Detection and biologic characterization of infectious HIV-1 in semen of seropositive men.

OBJECTIVE: Factors that influence the infectivity of an individual and the impact of antiviral treatment on infectivity are not well defined. This study investigated the value of a sensitive method for detecting infectious HIV in semen for use as a marker for infectivity. DESIGN: A cross-sectional study of infectious HIV in the semen of 33 HIV-positive men. METHODS: A sensitive method for detecting infectious HIV in semen was used. The correlation of culture in semen with clinical and laboratory data was investigated. Biological phenotypes of isolates from blood and semen were tested using an MT-2 assay. RESULTS: HIV cultures from seminal cells were positive in 18 patients (55%) and in one patient from seminal plasma. Higher recovery rates of HIV from semen correlated with a low CD4 count (80% in patients with a CD4 count > 100 x 10(6)/l versus 33% in patients with a CD4 count < 100 x 10(6) cells; P < 0.025) and symptomatic disease (78 versus 27% in asymptomatic patients; P < 0.01). Recovery of HIV from semen was independent of presence or absence of plasma viremia and the biological phenotype of blood isolates. Ten patients with syncytium-inducing (SI) isolates in their blood had positive semen cultures for HIV. Seven of the 10 patients had SI isolates recovered from their semen, whereas three had non-SI isolates only. CONCLUSION: Data from partner studies show higher rates of HIV transmission for patients with low CD4 counts and symptomatic disease. The compatibility of epidemiologic data with our finding that significantly more HIV is recovered in semen from patients with advanced disease, suggests that HIV culture of semen samples may provide a useful surrogate marker to measure infectivity in clinical studies. Further studies are needed to define the inoculum required to transmit HIV and to study the impact of sexually transmitted diseases and HIV-1 phenotype on semen infectivity.

Quantification of HIV in semen: correlation with antiviral treatment and immune status.

OBJECTIVE: This study examined the concentration of HIV in semen and the effects of biological factors on HIV excretion. METHODS: Semen samples from 101 men at different stages of the disease were evaluated by quantitative HIV culture and HIV RNA detection. Blood plasma samples were available from 56 patients. The effects of CD4 and CD8 count, blood plasma RNA levels, treatment status and clinical staging on the shedding of HIV were evaluated. RESULTS: HIV RNA levels in semen correlated with quantitative HIV culture of seminal cells and a strong association of positive seminal cell culture with high RNA levels was observed. CD4 count and antiviral treatment were inversely correlated with the concentration of HIV in semen. Blood plasma HIV RNA values were correlated with HIV RNA levels in semen, although some patients had highly discrepant results. CONCLUSIONS: The strong correlation between seminal cell culture and concentration of HIV RNA in seminal plasma suggested that HIV detected in seminal plasma was released by productively infected cells in the male genital tract. The study showed that the concentration of HIV in semen, which was likely to be correlated with HIV infectivity, was a function of the immune status of the HIV-infected individual. The results suggested that antiviral therapy may have reduced the concentration of HIV in semen.

Potent antiretroviral treatment of HIV-infection results in suppression of the seminal shedding of HIV. The Swiss HIV Cohort Study.

OBJECTIVE: The amount of HIV in semen likely influences infectiousness. Antiretroviral therapy decreases HIV-RNA in semen, but data on HIV concentrations in semen in a large cohort of men with suppressed HIV-RNA in blood is unavailable. METHODS: Male patients with a treatment-induced reduction of HIV-RNA load in plasma below 400 copies/ml were asked to donate a semen and blood sample. Blood and seminal plasma were tested for the presence of HIV-RNA by the NucliSens method (detection limit 400 copies/ml). Seminal cell samples from 67 patients were further analysed for the presence of HIV-DNA using a nested DNA-polymerase chain reaction. Results of RNA and DNA testing in semen were compared with 55 HIV-positive antiretroviral therapy-naive men. RESULTS: A total of 114 patients participated in the study. Seminal plasma HIV-RNA was detectable in only two patients [1.8%, 95% confidence ratio (CI), 0-4.2%] compared with a detection frequency of 67% in untreated controls [Odds ratio (OR), 0.01; 95% CI, 0-0.03]. Detection of cell-associated HIV-DNA in semen was significantly less frequent (16 versus 38%) in patients receiving suppressive therapy compared with untreated controls (OR, 0.32; 95% CI, 0.12-0.80). CONCLUSION: In patients with treatment-induced suppression of blood viral load the likelihood of having detectable HIV in semen is very low (< 4%). In addition, seminal shedding of cell-free and cell-associated HIV is significantly lower than in an untreated population of HIV-infected asymptomatic men. On a population basis, this effect of therapy may help to reduce sexual transmission of HIV. However, individual patients may still be infected as evidenced by continued shedding of cells harbouring the HIV provirus.

