemination.
Assisted reproduction when only the male partner is infected
Conception between an HIV-infected man and his HIV-uninfected female partner is more complicated. The risk of HIV transmission can be reduced by using timed intercourse when the HIV-infected man’s plasma HIV RNA is undetectable on cART. However, the HIV transmission of timed intercourse in this setting has been reported to be associated with inconsistent condom use outside the conception attempt.
Thus, the practice of timed intercourse alone to prevent HIV transmission to the female partner is not generally recommended in this setting. Additional PEP and/or PrEP may be used to reduce HIV transmission.
Sperm preparation and testing prior to intrauterine insemination (IUI) have been described as methods to reduce the chance of HIV transmission to the uninfected female partner. The sperm preparation involves a three-step process. First, the liquefied semen is filtered through a Percoll gradient. Next, the isolated spermatozoa are washed to eliminate seminal plasma and hyperosmotic gradient media. Finally, a modified swim-up method recovers highly motile spermatozoa from white blood cells. After this process, the final sperm specimen is tested by polymerase chain reaction (PCR) assays for the presence of HIV. If this final specimen tests negative, it is used for insemination. In men with severe dyspermia (difficult or painful emission of sperm during coitus), the final swim-up step that removes infected leukocytes cannot be performed and thus the semen should be tested for HIV DNA.
There have been recent data supporting the use of IVF/ICSI to reduce HIV transmission to uninfected women. Unfortunately, these techniques are generally prohibitively expensive. Although the data on efficacy and safety of the assisted reproduction techniques are encouraging, the potential risk of HIV transmission is not completely eliminated and more studies are required. Until then, serodiscordant couples (where one partner is HIV negative and the other is HIV positive) should also be counseled about other safer options, including using donor sperm, donor embryo, adoption, or not having children. If couples want to have their own biological children, they should be informed about available risk reduction techniques and the availability of centers that can provide effective methods of sperm preparation and testing. Fertility centers should use approved study protocols with informed consent and provide appropriate follow-up of sexual partners and their children.
Assisted reproduction when both partners are infected
While HIV seroconcordant couples do not have the same concerns about HIV transmission as do HIV serodiscordant couples, the risk of transmission of different strains of HIV between each other or superinfection exists. HIV superinfection in seroconcordant couples has been reported to increase the risk of HIV RNA rebound and decrease in CD4+ cell count following immune reactivation. The best way to minimize the risk of superinfection and optimize reproductive outcomes for couples and their offspring is to use cART to achieve HIV RNA suppression in both partners prior to conception attempts.
Process by which a woman donates eggs for purposes of assisted reproduction or biomedical research.
A micromanipulative fertilization technique in which a single sperm is injected directly into an egg.
The procedure in which a man (sperm donor) provides his sperm for fertility treatment.
A process in which an egg is fertilised by sperm outside the body: in vitro. Own or donated gametes may be used.