Effect of antiviral treatment on the shedding of HIV-1 in semen.

OBJECTIVE: The potential role of antiretroviral treatment on the infectiousness of HIV-1-infected men was examined by studying the effect of antiviral treatment on the shedding of HIV-1 in semen. METHODS: Forty-four patients enrolled in various treatment protocols were asked to donate a semen sample before they began a new antiviral treatment and at a follow-up visit after 6 to 15 weeks of treatment. Since most patients were on blinded protocols, patients were stratified by response of blood viral load. The effect of each patient's treatment was classified as good (n = 24), fair (n = 8) and marginal (n = 13) by measurement of the HIV RNA reduction in blood plasma (> 1.0 log10; 0.5-1.0 log10 and < 0.5 log10 HIV RNA copies/ml reduction, respectively). The effect of treatment on shedding of HIV-1 in semen was documented by the reduction of HIV RNA concentration in seminal plasma and by quantitative HIV-1 seminal cell culture. RESULTS: Overall, antiviral treatment resulted in a significant fall in the viral load in semen (RNA and culture) that paralleled the reduction of viral load in blood. More pronounced reductions of HIV RNA in semen were observed as the effectiveness of treatment on blood HIV RNA levels increased (median drop from baseline 0, 0.3 log10 and 0.8 log10 RNA copies/ml in patients with marginal, fair and good treatment effect, respectively). Thirteen patients lost detectable HIV RNA in blood on treatment and all of these had undetectable levels of HIV-1 in semen by culture and RNA analysis at follow-up. In 19 of the 31 patients (62%) who still had HIV RNA in their blood during treatment, semen HIV levels were below detection in semen at follow-up. CONCLUSIONS: Treatment-induced changes of HIV RNA concentration in blood are generally associated with a corresponding change in seminal HIV RNA: If confirmed in larger studies, potent antiretroviral therapy might reduce the spread of HIV-1.

HAART in HIV-infected patients: restoration of antigen-specific CD4 T-cell responses in vitro is correlated with CD4 memory T-cell reconstitution, whereas improvement in delayed type hypersensitivity is related to a decrease in viraemia.

OBJECTIVE: To analyse prospectively the effect of highly active antiretroviral treatment (HAART) on CD4 T-cell responses in vitro and in vivo in HIV-infected patients. DESIGN: Prospective study with 49 protease inhibitor-naive adult patients. Data were collected at baseline and after 3 and 6 months of HAART. METHODS: In vitro CD4 T-cell reactivity was analysed by stimulation of peripheral blood mononuclear cells with several antigens. In vivo CD4 T-cell reactivity (delayed type hypersensitivity) was assessed by Multitest Merieux. Both measurements were correlated to CD4 (memory) T-cell count and HIV-1 viraemia. RESULTS: Restoration of specific CD4 T-cell proliferation was observed in most patients. The in vitro T-cell response was restored more frequently against antigens to which the immune system is constantly exposed (Candida albicans, Mycobacterium tuberculosis, M. avium) as compared with a low-exposure antigen (tetanus toxoid). Overall, delayed type hypersensitivity detection rate increased under HAART. Multivariate analysis showed improvement of antigen-specific T-cell proliferation to be significantly associated with an increase in memory CD4 T-cells, whereas improvement of the delayed type hypersensitivity response was associated with a decrease in plasma HIV-1 RNA. CONCLUSIONS: HAART for 6 months restored antigen-specific CD4 T-cell response to several antigens. In vitro immune reconstitution was closely correlated with an increase in memory CD4 cells. Restoration of delayed type hypersensitivity was associated with suppression of viraemia. It appears that in addition to expansion of memory CD4 cells, suppression of viraemia following HAART may allow an improved inflammatory reaction, thus providing even stronger immune reconstitution.

Highly active antiretroviral therapy during early HIV infection reverses T-cell activation and maturation abnormalities. Swiss HIV Cohort Study.

OBJECTIVES: To evaluate the impact of early initiation of highly active antiretroviral therapy (HAART) on disease-induced T-cell activation and maturation abnormalities during asymptomatic HIV infection. DESIGN: A prospective open-label trial of zidovudine, lamivudine and ritonavir in treatment-naive asymptomatic HIV-infected individuals with CD4 cells > or = 400 x 10(6)/l. METHODS: Peripheral blood CD4+ and CD8+ T cells derived from 15 asymptomatic HIV-infected individuals (median baseline CD4+ cells, 608 x 10(6)/l; CD8+ cells, 894 x 10(6)/l; plasma HIV RNA, 3.93 log10 copies/ml) undergoing therapy with zidovudine (300 mg twice daily), lamivudine (150 mg twice daily), and ritonavir (600 mg twice daily) were assessed for changes in expression of phenotypic markers of T-cell activation (HLA-DR and CD38) and maturation (CD45RA and CD45RO). At weeks 0, 2, 4, 8, 12, 16, 20 and 24, T-cell subsets were quantified by flow cytometry and plasma HIV viral loads determined using reverse transcription PCR. RESULTS: HAART-induced decrease in plasma HIV RNA levels coincided with a significant reduction in numbers of activated CD4+/HLA-DR+ (maximum change, -36%; P < or = 0.05), CD8+/HLA-DR+ (maximum change, -66%; P < or = 0.005) and CD8+/CD38+ (maximum change, -51%; P < or = 0.01) T cells. A concomitant significant increase in numbers of naive CD4+/CD45RA+ (maximum change, +12%; P < or = 0.005) and memory CD4+/CD45RO+ (maximum change, +6%; P < or = 0.05) T cells was also evident, which contrasted with a significant decrease in memory CD8+/CD45RO+ cells (maximum change, -42%; P < or = 0.005). CONCLUSION: The observed ability of HAART during early asymptomatic HIV infection to initiate rapid reversal of disease-induced T-cell activation and maturation abnormalities, while preserving pretherapy levels of immune function, supports the concept that therapeutic advantage is to be gained by commencing early aggressive antiretroviral therapy.

Resistance of HIV-1 to antiretroviral agents in blood and seminal plasma: implications for transmission.

OBJECTIVES: To evaluate blood and genital secretions from HIV-infected men for HIV-1 resistant to antiretroviral agents. DESIGN: A longitudinal study of 11 men with HIV infection and persistent detectable HIV RNA levels in blood and semen on antiretroviral therapy. METHODS: HIV-1 from the blood and seminal plasma, obtained before the initiation of a new therapeutic regimen and on therapy, were evaluated by population-based sequencing of reverse transcriptase (RT) and protease RNA for the development of resistance to antiretroviral therapy. The genetic relatedness of sequences over time was compared. RESULTS: RT genotypic resistance markers were present in seminal plasma at baseline in three out of six individuals with previous RT inhibitor experience. Eight out of 10 men, from whom the viral sequence was available on new therapy, demonstrated the evolution of new resistance mutations in the blood or seminal plasma, or both. The evolution of resistance mutations in blood and semen were frequently discordant, although over time similar patterns were seen. In two individuals, protease inhibitor resistance mutations evolved in the blood but not in the major variant in seminal plasma. Comparisons of the viral sequences between blood and seminal plasma from six men revealed two patterns. Three men showed a clustering of sequences from blood and semen. Three had sequences that appeared to evolve separately in the two compartments. CONCLUSIONS: HIV-1 variants with genotypic resistance markers are present in the male genital tract and evolve over time on incompletely suppressive antiretroviral therapy. The absence of genotypic changes consistent with protease inhibitor resistance in the semen, despite their presence in blood plasma, suggests the possibility of limited penetration of these agents into the male genital tract. Sexual transmission of resistant variants may have a negative impact on treatment outcome in newly infected individuals and on the spread of the diseases within a population. Therapeutic strategies that fully suppress HIV-1 in the genital tract should be a public health priority.

A single-nucleotide polymorphism in the sterol-regulatory element-binding protein 1c gene is predictive of HIV-related hyperlipoproteinaemia.

A single-nucleotide polymorphism (3'322C/G) was identified in the gene encoding a key cholesterol/triglyceride regulator, sterol-regulatory element-binding protein 1c (SREBP-1c). Although it did not alter the amino acid sequence, SREBP-1c-3'322C/G was predictive of highly active antiretroviral therapy-related hyperlipoproteinaemia. Increases in cholesterol were less frequently associated with homozygous SREBP-1c-3'322G (genotype 22) than with heterozygous/homozygous SREBP-1c-3'322C (genotypes 11/12) and correlated with leptin and insulin increases, particularly in genotype 11/12 carriers. A functional mutation linked to SREBP-1c-3'322C/G or messenger RNA conformation differences may explain our findings.

Long-term hydroxyurea in combination with didanosine and stavudine for the treatment of HIV-1 infection. Swiss HIV Cohort Study.

OBJECTIVE AND METHODS: In 1998 we reported on a randomized comparison between stavudine plus didanosine plus placebo versus stavudine plus didanosine plus hydroxyurea (HU), in patients with a CD4 count of 200-500 x 10(6) cells/l. After 3 months, the HU group had a higher proportion of patients with viral load < 200 x 10 cells/l. At the end of the 3 months blinded period, patients in the placebo group had the option to add HU if their viral load remained > 200 x 10(6) cells/l. We report results after 24 months. RESULTS: Seventy-two patients were randomized to the HU arm, and a further 30 elected to add HU after 12 weeks. Twenty-four months after the start of the trial, only 25% of the 72 patients originally randomized to HU, and 20% of the 30 who added HU after week 12, were still taking it. The reasons for stopping HU were: lack of efficacy (45%), adverse events (37%) and patient or physician preference (18%). Side effects were more frequent in the didanosine/stavudine/HU group than in the didanosine/stavudine group: neuropathy (35 versus 15%, P< 0.02), fatigue (22 versus 7%, P< 0.01), and nausea or vomiting (26 versus 9%, P< 0.01). Of those who had discontinued HU, 73% were taking three drugs including a protease inhibitor. Patients who had started HU were compared with similar patients who had started protease inhibitors in the Swiss cohort. The probability of stopping HU was higher than the probability of stopping nelfinavir or indinavir, and similar to the probability of stopping ritonavir. CONCLUSION: HU increased the antiviral effect of stavudine plus didanosine. However, side effects were more frequent, and after 24 months the majority of patients had switched to protease inhibitor regimens.

A placebo-controlled trial of didanosine plus stavudine, with and without hydroxyurea, for HIV infection. The Swiss HIV Cohort Study.

OBJECTIVE: To explore the short-term effects on surrogate markers for HIV progression of didanosine (ddl) plus stavudine (d4T), with or without hydroxyurea. DESIGN: Randomized, double-blinded, prospective study. SETTING: Swiss HIV Cohort Study. PATIENTS: A total of 144 patients (75% antiretroviral-naive) were studied (mean baseline HIV-1 RNA, 4.53 log10 copies/ml; mean CD4 cell count, 370 x 10(6)/l). INTERVENTION: Patients received ddl (200 mg twice daily) plus d4T (40 mg twice daily), with additional hydroxyurea (500 mg twice daily) or placebo. MAIN OUTCOME MEASURES: The primary endpoint was a reduction of viraemia below 200 copies/ml after 12 weeks. At that time, patients who did not reach the primary endpoint were withdrawn in the hydroxyurea arm, whereas patients in the placebo group had the option of adding hydroxyurea to ddl and d4T. All patients were followed until week 24. RESULTS: After 12 weeks, 54% of the patients randomized to hydroxyurea had viraemia below 200 copies/ml, compared with 28% on placebo (P < 0.001). Using an ultrasensitive assay with a limit of detection of 20 copies/ml, 19% of patients receiving hydroxyurea had viraemia levels below 20 copies/ml, compared with 8% on placebo (P = 0.05). Mean decrease in HIV-1 RNA was 2.3 and 1.7 log10 copies/ml for hydroxyurea and placebo groups, respectively (P = 0.001). Hydroxyurea was found to induce lymphopenia (-124 x 10(6)/l). Increase in CD4 cell counts was +28 x 10(6)/l during hydroxyurea treatment compared with +107 x 10(6)/l on placebo (P = 0.001). CONCLUSIONS: Hydroxyurea improved the antiviral activity of d4T and ddl over a 12-week period, but was associated with a smaller increase in CD4 cell counts due to hydroxyurea-induced lymphopenia.

Viral burden in genital secretions determines male-to-female sexual transmission of HIV-1: a probabilistic empiric model.

OBJECTIVE: To develop a model to predict transmission of HIV-1 from men to women. DESIGN: HIV-1 in seminal plasma, and endocervical CCR5 receptors were correlated with epidemiological studies of HIV-1 transmission to develop a probabilistic model. SETTINGS: Semen samples were collected from patient subjects in Seattle Washington, Chapel Hill, North Carolina, and St. Gallen, Switzerland. Endocervical biopsy specimens were obtained from women in Chicago, Illinois. PARTICIPANTS: Eighty-six men (not receiving antiretroviral therapy) in whom CD4 cell count and semen volume were available, and 24 women in whom the number of endocervical CCR5 receptors were determined. MAIN OUTCOME MEASURES: Prediction of transmission of HIV-1 from men to women per episode of vaginal intercourse based on the absolute burden of HIV (volume x HIV RNA copies/ml seminal plasma). RESULTS: The model suggests efficient heterosexual transmission of HIV-1 when semen viral burden is high. When semen contains 100 000 copies of non-syncytium-inducing (NSI) HIV RNA the probability of HIV-1 transmission is 1 per 100 episodes of intercourse; conversely, with 1000 copies NSI HIV RNA in semen, transmission probability is 3 per 10 000 episodes of intercourse. CONCLUSIONS: This model links biological and epidemiological data related to heterosexual HIV-1 transmission. The model can be used to estimate transmission of HIV from men with high semen viral burden from inflammation, or reduced burden after antiretroviral therapy. The results offer a biological explanation for the magnitude of the HIV epidemic in places where earlier studies have shown men have high semen viral burden, such as in sub-Saharan Africa. The model can be used to develop and test HIV-1 prevention strategies.

Acute HIV infection: impact on the spread of HIV and transmission of drug resistance.

OBJECTIVE: To assess the impact of primary HIV infection (PHI) on the spread of HIV and the temporal trends in transmission of HIV drug resistance between 1996 and 1999 in Switzerland. METHODS: Sequencing of the genes for reverse transcriptase (RT) and protease was performed for 197 individuals with documented PHI. Phylogenetic analyses were confronted with epidemiological data. RESULTS: Significant clustering was demonstrated for 29% of the RT sequences. All these cases occurred closely together in place and time; contact tracing demonstrated transmission at the time of PHI in 30% of them. Genotypic drug resistance was detected in 8.6% of PHI individuals in 1996, 14.6% in 1997, 8.8% in 1998 and 5.0% in 1999. Drug-resistant variants were identified in 11.3% of individuals infected by homosexual contacts, 6.1% by heterosexual contacts, 13% of intravenous drug users and more frequently in men (10.4%) than women (2.6%). Potential factors involved in the recent decrease of transmission of drug-resistant variants include increase of HIV non-B subtypes from 23% in 1996 to 35% in 1999 (only one non-B subtype had resistance mutations) and a steady increase of patients with undetectable viraemia as documented in Swiss HIV Cohort Study (10% in 1996 vs 53% in 1999). CONCLUSIONS: Phylogenetic and epidemiological analyses underline the impact of PHI in the spread of HIV. Moreover, this study indicates that drug resistance transmission may have decreased recently in Switzerland through the increased frequency of infection with HIV non-B subtypes and the steady increase of patients with undetectable viraemia.

Didanosine plus stavudine with or without hydroxyurea in HIV-1-infected patients: 1 year follow-up. Swiss HIV Cohort Study.

A total of 144 human immunodeficiency virus (HIV)-infected patients (mean CD4 cell count, 367 cells/mm3) were included in a double-blind placebo-controlled trial testing the efficacy on surrogate markers of HIV progression of the combination didanosine (2',3'-dideoxyinosine or DDI) plus stavudine (2',3'-didehydro-2',3'-dideoxythymidine or D4T) with or without hydroxyurea. The primary end point was a reduction of HIV RNA levels to below 200 copies/ml after 12 weeks of treatment. The results showed that the triple combination was associated with a more profound decrease in HIV RNA with an increased proportion of patients with viraemia < 200 copies/ml. This effect persisted for the majority of the patients after a 48 week follow-up. In contrast, the increase in CD4 cell counts was less in patients treated with hydroxyurea because of lymphopenia, and adverse events were more frequent in hydroxyurea-treated patients. In conclusion, the addition of hydroxyurea consistently improved the antiviral activity of the didanosine/stavudine combination over a 48 week follow-up. Increased toxicity and decreased effect on CD4 cell counts might inspire caution.

Factors associated with changes in HIV shedding in semen.

The efficiency and duration of transmissibilty of HIV seems to be highly variable and dependent on a number of factors related to both the donor and the recipient as well as characteristics intrinsic to the virus itself. Some of the factors likely to be important in sexual transmission of HIV include stage of disease, antiretroviral therapy, and concomitant systemic or mucosal infections, including sexually transmitted diseases. This paper describes recent work from our group in each of these areas.

Sensitive method for the detection of infectious HIV in semen of seropositive individuals.

The aim of the study was to develop a sensitive culture method for the detection of HIV in semen. Antimicrobials were evaluated to suppress bacterial and fungal contamination of HIV cultures. Toxicity of seminal plasma was reduced using a short incubation of seminal fluid with culture cells. The detection rate was determined by adding known amounts of diluted primary virus isolates to uninfected cells. The sensitivity of the method was determined in a cohort of 33 HIV seropositive men. The use of a virus transport medium with high doses of antibiotics reduced contamination of HIV cultures. Toxicity of seminal plasma on culture cells was limited when seminal fluid was incubated with culture cells for only 90 min. Detection levels for cell-associated virus and cell-free virus from semen were 12 infected cells per ejaculate and 100 infectious units per milliliter of seminal fluid, respectively. Cell-associated HIV could be recovered from 18 semen samples of 33 HIV positive men (55%). Recovery of cell-free virus from seminal fluid was infrequent. It is concluded that the method is highly sensitive for the detection of HIV from semen. However, the recovery rate of infectious cell-free virus in seminal fluid from clinical samples is infrequent.

A randomised prospective study to evaluate a rapid HIV-antibody assay in the management of cases of percutaneous exposure amongst health care workers.

A rapid start of post-exposure prophylaxis with an antiretroviral regime is recommended after percutaneous exposure to blood from an HIV-positive source. Since the HIV-antibody status of the source is usually not known at the time of injury, antiretroviral treatment is started pending the results of HIV testing of the source. A randomised prospective study was designed to compare the use of a rapid-screening assay in the management of cases of percutaneous exposure with the conventional procedure. Prior to the comparative study, the accuracy of a rapid-screening assay performed by non-laboratory trained personnel was evaluated. 123 blinded HIV-positive and HIV-negative samples were correctly identified. In a randomised comparison with the conventional procedure, the application of the rapid-screening assay resulted in a significant reduction of psychological stress, drug use and cost. The estimated net benefit per case was CHF 93.-(62 US$). This study strongly supports the use of the rapid-screening assay in the management of post-exposure prophylaxis for HIV after percutaneous exposure in health care workers.

Predictive value of adherence in patients starting highly active antiretroviral treatment for HIV infection.

Strict adherence to the prescribed drug regimen is one of the most important predictors of success in the antiretroviral therapy of HIV infection. Ideally, patients should learn to optimise their drug adherence before they start antiviral therapy. This study evaluated the predictive role of adherence during the first four weeks of treatment for mid-term treatment outcome. Adherence was evaluated using electronic dosing systems during the first 25 days of therapy in 66 drug-naïve patients starting a new antiretroviral therapy. Treatment outcome (HIV-RNA suppression) was evaluated at week 24 of treatment. Good adherence (>95%doses taken) was associated with better rates of viral suppression (77% vs. 44% Patients with HIV-RNA below 50 copies/ml). Specific education programmes targeted at the achievement of optimal adherence during the first few weeks of therapy might result in better treatment results.

[Sexual transmission of HIV: effect of potent antiretroviral therapy]. / Sexuelle Ubertragung von HIV: Einfluss der potenten antiretroviralen Therapie.

The recent progress of our understanding of the pathophysiology of human immunodeficiency virus (HIV) infection and the availability of new antiretroviral compounds has markedly improved the prognosis of patients infected with HIV. It has been postulated as early as 1991 that potent community-wide treatment of HIV infection could paradoxically lead to an increased spread of the HIV epidemic if treatment is not associated with a reduced infectivity of HIV. In the past few years, several groups have demonstrated a good correlation of the quantity of HIV present in semen with factors that are known to increase the likelihood of sexual transmission of HIV. A similar correlation has recently been demonstrated for the presence of HIV in female genital secretions. During the past year, a number of studies have demonstrated a marked effect of antiretroviral treatment on the shedding of HIV in the male and female genital tract, indicating a potential role of antiretroviral treatment for the prevention of HIV infection. Although potent antiretroviral therapy is beneficial on a public health basis, patients with no detectable virus in their blood or semen under treatment should not be considered non-infectious and patients should keep up with safer sex practices.